Interleukin 28B genetic polymorphisms play a minor role in identifying optimal treatment duration in HCV genotype 1 slow responders to pegylated interferon plus ribavirin.

BACKGROUND: Pegylated interferon and ribavirin for 72 weeks improve sustained virological response (SVR) in HCV genotype 1 (HCV-1) slow viral responders. Whether interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and on-treatment viral responses can identify non-rapid virological response (RVR) patients who benefit from 48 or 72 weeks of therapy remains unclear.

METHODS: Treatment-naive HCV-1 patients who failed to achieve RVR were randomly assigned to receive 48 (n=168) or 72 (n=167) weeks of therapy. Baseline factors and on-treatment virological responses at weeks 8 and 12 were evaluated for SVR in 289 compliant patients who received ≥80% of drug dosages and treatment duration, and had end of follow-up viral response. The stratified SVR rates for independent factors were compared by treatment duration.

RESULTS: Treatment duration, IL28B rs8099917 genotypes, cirrhosis, week-8 viral response (undetectable HCV RNA at treatment week 8) and complete early virological response (cEVR) predicted SVR. In week-8 viral response patients, the SVR rates of 72-week and 48-week treatment were similar (75-88%), regardless of IL28B SNP genotypes or cirrhosis. In non-week-8 viral response patients who achieved cEVR, the SVR rate of 72-week treatment was higher than that of 48-week treatment for non-cirrhotic patients, regardless of IL28B SNP genotypes (91-100% versus 13-44%; P=0.001).

CONCLUSIONS: Although IL28B SNP genotypes predict SVR, they play a minor role when on-treatment viral responses are taken into consideration. On-treatment viral responses at weeks 8 and 12 are the key determinants to decide the optimal treatment duration in HCV-1 patients without RVR.