Changes in Gene Expression during Hepatitis C Treatment Distinguish Responders from Non-Responders
www.hivandhepatitis.com
By Liz Highleyman

While treatment of chronic hepatitis C using pegylated interferon plus ribavirin leads to sustained HCV clearance and clinical improvement in approximately half of all patients, response rates are lower in certain "difficult to treat" groups, including patients with genotype 1 HCV and African-Americans.

It is unclear why treatment response rates vary by race/ethnicity, but genetic factors may play a role.

As reported in the January 31, 2007 electronic edition of the Journal of Virology, researchers used DNA micro-arrays to assess gene expression in a group of 33 African-American and 36 Caucasian-American patients with genotype 1 chronic HCV infection during the first 28 days of treatment with pegylated interferon/ribavirin.

Results

• Patients showed a response to treatment at the gene expression level in RNA isolated from peripheral blood mononuclear cells (PBMCs) regardless of degree of decrease in HCV RNA levels.

• Gene expression responses were relatively blunted in patients with poor virological response (< 1.5 log10 IU/mL decrease in HCV RNA at 28 days) compared to those with a marked (> 3.5 log10 decrease) or intermediate (1.5-3.5 log10 decrease) response.

• The number of genes that were up-regulated or down-regulated by pegylated interferon/ribavirin was fewer in patients with a poor virological response compared to those with a marked or intermediate response.

• Induced levels of known interferon-stimulated genes such as OAS, MX1, IRF-7, and the toll-like receptor TLR-7 were lower in poor responders compared to patients with marked or intermediate responses.

• However, African-Americans had stronger interferon responses than Caucasian patients overall.

Conclusion

The authors concluded that, "the relative lack of viral response to interferon therapy of hepatitis C is associated with blunted interferon cell signaling. No specific regulatory gene could be identified as responsible for this global blunting or racial differences."
It remains unclear why African-Americans tend to respond more poorly to interferon-based therapy, given their overall stronger gene expression response to interferon.