ABSTRACT
INTRODUCTION AND OBJECTIVES: Practicing physicians often hesitate to use statins and/or other lipid-lowering therapies in NAFLD due to concern for hepatotoxicity. The aim of this study is to examine the safety of lipid lowering therapies in NAFLD patients. MATERIALS AND METHODS: Data from randomized control trials (RCT) among NAFLD patients were pooled to examine the effect of lipid-lowering therapies on liver chemistry, lipid profile, and liver histology. Results are reported as the mean difference of the change (pretreatment-posttreatment) between the treatment and control group. RESULTS: A total of 21 placebo-controlled RCT on 1900 patients (304 receiving statins, 520 other lipid-lowering therapies, and 61 combinations) were treated for 26 weeks [Interquartile range (IQR): 17.5-52 weeks]. Pooled data showed an improved lipid profile without any worsening of ALT, AST, total bilirubin, or alkaline phosphatase at the end of the treatment period. NAFLD activity score improved with other lipid-lowering agents but not with statins. There was no change in individual components of NAFLD activity score or fibrosis stage. CONCLUSION: This meta-analysis of randomized controlled trials examining statins and/or other lipid-lowering therapies in NAFLD patients showed no evidence of worsening liver chemistry. Studies with longer use of lipid-lowering therapies are suggested to examine the benefit of liver histology among patients with NAFLD.
Subject(s)
Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Non-alcoholic Fatty Liver Disease , Humans , Dyslipidemias/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Lipids , Non-alcoholic Fatty Liver Disease/drug therapy , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Data on prevalence and profile of nonalcoholic fatty liver disease (NAFLD) among individuals who are lean (normal body mass index) is unclear. Published data from studies comparing lean with obese NAFLD or with healthy subjects on prevalence, comorbidities, liver chemistry and histology, and metabolic/inflammatory markers were analyzed. Data were reported as odds ratio and 95% confidence interval for categorical variables and difference of means for continuous variables. Analysis of 53 studies on 65,029 subjects with NAFLD (38,084 lean) and 249,544 healthy subjects showed a prevalence of lean NAFLD at 11.2% in the general population. Among individuals with NAFLD, the prevalence of lean NAFLD was 25.3%. Lean NAFLD versus healthy subjects had higher odds for abnormalities on metabolic profile, including metabolic syndrome and its components, renal and liver function, and patatin-like phospholipase domain-containing protein 3 (PNPLA3) G allele; and inflammatory profile, including uric acid and C-reactive protein. The abnormalities were less severe among lean versus obese NAFLD on metabolic syndrome with its components, renal and liver chemistry, liver stiffness measurement, PNPLA3 and transmembrane 6 superfamily member 2 polymorphisms, and uric acid levels as markers of inflammation. Lean NAFLD had less severe histologic findings, including hepatocyte ballooning, lobular inflammation, NAFLD activity score, and fibrosis stage. Limited data also showed worse outcomes between obese versus lean NAFLD. Conclusion: Lean NAFLD is a distinct entity with metabolic, biochemical, and inflammatory abnormalities compared to healthy subjects and a more favorable profile, including liver histology of steatohepatitis and fibrosis stage, compared to obese NAFLD. We suggest that prospective multicenter studies examine long-term hepatic and extrahepatic outcomes in individuals with lean NAFLD.
