Cholesterol-lowering therapy for the treatment of nonalcoholic fatty liver disease: an update

To review recent human trials assessing cholesterol-lowering agents in nonalcoholic fatty liver disease (NAFLD).

Four randomized controlled trials (RCTs) assessed statins in NAFLD. In the only RCT with post-treatment biopsy, simvastatin did not change liver histology. In the remaining RCTs, atorvastatin was well tolerated, significantly improved radiological/biochemical markers of steatosis and plasma lipids, with neutral effects on glucose metabolism; in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study, atorvastatin reduced incident cardiovascular disease compared with both untreated NAFLD patients and with statin-treated patients without NAFLD. Ezetimibe was evaluated in two uncontrolled trials and two RCTs, consistently improving liver histology and plasma lipids, whereas glucose metabolism was generally unaffected; however, HbA1c increased with ezetimibe in one RCT.

From the analysis of available trials, it emerges that cholesterol-lowering agents may considerably benefit NAFLD patients. Statins are well tolerated, and atorvastatin improved surrogate markers of liver disease, whereas their effect on liver histology is unknown. Furthermore, the GREACE study was the first trial to show clinical benefit from the use of a pharmacological agent in NAFLD. Ezetimibe improved liver histology. The benefit of combination therapy, as well as the safety on glucose metabolism, need further evaluation.