Influence
of HCV Subtype and Quasispecies on Virological Response
to Interferon-Based Therapy
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| SUMMARY:
The hepatitis C virus (HCV) is highly variable,
with at least 6
distinct genotypes. It is well known
that genotype has a major influence on response
to interferon-based therapy, with genotypes
1 and 4 being harder to treat than genotypes
2 or 3. But viral subtypes -- or divisions
within genotypes -- may also play a role.
According to a study in the December
2009 Journal of Medical Virology,
subtype 1a is associated with a lower response
rate than 1b. Another recent study found
that greater diversity of HCV quasispecies
-- or minor variations within a single individual
-- may increase the likelihood of early
virological response. |
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By
Liz Highleyman
In the first study, Florence Legrand-Abravane and
colleagues with the French AC11 HCV Study Group evaluated
the influence of HCV subtype on sustained virological
response (SVR) in people infected with genotypes 1,
4, 5, or 6.
The
study included 597 chronic hepatitis C patients who
were treated with pegylated
interferon plus ribavirin for 48 weeks.
Results
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The
overall SVR rate for the 597 patients was 37.8%.
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In
a univariate analysis, individuals with HCV subtype
1b tended to have a higher sustained response
rate (39.0%) than those with subtype 1a (30.6%)(P
= 0.06, just short of statistical significance). |
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SVR
rates were similar for patients infected with
HCV subtypes 4a (51.3%) or 4d (51.7%). |
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In
a multivariate analysis, 5 factors were independently
associated with sustained virological response: |
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Patient
age: odds ratio (OR) 0.97; |
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Absence
of liver cirrhosis: OR 2.92 (P < 0.01); |
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Absence
of HIV coinfection: OR 2.08 (P < 0.01); |
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Low
baseline HCV RNA: OR 1.74 (P < 0.01); |
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Infection
with HCV subtype 1b (OR 1.61; P = 0.04)
or 4a/4d (OR 2.03; P = 0.03). |
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In
conclusion, the study authors wrote, "among difficult-to-treat
genotypes, the subtype 1a is associated with a lower
response to anti-HCV therapy than subtypes 1b, 4a,
and 4d."
HCV
Quasispecies
In
the second study, published in the December
2009 issue of Hepatology, Xiaofeng Fan
from St Louis University School of Medicine and colleagues
from the U.S. and China performed a large quasispecies
analysis of patients with HCV genotype 1.
Among many factors that may affect response to antiviral
therapy, HCV quasispecies have been a major focus
of previous studies, but research to date has yielded
conflicting results, the study authors noted as background.
The present analysis included 153 participants with
HCV genotype 1 strains. The investigators produced
a total of 4314 viral clones spanning the HCV hypervarible
region 1 from these patients during the first 12 weeks
of therapy, followed by detailed genetic analyses.
Results
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The
analysis revealed an exponential distribution
pattern of quasispecies diversity within patients
in this study population. |
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A
majority of participants (63%) had minimal quasispecies
diversity, with genetic distance less than 0.2. |
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A
subgroup of patients with high quasispecies diversity
indicated by genetic distance in the decay region
(d > 0.53) had a significantly higher early
virological response (EVR) rate, at 89.5%. |
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This
subset contributed substantially to the overall
association between EVR and increased baseline
quasispecies diversity. |
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EVR
was also associated with a clustered evolutionary
pattern of quasispecies dynamic changes.
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Based
on these findings, the authors concluded, "EVR
is associated with elevated HCV quasispecies diversity
and complexity, especially in patients with significantly
higher HCV genetic heterogeneity."
1/12/10
References
F
Legrand-Abravanel, P Colson, H Leguillou-Guillemette,
and others. Influence of the HCV subtype on the virological
response to pegylated interferon and ribavirin therapy.
Journal of Medical Virology 81(12): 2029-2035
(Abstract).
December 2009.
X
Fan, Q Mao, D Zhou, and others. High diversity of
hepatitis C viral quasispecies is associated with
early virological response in patients undergoing
antiviral therapy. Hepatology 50(6): 1765-1772
(Abstract).
December 2009.
