Early prediction of sustained virological response at day 3 of treatment with albinterferon-α-2b in patients with genotype 2/3 chronic hepatitis C

Background: Albinterferon-α-2b (albIFN) is a long-acting fusion polypeptide composed of albumin and IFN-α-2b. In a phase 2 study of albIFN 1500 μg q2wk or q4wk in patients with genotype 2/3 chronic hepatitis C, albIFN demonstrated sustained virological response (SVR) rates of 62-77% (intent-to-treat population). Aims: To assess the association of initial viral kinetics during albIFN therapy with baseline factors and SVR prediction. Methods: In all, 43 patients were treated with albIFN 1500 μg (q2wk/q4wk) plus ribavirin (RBV) 800mg/day for 24 weeks. Hepatitis C virus (HCV)-RNA levels were measured by real-time polymerase chain reaction, insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) and serum albIFN levels by enyzme-linked immunosorbent assay. Prediction analysis was performed in a per protocol 28-patient subset who were ≥80% adherent to albIFN/RBV and had HCV-RNA levels measured at treatment day 3. Results: Day-3 HCV-RNA level and firstphase viral decline as well as second-phase slope of viral decline were significantly associated with SVR. In adherent patients, 82.1% had a day-3 viral load <4.2 log₁₀ IU/ml or first-phase decline >1.25 log₁₀ IU/ml, which was predictive of SVR, both positively (95.7%; sensitivity: 100%) and negatively (100%; specificity: 83.3%). As low first-phase decline was associated with a high pretreatment HOMA-IR index (P = 0.004) and a low day-3 serum albIFN level (P = 0.01). Conclusions: First-phase viral decline with albIFN/RBV was predictive of SVR in this study and may be modulated in part by IR.