Objectives Genotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy.
Methods 2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR.
Results Paired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10%; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes.
Conclusions SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.
- albinterferon alpha-2b
- hepatitis C virus
- insulin resistance
- sustained virologic response
- diabetes mellitus
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↵* A complete list of the ACHIEVE-1 and -2/3 investigators appears in online appendix 1
Funding This study was supported by Human Genome Sciences Inc, Rockville, Maryland, USA and Novartis Pharma AG, Basel, Switzerland. Geoff Marx of BioScience Communications, New York, New York, provided editorial assistance supported by HGS and Novartis. The parent study from which data were collected for this analysis was funded by Human Genome Sciences Inc and Novartis.
Competing interests AJT received funding support from the Duke Clinical Research Institute, the National Health and Medical Research Council of Australia and the Gastroenterology Society of Australia. EJL has received research grants from Human Genome Sciences (HGS), Hoffman-LaRoche Inc, Nutley, New Jersey, and Novartis. MR-T has received research grants from Novartis and Roche and is a consultant to Roche. VKR is a consultant for HGS and Novartis. RF is a consultant for HGS. SP is a consultant for, advises and is on the speakers' bureau of HGS, Novartis and Roche. SA has received research support from and is a consultant to HGS. GRF has received funding from Novartis and Roche. YB has received grant support from and has contributed to clinical trials, is a member of speakers' bureaus and has consulted for HGS, Novartis and Roche. DRN has received research support from and is a consultant to HGS. MSS is a consultant for HGS and Novartis. SZ has received consulting fees from HGS, Novartis and Roche and lecture fees from Novartis and Roche. EP and GMS are employees of and own stock in HGS. JGMcH has received research grants from and is a consultant to HGS, Novartis and Roche. No other potential conflicts of interest relevant to this article were reported.
Ethics approval This study was approved by the institutional review board of each participating site (represented by each of the authors contained in appendix 1) and informed consent was obtained from each patient.
Provenance and peer review Not commissioned; externally peer reviewed.
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