Impact of obesity on the bioavailability of peginterferon-α2a and ribavirin and treatment outcome for chronic hepatitis C genotype 2 or 3.

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-α2a 180 µg 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 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 day 29, and baseline HCV RNA levels were independent predictors of achieving SVR among patients treated for 24 weeks (n = 140).

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.

• Authors: Åsa Alsiö, Karolina Rembeck, Galia Askarieh, Peer Brehm Christensen, Martti Färkkilä, Nina Langeland, Mads Rauning Buhl, Court Pedersen, Kristine Mørch, Bart L Haagmans, Salmir Nasic, Johan Westin, Kristoffer Hellstrand, Gunnar Norkrans, Martin Lagging
• Journal: PloS one (PLoS One) Vol. 7 Issue 5 Pg. e37521 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22655053 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2a

Topics

• Adult
• Antiviral Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Biological Availability
• Female
• Genotype
• Hepacivirus (drug effects)
• Hepatitis C, Chronic (complications, drug therapy, genetics, pathology)
• Humans
• Interferon-alpha (administration & dosage, pharmacokinetics, therapeutic use)
• Liver (drug effects, metabolism, pathology, virology)
• Male
• Obesity (complications)
• Polyethylene Glycols (administration & dosage, pharmacokinetics, therapeutic use)
• Recombinant Proteins (administration & dosage, pharmacokinetics, therapeutic use)
• Ribavirin (administration & dosage, pharmacokinetics, therapeutic use)
• Treatment Outcome
• Viral Load (drug effects)