Transcript Hepatitis C: Epidemiology, Diagnosis and Treatment

Hepatitis C:
Epidemiology, Diagnosis
and Treatment
Mitchell L. Shiffman, MD
Professor of Medicine
Chief, Hepatology Section
Medical Director, Liver Transplant Program
Virginia Commonwealth University Health System
Richmond, Virginia
Hepatitis C:
Epidemiology
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus Infection
Magnitude of the Problem
 Nearly 4 million persons in United States infected
 Approximately 35,000 new cases yearly
 85% of new cases become chronic
 Leading cause of
 Chronic liver disease
 Cirrhosis
 Liver cancer
 Liver transplantation
Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at:
http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus
Fate of Acute Infection
Spontaneous
resolution
15%
Chronic
85%
Alter MJ, et al. N Eng J Med. 1999;341:556-562.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus
Response to Acute Infection
ALT (IU/l)
200
+/-
150
HCV RNA
+ Resolution
100
Chronic
50
0
0
6
12
18
24
Month
Illustration by Mitchell L. Shiffman, MD.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus Infection
Natural History
Acute HCV
Resolved
15% (15%)
Chronic HCV
85% (85%)
Stable
80% (68%)
HCC, hepatocellular carcinoma
Cirrhosis
20% (17%)
Slowly
progressive
75% (13%)
HCC
Liver failure
25% (4%)
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus Infection
Population at Risk
 Transfusion of blood products before 1992
 Intravenous drug use
 Nasal inhalation of cocaine
 Chronic renal failure on dialysis
 Incarceration
 Occupational exposure to blood products
 Transplantation of an organ/tissue graft from an HCVpositive donor

Body piercing and potentially tattoo
Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at:
http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Anti-HCV Positive (%)
Hepatitis C Virus Infection
Prevalence
4.0
3.0
2.0
1.8%
1.0
0
All
W
B
Race
H
M
F
Sex
B, Blacks; F, female; H, Hispanic; M, male; W, Whites.
Alter MJ, et al. N Eng J Med. 1999;341:556-562.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Anti-HCV Positive (%)
Hepatitis C Virus Infection
Prevalence by Age
5.0
4.0
3.0
2.0
1.0
0
< 11 11-19 20-29 30-39 40-49 50-59 60-69 ≥ 70
Age Group
Alter MJ, et al. N Eng J Med. 1999;341:556-562.
clinicaloptions.com/hep
Hepatitis C:
Diagnosis and Management
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Management of Chronic HCV
Tests Utilized
Disease Severity
Response to Therapy
AST/ALT
ALT
Bilirubin
HCV RNA
Albumin
Pro-time (INR)
LFTs
HCV genotype
Liver histology
Platelet count
Liver histology
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Viral Hepatitis
Role of Diagnostic Testing
 Identify patients with viral hepatitis infection
– Previous exposure to hepatitis virus
– Active infection
– Inactive infection
– Resolved infection
 Assess response to therapy
– Prior to onset of treatment
– During and following treatment
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus
Diagnostic Testing
Diagnostic Test Type
Specifications
Serologic
Virologic
Mode of detection
Antibodies
Virus
Sensitivity
> 95%
> 98%
Specificity
Variable
> 98%
Detection postexposure
2-6 months
2-6 weeks
Use
Screening
Confirmation
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus
Host Production of HCV Antibodies
 HCV infects cell
 HCV proteins expressed
on surface of hepatocytes
 Antibodies to HCV
proteins produced by host
 HCV antibodies DO NOT
convey immunity
Illustration by Mitchell L. Shiffman, MD.
Y YY
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Testing for Hepatitis C Virus
Anti-HCV Antibodies
 ELISA screening test
– Sensitivity: 97%
– Detects circulating HCV antibodies
 False positive reactions may occur
– Cross-reacting circulating antibodies
– Nonspecific binding of anti-HCV antibodies
 Positive predictive value
– 95% with risk factors and elevated ALT
– 50% without risk factors and normal ALT
Illustration by Mitchell L. Shiffman, MD.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV Antibody Testing
Limitations
 False positives
– Autoimmune disorders
– Spontaneous resolution of viral infection
 False negatives
– Chronically immune suppressed
– Transplant recipients
– Chronic renal failure on dialysis
– HIV positive
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Testing for Hepatitis C Virus
Recombinant Immunoblot Assay
 Supplemental assay
 Detects circulating
antibodies to 4 HCV proteins
 Antigen-antibody reaction
 More specific than anti-HCV
enzyme immunoassay
 False positive reaction can
still occur
 Largely replaced by HCV
RNA testing
Illustration by Mitchell L. Shiffman, MD.
Control
Positive
≥ 2 bands
Indeterminate
1 band
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Testing for Hepatitis C Virus
Indications for HCV RNA
 Confirm HCV infection
– Persistently normal serum ALT
– No risk factors
– HCV antibody positive
– Antinuclear antibodies
– Prior to initiating therapy
 Assess effectiveness of treatment
– Predict likelihood of response before and during therapy
– Confirm response after therapy completed
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Testing for Hepatitis C Virus
Virologic Assays
PCR
TMA
b-DNA
Polymerase chain
reaction
Transcription
mediated
amplification
Branched chain DNA
Amplifies target
Amplifies target
Amplifies probe
Qualitative
Quantitative
Qualitative
Quantitative
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Quantitative HCV RNA Assays
Inherent Variability
 Normal variation of 1 log
unit in HCV RNA assays
 HCV RNA titer best
reported in log units
HCV RNA (IU/mL)
 Differences of < 1 log
between samples of
probably NOT significant
100,000,000
10,000,000
1,000,000
100,000
10,000
1000
100
10
1
I
II
III
IV
V
Sample
Nolte FS, et al. J Clin Microbiol. 2001;39:4005-4012.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Serum HCV RNA Level
Stability Over Time
Log HCV RNA
(IU/mL)
8
Patient
1
2
3
4
5
6
4
2
Limit of detection
0
Baseline
1
2
3
4
Time (Years)
Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV RNA and Liver Histology
Fibrosis
 Serum HCV RNA does not correlate with level of fibrosis
Log HCV RNA
(copies/mL)
8
Genotype
1
2
3
4
6
4
2
0
No
Portal Bridging Cirrhosis
Fibrosis Fibrosis Fibrosis
Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV RNA and Liver Histology
Inflammation
 Serum HCV RNA does not correlate with level of
inflammation
Log HCV RNA
(copies/mL)
8
Genotype
1
2
3
4
6
4
2
0
0
2
4
6
8
10
12
Inflammation Score
Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus
Genotypes in the USA
Type 2
17%
Type 1
72%
McHutchinson JG, et al. N Engl J Med. 1998;339:1485-1492.
Type 3
10%
All others
1%
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Determination of HCV Genotype
INNOLiPA Assay
PCR
1a
1b
2a
 HCV genotype
– Best pretreatment
predictor of response
– Determines duration of
therapy
 All patients should have
genotype determined
prior to initiating therapy
Illustration by Mitchell L. Shiffman, MD.
2b
3a
3b
4
5
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus Infection
Liver Biopsy
 Only test that can accurately assess
– Severity of inflammation
– Degree of fibrosis
 Determines the following
– Risk for developing cirrhosis in future
– Need for therapy
– Need for ongoing therapy when initial treatment has failed
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Management of Chronic HCV
Is Liver Biopsy Necessary?
NO
YES
 Patient wants treatment even
if no fibrosis
 Patient would only accept
treatment if advanced fibrosis
 Patient does not want
treatment or treatment
contraindicated even if
advanced fibrosis
 Labs or radiographic studies
suggest cirrhosis may be
present
 Labs and radiographic studies
do not suggest cirrhosis
 Patient fails to achieve SVR
and no recent biopsy
available
 Patient achieves SVR
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
1.0
1.0
0.8
0.8
ACTITEST
FIBROTEST
Assessment of Liver Histology
Noninvasive Serum Tests
0.6
0.4
0.6
0.4
0.2
0.2
0
0
0
1
2
3
4
Fibrosis Stage
Poynard T, et al. Hepatology. 2003;38:481-492.
0
1
2
3
Activity Grade
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic HCV With Normal Serum ALT
ALT Patterns and Flares
120
Single elevations
Periodic elevations
Always normal
ALT (IU/l)
100
80
60
ULN
40
20
0
0
3
6
9
12
15
18
21
24
Month
Illustration by Mitchell L. Shiffman, MD.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic HCV Infection
Normal Serum ALT
Normal ALT
Elevated ALT
n = 37
n = 58
48
29
52
71
Serum ALT, IU/L
46.6 ± 5.2
76.7 ± 6.0
Log HCV RNA, copies/mL
5.42 ± 0.13
5.50 ± 0.07
4.2 ± 0.1
0.7 ± 0.2
5.3 ± 0.1
1.6 ± 0.2
Race
 White, %
 Black, %
Histology score
 Inflammation
 Fibrosis
Shiffman ML, et al. J Infect Dis. 2000;182:1595-1601.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic HCV Infection
Normal vs Elevated Serum ALT
Portal
26%
No
fibrosis
23%
Bridging
6%
Bridging
13%
Cirrhosis
18%
Portal
20%
Cirrhosis
6%
Mild
39%
Normal ALT
Shiffman ML, et al. J Infect Dis. 2000;182:1595-1601.
No
fibrosis
16%
Mild
33%
Elevated ALT
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic HCV Infection
Symptoms
Cirrhosis
7%
56%
Asymptomatic
100
Percentage of Patients
Symptomatic
37%
80
60
40
20
0
Fatigue
Unpublished data from MCV Hepatitis Program, 1995.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic HCV Infection
Progression to Cirrhosis
Approximate Percentage of
Patients With Cirrhosis
Proportion of Patients Developing Cirrhosis
According to Initial Level of Fibrosis
100
80
Bridging
Portal
None
60
40
20
0
0
5
10
15
20
Time (Years)
Yano M, et al. Hepatology. 1996;23:1334-1340.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Fibrosis Progression of HCV
Effect of Inflammation
Change in Fibrosis Score According to
Necrosis Score at Baseline
Piecemeal Necrosis Score at Baseline
0-1
3-2
>4
Number of patients
30
66
27
Mean change in
fibrosis score per year
.05
.19
.37
Ghany MG, et al. Gastroenterol. 2003;124:97-104.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV Fibrosis Progression
Effect of Alcohol
Fibrosis Score
4.0
3.0
Alcohol intake
> 50 g/day*
< 50 g/day
2.0
1.0
0
< 10
11-20
21-30
31-40
> 40
Duration of Infection (Years)
*50 g is equal to approximately 3.5 drinks
Poynard T, et al. Lancet. 1997;349:825-832.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV Fibrosis Progression
Effect of Age
Fibrosis Score
4.0
3.0
Age at time
of infection
> 40 years
< 40 years
2.0
1.0
0
< 10
11-20
21-30
31-40
> 40
Duration of Infection (Years)
Poynard T, et al. Lancet. 1997;349:825-832.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV Fibrosis Progression
Effect of Histology
Grade or Stage
4.0
3.0
Fibrosis
2.0
Inflammation
1.0
0
< 10
11-20
21-30
31-40
> 40
Duration of Infection (Years)
Poynard T, et al. Lancet. 1997;349:825-832.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV and Alcohol
Risk of Cirrhosis
Cirrhosis (%)
100
80
60
HCV
HCV + alcohol
40
20
0
10
20
30
40
Years Following Exposure
Excessive alcohol intake characterized as > 40 g/day for women and > 60 g/day for men.
Wiley TE, et al. Hepatology. 1998:28:805-809.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Cumulative Probability of
Fibrosis Progression (%)
Fibrosis Progression in HCV
Effect of Steatosis
Cumulative Probability of Fibrosis
According to Level of Steatosis
100
80
60
40
30%
0
18%
18%
20
2% 6%
< 5%
4%
33%
Year 4
Year 6
7%
5%-10% 11%-30%
> 30%
Percentage of Steatosis at Initial Biopsy
Fartoux L, et al. Hepatology. 2005;41:82-87.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV in Patients With Cirrhosis
Survival and Rate of Decompensation
10-Year
Cumulative Survival
Decompensation
Stable
80
60
40
20
0
Percentage of Patients
Survival (%)
100
Cumulative Probability
50
Decompensation
HCC
40
30
20
10
0
0
2
4
6
8
10
Years
Fattovich G, et al. Gastroenterology. 1997;112:463-472.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatocellular Carcinoma
Incidence in the United States
12
Cases/100,000
10
Black male
White male
Black female
White female
8
6
4
2
0
1976-1980
El-Serag HB, et al. N Engl J Med. 1999;340:745-750.
1991-1995
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic Hepatitis C Infection
Progression to Cirrhosis
Mild
15%-33%
Moderate
Severe
Cirrhosis A
20%-33%
Cirrhosis C
HCC
0
10
20
30
40
50
Years
Shiffman ML. Viral Hepatitis Rev. 1999;5:27-43.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Anti-HCV Positive (%)
Hepatitis C Virus Infection
The Burden of Disease
3.0
All patients
Infection for
> 20 years
2.0
1.0
0
1960
1980
2000
2020
Year
Armstrong GL, et al. Hepatology. 2000;31:777-782.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Hepatitis C Virus Infection
Identification of Patients
 Found to have elevated serum ALT during
– Routine physical examination
– Routine blood testing after starting certain medications
 Test positive for anti-HCV during
– Volunteer blood donation
– Health or life insurance applications
 Physician
– Inquires about previous risk behaviors
clinicaloptions.com/hep
Hepatitis C:
Extrahepatic Manifestations
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic Hepatitis C Virus
Extrahepatic Manifestations










Nonspecific antibodies
Essential mixed cryoglobulinemia
Glomerulonephritis
Porphyria cutanea tarda
Leukocytoclastic vasculitis
Mooren’s corneal ulcer
Non-Hodgkin’s lymphoma
Autoimmune thyroiditis
Diabetes mellitus
Sjögren’s syndrome
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic Hepatitis C Virus
Autoantibodies
HCV, %
Control, %
Rheumatoid factor
70
8
Cryoglobulins
36
<1
21
13
10
2
21
7
2
<1
Anti–liver-kidney microsome
5
<1
Antithyroid
7
2
ANA
 > 1:40
 > 1:180
Antismooth muscle
 > 1:40
 > 1:180
Pawlotsky JM, et al. Hepatology. 1994;19:841-848.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic Hepatitis C Virus
Autoantibodies (cont’d)
 No relationship between presence of autoantibodies and
– Severity of chronic HCV
– HCV genotype
 Correlation between rheumatoid factor titer and
– Cryoglobulinemia
– But not symptomatic cryoglobulinemia
 Circulating autoantibodies from autoimmune disorders
may result in
– False positive anti-HCV
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Cryoglobulinemia
Classification
Immunoglobulin
I
II
Monoclonal
No rheumatoid factor
Polyclonal IgG
Monoclonal IgM
Rheumatoid factor
Classification
Primary
Secondary mixed
HCV infection
Secondary mixed
III
Polyclonal IgG
Infections
Polyclonal IgM
Autoimmune disorders
Lymphoproliferative diseases
Cacoub P, et al. Curr Opin Rheumatol. 2002;14:29-35.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Immune Manifestations of HCV
Pathogenesis
HCV evades the
immune response
Chronic immune
stimulation by
single HCV antigen
Y Y
Y
Y
Poly clonal IgG
Cry oglobulin
traps HCV
Illustration by Mitchell L. Shiffman, MD
Genetic and
env ironmental
f actors
Monoclonal IgM
rheumatoid f actor
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV and Cryoglobulinemia
Dermatitis
 Occurs in dependent
areas
 Deposition of
cryoglobulins in small
capillaries
 Ulcerations may develop
 Pruritic
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Percentage of Patients
Extrahepatic Effects of HCV
Cryoglobulinemia
100
80
Elevated ALT
Anti-HCV
HCV RNA
60
40
20
0
Cryoglobulinemia
Misiani R, et al. Ann Int Med. 1992;117:573-577.
Controls
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
HCV and Cryoglobulinemia
Manifestations
 Dermatitis (dependent areas)
 Vasculitis
 Myalgias (fibromyalgia?)
 Arthralgias (RA and/or ANA positive)
 Membranoproliferative glomerulonephritis
 Neuropathy
 Chronic fatigue syndrome (?)
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Extrahepatic Effects of HCV
Lymphocytic Sialadenitis
Characteristic
SS-A, SS-B
Lymphocytic capillaritis
HCV
Sialadenitis
Primary
Sjögren’s Syndrome
Negative
Positive
Mild
Severe
Pericapillary
Periductal
Mostly CD8 cells
Mostly CD4 cells
Absent
Present
8%-36%
Present
Sicca syndrome:
 Xerophthalmia
 Xerostomia
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Extrahepatic Effects of HCV
B-Cell Lymphoma
Ferri (1994)
8 case series
1754 pts evaluated
Mazzaro (1996)
Silvestri (1996)
Izumi (1996)
McColl (1996)
Zignego (1997)
DeRosa (1997)
Zuckerman (1997)
30
20
10
0
B Cell Lymphoma
10
20
30
Controls
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Chronic HCV and Diabetes Mellitus
Case Prevalence
 N = 179 with chronic HCV
 Prevalence of diabetes
mellitus and insulin
resistance noted
 Compared with expected
rate based on NHANES III
study after adjusting for
Number of Cases
20
16
Observed
Expected
12
8
– Age
– Sex
– Race
4
0
Females
Males
Zein CO, et al. Am J Gastroenterol. 2005;100:48-55.
 Prevalence of DM or insulin
resistance higher in those
with chronic HCV
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Percentage of Patients
Chronic HCV and Diabetes Mellitus
Relationship to Fibrosis Stage
40
30
20
10
0
0
1
2
3
4
Histologic Stage
Zein CO, et al. Am J Gastroenterol. 2005;100:48-55.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Extrahepatic Effects of HCV
Porphyria Cutanea Tarda
Fargion (1992)
De Castro (1993)
Criber (1995)
2 case series
3 uncontrolled series
280 patients
Alcohol: 36%-77%
Stolzel (1995)
Kondo (1997)
100 80
60
40
PCT
20
0
5
10
15
20
Control
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Extrahepatic Effects of HCV
Lichen Planus
 Occurs in < 1% of the general population
 10%-30% of patients with chronic HCV
 Appearance
– Flat topped, violaceous, pruritic papules
– Throughout body
– Oral mucosa
 Histology
– Dense infiltration of dermis with T lymphocytes
Nagao Y, et al. J Gastroenterol Hepatol. 2004;19:1101-1113.
clinicaloptions.com/hep
Hepatitis C:
Treatment
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Sustained Virologic
Response (%)
Treatment of Chronic HCV
Peginterferon and Ribavirin
100
80
60
PegIFN-2a/RBV
PegIFN-2b/RBV
40
20
0
1
2-3
Genotype
Fried MW, et al. N Eng J Med. 2002;347:975-982. Manns MP, et al. Lancet 2001;358:958-965.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Treatment of Chronic HCV
Effect on Survival
 Interferon treatment reduces risk of death,
transplantation, and complications of cirrhosis
Risk Factors for Survival (Multivariate Cox Regression Analysis)
Survival Outcome
Risk Ratio 95% Confidence Interval
Interferon therapy vs no therapy
 Death and liver transplantation
0.5*
0.3-0.9
 Death, liver transplantation, and
complications
0.5*
0.3-0.7
 Development of HCC
0.7
0.2-2.7
*P < .05.
Niederau C, et al. Hepatology. 1998;28:1687-1695.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
Treatment of Chronic HCV
Effect on Development of HCC
 Interferon treatment reduces the risk of developing
hepatocellular carcinoma among patients with chronic
HCV (P = .002)
 Hepatocellular carcinoma incidence
– Untreated controls: 38% (24%-58%)
– Interferon-treated patients: 4% (1%-15%)
 HCC risk ratio: 0.067 (0.009-0.530; P = .01)
Nishiguchi S, et al. Lancet. 1995;346:1051-1055.
clinicaloptions.com/hep
Hepatitis C: Epidemiology, Diagnosis, and Treatment
The Many Faces of HCV Infection
Summary
 Chronic HCV infection leads to cirrhosis and liver failure
in a large number of persons
 Primary care physicians must recognize that chronic
HCV is common in specific nonliver disorders
 Effective treatment of chronic HCV can prevent fibrosis
progression and reduce complications of HCV
clinicaloptions.com/hep
Go Online to View
More CCO Programs!
Conference Coverage of all the key data presented at major
hepatitis meetings
News and Capsule Summaries covering the latest findings in the
field of hepatitis
Downloadable Slides, and much more!
clinicaloptions.com/hep