Hepatitis Therapeutics

David Gretch, MD, PhD

This study is concerned with the relationship of hepatitis C virus genomic variability and patient response to therapy with recombinant a interferon (aIFN). It has been speculated that the emergence of HCV quasispecies during infection could result in a high rate of resistance to IFN therapy through therapeutic selection. The investigators are analyzing HCV genomic heterogeneity to determine if mutations arise during IFN therapy and if variable regions can confer resistance to IFN.

The investigators have recently shown that a conserved sequence within the HCV nonstructural 5A gene, described by a Japanese group as an interferon sensitivity determining region (ISDR), is not associated with or responsible for IFN resistance in North American patients infected with HCV genotype 1b. In addition, this study has preliminary evidence of a role for HCV quasispecies genetic diversity in the HVR1 region in patient response to IFN therapy. GSA quantitation of HVR1 heterogeneity in pretreatment sera demonstrated that genetic diversity was predictive of response failure. This finding suggests a need for analyses of other HCV genes.

Report courtesy of Anna Marie Beckmann

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Recent Publications

Hofgartner WT, Polyak SJ, Sullivan DG, Carithers RL Jr, Gretch DR. Mutations in the NS5A gene of hepatitis C virus in North American patients infected with HCV genotype 1a or 1b. J Med Virol 1997; 53:118-26.

Polyak SJ, Faulkner G, Carithers RL Jr, Corey L, Gretch D. Assessment of hepatitis C quasispecies heterogeneity by gel shift analysis: correlation with response to interferon therapy. J Infect Dis 1997; 175:1101-7.