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Influence of HCV Subtype and Quasispecies on Virological Response to Interferon-Based Therapy

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.

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

The overall SVR rate for the 597 patients was 37.8%.
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).
SVR rates were similar for patients infected with HCV subtypes 4a (51.3%) or 4d (51.7%).
In a multivariate analysis, 5 factors were independently associated with sustained virological response:
 
Patient age: odds ratio (OR) 0.97;
Absence of liver cirrhosis: OR 2.92 (P < 0.01);
Absence of HIV coinfection: OR 2.08 (P < 0.01);
Low baseline HCV RNA: OR 1.74 (P < 0.01);
Infection with HCV subtype 1b (OR 1.61; P = 0.04) or 4a/4d (OR 2.03; P = 0.03).

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

The analysis revealed an exponential distribution pattern of quasispecies diversity within patients in this study population.
A majority of participants (63%) had minimal quasispecies diversity, with genetic distance less than 0.2.
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%.
This subset contributed substantially to the overall association between EVR and increased baseline quasispecies diversity.
EVR was also associated with a clustered evolutionary pattern of quasispecies dynamic changes.

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.


 


 




 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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