Insulin Resistance Impairs Viral Dynamics Independently of Ethnicity or Genotypes

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Abstract

Background and Aim:

Data concerning the influence of insulin resistance (IR) and ethnicity on early phases of viral kinetics after initiation of peginterferon plus ribavirin in treatment-naive, chronic hepatitis C (CHC) patients are limited.

Methods:

A total of 263 nondiabetic CHC patients treated with peginterferon plus ribavirin were enrolled for analysis from an Egyptian and Spanish center. IR was evaluated by homeostasis model assessment (HOMA)-IR. Hepatitis C virus (HCV) RNA levels were measured at baseline, 48 hours, 2, 4, and 12 weeks after treatment initiation. Sustained virological response (SVR) was examined 24 weeks after therapy discontinuation.

Results:

Baseline HOMA-IR strongly influenced 48 hours viral dynamics. HCV-RNA decay observed at 48 hours after the first injection of peginterferon was significantly lower (0.91±0.51 log) in patients with HOMA ≥2 compared with those with HOMA <2 (1.8±0.95 log, P=0.005) this effect was independent of stage of liver fibrosis, HCV genotype, and ethnicity. These differences remained with several cutoffs such as HOMA >3 or HOMA >4. Multivariate analysis identified baseline insulin levels as the main independent variable affecting the 48-hour response in addition to baseline HCV-RNA. The difference in early viral kinetics between patients with HOMA ≥2 or <2 is associated with a significant difference in the percentage of patients achieving both rapid virological response and SVR.

Conclusions:

IR is a major determinant of the early viral kinetic response to peginterferon plus ribavirin, which has a great impact on subsequent rapid virological response and SVR in CHC patients. This suggests that strategies to improve IR may have a positive effect on SVR and may be early monitored.

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