Nonalcoholic fatty liver disease: from lipid profile to treatment

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation in the liver. Although the majority of NAFLD is benign simple steatosis, a subset of NAFLD includes nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and liver cancer. In both simple steatosis and steatohepatitis, triglyceride is well known as the major lipid that accumulates in the liver. However, we have little information on the other lipids that deposit in the liver. Thus, lipid profiling is necessary to understand the pathogenesis of NAFLD. In addition, these data provide further information on early detection of NASH and optimal treatment for NAFLD. Although plasma and hepatic lipid profiles are similar between simple steatosis and steatohepatitis, recent intensive researches demonstrate that free cholesterol, polyunsaturated fatty acid (PUFA), and phospholipid levels are altered in human NAFLD. In experimental models, liver injury is induced by free cholesterol accumulation and compositional changes of n-6/n-3 PUFAs and phospholipids. Therefore, these lipid levels are candidates to predict the progression to NASH. Lipid-lowering agents have potential to normalize these lipid levels. Currently, favorable results are obtained using statins, ezetimibe, and n-3 PUFAs in simple steatosis. But the effects of these agents for NASH are limited. These unsatisfactory results may partially depend on the study design because most studies are relatively short-term and small number of patients. Larger studies are necessary to determine the promising effects of lipid-lowering agents for NASH and its comorbidities.