Statin Therapy Decreases Risk of Hepatic Steatosis and Lobular Inflammation in Patients with Nonalcoholic Fatty Liver Disease

Abstract

Purpose: Lipid-lowering therapies, and statins in particular, are routinely used for patients with risk factors for nonalcoholic fatty liver disease (NAFLD). There is unequivocal data that use of statins decreases cardiovascular morbidity and mortality (the leading cause of death in patients with NAFLD). Although use of statins may be safe in patients with NAFLD, the beneficial effect on histologic features of NAFLD remains unknown. The purpose of this study is to assess the histologic benefit of statin therapy in patients with biopsy-proven NAFLD. Methods: 362 patients with biopsy-proven NAFLD registered in the NAFLD Clinical Database at Duke University were analyzed. All demographical, laboratory, and concomitant medication at time of liver biopsy were reviewed. Liver histology was graded and staged for histologic features of NAFLD according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Chi-square test and multiple ordinal logistic regressions were used. Results: Of the 362 patients, 60% were women, with mean age 48±11 years, and mean body mass index (BMI) 37±9. Prevalence of diabetes mellitus, hypertension, and hyperlipidemia was 29%, 59%, and 31% respectively. Statin vs. non-statin lipid lowering agent (i.e. fibrates, niacin, and/or bile-acid binding resin) use was 26% vs. 8%. In univariate analysis, statin use was inversely associated with steatosis grade (p<0.003) and a trend toward less lobular inflammation (p<0.07). After controlling for age, gender, BMI, diabetes mellitus, use of oral insulin-sensitizing agents and non-statin therapy, the use of statins was significantly associated with a 50% decreased risk of having more severe steatosis [adjusted cumulative odds ratio and 95% CI=0.5 (0.3-0.86), p=0.01] and a 45% decreased risk of having more severe lobular inflammation [adjusted cumulative odds ratio and 95% CI=0.55 (0.3-1.0), p=0.047]. No association between use of statins or non-statin lipid-lowering therapy was observed on the grade of portal inflammation, hepatocyte ballooning or fibrosis stage. Conclusion: Use of statins in patients with NAFLD is associated with decreased risk of hepatic steatosis and lobular inflammation. The anti-steatotic and antiinflammatory properties of statins in patients with NAFLD, and in those with chronic liver disease in general, warrant further prospective investigation.