Challenges and opportunities in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) has emerged as the leading cause of chronic liver disease worldwide and is rapidly increasing in prevalence due to the obesity epidemic. There are currently no Food and Drug Administration (FDA) approved drugs to treat NASH, and therefore a critical need exists for novel therapies that can halt or reverse the progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Clinical trials to date using single drugs to treat NASH have shown disappointing efficacy. Combination therapies to attack different targets underlying disease pathogenesis of NASH are being explored as a strategy currently. Novel RNA therapies are also being developed to target previously "undruggable" targets and are close to the maturity necessary to be viable therapeutic approaches for the treatment of NASH and fibrosis. Identifying circulating biomarkers of fibrosis could serve as a valuable, non-invasive diagnostic tool to guide clinical practice. Despite progress in translational and clinical research, one of the major reasons for the absence of effective therapeutics is our incomplete understanding of the pathophysiology that underlies the progression from steatosis to NASH and its most deadly consequence-fibrosis. Multi-omics platforms will help to drive effective precision medicine development in NASH and hepatology.