Liver Fibrosis Progression Rates in HCV Monoinfected and HIV-HCV Coinfected Individuals
Studies
to date have produced widely varying estimates of liver
fibrosis progression in people with chronic hepatitis
C virus (HCV) infection.
To shed further light on this issue, Hla-Hla
Thein and colleagues conducted systematic literature reviews and performed meta-analyses
and meta-regression to estimate annual rates of liver disease progression according
to current fibrosis stage in HCV monoinfected and
HIV-HCV coinfected individuals. 
Study
1: HCV Monoinfection
In
the first study, published in the August 2008 issue of Hepatology, the
investigators looked at published studies of individuals with HCV alone. They
included 111 studies -- with a total of 33,121 participants -- that collected
information about patient age at the time of liver disease assessment or HCV acquisition,
duration of HCV infection, and histological and/or clinical diagnosis of cirrhosis.
In a meta-analysis of the data from these studies, the researchers used
a mathematical model (Markov maximum likelihood estimation) to estimate the annual
probability of progressing from each successive fibrosis stage to the next.
Results
•
The estimated
mean annual transition probabilities were:
•
Stage F0 (absent)
to F1 (mild) fibrosis: 0.117;
•
Stage F1 to
F2 (moderate) fibrosis: 0.085;
•
Stage F2 to
F3 (advanced) fibrosis: 0.120;
•
Stage F3 to
F4 (severe fibrosis or cirrhosis): 0.116.
•
Duration of
HCV infection was the most consistent factor significantly associated with fibrosis
progression.
•
The estimated
prevalence of cirrhosis after 20 years of infection was 16% across all studies
(range 14%-19%):
•
18% (range
15%-21%) for cross-sectional/retrospective studies;
•
7% (range 4%-14%)
for retrospective-prospective studies;
•
18% (range
16%-21%) for studies conducted in clinical settings;
•
7% (range 4%-12%)
for studies conducted in non-clinical settings.
"Our
large systematic review provides increased precision in estimating fibrosis progression
in chronic HCV infection and supports nonlinear disease progression," the
study authors concluded. "Estimates of progression to cirrhosis from studies
conducted in clinical settings were lower than previous estimates."
Study
2: HIV-HCV Coinfection
In
the October 1, 2008 issue of AIDS, the researchers reported results from
a similar analysis looking at HIV-HCV
coinfected individuals. This analysis included data from 17 natural history
studies with a total of 3567 participants. The risk of cirrhosis in HCV monoinfected
and coinfected patients was compared according to HAART
use.
Results
•
The estimated
mean annual transition probabilities were:
•
Stage F0 (absent)
to F1 (mild) fibrosis: 0.122;
•
Stage F1 to
F2 (moderate) fibrosis: 0.115;
•
Stage F2 to
F3 (advanced) fibrosis: 0.124;
•
Stage F3 to
F4 (severe fibrosis or cirrhosis): 0.115.
•
The prevalence
of cirrhosis was 21% (range 16%-28%) after 20 years and 49% (range 40%-59%) after
30 years.
•
Longer duration
of HCV infection was significantly associated with a slower rate of fibrosis progression.
•
Across 27 studies,
the overall rate ratio of cirrhosis between HIV-HCV coinfected patients and HCV
monoinfected individuals was 2.1, but this varied by HAART status:
•
Coinfected
patients on HAART were 1.7 times more likely to develop cirrhosis compared with
HCV monoinfected individuals.
•
Coinfected
patients not receiving HAART were 2.5 times more likely to develop cirrhosis than
HCV monoinfected individuals.
"The
rate of fibrosis progression among individuals coinfected with HIV-HCV appears
constant," the researchers concluded.
"Our results confirm that
chronic hepatitis C outcomes are worse among coinfected individuals," they
continued. "Over the period studied, HAART did not appear to fully correct
the adverse effect of HIV infection on HCV prognosis."
While the annual
mean probabilities of progressing from one fibrosis stage to the next were not
that much higher among coinfected compared with monoinfected individuals, the
likelihood of developing cirrhosis was significantly higher over time. These findings
suggest that HIV positive individuals may benefit from earlier hepatitis C treatment
to slow or prevent liver disease progression.
University of Toronto,
Toronto, Ontario, Canada; University Health Network, Division of Clinical Decision-Making
and Healthcare Research, Toronto, Canada; Toronto Health Economics and Technology
Assessment Collaborative (THETA), University of Toronto, Toronto, Canada; National
Epidemiology and Surveillance, Canadian Blood Service, Ottawa, Ontario, Canada;
National Centre in HIV Epidemiology and Clinical Research, University of New South
Wales, Sydney, Australia.
9/16/08
References
HH
Thein, Q Yi, GJ Dore, and MD Krahn. Estimation of stage-specific fibrosis progression
rates in chronic hepatitis C virus infection: A meta-analysis and meta-regression.
Hepatology 48(2): 418-431. August 2008.
HH
Thein, Q Yi, GJ Dore, and MD Krahn. Natural history of hepatitis C virus infection
in HIV-infected individuals and the impact of HIV in the era of highly active
antiretroviral therapy: A meta-analysis. AIDS 22(15): 1979-1991. October
1, 2008. (Abstract). |
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