Clinical trial: low plasma cholesterol and oxidative stress predict rapid virological response to standard therapy with peginterferon and ribavirin in HCV patients

Abstract

Rapid virological response (RVR) is the best predictor of sustained response to standard HCV treatment. To evaluate predictive factors of RVR. Sixty-five patients (mean age 52.6 +/- 13.8; 37 genotype-1, and 28 genotypes-2/3) were consecutively treated with pegIFN-alpha 2a or 2b once weekly plus daily ribavirin based on body weight for 24 or 48 weeks, according to genotype. RVR was defined as undetectable HCV-RNA at week 4. Twenty-seven percent of patients achieved RVR in genotypes 1 and 60.7% in genotypes 2/3 (P < 0.01). Rapid responders had higher mean serum baseline total and LDL-cholesterol levels (P < 0.01). RVR was 20.0% in the bottom tertile of total cholesterol and 63.6% in the top tertile (P < 0.01). HCV-RNA levels at week 4 were positively correlated with baseline serum insulin (P < 0.01), HOMA-IR (P < 0.01), body mass index (P < 0.05) and number of components of metabolic syndrome (P < 0.01) and negatively correlated with cholesterol levels (P < 0.05). At multivariate analysis, age, LDL-cholesterol, HCV genotype and serum 8-iso-PGF 2 alpha, a marker of oxidative stress, were independent predictors of RVR. Our prospective study supports a role of low serum total and LDL-cholesterol and of oxidative stress as positive independent predictive factors of poor RVR in HCV patients.