Impact of obesity on the bioavailability of peginterferon-α2a and ribavirin and treatment outcome for chronic hepatitis C genotype 2 or 3.
OBJECTIVE
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.
Department of Infectious Diseases/Virology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Åsa
Å
Alsiö
Karolina
K
Rembeck
Galia
G
Askarieh
Peer Brehm
PB
Christensen
Martti
M
Färkkilä
Nina
N
Langeland
Mads Rauning
MR
Buhl
Court
C
Pedersen
Kristine
K
Mørch
Bart L
BL
Haagmans
Salmir
S
Nasic
Johan
J
Westin
Kristoffer
K
Hellstrand
Gunnar
G
Norkrans
Martin
M
Lagging
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D009765:Obesity / Q000150:complications*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a