Insulin resistance impairs viral dynamics independently of ethnicity or genotypes.
OBJECTIVE
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.
Unit for the Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Ctra de Cadiz s/n, Sevilla, Spain.
Mohammed
M
Eslam
Reyes
R
Aparcero
Youssef I
YI
Mousa
Lourdes
L
Grande
Yehia
Y
Shaker
Ahmed
A
Ali
José A
JA
Del Campo
Mahmoud A
MA
Khattab
Manuel
M
Romero-Gomez
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D044383:Black People / Q000208:ethnology; D004359:Drug Therapy, Combination; D004534:Egypt; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000208:ethnology* / Q000235:genetics / Q000821:virology; D006785:Hospitals, University; D006801:Humans; D007333:Insulin Resistance; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D013030:Spain; D016896:Treatment Outcome; D019562:Viral Load; D044465:White People / Q000208:ethnology
D000998:Antiviral Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D012254:Ribavirin