Clinical

Genetic variability of hepatitis C virus may influence treatment outcome

Last Updated: 2003-05-23 15:29:23 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Genetic variation in hepatitis C virus (HCV) may influence the outcome of alpha-interferon (IFN) treatment, including the response to different alpha-IFN preparations, according to a report in the May Journal of Medical Virology.

The persistence of HCV infection has been attributed in part to its high rate of genetic variability, the authors explain, and alpha-IFN treatment is known to influence the HCV quasispecies distribution.

Dr. Peter Karayiannis from Imperial College of Science, Technology and Medicine in London, UK and colleagues used cloning and sequencing to investigate the pattern and significance of variability in the HVR-1 and NS5A regions of the HCV genome during alpha-IFN treatment in 12 patients with chronic HCV infection.

Nucleotide and amino acid complexity during alpha-IFN treatment decreased markedly among responder-relapsers, the authors report, but viral complexity increased in 3 of 4 nonresponders.

Moreover, baseline HCV diversity was significantly higher among responder-relapsers, the report indicates, and decreased during treatment. In contrast, HCV diversity did not change or increased with treatment in nonresponders.

The diversity of quasispecies that survived in responder-relapsers was significantly reduced, the researchers note, whereas the pretreatment isolates in nonresponders persisted at 12 weeks and evolved to an even more diverse population by week 24.

In baseline samples, amino acids G406 and Q409 within the HVR-1 region were highly conserved, according to the report, and both were unchanged after alpha-IFN administration.

NS5A mutations were significantly more common among responder-relapsers than among nonresponders, the results indicate, but mutation prevalence did not correlate with viral load.

Treatment with lymphoblastoid alpha-IFN selected for intermediate IFN sensitivity determining region sequences, the investigators report, while recombinant-2b alpha-IFN favored maintenance or selection of conserved such sequences.

"Our data do not allow us to speculate at present on which preparation might be more beneficial in the treatment of chronic hepatitis C virus infection," Dr. Karayiannis told Reuters Health.

"In vitro studies have already demonstrated potent anti-viral effects by several alpha IFN subtypes, as well as beta IFN," Dr. Karayiannis explained. "This is highly significant at present, since there exists the possibility of chemically modifying individual alpha-IFN sub-types by pegylation. Pegylation of alpha-IFN has improved response rates, and pegylating other subtypes could further enhance the efficacy of anti-HCV treatment."

"Failure to respond to antiviral treatment may be the result of emergence of IFN resistant virus variants," Dr. Karayiannis concluded. "These may respond better to other IFN formulations."

J Med Virol 2003; 70:62-73.