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Management of Chronic Liver Failure
DEIRDRE KELLY
ESPGHAN GOES TO AFRICA
CAPETOWN
October 2013
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End Stage Liver Failure
Aetiology of Chronic Liver Disease
- Neonatal liver disease
- Chronic hepatitis
- Metabolic
- Fibropolycystic liver disease
- Drugs
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Neonatal Cholestasis
Extrahepatic:- Biliary atresia
Neonatal Hepatitis Syndrome (NHS)
- Intrauterine infection
- Inborn error of metabolism
- Biliary hypoplasia (Alagille/PFIC)
- Inborn errors of bile salt metabolism
- Prematurity
- Endocrine
TPN cholestasis
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Chronic Liver Disease
- Chronic viral hepatitis (B&C)
- Autoimmune hepatitis
Type I (ANA, SMA +ve)
Type II (LKM +ve)
Sclerosing cholangitis
- Metabolic liver disease
Alpha-1-antitrypsin deficiency
Cystic fibrosis
Wilson’s disease
- Non Alcoholic Fatty Liver Disease
- Drugs
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Chronic Liver Disease
Jaundice may be absent
Malnutrition
Stunting
Hypersplenism
Low Hb, white cells and platelets
Bruising/petechiae/epistaxis
Hepatosplenomegaly
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Viral Hepatitis B & C
• World wide disease
• Perinatal transmission
• Chronic Asymptomatic Infection
• Acute Infection
– Rare in childhood
• Significant risk of chronic liver disease
• Hepatocellular Carcinoma
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Wilson’s Disease
• Autosomal recessive:
• Incidence of 1:30,000 live births.
• The gene is on chromosome 13
• Encodes a copper transporting P-type ATPase-ATP7B ATPase.
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Wilson’s Disease
• Hepatic presentation < 12 years
– Acute or chronic hepatitis/Failure
– Haemolysis
– Low alkaline phosphatase
• Neurological > 12 years
– Slurred speech/Tremor /poor co-ordination
• Kayser Fleischer rings
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Tyrosinaemia Type I
Incidence 1:50,000
Deficiency of fumaryl-aceto-acetase
Succinyl acetone in urine
Deficiency of FAA in fibroblasts
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Clinical Presentation of TTI
Chronic Liver Failure
- Failure to thrive
- Hepatosplenomegaly
- Rickets
- Cardiomyopathy
- Renal failure
- Neurological symptoms
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Fatty Liver Disease
Definitions:
Non Alcoholic Fatty Liver Disease (NAFLD)
- hepatic steatosis without inflammation
Non Alcoholic Steatohepatitis (NASH)
- hepatic steatosis with hepatocellular injury +/- fibrosis/cirrhosis
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Fatty Liver Disease Increasingly common cause of
- elevated transaminases
- hepatomegaly
- “bright” liver on ultra sound
Associated with Insulin Resistance Diabetes type 2
Alstrom Syndrome
Bardet – Biedl Syndrome
Polycystic Ovary
Turner Syndrome
Lipodystrophy
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Clinical features of Fatty Liver Disease
Children more likely to be symptomatic
RUQ pain
Fatigue/malaise
Most present coincidentally
Hepatomegaly
ALT/AST (1.5 – 5 times normal)
ALT/AST ratio > 1 in most NAFLD
elevated triglycerides
acanthosis nigricans
insulin resistance
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Treatment for Fatty Liver Disease
• WEIGHT LOSS – Diet and Exercise
– cannabinoid receptor blockade (Rimonabant/Acomplia) – Lipase inhibition Orlistat
• ANTIDIABETIC THERAPY – Insulin sensitizer – Glitazone – Metformin
• ANTIOXIDATIVE THERAPY
– Vitamin E
• ANTI LIPID THERAPY – Statin
• URSODEOXYCHOLIC ACID
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Hepatocellular Dysfunction in Children
Multi-organ failure
Primary: Cardiac (Alagille, HOCM)
Renal (RTA)
Cerebral (mitochondrial disease)
Secondary: Encephalopathy
Functional renal failure
Cardiac failure
Coagulopathy
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Chronic Liver Disease in Children
Persistent liver disease (>8 weeks)
- Sustained hepatic dysfunction
- Biochemical/histological
- Functionally - Jaundice
- Coagulopathy
- Hypoglycaemia
- Portal hypertension
- Malnutrition
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Effect of Hepatic Dysfunction
Cholestasis
- Pruritus
- Steatorrhoea
- Fat soluble vitamin deficiency
- Malnutrition
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Management of End Stage Liver Failure
Supportive:
Prevention therapy:-
- Hepatic complications
- Sepsis
Nutritional support
Psychosocial
- child/family
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Nutritional Management of End Stage Liver Failure
Modular feed: High protein/CHO
Balanced MCT/LCT
Low salt
150% RDA
Fat soluble vitamins A, D, E, K
- Oral
- Nasogastric
- Parenteral
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Management of End Stage Liver Failure
Hepatic Encephalopathy
- Low protein diet (2g/kg)
- Lactulose 5.20 ml/day
- Neomycin 0.5 g TID
- Rifaxamine
Prompt treatment of sepsis/haemorrhage
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Hepatocellular Dysfunction in Children
Fluid Management
Pathophysiology: Na/water retention
Ascites
Fluid overload
Management: Fluid restriction
Calorie requirement
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Management of End Stage Liver Failure Ascites and Fluid Retention
- Fluid and salt restriction
- (2/3 maintenance)
- Diuretics: Spironolactone 3mg/kg
Frusemide 1-2 mg/kg
- Ascitic tap/drainage
- Haemofiltration/Dialysis
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Management of Pruritus
Enzyme inducers:-
- Phenobarbitone (5-15 mg/kg)
- Rifampicin (3 mg/kg)
Bile Diversion:-
- Ursodeoxycholic acid (20 mg/kg)
- Cholestyramine (1-4G/d)
- Biliary diversion
Central:-
- Naloxone
- Ondansetron
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Management of End Stage Liver Failure
Coagulopathy:
Vitamin K 2-10 mgm/kg
Fresh frozen plasma 10 ml/kg
Cryoprecipitate
Platelets
Anaemia:
Oral iron
Transfusion
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Management of End Stage Liver Failure
Specific:
Immunosuppression (CAH)
Penicillamine (Wilsons)
Ursodeoxycholic acid (CF)
Anti-viral therapy (Hep B/C)
Diet
Liver Transplantation
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Hepatocellular Dysfunction in Children
Portal Hypertension:
- Varices
- Portal gastropathy
- Hypersplenism
Implications for a normal life:
- School
- Contact sports
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Managing Portal Hypertension in Children
Medical Therapy
Diagnostic endoscopy and therapy
Drug therapy
Transjugular intrahepatic porto-systemic
stent shunt (TIPSS)
Prophylaxis
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Pharmacological Treatment of Portal Hypertension
Hepatic vascular resistance
Reduced by - nitric oxide
prostacyclin
adrenergic antagonists
calcium channel blocker
Portal blood flow
Reduced - vasopressin/glypressin
Somatostatin/octreotide
propranolol
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Prophylaxis of Portal Hypertension in Children
Drug therapy:
• Beta-blockers:
– Propranolol, Nadolol
• 3 small studies in children – Bleeding in 15-33%
• No trials in children with CF
• ? Propranolol contraindicated in CF
• ? Losartan - angiotensin II receptor antagonist
• No trials of prophylactic band ligation in CF
Shashidar et al 1999; Ozsoylu et al, 1985, 2000
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Variceal Bleed
Access site/extent of bleed/stabilise patient IV octreotide/Glypressin
Endoscopic: Band ligation
Sclerotherapy
Successful Unsuccessful
Further Variceal ablation Sengstaken-Blake More Tube
Liver disease EHPVO TIPPS
Portosystemic shunt Transplantation
Management of Acute Variceal Bleed in Childhood
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Results of Variceal Band Ligation in Children
N Ablation Rebleeding
Price 18 70% 30%
Fox 7 100% 28%
Karrer 7 100% 15%
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Limitations of TIPPS Procedures in Children
Age/size of child
Size of portal vein (<2mm)
Size of stent (5-6 mm diameter)
Length of stent:- allow for growth
Long Term Outcome:
Encephalopathy
Occlusion/infection
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Prognosis of Chronic Liver Disease
Depends on:-
- Aetiology
- Severity of insult
- Progression to cirrhosis
- Portal hypertension
Access to liver transplantation
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Indications for Transplantation in Chronic Liver Failure
Laboratory Indices
Serum cholesterol <2.6 mmol/l (100 mg/dl)
Indirect bilirubin >100 mol/l (6mg/dl)
Serum albumin <35 g/l (3.5 mg/dl)
Prothrombin ration (INR) >1.4
Portal vein reverse flow on ultrasonography
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Indications for Transplantation in Chronic Liver Failure
Clinical:-
Severe portal hypertension
Recurrent variceal bleeding
Refractory ascites
Intractable pruritus
Growth retardation
Unacceptable quality of life
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0.00 5.00 10.00 15.00 20.00 25.00
Years post OLT
0.0
0.2
0.4
0.6
0.8
1.0
Cu
mu
lati
ve s
urv
ival
Hepatoblastoma n= 16
EHBA n = 190
Fulminant n =70
AIH n = 22
Others n = 144
Survival post transplant by disease (1989-2005)
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Chronic Liver Disease
Chronic liver disease
Early referral and recognition of liver disease
Referral to Specialist centre
• Early diagnosis
• Consideration of Treatment
• Improve outcomes for children