Patients with treatment-naive chronic hepatitis C virus infection who carry the rs12979860 C/C or rs8099917 T/T polymorphisms in the region of the IL28B gene are more likely than are noncarriers to show an early virologic response, as well as a sustained virologic response, to interferon-based therapy, Dr. Albert Stättermayer and his colleagues reported in the April issue of Clinical Gastroenterology and Hepatology.
Currently, the IL28B status of patients is obtained routinely and is used to predict the likelihood of their response to combined peginterferon/ribavirin therapy. If further prospective, controlled research confirms the findings of this study, determining patients’ status regarding these polymorphisms will also become useful in treatment planning, the researchers said (Clin. Gastroenterol. Hepatol. 2011 April [doi:10.1016/j.cgh.2010.07.019]).
Previous genome-wide association studies in patients with chronic HCV infection found strong associations between treatment response and the single-nucleotide polymorphisms (SNPs) rs12979860 and rs8099917. Dr. Stättermayer of the Medical University of Vienna and his associates examined these associations in 682 treatment-naive patients with chronic HCV.
The study subjects were patients who completed a full course of peginterferon-alpha plus ribavirin treatment in 2001-2009 at several medical centers across Austria. All had tested positive for HCV RNA for at least 6 months before beginning the therapy.
HCV RNA levels were assessed at baseline, after 4 weeks of treatment, and after 12 weeks of treatment. Treatment duration ranged from 24 to 72 weeks. Patients’ SNP status was determined from whole blood samples using real-time PCR.
A total of 36% of patients showed a rapid virologic response to peginterferon-based therapy. These patients also had a high rate of sustained virologic response (92%), compared with patients who had not shown a rapid response (46%). A rapid virologic response was the single strongest predictor of achieving a sustained virologic response, with an odds ratio of 17.
Overall, 63% of patients showed a sustained virologic response to peginterferon-based therapy. Patients with either the rs12979860 SNP or the 8099917 SNP were the most likely to achieve a sustained virologic response, with rates of over 80%. Baseline viral load, patient age, and fibrosis stage all were independent predictors of a sustained virologic response, but SNP status remained the most strongly predictive factor.
"Our study confirms the previously reported findings in various populations around the world," Dr. Stättermayer and his colleagues said. "The precise role of this polymorphism remains unknown. Based on our data, the SNP in the IL28B region appears to be associated with the early phases of viral clearance.
"Differences in viral load reduction between genotypes were detectable as early as week 2, which was the earliest time point evaluated." In addition, the divergence in treatment response peaked at week 4.
"The main focus of our study was the clinical applicability of genetic testing. The positive predictive value of rs12979860 C/C (the favorable genotype) for a sustained virologic response was high, but specificity and sensitivity were low," the researchers noted.
Their results indicate that "a patient with a low baseline viral load and 2 C alleles may benefit from standard of care, with a possible reduction of treatment duration to 24 weeks. On the other hand, T-allele carriers with advanced fibrosis and a high baseline viral load could possibly benefit from novel therapeutic strategies such as polymerase or protease inhibitors added to peginterferon and ribavirin, to maximize viral response," the investigators said.
Dr. Stättermayer had no disclosures, but several coauthors, including Dr. Peter Ferenci, the principal investigator, reported financial relationships with Roche. Dr. Ferenci receives an unrestricted research grant from Roche Austria.