Dr. David Pearson
Gastroenterology, Victoria
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None relevant to this presentation
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Progressive fibrosis may lead to debility and
death from liver failure or cancer
Advanced fibrosis (F3-4) means reduced
response to Hepatitis C therapies
Successful treatment of Hepatitis C infection
will halt the progression of liver disease in
these patients at high risk of symptomatic
decompensation
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Before the onset of advanced fibrosis
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Better response in early disease: F0-2
Treatment better tolerated if patient is healthier
 Fatigue and other symptoms
 Anemia
 No risk of decompensation from loss of functioning
liver mass
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Best response to therapy:
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Younger age
Less fibrosis
Elevated ALT
Female
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Architectural description of the liver after long
term injury and regeneration with replacement
of functioning liver tissue by fibrosis.
Is partially reversible if the noxious agent is
removed and the liver is able to regenerate.
Eventually leads to functional liver
impairment.
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History
Alcohol excess
 Male sex
 Longer duration of infection (>20 years)
 Steatosis
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Physical exam
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Liver contour (enlarged left lobe, rounded, firm)
Splenomegally, ascites, caput: portal HTN
Spider angiomas, gynecomastia: estrogenic
Jaundice
Asterixis
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Imaging
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Lab
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Nodular contour, altered shape
Enlarged spleen, abdominal varices
Ascites
Thrombocytopenia, anemia, leukopenia
INR, albumin, bilirubin
AST/ALT ratio (often normal ALT)
Biopsy
Fibroscan: Transient elastography
Fibrotest/FibroSure
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Education and preparation are important
Vaccinations (CDC)
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HBV, HAV, Strep pneumonia (Pneumovax)
Influenza, varicella, MMR, tetanus, diptheria
Screening Gastroscopy
Abdominal U/S
Portal Hypertension
 Portal vein thrombosis
 Hepatocellular carcinoma
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Contraindications to treatment
Pregnancy/contraception advice
 Auto-immune hepatitis
 Renal insufficiency
 Severe cardiopulmonary disease
 Uncontrolled affective disorder/psychosis
 Hepatocellular carcinoma
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Is there a history of liver decompensation?
Potential drug interactions
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Is there an opportunity for improvement?
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Alcohol/smoking cessation
Other comorbidities to optimize?
 Diabetes, cardiac, pulmonary
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Relative contraindications to treatment
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Decompensated cirrhosis
 Ascites, encephalopathy, jaundice
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Albumin <35
Bilirubin >25
Platelets <75, 000
Anemia: Hg <130 male; <120 female
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What about non medical factors?
Housing
 Disability coverage/income replacement
 Drug coverage
 Preparing patient expectations for the experience on
therapy
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48 wks therapy for G1; 24 wks for G2/3
More likely to need medications tapered, more
frequent measurement of hematology
recommended.
Less able to tolerate therapy: need closer follow
up and reassessment
Higher rate of drop out due to adverse effects,
esp G1’s
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Recent French report treating cirrhotics with
triple therapy: 35-45%signficant adverse events
(anemia, infection, renal failure,
decompensation)
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1% death from infection, bleeding
50% significant anemia and EPO use
5% significant neutropenia and thrombocytopenia
Esp age>65, female, low initial Hg
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Anticipate trouble!
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Identify the fragile cirrhotic: Thorough work up
before treatment should identify those most at risk
4 week lead in may be illuminating….
How bad is a patient’s liver disease
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Compensated
Previously decompensated: “Recompensated”
Currently decompensated
Abnormal liver functions: bilirubin, albumin, INR
Abnormal hematology at baseline predicts
cytopenias on therapy
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Symptomatic decompensation
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Variceal bleeding, ascites, encephalopathy
Treatment of symptoms
Is there an identifiable precipitant?
 Alcohol, new medication, infection
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Does therapy need to be stopped?
Infection
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Low threshold for antibiotic use with bacterial
infection; patient are immune compromised
 Respiratory, urinary, skin
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Treatment related issues
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Cytopenias: dose reductions; growth factors
Symptoms: Fatigue, mucositis
Other organ systems: cardiac, skin rash, diarrhea
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Limited options
Anemia: taper Riba/IFN; NOT DAA’s
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?role of EPO
Platelets/WBC: taper IFN
Diarrhea
Rash
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Futility rules
Decompensation
Medication intolerance
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Fatigue, Rash, Diarrhea
Low doses, regression to single agent IFN
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54 yr old man; G1a, start Pegasys Sept 2010
Cirrhosis: ex-IVDU/Alcohol; compensated
2007 Thoracic aortic aneurysm repair
2009 Aortic valve endocarditis
Baseline: WBC 3.8/Hg121/plt 68
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INR 1.1, ALT 94, alb 40, bili 25
IFN 1000 mg/ IFN 180 mcg
Week 5
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Hg 95, plt 30
Hold riba a week, restart at 600
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Week 12
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Week 26
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Hg 80-95, plt 30-40; fatigue – off work
Riba 400-600, IFN 2/3 – PCR 2 log drop
Riba stopped, had been interrupted and dose
reduced
IFN 2/3 dose
Week 24 PCR negative
Week 30 ascites, increased fatigue, 25 lb wt loss
then 12 lb gain
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Stop all Rx
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PCR negative at wk 30 = end treatment
PCR relapsed 12 weeks later
Ascites slow to resolve; issues with congestive
failure and required urgent aortic valve
replacement May 2011
Now wants to be retreated!
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Educator
Advisor
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The
Plan
An Individual Effort
Inspiration
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Questions?