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

P>Background Rapid virological response (RVR) is the best predictor of sustained response to standard HCV treatment. Aim To evaluate predictive factors of RVR. Methods Sixty-five patients (mean age 52.6 +/- 13.8; 37 genotype-1, and 28 genotypes-2/3) were consecutively treated with pegIFN-alpha2a 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. Results 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-PGF2alpha, a marker of oxidative stress, were independent predictors of RVR. Conclusions 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.