Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load

Background

This study explores pretreatment predictive factors for ultimate virological responses to pegylated interferon-α (1.5?μg/kg/week) and ribavirin (600–1000?mg/day) (PEG-IFN/RBV) combination therapy for patients infected with hepatitis C virus (HCV)-1b and a high viral load.

Methods

A total of 75 patients underwent PEG-IFN/RBV combination therapy for 48?weeks. HCV amino acid (aa) substitutions in non-structural protein 5a, including those in the IFN/RBV resistance-determining region (IRRDR) and the IFN sensitivity-determining region and the core regions, as well as the genetic variation (rs8099917) near the interleukin 28B (IL28B) gene (genotype TT) were analyzed.

Results

Of the 75 patients, 49?% (37/75) achieved a sustained virological response (SVR), 27?% (20/75) showed relapse, and 24?% (18/75) showed null virological response (NVR). Multivariate logistic regression analysis identified IRRDR with 6 or more mutations (IRRDR ≥6) [odds ratio (OR) 11.906, p?p?=?0.015) as significant determiners of SVR and IL28B minor (OR 14.618, p?=?0.0019) and platelets <15?×?10⁴/mm³ (OR 0.113, p?=?0.0096) as significant determiners of NVR. A combination of IRRDR ≥6 and age <60?years improved SVR predictability (93.3?%), and that of IRRDR ≤5 and age ≥60?years improved non-SVR predictability (84.0?%). Similarly, a combination of IL28B minor and platelets <15?×?10⁴/mm³ improved NVR predictability (85.7?%), and that of IL28B major and platelets ≥15?×?10⁴/mm³ improved non-NVR (response) (97.1?%) predictability.

Conclusion

IRRDR ≥6 and age <60?years were significantly associated with SVR. IL28B minor and platelets <15?×?10⁴/mm³ were significantly associated with NVR. Certain combinations of these factors improved SVR and NVR predictability and could, therefore, be used to design therapeutic strategies.