Does genotype matter?

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Does hepatitis C virus (HCV) subtype have clinical importance?

According to a recent review published in Medscape Gastroenterology, the identification of viral subtypes is of clinical importance because it can be predictive of response to therapy. Many of the clinical trials that have investigated interferon treatment of chronic hepatitis C infection have demonstrated the effect of HCV genotype on response to therapy. Genotype 1b is not effectively treated with interferon monotherapy, with only 10%-15% of treated patients exhibiting long-term response. By contrast, individuals infected with HCV of genotypes 1a, 2a, 2b, and 3a have significantly higher long-term response rates. Additionally, the identification of subtypes is of clinical importance, because it has been demonstrated that subtype 1a-infected individuals respond better to interferon monotherapy than their 1b-infected counterparts.

There are 6 main genotypes of HCV, which are classified numerically from 1 to 6. Each genotype is further stratified by subtype, which is alphabetically assigned as "a," "b," and so on. Molecular characterization of the virus has revealed heterogeneity between isolates from different genotypes and individual subtypes. The prevalence of individual genotypes varies by geographic region, with genotype 1 showing a worldwide distribution. Other HCV isolates are region specific.

This effect of HCV viral genotype and subtype on response to therapy was observed to be independent of age, gender, and duration of disease. Large clinical trials conducted by both McHutchison and colleagues and Poynard and associates demonstrated an efficacy rate of 65% for combination therapy in non-1b-infected individuals. The percentage of sustained responders for genotype 1b-infected individuals was almost twice as great with combination therapy as with interferon monotherapy. These findings represent considerable improvements in the treatment options for both clinicians and patients.

Further advances in understanding the dynamics of viral replication, the evolution of treatment-resistant quasispecies, and how these events are likely to affect antiviral strategies will aid in the development of novel therapeutic approaches.

Source: Fanning LJ, Shanahan F.: The Hepatitis C Virus: Master of Diversity and Challenging Adversary. Medscape Gastroenterology, 2000. © 2000 Medscape, Inc.


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