Impact of Obesity on the Bioavailability of Peginterferon-alpha 2a and Ribavirin and Treatment Outcome for Chronic Hepatitis C Genotype 2 or 3

A Alsio, K Rembeck, G Askarieh, PB Christensen, M Farkkila, N Langeland, MR Buhl, C Pedersen, K Morch, Bart Haagmans, S Nasic, J Westin, K Hellstrand, G Norkrans, M Lagging

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)
10 Downloads (Pure)

Abstract

Background and Aims: Having a body mass index above or equal to 30 kg/m(2) 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-alpha 2a 180 mu g 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/m(2) 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 Conclusions: Reduced bioavailability of interferon and ribavirin along with higher baseline viral load are dominant risk factors for treatment failure in obese patients with chronic hepatitis C.
Original languageUndefined/Unknown
JournalPLoS One (print)
Volume7
Issue number5
DOIs
Publication statusPublished - 2012

Research programs

  • EMC MM-04-27-01

Cite this