Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy

Abstract

Elevated low-density lipoprotein (LDL) levels and statin use have been associated with higher sustained virological response (SVR) rates in patients receiving chronic hepatitis C therapy. However, these relationships have not been well characterized in randomized controlled trials. Furthermore, little is known about the relationship between high-density lipoprotein (HDL) and virological response. To determine whether baseline LDL or HDL levels and statin use affect SVR rates, we retrospectively evaluated the IDEAL (Individualized Dosing Efficacy Versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial, in which 3070 treatment-naive, hepatitis C virus (HCV) genotype 1-infected patients were treated for up to 48 weeks in one of the following arms: (1) peginterferon (PEG-IFN) alfa-2b at 1.5 lg/kg/week with ribavirin (RBV) at 800 to 1400 mg/day, (2) PEG-IFN alfa2b at 1.0 lg/kg/week with RBV at 800 to 1400 mg/day, or (3) PEG-IFN alfa-2a at 180 lg/week with RBV at 1000 to 1200 mg/day. Virological responses were assessed by pretreatment statin use and baseline elevated LDL levels (!130 mg/dL) or low HDL levels (<40 mg/dL for men and <50 mg/dL for women). In 1464 patients with baseline elevated LDL levels or low HDL levels, the SVR rate was significantly higher than that in patients with normal levels (44.9% versus 34.0%, P < 0.001). In 66 patients receiving a statin pretreatment, the SVR rate was higher than the rate of those not receiving it (53.0% versus 39.3%, P 5 0.02). In a multivariate logistic regression analysis using the stepwise selection method with baseline characteristics, a high LDL level [odds ratio (OR) 5 1.6, 95% confidence interval (CI) 5 1.4-1.8, P < 0.001], a low HDL level (OR 5 0.5, 95% CI 5 0.3-0.8, P 5 0.004), and statin use (OR 5 2.0, 95% CI 5 1.1-3.7, P 5 0.02) were independently associated with SVR. Conclusion: Baseline elevated LDL levels or low HDL levels and preemptive statin usage were associated with higher SVR rates. Prospective studies may be considered to explore the biological impact of these factors on HCV RNA replication and treatment response. (HEPATOLOGY 2010;52:864-874)

HCV genotype 3: a wolf in sheep’s clothing

“…Is the damage the consequence of the virus or of its proteins in infected hepatocytes? Given that, in previous studies, the variables independently associated with SVR were high LDL levels, [19,20] low HDL levels [19] and statin use, [19] one might think that statins would be a useful option for such patients. Nonetheless, this is not actually the case with HCV G3.…”

Statin Use and Survival with Early-Stage Hepatocellular Carcinoma

“…A secondary aim was to examine the statin-survival association by HCV infection status given the purported influence of statin on HCV replication, and virologic response to HCV treatment (6)(7)(8). We performed subgroup analyses by HCV infection status, and tested for effect modification by a two-way interaction term between statin and HCV using the likelihood ratio test.…”

“…6). Accordingly, statins have been shown to improve the antiviral activity of HCV polymerase and protease inhibitors in vitro (7), and are associated with an enhanced virologic response to peginterferon and ribavirin therapy in humans (8). In line with these pleotropic effects, statins have been reported to decrease the risk of HCC (9,10).…”

Lipid Involvement in Viral Infections: Present and Future Perspectives for the Design of Antiviral Strategies

“…Treatment of patients with different statins (i.e. lovastatin, simvastin, or fluvastin) resulted in diverse effects on HCV infection, ranging from an absence of antiviral effect to a modest improvement of sustained antiviral response, or a reduction of viremia [172,173,[187][188][189]. Beneficial effects derived from treatment with statins of infection with diverse influenza strains have also been reported in animal models and human studies [170,171], although other studies do not support these conclusions [190].…”