1. Dr. David Pearson Gastroenterology, Victoria

2.  None relevant to this presentation

3.  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

4.  Before the onset of advanced fibrosis  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  Best response to therapy:  Younger age  Less fibrosis  Elevated ALT  Female

5. What is cirrhosis?

6.  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.

7.  History  Alcohol excess  Male sex  Longer duration of infection (>20 years)  Steatosis  Physical exam  Liver contour (enlarged left lobe, rounded, firm)  Splenomegally, ascites, caput: portal HTN  Spider angiomas, gynecomastia: estrogenic  Jaundice  Asterixis

8.  Imaging  Nodular contour, altered shape  Enlarged spleen, abdominal varices  Ascites  Lab  Thrombocytopenia, anemia, leukopenia  INR, albumin, bilirubin  AST/ALT ratio (often normal ALT)  Biopsy  Fibroscan: Transient elastography  Fibrotest/FibroSure

9.  Education and preparation are important  Vaccinations (CDC)  HBV, HAV, Strep pneumonia (Pneumovax)  Influenza, varicella, MMR, tetanus, diptheria  Screening Gastroscopy  Abdominal U/S  Portal Hypertension  Portal vein thrombosis  Hepatocellular carcinoma

10.  Contraindications to treatment  Pregnancy/contraception advice  Auto-immune hepatitis  Renal insufficiency  Severe cardiopulmonary disease  Uncontrolled affective disorder/psychosis  Hepatocellular carcinoma  Is there a history of liver decompensation?  Potential drug interactions

11.  Is there an opportunity for improvement?  Alcohol/smoking cessation  Other comorbidities to optimize?  Diabetes, cardiac, pulmonary  Relative contraindications to treatment  Decompensated cirrhosis  Ascites, encephalopathy, jaundice  Albumin <35  Bilirubin >25  Platelets <75, 000  Anemia: Hg <130 male; <120 female

12.  What about non medical factors?  Housing  Disability coverage/income replacement  Drug coverage  Preparing patient expectations for the experience on therapy

13.  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

14.  Recent French report treating cirrhotics with triple therapy: 35-45%signficant adverse events (anemia, infection, renal failure, decompensation)  1% death from infection, bleeding  50% significant anemia and EPO use  5% significant neutropenia and thrombocytopenia  Esp age>65, female, low initial Hg

15.  Anticipate trouble!  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  Compensated  Previously decompensated: “Recompensated”  Currently decompensated  Abnormal liver functions: bilirubin, albumin, INR  Abnormal hematology at baseline predicts cytopenias on therapy

16.  Symptomatic decompensation  Variceal bleeding, ascites, encephalopathy  Treatment of symptoms  Is there an identifiable precipitant?  Alcohol, new medication, infection  Does therapy need to be stopped?  Infection  Low threshold for antibiotic use with bacterial infection; patient are immune compromised  Respiratory, urinary, skin

17.  Treatment related issues  Cytopenias: dose reductions; growth factors  Symptoms: Fatigue, mucositis  Other organ systems: cardiac, skin rash, diarrhea

18.  Limited options  Anemia: taper Riba/IFN; NOT DAA’s  ?role of EPO  Platelets/WBC: taper IFN  Diarrhea  Rash

19.  Futility rules  Decompensation  Medication intolerance  Fatigue, Rash, Diarrhea  Low doses, regression to single agent IFN

20.  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  INR 1.1, ALT 94, alb 40, bili 25  IFN 1000 mg/ IFN 180 mcg  Week 5  Hg 95, plt 30  Hold riba a week, restart at 600

21.  Week 12  Hg 80-95, plt 30-40; fatigue – off work  Riba 400-600, IFN 2/3 – PCR 2 log drop  Week 26  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  Stop all Rx

22.  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!

23.  Educator  Advisor  Coach  Confidant

24. The Plan

25. An Individual Effort

26. Inspiration

27. Encouragement

28. Motivation

29. Questions?