the cirrhotic patient on HCV therapy

1. the cirrhotic patient on HCV therapy Dr. David Pearson Gastroenterology, Victoria

2. Disclosures • None relevant to this presentation

3. Why is Fibrosis/Cirrhosis Important? • 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. When to treat? • 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. What is cirrhosis? • 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. How do we know the patient is cirrhotic? • 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. How do we know the patient is cirrhotic? • 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. Pretreatment evaluation of the cirrhotic patient • 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. Pretreatment evaluation of the cirrhotic patient • 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. Pretreatment evaluation of the cirrhotic patient • 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. Pretreatment evaluation of the cirrhotic patient • What about non medical factors? • Housing • Disability coverage/income replacement • Drug coverage • Preparing patient expectations for the experience on therapy

13. Cirrhosis: Implications for treatment • 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. Cirrhosis: Implications for treatment • 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. A practical approach • 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. How do you know you’re in trouble? • 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. How do you know you’re in trouble? • Treatment related issues • Cytopenias: dose reductions; growth factors • Symptoms: Fatigue, mucositis • Other organ systems: cardiac, skin rash, diarrhea

18. What to do when you’re in trouble • Limited options • Anemia: taper Riba/IFN; NOT DAA’s • ?role of EPO • Platelets/WBC: taper IFN • Diarrhea • Rash

19. When to stop • Futility rules • Decompensation • Medication intolerance • Fatigue, Rash, Diarrhea • Low doses, regression to single agent IFN

20. The case • 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. The case • 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 lbwt loss then 12 lb gain • Stop all Rx

22. The case • 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. Role of the Hepatitis Nurse • Educator • Advisor • Coach • Confidant

24. The Plan

25. An Individual Effort

26. Inspiration

27. Encouragement

28. Motivation

29. Thank you for your attention Questions?