Impact of Obesity on the Bioavailability of Peginterferon- a2a and Ribavirin and Treatment Outcome for Chronic

Background and Aims: Having a body mass index above or equal to 30 kg/m2 in conjunction with chronic hepatitis C virus infection is associated with non-responsiveness to treatment with interferon and ribavirin, but details regarding the mechanisms whereby obesity reduces the efficacy of therapy remain unclear. Methods: This study evaluated impact of obesity on outcome as well as interferon and ribavirin concentrations following standard-of-care fixed dosing with peginterferon-a2a 180 mg once weekly and ribavirin 800 mg daily among 303 HCV genotype 2/3-infected patients enrolled in the per-protocol analysis of a recently completed phase III trial (NORDynamIC). Results: Patients with BMI $30 kg/m2 showed poorer outcome following 24 weeks of therapy (SVR 62 % vs. 89 % for BMI $30 vs.,30; P = 0.006) along with significantly higher steatosis grade (P = 0.002), HOMA-IR (P,0.0001), triglyceride levels (P = 0.0002), and baseline viral load (P = 0.028). Obesity was also significantly associated with lower plasma interferon concentrations on days 3, 7, and 29 (P = 0.02, P = 0.0017, and P,0.0001, respectively) and lower plasma ribavirin concentrations day 29 (P = 0.025), and lower concentration of interferon in turn was associated with a poorer first phase reduction in HCV RNA (P,0.0001). In multivariate analysis, ribavirin concentrations week 12, interferon concentrations da