Hepatitis C Update: A Primary Care Perspective

1. Hepatitis C Update: A Primary Care Perspective Jay Fathi, M.D. February 2003

2. Overview—an epidemic • RNA virus; discovered by cloning in 1988 • First serologic test 1990 • Approximately 4 million Americans infected; most common liver disease in US, most common indication for transplantation • Roughly 30,000 new cases annually; only 30% diagnosed

3. Overview (cont.) • 85% become chronically infected • 10,000 deaths annually • Incidence falling recently; prevalence increasing over last decade

4. Natural Course • Acute infection: asymptomatic or mild illness • Virus detectable by PCR-RNA in 2-4 weeks after exposure usually • Roughly 15% spontaneously clear virus; remain Ab-positive but are PCR-RNA negative • 20% (3-30% depending on study) develop cirrhosis, usually over many years • Alcohol, co-morbid HIV, Hep B increase risk

5. Natural Course (cont.) • 20% cirrhotic patients (5% of total) develop hepatocellular carcinoma; survival after Dx of HCC is 6 months-2 years • Clinic course varies greatly case by case

6. Transmission • Contaminated blood most infectious (transfusions prior to 1992, now needle-sharing, intranasal cocaine) • Sexual transmission (less than 5%) • Perinatal transmission (approx. 5%); dependent on maternal viral load • Shared razors, toothbrushes, open cuts, etc.

7. Transmission (cont.) • Occupational exposure (roughly 2% with needlesticks) • ALWAYS USE UNIVERSAL PRECAUTIONS

8. Diagnosis • Enzyme immunoassays • PCR (viral load), qualitative vs. quantitative useful to follow treatment response • Viral load not correlated with disease progression • Genotyping (when considering treatment) • Complete Hep screen, HIV

9. LFTs • LFTs are not well correlated with hepatic fibrosis • Fairly specific; poor sensitivity • Normal LFTs somewhat reassuring, but hepatic fibrosis can still exist • Biopsy-gold standard for assessing disease progression

10. Patient Education • Avoid hepatotoxins (esp. ALCOHOL!!!) • General healthcare maintenance (diet, smoking cessation, exercise, etc.) • Weight loss—can help steatosis and may possibly alter course of disease • Immunizations (Hep A, B, pneumovax, Td, flu shot, etc.)

11. Education (cont.) • Do not donate blood, share needles or inhalation devices for recreational drugs, cover wounds, discuss possible sexual/perinatal transmission • Support groups

12. Treatment • 18-60 years old (**) • Persistently elevated LFTs (?) • PCR positive, biopsy positive • Studies currently ongoing in other populations (children, older adults, severe cirrhotics, etc.)

13. Treatment (cont.) • No current substance abuse • Patient interested in therapy • *No current substance abuse, generally healthy, no unstable psychiatric disorders*

14. Treatment (cont.) • Interferon plus oral ribavirin • Usually 12 months, 1-3 weekly injections, very costly ($15,000 for Ribavirin alone) • Side effects –flu-like symptoms, alopecia, bone marow suppression, cardiac and pulmonary impairment, thyroid/ocular abnormalities, seizures, exacerbation of any pre-existing psychiatric abnormalities

15. Treatment (cont.) • Pegylated interferon: higher clearance rates, once-weekly injections, less psychiatric SE • Lasting (?) clearance of virus in 20-50% patients • Resposne to treatment somewhat dependent on genotype (1 most prevalent in US, likely most virulent also) • Genotype I, previous non-responders, African Americans less responsive to treatment

16. Treatment (cont.) • Depression (‘emotional disturbances’) most common reason for discontinuation • 20% or more drop out of treatment before 48 week course completed • Protease Inhibitors: promising preliminary data • Milk thistle? Data shows no improvement

17. Frequent Co-morbidities • HIV, Hep B, alcohol abuse, other substance abuse, psychiatric disorders (depression, bipolar), homelessness, etc.

18. Suggested Management Plan • Check PCR; if negative, periodically screen with ALT and/or PCR (Q2-5 years?) to ensure patient has definitively cleared virus • If PCR positive, assess if patient is candidate for therapy and give thorough counselling about disease/treatment/etc. to see if they are interested

19. Management plan (cont.) • If yes to both (PCR positive, interested in treatment), refer for liver biopsy • Primary care clinician must be able to competently counsel patients regarding the myriad of complicating issues • Each patient must be managed individually

20. Hepatitis B • Double-stranded DNA virus • Global prevalence: 5% • Approximately 400 million people! • Mostly in SE Asia, Philippines, Middle East, Africa, parts of S. America • Lowest prevalence: US, Canada, N. Europe • US: 1 million chronically infected (chronic carriers)

21. Transmission • Blood, body fluids (saliva, semen) • Most common mode of spread in US: sexual contact (heterosexual and homosexual) • Most common mode of spreas worldwide: VERTICAL TRANSMISSION

22. Acute to chronic infection • After acute infection, 5-10% of adults become chronically infected • Up to 90% of neonates become chronically infected when vertical transmission occurs • HBcAB+ evidence of prior infection • HBsAg + chronically infected • HBcAB + and HBsAg negative: prior infection, have cleared virus

23. Chronic Hep B • HBeAg—indicative of replication and infectivity • HBeAg + “Replicators,” more infections, poor prognosis • 15-20% progress to cirrhosis in 5 years • HBeAg negative---- “Non-replicators,” less infectious, better prognosis • Both should be referred to specialist for likely liver biopsy, treatment evaluation

24. Treatment • Interferon, 3TC (lamivudine) • Fairly low numbers re: response rates • Hepsera (Adefovir)—new treatment • 50-60% ‘cure rate’ (?) in studies • Liver fibrosis improved on biopsy • SE: 25% can experience exacerbation of hepatitis

25. Prevention • IMMUNIZATION !!!!!!!!!!!!!!!!!!!!!!!!! • ALL infants • High risk adults • All adults?