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Hepatitis C Primer for HIV Care Providers

Hepatitis C Primer for HIV Care Providers. Adeel A. Butt, MD Assistant Professor of Medicine Division of Infectious Diseases University of Pittsburgh Director, Pittsburgh VAMC ID-HIV Clinics Center for Health Equity Research and Promotion. Member of Academic Research Council

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Hepatitis C Primer for HIV Care Providers

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  1. Hepatitis C Primer for HIV Care Providers Adeel A. Butt, MD Assistant Professor of Medicine Division of Infectious Diseases University of Pittsburgh Director, Pittsburgh VAMC ID-HIV Clinics Center for Health Equity Research and Promotion Member of Academic Research Council A non-profit organization dedicated to improving medical education and fostering research

  2. Overview • Prevalence of HCV • A word of virology • Risk Factors • Natural History of HCV • Treatment of HCV • Treatment Indications and Goals • HCV-HIV Co-infection • Treatment of HCV-HIV co-infection Adeel A. Butt, MD

  3. HCV - Epidemiology • Epidemiology: • 1.8% of the U.S. population • ~ 4 million infected persons in the U.S. • 8,000 – 10,000 deaths per year • Global prevalence – 170 million • 5 X more prevalent than HIV Lauer, NEJM 2001;345:41-52 Adeel A. Butt, MD

  4. HCV – Global Prevalence WHO Region Total Population (Millions) Hepatitis C prevalence Rate % Infected Population (Millions) Number-of countries by WHO Region where data are not available 31.9 Africa 602 5.3 12 Americas 785 1.7 7 13.1 Eastern Mediterranean 466 4.6 21.3 7 Europe 858 1.03 8.9 19 South-East Asia 1 500 2.15 32.3 3 Western Pacific 1 600 3.9 62.2 11 Adeel A. Butt, MD Total 5 811 3.1 169.7 57

  5. HCV - Virology • The Virus • Single stranded, positive sense, RNA • Falviviridae family • Spherical, enveloped • ~ 50 nm • Discovered in 1989 Choo, Science 1989;244:359-62 Adeel A. Butt, MD

  6. HCV - Genetics • Six genotypes, 1 through 6 • Multiple subtypes, a, b, c, etc. • Further divided into quasispecies, varying in RNA sequence by 1-9% • RNA sequence may vary by 35% between genotype • Great genetic diversity Farci, Semin Liver Dis 2000;20:103-26 Adeel A. Butt, MD

  7. HCV Genotype Distribution Genotype/Subtype Geographic Distribution 1 1a 1b 1c America, Europe, Japan North America, Western Europe Japan Indonesia (20% of total) 2 2c Worldwide distribution Northern Italy 3 3a 3b 3c Younger population in Western countries, especially IDUs Predominant genotype in Pakistan Japan, Nepal, Thailand, Indonesia Nepal 4 4a Africa Egypt 5 South Africa Adeel A. Butt, MD 6 Asia

  8. HCV – Risk factors • Transfusion • Dependent on prevalence in general population • Screening methods and diligence in screening • In the US, it dropped from 25% to 0.1% after initiation of screening • 1996 risk in the US was 1 in 103,000 units • (for HIV this risk was 1 in 493,000 units) • Current risks: • HCV – 1 in 1,600,000 units • HIV – 1 in 1,800,000 units • HBV – 1 in 220,000 units Adeel A. Butt, MD

  9. Decline in transfusion transmitted viral infections Adeel A. Butt, MD

  10. Blood Supply Screening • Antibody based • Antigen based • Nucleic acid technology (NAT) • Introduced in 1998 • Reduces window period • For HCV: from 70 days to 10 days • For HIV: from 22 days (antibody) to 11 days • Potential reasons for transmission • Window period • Immunovariant strains • Persistently antibody negative carriers • Testing errors Adeel A. Butt, MD

  11. HCV – Risk Factors (contd.) • Sexual Transmission • Inefficient route of transmission • ?risk 1-3% • 1 of 85 long term sexual partners1 • 2 of 42 index cases (one had independent risk factors)2 • Probably enhanced by HIV co-infection3 1 Conry-Cantilena NEJM 1996;334:1691-6 2 Feldman, STD 2001;27:338-42 3 Bonacini, Arch Int Med 2000,160:3365-73 Adeel A. Butt, MD

  12. HCV – Risk factors (contd.) • Other risk factors and routes of transmission: • Tattoos • Person-to-person in hemodialysis units • Person-to-person by HCW • Nosocomial outbreaks reported • Organ and tissue transplant Adeel A. Butt, MD

  13. HCV – Transmission • Pregnancy and Vertical Transmission • Prevalence in pregnant women 0.3-4.4% • Over 40% in IDU from NY • Overall vertical transmission rate ~ 6% • HIV co-infection increases transmission rates • Role of HCV VL and mode of delivery unclear • No known transmission from breast milk Adeel A. Butt, MD

  14. HCV and Health Care Workers • 600,000-800,000 needlestick injuries occur each year • Prevalence in Public Safety workers 1.3-3.2% • Prevalence in Scottish HCW 0.28% • Risk of HCV from a needlestick estimated to be 2.7-6% • Multiple reported cases of transmission from HCW to patients • Risk of HCV+ surgeon transmitting it a patient estimated at 1 in 1,750-16,000 procedures Adeel A. Butt, MD

  15. HCV – Natural History Acute HCV-100 patients 20 – 30 years Accelerated by: alcohol HIV Resolved - 25 Chronic - 75 Stable – 45-55 Cirrhosis – 20-30 Stable – 15-25 Decompensation – 5-8 HCC – 1-3 per year Adeel A. Butt, MD

  16. Goals of Treatment Butt, Singh. Hepatitis C: Prevention, Therapy and Role of Transplantation. In Wenzel (ed) Prevention and Control of Nosocomial Infections. Fourth Edition. Lippincott, Williams and Wilkins. Adeel A. Butt, MD

  17. HCV - Treatment • Indications for treatment Adeel A. Butt, MD

  18. HCV – Pretreatment Workup • History and Physical Exam • Psychiatric history/evaluation • Blood counts • Chemistry panel • Liver panel, including PT • TFTs • HCV genotype • HCV RNA • AFP; ?liver imaging • Liver biopsy Adeel A. Butt, MD

  19. HCV - Treatment Drugs approved for the treatment of HCV infection Adeel A. Butt, MD

  20. HCV – Treatment (non-HIV Patients) Sustained Virologic Response Rates 60 54 50 41 39 40 30 24 16 20 6 10 0 IFN 24 IFN 48 IFN/RBV IFN/RBV PEG-IFN PEG/RBV wks wks 24 wks 48 wks Adeel A. Butt, MD Source: Multiple randomized controlled trails

  21. Treatment Patterns in HCV Infected Patients Demographics of patients with HCV (N=237) Age (mean) 48 years Gender (%) Male Female 98 2 Race (%) Caucasian African-American Other 72.5 26.6 < 1 Estimated duration of HCV infection (years) Mean Range 23 1 to 36 Number of patients who did not receive treatment for HCV (%) Adeel A. Butt, MD 155 (65)

  22. Reasons for non-treatment in HCV only infected patients Ten most common reasons for non-treatment of HCV in 155 patients. (excludes the unknown category) n (%) Non compliance with follow up visits 37 (24) Current drug or alcohol use 15 (10) Normal liver enzymes 15 (10) Undetectable HCV RNA 12 (8) Psychiatric problems 12 (8) Concurrent medical problems 11 (7) Patient refused treatment 9 (6) Referred for transplant evaluation 7 (4) End stage liver disease 5 (3) Deferred while waiting for approval for pegylated interferon Adeel A. Butt, MD 3 (2)

  23. Treatment Patterns in HCV-HIV Co-infected Patients (VACS-3 Cohort) 881 Patients 181 (20.5%, 20.5%) Not Tested 700 (79.5%, 79.5%) Tested 400 (57.1%, 45.4%) Hepatitis C Negative 300 (42.9%, 34.1%) Hepatitis C Postive 210 (70.0%, 23.8%) without GI Referral 90 (30.0%, 10.2%) with GI Referral 67 (31.9%, 7.6%) with No Indication 26 (28.9%, 3.0%) with No Indication 143 (68.1%, 16.2%) with Indications 64 (71.1%, 7.3%) with Indications 38 (26.6%, 4.3%) Eligible for Treatment 27 (42.2%, 3.1%) Eligible for Treatment 12 (44.4%, 1.4%) Underwent Liver Biopsy Adeel A. Butt, MD 2 (16.7%, 0.2%) Received Interferon

  24. HCV - Treatment • Predictors of a Favorable Response • Genotype 2 or 3 • Low HCV Viral Load (<2 million) • No or only portal fibrosis • Female gender • Age < 40 years • Role of gender not an independent factor if controlled for body weight Poynard, Hepatlogy 2000;31:211-8 Manns, Lancet 2001;358:958-65 Adeel A. Butt, MD

  25. Functional Characteristics of PEGylated Proteins • Protected from proteolytic degradation • Restricted distribution • Reduced renal clearance • Enhanced solubility • PEG-moiety is biocompatible and nontoxic Harris JM, Poly (Ethylene Glycol) Chemistry. 1992. Katre NV. Adv Drug Delivery Rev. 1993. Adeel A. Butt, MD

  26. The Inherent Qualities of PEG-alfa 2a Mon Tue Wed Thu Fri Sat Sun 30 25 20 Concentration (ng/mL) 15 10 5 0 0 24 48 72 96 120 144 168 192 Time (hours) PEGASYS (PEG-IFN) 180 mcg SC qw in patients with CHC* (Week 48) *CHC=chronic hepatitis C Roche, data on file, Phase II trial. Adeel A. Butt, MD

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