As reported in the October 2008 Journal of Hepatology, investigators with the HALT-C trial evaluated genetic factors associated with outcomes among patients with HCV genotype 1 who did not achieve sustained virological response (SVR) to previous interferon treatment.

HALT-C was designed to assess whether long-term, low-dose pegylated interferon maintenance monotherapy would improve outcomes in prior non-responders. More than 1000 participants were enrolled and treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day ribavirin for 24 weeks. Patients who had undetectable HCV RNA at week 20 continued combination therapy until week 48. The 662 patients who did not clear the virus at this point were randomly assigned to either continue treatment with 90 mcg/week pegylated interferon monotherapy for an additional 42 months or to discontinue all treatment.

As previously reported, the study's primary analysis found that maintenance therapy conferred no benefit with regard to reduced liver disease progression after 3.5 years, even though an interim analysis had shown that low-dose pegylated interferon led to improvements in ALT level, HCV viral load, and necroinflammation.

In the present analysis, the investigators used polymerase chain reaction assays to assess participant genotypes. They looked at 8 single nucleotide polymorphisms (SNPs) selected on the basis of previously reported associations with treatment response. SVR was determined 24 weeks after completing treatment with pegylated interferon plus ribavirin (not including the maintenance phase). The percentage of patients who achieved SVR was determined for each genotype and for an IL10 promoter diplotype.

Results

Conclusions

Based on these findings, the investigators concluded, "Among non-Hispanic Caucasian patients treated with peginterferon and ribavirin after failing previous treatment with interferon, homozygosity for the ACC IL10 promoter diplotype was associated with SVR."

Further study will be needed to determine whether such genetic variations help explain observed racial/ethnic differences in treatment response.

University of California-Irvine, Irvine, CA; VA Long Beach Healthcare System, Long Beach, CA; University of Connecticut Health Center, Farmington, CT; Carolinas Medical Center, Charlotte, NC; Massachusetts General Hospital and Harvard Medical School, Boston, MA; New England Research Institutes, Watertown, MA; Virginia Commonwealth University Medical Center, Richmond, VA; University of Michigan, Ann Arbor, MI; University of Texas Southwestern Medical Center, Dallas, TX; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; National Cancer Institute, National Institutes of Health, Bethesda, MD.

9/09/08

Reference
T Morgan, R Lambrecht, H Bonkovsky, and others (HALT-C Trial Group). DNA polymorphisms and response to treatment in patients with chronic hepatitis C: Results from the HALT-C trial. Journal of Hepatology 49(4): 548-556. October 2008. (Abstract)