Lipid modifiers and NASH: statins, ezetimibe, fibrates and other agents

Nonalcoholic fatty liver disease (NAFLD) frequently coexists with hyperlipidemia and conveys an increased cardiovascular risk, regardless of traditional risk factors. Furthermore, altered fatty acid and cholesterol metabolism are increasingly recognized to be central for the pathogenesis of liver injury in non-alcoholic steatohepatitis (NASH). Therefore, lipid-lowering drugs are attractive therapeutic tools in NAFLD. Statins ameliorated surrogate markers of steatosis in several randomized controlled trials, but their impact on liver histology is unknown. Furthermore, statins were the only class of lipid-lowering drugs to reduced cardiovascular risk in NAFLD. Preliminary evidence suggests ezetimibe, an inhibitor of intestinal and hepatic cholesterol absorption, may improve liver histology, but its impact on CVD risk and on clinical outcomes remains to be determined. Despite strong experimental evidence supporting the use of omega-3 polyunsaturated fatty acids in NAFLD, the published human studies consisted of small sample size and had many methodological flaws, including the absence of post-treatment histology.