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Atorvastatin and Fluvastatin Are Associated With Dose-Dependent Reductions in Cirrhosis and Hepatocellular Carcinoma, Among Patients With Hepatitis C Virus: Results From ERCHIVES
Simon TG, et al .
Hepatology 2016; 64:47-57.

Statins are associated with delayed fibrosis progression and a reduced risk of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV). Limited data exist regarding the most effective type and dose of statin in this population. We sought to determine the impact of statin type and dose upon fibrosis progression and HCC in patients with HCV.

Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database, we identified all subjects initiated on HCV antibody (anti-HCV) therapy from 2001 to 2014, and all incident cases of cirrhosis and HCC. Statin use was measured using cumulative defined daily dose (cDDD). Multivariable Cox's proportional hazard regression models were used to examine the relationship between statin use and development of cirrhosis and HCC.

Among 9,135 eligible subjects, 1,649 developed cirrhosis and 239 developed incident HCC. Statin use was associated with a 44% reduction in development of cirrhosis (adjusted hazard ratio [HR]: 0.6; 95% confidence interval [CI]: 0.53, 0.68). The adjusted HRs (95% CI) of fibrosis progression with statin cDDD 28-89, 89-180, and >180 were 0.74 (0.59, 0.93), 0.71 (0.59, 0.88), and 0.6 (0.53, 0.68), respectively. Mean change in FIB-4 score with atorvastatin (n = 944) and fluvastatin (n = 34) was -0.17 and -0.13, respectively (p = 0.04), after adjustment for baseline FIB-4 score and established predictors of cirrhosis. Statin use was also associated with a 49% reduction in incident HCC (adjusted HR: 0.51; 95% CI: 0.36, 0.72). A similar dose-response relationship was observed.

Conclusion: In patients with chronic HCV, statin use was associated with a dose dependent reduction in incident cirrhosis and HCC. Atorvastatin and fluvastatin were associated with the most significant antifibrotic effects, compared with other statins.

Expert's Commentary

« Different studies have shown that statins play a role in patients with chronic hepatitis C (CHC) decreasing the risk of disease progression and development of hepatocellular carcinoma (HCC). The proposed mechanisms of action of statins are blocking proteins needed for lipid formation and HCV replication. In an observational study, the Erchives study, Simon et al. suggest that not all statins, only atorvastain and fluvastatin are associated with a dose-dependent reductions in cirrhosis and HCC. The study has been performed in patients treated with Peg-IFN and Ribavirin, this is a selected group of patients with compensated liver disease completely different that those currently treated with direct acting antivirals (DAAs) . The advantage of the study is the large number of patients and the broad information included. All patients received statins to treat hyperlipidemia and probably they ameliorated the metabolic syndrome. This fact can not been proven in this study because there were no liver biopsies and fibrosis was evaluated by non invasive markers that has been associated with more disease progression and HCC, even in patients with CHC. Further prospective studies particularly with DAAs and statins are needed to define the role of these drugs in CHC outcomes. »

Pr Maria Butti,
Hospital General Universitari Valle Hebron, Barcelona