UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis OverviewOverview
BasicBasic
Clinical AspectsClinical Aspects
ManagementManagement
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is Cystic FibrosisWhat Is Cystic Fibrosis
bull Autosomal recessive diseasebull W-13000 H-110000 AA-115000
bull Mutations of CFTRhellipdefective Cl- transport
bull CFTRbull Lung pancreas GI sweat bile ducts
bull Autosomal recessive diseasebull W-13000 H-110000 AA-115000
bull Mutations of CFTRhellipdefective Cl- transport
bull CFTRbull Lung pancreas GI sweat bile ducts
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
NBD1NBD1
MSD1MSD1
cAMP-PKA-ATPcAMP-PKA-ATP
NBD2NBD2
MSD2MSD2
RATPATP ATPATP
Secretin
uarrcAMP
Phosphorylation
Channel OPENS
SecretinSecretin
uarruarrcAMPcAMP
Phosphorylation Phosphorylation
Channel Channel OPENSOPENS
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFrdquo
What is CFldquoAnatomy amp Physiology 101 of CFrdquo
NBD2NBD2NBD1NBD1
MSD1MSD1 Secretin
uarrcAMP
Phosphorylation
Channel OPENS
SecretinSecretin
uarruarrcAMPcAMP
Phosphorylation Phosphorylation
Channel Channel OPENSOPENS
R
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
NBD1NBD1
MSD1MSD1
R
darr FlowhellipuarrViscosity
Focal obstruction
uarrldquoBADrdquo bile acids
Liver cell injury
Stellate cells
Fibrosisdarr Secretion of Mucin
darrdarr FlowFlowhelliphellipuarruarrViscosityViscosity
Focal obstructionFocal obstruction
uarruarrldquoldquoBADBADrdquordquo bile acidsbile acids
Liver cell injuryLiver cell injury
Stellate cellsStellate cells
FibrosisFibrosisdarrdarr Secretion of MucinSecretion of Mucin
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFRetrospective
Prevalence of Liver Disease in CFRetrospective
Country No studied uarr LFT Cirrhosis GB Sx HSMUS 19064 24 01-17
(1)03
UK 1100 129 06 42
UK 233 25 25
France 450 30 7 08
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFProspective
Prevalence of Liver Disease in CFProspective
Country No studied uarr LFT HepatomegalyUS 99 38
US 526 46
Australia 153 9 30
Italy 189 17 30
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Clinical PresentationWhat Is the Clinical Presentation
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is Cystic FibrosisWhat Is Cystic Fibrosis
bull Autosomal recessive diseasebull W-13000 H-110000 AA-115000
bull Mutations of CFTRhellipdefective Cl- transport
bull CFTRbull Lung pancreas GI sweat bile ducts
bull Autosomal recessive diseasebull W-13000 H-110000 AA-115000
bull Mutations of CFTRhellipdefective Cl- transport
bull CFTRbull Lung pancreas GI sweat bile ducts
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
NBD1NBD1
MSD1MSD1
cAMP-PKA-ATPcAMP-PKA-ATP
NBD2NBD2
MSD2MSD2
RATPATP ATPATP
Secretin
uarrcAMP
Phosphorylation
Channel OPENS
SecretinSecretin
uarruarrcAMPcAMP
Phosphorylation Phosphorylation
Channel Channel OPENSOPENS
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFrdquo
What is CFldquoAnatomy amp Physiology 101 of CFrdquo
NBD2NBD2NBD1NBD1
MSD1MSD1 Secretin
uarrcAMP
Phosphorylation
Channel OPENS
SecretinSecretin
uarruarrcAMPcAMP
Phosphorylation Phosphorylation
Channel Channel OPENSOPENS
R
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
NBD1NBD1
MSD1MSD1
R
darr FlowhellipuarrViscosity
Focal obstruction
uarrldquoBADrdquo bile acids
Liver cell injury
Stellate cells
Fibrosisdarr Secretion of Mucin
darrdarr FlowFlowhelliphellipuarruarrViscosityViscosity
Focal obstructionFocal obstruction
uarruarrldquoldquoBADBADrdquordquo bile acidsbile acids
Liver cell injuryLiver cell injury
Stellate cellsStellate cells
FibrosisFibrosisdarrdarr Secretion of MucinSecretion of Mucin
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFRetrospective
Prevalence of Liver Disease in CFRetrospective
Country No studied uarr LFT Cirrhosis GB Sx HSMUS 19064 24 01-17
(1)03
UK 1100 129 06 42
UK 233 25 25
France 450 30 7 08
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFProspective
Prevalence of Liver Disease in CFProspective
Country No studied uarr LFT HepatomegalyUS 99 38
US 526 46
Australia 153 9 30
Italy 189 17 30
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Clinical PresentationWhat Is the Clinical Presentation
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
NBD1NBD1
MSD1MSD1
cAMP-PKA-ATPcAMP-PKA-ATP
NBD2NBD2
MSD2MSD2
RATPATP ATPATP
Secretin
uarrcAMP
Phosphorylation
Channel OPENS
SecretinSecretin
uarruarrcAMPcAMP
Phosphorylation Phosphorylation
Channel Channel OPENSOPENS
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFrdquo
What is CFldquoAnatomy amp Physiology 101 of CFrdquo
NBD2NBD2NBD1NBD1
MSD1MSD1 Secretin
uarrcAMP
Phosphorylation
Channel OPENS
SecretinSecretin
uarruarrcAMPcAMP
Phosphorylation Phosphorylation
Channel Channel OPENSOPENS
R
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
NBD1NBD1
MSD1MSD1
R
darr FlowhellipuarrViscosity
Focal obstruction
uarrldquoBADrdquo bile acids
Liver cell injury
Stellate cells
Fibrosisdarr Secretion of Mucin
darrdarr FlowFlowhelliphellipuarruarrViscosityViscosity
Focal obstructionFocal obstruction
uarruarrldquoldquoBADBADrdquordquo bile acidsbile acids
Liver cell injuryLiver cell injury
Stellate cellsStellate cells
FibrosisFibrosisdarrdarr Secretion of MucinSecretion of Mucin
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFRetrospective
Prevalence of Liver Disease in CFRetrospective
Country No studied uarr LFT Cirrhosis GB Sx HSMUS 19064 24 01-17
(1)03
UK 1100 129 06 42
UK 233 25 25
France 450 30 7 08
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFProspective
Prevalence of Liver Disease in CFProspective
Country No studied uarr LFT HepatomegalyUS 99 38
US 526 46
Australia 153 9 30
Italy 189 17 30
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Clinical PresentationWhat Is the Clinical Presentation
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFrdquo
What is CFldquoAnatomy amp Physiology 101 of CFrdquo
NBD2NBD2NBD1NBD1
MSD1MSD1 Secretin
uarrcAMP
Phosphorylation
Channel OPENS
SecretinSecretin
uarruarrcAMPcAMP
Phosphorylation Phosphorylation
Channel Channel OPENSOPENS
R
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
NBD1NBD1
MSD1MSD1
R
darr FlowhellipuarrViscosity
Focal obstruction
uarrldquoBADrdquo bile acids
Liver cell injury
Stellate cells
Fibrosisdarr Secretion of Mucin
darrdarr FlowFlowhelliphellipuarruarrViscosityViscosity
Focal obstructionFocal obstruction
uarruarrldquoldquoBADBADrdquordquo bile acidsbile acids
Liver cell injuryLiver cell injury
Stellate cellsStellate cells
FibrosisFibrosisdarrdarr Secretion of MucinSecretion of Mucin
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFRetrospective
Prevalence of Liver Disease in CFRetrospective
Country No studied uarr LFT Cirrhosis GB Sx HSMUS 19064 24 01-17
(1)03
UK 1100 129 06 42
UK 233 25 25
France 450 30 7 08
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFProspective
Prevalence of Liver Disease in CFProspective
Country No studied uarr LFT HepatomegalyUS 99 38
US 526 46
Australia 153 9 30
Italy 189 17 30
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Clinical PresentationWhat Is the Clinical Presentation
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
bull Impaired CFTR RNA synthesisbull Defective folding and maturation
bull ∆F508bull Abnormal regulation of Cl- conductionbull Inhibition of Cl- conductionbull Reduced synthesis of normal protein
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
NBD1NBD1
MSD1MSD1
R
darr FlowhellipuarrViscosity
Focal obstruction
uarrldquoBADrdquo bile acids
Liver cell injury
Stellate cells
Fibrosisdarr Secretion of Mucin
darrdarr FlowFlowhelliphellipuarruarrViscosityViscosity
Focal obstructionFocal obstruction
uarruarrldquoldquoBADBADrdquordquo bile acidsbile acids
Liver cell injuryLiver cell injury
Stellate cellsStellate cells
FibrosisFibrosisdarrdarr Secretion of MucinSecretion of Mucin
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFRetrospective
Prevalence of Liver Disease in CFRetrospective
Country No studied uarr LFT Cirrhosis GB Sx HSMUS 19064 24 01-17
(1)03
UK 1100 129 06 42
UK 233 25 25
France 450 30 7 08
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFProspective
Prevalence of Liver Disease in CFProspective
Country No studied uarr LFT HepatomegalyUS 99 38
US 526 46
Australia 153 9 30
Italy 189 17 30
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Clinical PresentationWhat Is the Clinical Presentation
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
NBD1NBD1
MSD1MSD1
R
darr FlowhellipuarrViscosity
Focal obstruction
uarrldquoBADrdquo bile acids
Liver cell injury
Stellate cells
Fibrosisdarr Secretion of Mucin
darrdarr FlowFlowhelliphellipuarruarrViscosityViscosity
Focal obstructionFocal obstruction
uarruarrldquoldquoBADBADrdquordquo bile acidsbile acids
Liver cell injuryLiver cell injury
Stellate cellsStellate cells
FibrosisFibrosisdarrdarr Secretion of MucinSecretion of Mucin
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFRetrospective
Prevalence of Liver Disease in CFRetrospective
Country No studied uarr LFT Cirrhosis GB Sx HSMUS 19064 24 01-17
(1)03
UK 1100 129 06 42
UK 233 25 25
France 450 30 7 08
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFProspective
Prevalence of Liver Disease in CFProspective
Country No studied uarr LFT HepatomegalyUS 99 38
US 526 46
Australia 153 9 30
Italy 189 17 30
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Clinical PresentationWhat Is the Clinical Presentation
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFRetrospective
Prevalence of Liver Disease in CFRetrospective
Country No studied uarr LFT Cirrhosis GB Sx HSMUS 19064 24 01-17
(1)03
UK 1100 129 06 42
UK 233 25 25
France 450 30 7 08
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFProspective
Prevalence of Liver Disease in CFProspective
Country No studied uarr LFT HepatomegalyUS 99 38
US 526 46
Australia 153 9 30
Italy 189 17 30
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Clinical PresentationWhat Is the Clinical Presentation
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Prevalence of Liver Disease in CFProspective
Prevalence of Liver Disease in CFProspective
Country No studied uarr LFT HepatomegalyUS 99 38
US 526 46
Australia 153 9 30
Italy 189 17 30
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Clinical PresentationWhat Is the Clinical Presentation
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Clinical PresentationWhat Is the Clinical Presentation
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Hepatomegaly bull Vertical spanbull Xiphoid
bull Portal HTNbull Cirrhosisbull Stigmata
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
bull Abnormal ldquoLFTrsquosrdquobull Jaundice late
bull Obstructionbull Reduced synthetic fxn
bull Neonatal cholestasisbull Fatty liverbull Gallbladder
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
0
20
40
60
80
100
0
20
40
60
80
100
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
CFTR Pancreatic Gender Meconium Mec ileusGenotype Function (MF) Ileus Equivalent
Can liver disease be ldquopredictedrdquoCan liver disease be ldquopredictedrdquo
Lung diseaseWeightHeight
Age
Wilschanski 1999 n=288 (liver dz 80)
Live
r dis
ease
()
Live
r dis
ease
()
Live
r dis
ease
()
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
What Is the Natural HistoryWhat Is the Natural HistoryItalian-prospective Follow-upTotal studied 177 143 yr
Liver Disease 48
Cirrhosis 17 85 yrsPortal HTN 13Esophageal varices 4Liver Transplant 1
Colombo et al Hepatology 2002Colombo et al Hepatology 2002
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
What is Natural HistoryWhat is Natural HistoryNormal Ultrasound
(n=106)Normal Ultrasound
(n=106)
Normal (n=87)Normal (n=87)
Hetero(n=5)
Hetero(n=5)
Nodular (n=6)
Nodular (n=6)
PHT(n=8)PHT(n=8)
Hetero(n=15)Hetero(n=15)
Nodular (n=10)
Nodular (n=10)
11
33
77
443355
AgeGender
Meconium ileus-equivLung disease
WeightHeight
AgeGender
Meconium ileus-equivLung disease
WeightHeight
Age 6 yoFU 10 yrs6 scanspt
Age 6 yoFU 10 yrs6 scanspt
Lenaerts et al J Peds 2003Lenaerts et al J Peds 2003
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
bull Historybull Liver-related issues
bull Toxinsbull Medicationsbull Alcoholbull Herbs and supplements
bull Physical examhellipfocus on liver
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Viral hepatitisbull HAV HBV HCV
bull Metabolicbull A1AT deficiencybull Wilsonrsquos Dzbull Hemochromatosis
bull Autoimmune
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
bull Drugsbull Hepatic congestion
bull Heart failurebull Anatomical disorders
bull Choledochal cystsbull Congenital hepatic
fibrosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Evaluation of Liver Disease in CFEvaluation of Liver Disease in CF
lsquoIDArsquo ScanlsquoIDArsquo Scan EndoscopyEndoscopy
ERCPERCP
Specialized TestingSpecialized TestingSpecialized Testing
Liver BxLiver Bx
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CF
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
bull Screeningbull Liver sizehellipedgebull Liver biochemistry
bull Medicalbull Fatty liver optimize nutritionbull Hepatic congestionbull Cholestasis-fibrosis-cirrhosis
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
bull Ursodeoxycholic acid
bull Mechanisms of actionbull Promotes HCO3-rich bile flowbull Displaces ldquotoxicrdquo bile acids
bull Significantly retards fibrosis in PBC
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
bull Colombo 1996bull 28 children
bull 138 yrsbull Liver disease
bull Hepatomegalybull uarr LFTrsquos
bull UDCA 15 mgkgd x 1y
GGT 5nuc AST ALTGGT 5nuc AST ALT
Management of Liver Disease in CFManagement of Liver Disease in CFCholestasis-fibrosis-cirrhosis
No direct evidence delay or reversal
of progressive fibrosis
No direct evidence delay or reversal
of progressive fibrosis
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UDCACirrhosis
112 to 32
No differencePortal HTNEsophageal varices
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
URSODEOXYCHOLIC ACIDURSODEOXYCHOLIC ACID
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
AUC C max T max
Urso250 Urso250 Ursolvan Actigall
ARE THEY ALL ALIKE
lsquoWilliamrsquos ReportrsquolsquoWilliamrsquos Reportrsquo
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFPortal hypertensionPortal hypertension
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
bull Varicesbull Endoscopicbull Beta-blockers
bull Ascitesbull Salt restrictionbull Diuretics
SurgicalPorto-systemic shunt
Liver replacement
SurgicalPorto-systemic shunt
Liver replacement
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Management of Liver Disease in CFManagement of Liver Disease in CFLiver TransplantationLiver Transplantation
Pts Survival1 yr 5 yrs
Favorable lung fxn
Mack 1995 8 75 62 55
Fridell 2003 12 92 75
68
89
UF Program 2005 8 100 68
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Experimental Therapy for CF∆F508
Experimental Therapy for CF∆F508
4-phenyl butyrate44--phenyl butyratephenyl butyrate
Enhanced expression and Cl- secretionRestoration of Cl- transport
Enhanced expression and ClEnhanced expression and Cl-- secretionsecretionRestoration of ClRestoration of Cl-- transporttransport
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
Liver Disease in Cystic Fibrosis Liver Disease in Cystic Fibrosis ConclusionsConclusions
ImportantImportant
Medical TherapyMedical Therapy
FutureFuture
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
The Liver in Cystic Fibrosis The Liver in Cystic Fibrosis
Regino P Gonzaacutelez-Peralta MDRegino P Gonzaacutelez-Peralta MD
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
Pediatric Hepatology and Liver TransplantationUniversity of Florida College of Medicine
Gainesville Florida
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
AcknowledgementsAcknowledgements
UF-Pediatric PulmonaryUF-Pediatric Pulmonary
Axcan-Scandipharm Pharmaceuticals
Axcan-Scandipharm Pharmaceuticals
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-
UF Pediatric Liver CenterUF Pediatric Liver Center
- Liver Disease in Cystic Fibrosis
- What Is Cystic Fibrosis
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFrdquo
- What Is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- What is CFldquoAnatomy amp Physiology 101 of CFTRrdquo
- Prevalence of Liver Disease in CFRetrospective
- Prevalence of Liver Disease in CFProspective
- What Is the Clinical Presentation
- Can liver disease be ldquopredictedrdquo
- What Is the Natural History
- What is Natural History
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Evaluation of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- URSODEOXYCHOLIC ACID
- Management of Liver Disease in CF
- Management of Liver Disease in CF
- Experimental Therapy for CFΔF508
- Liver Disease in Cystic Fibrosis
- The Liver in Cystic Fibrosis
- Acknowledgements
-