end stage liver isease in p c s professionals/gp-liaison-centre... · further blood tests: bill 34,...
TRANSCRIPT
END STAGE LIVER DISEASE
IN
PRIMARY CARE SETTING
Thwin Maung Aye
National University Hospital
18th October 2014
ROLE OF FAMILY PHYSICIAN
Understanding natural history of cirrhosis and
shared care with the institution
Prevention of liver cirrhosis
Understanding tumor (HCC) biology and surveillance
Understanding role of liver transplant and timely referral
OBJECTIVES OF THE TALK
To acknowledge the common scenarios, outline
management plan and appreciate role of primary
physician
To update new DAA for hepatitis C
To understand the rationale and indication of
transplantation for appropriate referral
COMMON SCENARIOS?
1. Known fatty liver, regular follow up with LFT and
USG which was reported as nodular surface
2. First time diagnosis of HBsAg+ve in view of
abnomal LFT. USG reported as nodular surface
3. Patient present with leg swelling. Blood tests
showed abnormal LFT and nodular liver surface
COMMON SCENARIOS?
4. Patient known cirrhotic but defaulted follow up and
came to see you with bleeding PR
5. Known cirrhotic patient, on diuretics, lactulose and
propranolol and come to see with confusion and
worsening of ascites before hospital appointment
6. Patient came for weight loss, jaundice and palpable
mass in RHC
CASE SCENARIO FOR ESLD
50 years old man, Mr Ng, came to see you as a routine
follow up for her hypertension, diabetes and
hyperlipidaemia. He has been taking amlodipine, glipizide
and simvastatin. He had no compliant. His BP was 140/90
mmHg and BMI was 30. Other clinical examination were
unremarkable. USG done was reported as early cirrhosis
and mild splenomegaly. His blood tests were as followed.
Hb 12, TWC 5.2, Platelet 120
Na 135, K 3.5, Urea 7, creatinine 98,
AST 80, ALT 68, Albumin 32, Bilirubin 8, AFP 5, INR 1.2
HBA1c 7.8, LDL 3.2, cholesterol 5.8, Tg 1.2
WHAT ARE YOU GOING TO DO NEXT?
A)
Review
his.
..
B) R
efer t
o ho...
C) R
efer t
o ho...
D) A
+B
E) A
+C
0% 0% 0%0%0%
A) Review history & investigations
and optimize the control his
metabolic syndrome and review
in 3-6 months
B) Refer to hospital in view of USG
finding
C) Refer to hospital in view of
transaminitis
D) A+B
E) A+C
Countdown
15
IF YOU PLAN TO REFER, WHAT WILL YOU DO
BEFORE REFERRAL?
A) F
urther r
eleva
nt hist
...
B) H
epatitis
mark
er
C) D
ietic
ian re
view
D) C
omplia
nce to
medic.
..
E) A
ll of a
bove
0% 0% 0%0%0%
A) Further relevant history
including social history
B) Hepatitis marker
C) Dietician review
D) Compliance to medication
E) All of above
Countdown
15
IF HBSAG+VE, WHAT IS POSSIBLE DIAGNOSIS?
A) N
ASH
B) H
epB liver .
..
C) C
rypto
genic...
D) A
lcoholic
c...
D) A
+B
0% 0% 0%0%0%
A) NASH
B) HepB liver cirrhosis
C) Cryptogenic cirrhosis
D) Alcoholic cirrhosis
D) A+B
Countdown
15
WHAT IS/ARE YOUR PLAN(S) OF MANAGEMENT?
A) L
ife st
yle ..
.
B) O
ptimiza
tio...
C) F
urther e
va...
D) R
eferra
l to...
E) A
ll of a
bov...
0% 0% 0%0%0%
A) Life style modification (dietician
review , exercises)
B) Optimization of his metabolic
syndrome control
C) Further evaluation of hepatitis B
/ other aetiologies
D) Referral to hospital for
evaluation of possible cirrhosis
E) All of above
Countdown
15
MR NG WAS REFERRED TO NUH DC
Here are the tests / evaluation done in NUH
Confirmed Child A cirrhosis after the followings.
Hepatitis B viral load: 6 log, HBeAg-ve, HBeAb+ve
Hepatitis C (-)ve, HIV (-)ve, Autoimmune screening (-)ve
Fibroscan: 19.8 kpa
Liver biopsy: NI 4/16, Fibrosis 5/6
Tenofovir was started
OGD: Small 2 column of varices, for surveillance
Advice on low salt diet
Advice for regular 6 monthly follow up in NUH
MR NG HAS REGULAR FOLLOW UP WITH YOU
FOR HIS METABOLIC SYNDROME. WHAT IS
YOUR CONCERN REGARDING HIS CIRRHOSIS?
A) N
o conce
rn ..
.
B) A
dequate co
...
C) m
ake su
re h
...
D) A
ll ab
ove
E) A
ll above e
...
0% 0% 0%0%0%
A) No concern as he has
appointment with NUH
B) Adequate control of his
metabolic syndrome
C) make sure he has regular
follow up for varices and HCC
D) All above
E) All above except A
Countdown
15
BEFORE HIS NUH APPOINTMENT , YOU SAW HIM
FOR HIS REGULAR CLINIC. MR NG SAID HE NOTICED
ABDOMINAL DISTENSION WITHIN 1-2 WEEKS. WHAT
IS YOUR IMPRESSION?
A) a
scite
s fro
m ci
rrhosis
...
B) P
ortal
vein th
rom
bosis..
C) P
oor com
pliance
to d
i..
D) T
o rule
out C
ardia
c / ..
.
E) A
ll of a
bove
0% 0% 0%0%0%
A) ascites from cirrhosis
progression
B) Portal vein thrombosis
/ HCC
C) Poor compliance to diet
particularly salt
intake
D) To rule out Cardiac /
Renal failure
E) All of above
Countdown
15
WHAT WILL YOU DO NEXT?
A) S
tart
diu
r...
B)
Furth
er ev...
C)
Bring fo
rw...
D) A
ll ab
ove
E) A
ll above e
...
0% 0% 0%0%0%
A) Start diuretics
straightaway and
review again
B) Further evaluation
including blood tests
and USG
C) Bring forward his
appointment with
NUH
D) All above
E) All above except A
Countdown
15
MR NG HAS USG AND BLOOD TESTS DONE BY
YOU. THE RESULTS WERE AS FOLLOWED.
USG: moderate ascites, no focal lesion in the liver
was reported
Albumin 28
INR 1.5
Creatinine 98, Na 130
Bilirubin 10, ALP 150
AFP 7.5,
Hb 10.5, TWC 3.8, Platelet 110
Child B
WHAT IS YOUR NEXT PLAN OF MANAGEMENT?
A)
Start
Diuretic
s and re
...
B) T
o monito
r his
weigh...
C) Dieta
ry advic
e toge
th..
D) S
end to N
UH for f
ur...
E) A
ll above exce
pt D
0% 0% 0%0%0%
A) Start Diuretics and
review in 1-2 weeks
B) To monitor his weight
and renal function
C) Dietary advice
together with salt
restriction
D) Send to NUH for
further management
rather than bringing
forward
E) All above except D
Countdown
15
MR NG WAS SEEN BY NUH AS APPOINTMENT
WAS BROUGHT FORWARD
NUH made minor adjustment of diuretics for ascites
Dignostic paracentesis showed neutrophil count of > 250
and ciprofloxacin was started
Repeat OGD: Moderate varices 2 columns and beta
propranolol was started
Appointment was given in 3 months to review (with scan
and blood tests)
WHAT IS YOUR CONCERN NOW?
A) C
irrhosis
care
must
b...
B) J
oint c
are w
ith you is
s...
0%0%
A) Cirrhosis care must be
under NUH
B) Joint care with you is
still possible titrating
diuretics, monitoring
compliant of meds and
diet and follow up
Countdown
15
JUST BEFORE APPOINTMENT WITH NUH , HIS SON
CALLED YOU TO TELL YOU THAT MR NG IS
CONFUSED AND VERY SLEEPY. WHAT DO THINK
THE POSSIBLE CAUSE(S)?
A) H
epatic encephalopath
y
B) S
troke
C) Sepsis
D) D
ehydratio
n and ure...
E) Possib
le all above
0% 0% 0%0%0%
A) Hepatic encephalopathy
B) Stroke
C) Sepsis
D) Dehydration and
ureamic
encephalopathy
E) Possible all above
Countdown
15
WHAT WILL YOU DO NEXT?
A) R
eview
the ..
.
B) A
dvice to
s...
0%0%
A) Review the
patient to find
out precipitating
causes
B) Advice to send to
NUH
straightaway
Countdown
15
THE FOLLOWINGS ARE FINDINGS WHEN YOU
REVIEW.
GCS 15/15, drowsy but orientated to time, place , person
BP 100/70mmHg, HR 90/min, afebrile, HC 7, neurology: NAD,
PR: stale maleana
Bloods: Na 130, Urea 18, Creatinine 180, CRP 15, INR 1.5, Hb
10.2, platelet 120
No new drugs were taken lately
WHAT IS YOUR IMPRESSION?
A) E
lectrolyte
imbala
nce
B) G
rade I e
ncephalo
pathy
C) Varic
eal Bleedin
g
D) S
epsis
E) P
ossible all o
f above
0% 0% 0%0%0%
A) Electrolyte imbalance
B) Grade I encephalopathy
C) Variceal Bleeding
D) Sepsis
E) Possible all of above
Countdown
15
WHAT IS YOUR NEXT ACTION?
A) G
ive st
at dose
of b
ro..
B) S
top d
iure
tics
C) 2
larg
e bore
IV p
lug an...
D) A
dvice to
go to E
D, ...
E) A
ll of a
bove
0% 0% 0%0%0%
A) Give stat dose of broad
spectrum antibiotics
B) Stop diuretics
C) 2 large bore IV plug and IV
drip
D) Advice to go to ED, NUH
ASAP
E) All of above
Countdown
15
MR NG WAS ADMITTED TO NUH. HE WAS TREATED FOR
VARICEAL BLEEDING BY EVL, ANTIBIOTICS, PPI.
ELECTROLYTE WAS CORRECTED. HE HAD REPEAT USG
SCAN DURING ADMISSION.
USG showed suspicious lesion in segment 6 about 1.2 cm and
confirmed HCC with CT after his AKI settled
Further blood tests: Bill 34, INR 1.8, Creatinine 132, Albumin
27, Moderate ascites, Ecolic in blood
Multidisciplinary team discussion on risk of treatment of HCC
in view of his Child C status vs liver transplant option as of
MELD 20 (MELD 20-29: mortality 76% 3 months) once
infection is under control
LEARNING POINTS
Natural history of cirrhosis
stable but can be suddenly deteriorating
Joint care will optimize patient’s condition
Adjusting threshold of both sides for optimizing care
Recognition of primary care involvement in cirrhosis
Antiviral reduced risk of HCC not prevent HCC
ROLE OF FAMILY PHYSICIAN
Shared care of patients with institution Ascites, hepatic encephalopathy, GI bleeding
HCC surveillance / understanding of tumor biology 6-12 monthly scan and LFT, AFP
Timely referral to liver transplant centre Clinical indications (CP score, bleeding, ascites, HE, HCC)
MELD ≥15
Prevention of cirrhosis Alcohol abuse, screening for viral hep, control risk factors for NAFLD
Vaccination programme
NATURAL HISTORY OF END STAGE LIVER DISEASE
Fattovich et al. Hepatology 1995; Liaw et al. Liver 1989; Ikeda et al. J Hepatol 1998.
Cirrhosis 18-20%
HCC 6-15% Decompensation 20-30%
Death
DIAGNOSIS OF CIRRHOSIS
Modality Ultrasound CT MRI
Sensitivity 65-95% 65-84% 68-87%
Specificity 38-93% 68-80% 70-92%
Accuracy 64-88% 67-72% 68-70%
Kudo M et al. Intervirology 2008; 51: Suppl 1,
Ito K et al. Radiology 1999; 211(3): 723-36.
Kristin N et al. Scan J Gastroenterol 2005;40:76-82.
TRANSIENT ELASTOGRAPHY
Shaheen, Am j Gastro 2007, Castera J Hepatol 2008
Metavir score All HBV NAFLD/NASH PSC/PBC HCV
% >F2 fibrosis 50-82% 58% 49-50.4% 60% 2.5-65%
Cutoff level 4-7.9 7 6.6-8.7 7.3 4.5-8.7
AUROC 0.74-0.86 0.81 0.86-0.87 0.920 0.72-0.83
PORTAL HYPERTENSION & CONSEQUENCES
Ascites and its consequences Ascites responsive to diuretics
Recurrent ascites (intolerance, poor compliance, resistant)
SBP
Hepatic encephalopathy Precipitating causes (infection, electrolyte, GI bleeding, stroke,
constipation, poor compliance, neuro meds)
GI bleeding Variceal bleeding (oesophageal / gastric)
ASCITES
Treatment of underlying cause
Salt (/fluid) restriction(2g/day ie 88mmol/day) when?
Diuretics (Spironolactone / +/- frusemide) Stop beta blocker, ACEI and ARB
Weight monitoring (weight loss ≤ 0.5kg)
Spontaneous bacterial peritonitis
Primary prophlaxis (ascite fluid albumin <1.0g/dL, bil>2.5) Secondary prophylaxis
Response assessment Responsive, intolerant, compliance, resistant
ROLE OF MIDODRINE FOR ASCITES
Hepato-renal syndrome
hypotension, post ascites drainage
Diuretics resistant recurrent ascites
Oral formula 7.5-12.5 mg TDS
Improve clinical outcome and survival
Comparison of midodrine and albumin in the prevention of paracentesis-induced circulatory
dysfunction in cirrhotic patients: a randomized pilot study J Hepatol 2012;56:348-354
VAPTANS FOR ASCITES
Vasopressin receptor antagonists
For euvolaemic and hypervolaemic hyponatraemia
(tolvaptan1)
For ascites rather then HypoNa (Satavaptan2)
Side effects, doubtful survival benefit and cost
effectiveness
1. Cardenas A, Gines P, Marotta P, Czerwiec F, Oyuang J, Guevara M, Afdhal NH. Tolvaptan, an oral
vasopressin antagonist, in the treat- ment of hyponatremia in cirrhosis. J Hepatol 2012;56:571-578
2. Wong F, Watson H, Gerbes A, Vilstrup H, Badalamenti S, Bernardi M, Gines P, et al. Satavaptan for the
management of ascites in cirrho- sis: efficacy and safety across the spectrum of ascites severity. Gut
2012;61:108-116
HEPATIC ENCEPHALOPATHY
• Lactulose (reduced absorption of ammonia)
• Rifaximine
• BO at least 2-3 /day
• Precipitating factors • Infection
• Electrolyte
• Compliance
• GI bleeding
• CVA
• Constipation
• Drugs (neuro suppressant)
RIFAXIMIN IN HEPATIC ENCEPHALOPATHY
Prevention of recurrent HE
Minimal, Overt or prevention of recurrent HE
The Effects of Rifaximin in Hepatic Encephalopathy.
Aliment Pharmacol Ther. 2014;40(2):123-132
VARICEAL BLEEDING
• Baseline severity of cirrhosis (Child-Pugh)
• Rate of progression of cirrhosis
• ± Medication and Compliance (Propranolol/Carveidolol)
• Last scope and findings (site of varices) & treatment
• Splanchnic vasoconstrictors and antibiotics
Carveidolol Vs Propranolol ?
Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to
propranolol.Gut.2013 Nov;62(11):1634-41. doi: 10.1136/gutjnl-2012-304038. Epub 2012 Dec 18
HEPATOCELLULAR CARCINOMA (HCC)
• Tumor biology • High risk nature of tumor • Size and number of tumor • Level of AFP
• Treatment history • Last surveillance duration • Previous treatment and modality • Resection • TACE • RFA
STEREOTACTIC BODY RADIATION THERAPY
(SBRT)
Precisely deliver external radiation therapy to tumor
Few side effects
Requires high degree of precision
Un-resectable tumor, not suitable for convetional RT
RISK FOR HCC & LIVER-RELATED DEATH
IN HEPB IMMUNE CONTROL CARRIER
1932 inactive carriers in REVEAL-HBV
Seronegative for HBeAg
Serum HBV DNA <10,000 copies (<2000 IU)/mL
No cirrhosis, HCC, nor elevated ALT
Annual incidence
rates
Inactive
carriers
Controls
(sAg-ve)
Adjusted
hazard
ratio
95% CI
HCC 0.06% 0.02% 4.6 2.5-8.3
Liver-related
deaths
0.04% 0.02% 2.1 1.1-4.1
Older age and alcohol drinking habits were independent predictors of risk for
carriers of inactive HBV to develop HCC
Chen JD et al. Gastroenterology 2010;138:1747-54.
GOALS OF TREATMENT
APASL guidelines 2008
To permanently suppress HBV replication.
The ultimate long-term goal is to achieve “durable response” to prevent hepatic decompensation, reduce or prevent progression to cirrhosis and/or HCC, and prolong survival
AASLD guidelines 2012
To achieve sustained suppression of HBV replication and remission of liver disease.
The ultimate goal is to prevent cirrhosis, hepatic failure and HCC.
EASL guidelines 2009 To improve quality of life and survival by preventing progression of
the disease to cirrhosis, decompensated cirrhosis, end-stage liver disease, HCC and death.
This goal can be achieved if HBV replication can be suppressed in a sustained manner.
Liaw YF et al. Hepatol Int 2008; 2: 263–83; Lok AS et al. Hepatol 2009; AASLD Practice Guidelines; EASL, J Hepatol 2012; Vol.57 167-185.
SELECTION OF TREATMENT FOR CHB
Oral nucleosides
One tab/d
Very few side effects
Can be used for the whole
spectrum of CHB cases
Suppresses virus but does
not eradicate
HBeAg seroconversion 20-
25%
Long term therapy is the
norm
Moderate cost
Immunomodulators
Once weekly injections
Many side effects but usually
tolerable
Cannot be used for advanced
liver disease
Can clear virus in small % of
patients
HBeAg seroconversion >30%
Treatment course is 48 wks
Expensive
INTERNATIONAL GUIDELINES ON RECOMMENDATIONS
AASLD Chronic Hepatitis B: Update 2009. Hepatology 2009;50:1-36 EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol. 2012; Vol.57 167-185
Liaw, Hpeatol Int (in press) 20112
2012
EASL
• Drugs with high potency and low resistance rate , eg. ETV, TDF
2009
AASLD
• Drugs with high potency and high genetic barrier, eg. ETV, TDF
• LAM, ADV and LdT are not preferred for for naïve patients
2012
APASL
• ETV or TDF is the preferred Nuc
IMPROVEMENT IN FIBROSIS (ENTECAVIR)
IMPROVEMENT IN FIBROSIS (TENOFOVIR)
REDUCE HCC OCCURENCE
HCC INCIDENCE IN ENTECAVIR TREATMENT
HCC INCIDENCE IN NON-CIRRHOTICS
Hepatitis C structure target for new Direct Antiviral Agent
Combination therapy
Future speculation
New drugs on the horizon
Predictors of response
Combination therapy
concept
Timeline?
Now or wait ?
WHY PATIENT NEEDS TRANSPLANT AND WHEN?
Patient’s ESLD survival
Life expectancy and OLT survival (1 yr 80-90%)
Organ availability and waiting time
Blood group
Child score / MELD
Quality of life from the disease
Summary flowchart for cirrhosis and complication
PREVENTIVE AND COMMUNITY ASPECT
Ensure adequate nutrition (including calorie & protein
intake) and supplement (eg. Zinc)
Alcohol cessation, community programme
Prophylactic antibiotics for SBP (for bleeding)
Osteoporosis risk assessment and primary prevention
Life style modification for NAFLD/NASH
Vaccination for hepatitis A, B, pneumonia, influenza
Compliance to treatment and follow up
Thank you for your attention