Gene Response to Interferon Therapy for Hepatitis C Differs by Race

Several studies have shown that individuals of African descent respond less well to interferon-based therapy for chronic hepatitis C, with a significantly lower proportion of black than white patients achieving sustained virological response.

As reported in the August 2006 issue of Hepatology, researchers from Stanford University School of Medicine conducted a study to investigate the underlying host immune responses associated with interferon treatment outcomes. The authors collected peripheral blood mononuclear cells from chronic hepatitis C patients before initiation of interferon therapy; cells were incubated with or without interferon-alpha for six hours. They then used a microarray assay to identify whether gene transcription was stimulated by interferon.

Results

The global induction of interferon-stimulated genes was significantly greater in sustained virological responders compared with non-responders.

Interferon-stimulated gene transcription was also greater in white patients compared with black patients.

Significantly greater global induction of interferon-stimulated genes was observed in sustained virological responders compared with nonresponders within the group of white patients.

The level of interferon-induced signal transducer and activator of transcription (STAT)-1 activation -- a key component of the JAK-STAT interferon-signaling pathway -- correlated with the global induction of interferon-stimulated genes.

STAT-1 activation was significantly higher in white patients than in black patients.

Conclusion

"[B]oth treatment outcome and race are associated with different transcriptional responses to interferon-alpha," the authors concluded. "Because this difference is evident in the global induction of interferon-stimulated genes rather than a selective effect on a subset of such genes, key factors affecting the outcome of interferon-alpha therapy are likely to act at the JAK-STAT pathway that controls transcription of downstream interferon-stimulated genes."

8/21/06

Reference
X S He, X Ji, M B Hale, and others. Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race. Hepatology 44(2): 352-359. August 2006.