Hepatitis C Primer for HIV Care Providers

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

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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 200134541-52
4
HCV Global Prevalence
Number-of countries by WHO Region where data are
not available
Infected Population (Millions)
Hepatitis C prevalence Rate
Total Population (Millions)
WHO Region
31.9
12
5.3
602
Africa
7
1.7
785
Americas
13.1
7
21.3
4.6
 466
Eastern Mediterranean
19
8.9
1.03
858
Europe
3
32.3
2.15
1 500
South-East Asia
11
62.2
3.9
1 600
Western Pacific
57
169.7
3.1
5 811
Total
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HCV - Virology

• The Virus
• Single stranded, positive sense, RNA
• Falviviridae family
• Spherical, enveloped
• 50 nm
• Discovered in 1989

Choo, Science 1989244359-62
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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 200020103-26
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HCV Genotype Distribution
Genotype/Subtype
Geographic Distribution
America, Europe, Japan North America,
Western Europe Japan Indonesia (20 of
total)
1 1a 1b 1c
Worldwide distribution Northern Italy
2 2c
Younger population in Western countries,
especially IDUs Predominant genotype in
Pakistan Japan, Nepal, Thailand, Indonesia
Nepal
3 3a 3b 3c
Africa Egypt
4 4a
South Africa
5
Asia
6
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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

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Decline in transfusion transmitted viral
infections
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

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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 19963341691-6 2 Feldman,
STD 200127338-42 3 Bonacini, Arch Int Med
2000,1603365-73
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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

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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

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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

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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
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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.
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HCV - Treatment

• Indications for treatment

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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

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HCV - Treatment
Drugs approved for the treatment of HCV infection
20
HCV Treatment (non-HIV Patients)
Sustained Virologic Response Rates
54
60
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
Source Multiple randomized controlled trails
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Treatment Patterns in HCV Infected Patients
Demographics of patients with HCV (N237)
48 years
Age (mean)
Gender () Male Female
98 2
Race () Caucasian
African-American Other
72.5 26.6 lt 1
Estimated duration of HCV infection (years)
Mean Range
23 1 to 36
Number of patients who did not receive treatment
for HCV ()
155 (65)
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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 ()
37 (24)
Non compliance with follow up visits
15 (10)
Current drug or alcohol use
15 (10)
Normal liver enzymes
12 (8)
Undetectable HCV RNA
12 (8)
Psychiatric problems
11 (7)
Concurrent medical problems
9 (6)
Patient refused treatment
7 (4)
Referred for transplant evaluation
5 (3)
End stage liver disease
Deferred while waiting for approval for pegylated
interferon
3 (2)
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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
2 (16.7, 0.2) Received Interferon
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HCV - Treatment

• Predictors of a Favorable Response
• Genotype 2 or 3
• Low HCV Viral Load (lt2 million)
• No or only portal fibrosis
• Female gender
• Age lt 40 years
• Role of gender not an independent factor if
  controlled for body weight

Poynard, Hepatlogy 200031211-8 Manns, Lancet
2001358958-65
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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.
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The Inherent Qualities of PEG-alfa 2a
Tue
Wed
Thu
Fri
Sat
Sun
Mon
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)
Roche, data on file, Phase II trial.
CHCchronic hepatitis C