Comprehensive molecular mechanisms and clinical therapy in nonalcoholic steatohepatitis: An overview and current perspectives

Our understanding of nonalcoholic steatohepatitis (NASH) pathophysiology continues to advance rapidly. Given the complexity of the pathogenesis of NASH, the field has moved from describing the single pathogenesis of NASH to deeply phenotyping with a description of the multi-mechanism and multi-target pathogenesis that includes glucose, lipid and cholesterol metabolism, fibrotic progression, inflammation, immune reaction and apoptosis. To make the picture more complex, the pathogenesis of NASH involves pathological connections between the liver and several organs such as the adipose, pancreas, kidney and gut. Numerous pharmacologic candidates have been tested in clinical trials and have generated some positive results. Importantly, PPAR as triglyceride synthesis inhibitor and FXR as bile acids synthesis inhibitor have displayed beneficial effects on candidates for lipid and cholesterol metabolism. Although the efficacy of these drugs has been affirmed, serious side effects hinder their further development. It is a particularly important task to carry out the in-depth long-term research. Additionally, drug combination increases response rate and reduces side effects of a single drug. Mastering the advantages and limitations of clinical candidate drugs and continuous improvement and innovation are necessary to formulate a new strategy for the future treatment of NASH.