Perspectives on Treatment for Nonalcoholic Steatohepatitis

Abstract

It is important to provide treatment to patients with nonalcoholic steatohepatitis (NASH) because one third of patients with the metabolic syndrome die of liver disease. Basic research studies have elucidated mechanisms of NASH pathogenesis, which could lead to therapeutic targets. Health agencies have confirmed strategies for the optimal management of NASH and approved new drugs and treatments, which urgently are needed. The US Food and Drug Administration recently endorsed end points for NASH therapy. The reversal of NASH with no evidence of progression to advanced fibrosis has been defined as the end point for phase 2b and phase 3 trials in patients with NASH and early stage fibrosis. Although a decrease in the nonalcoholic fatty liver disease activity score could serve as an end point in clinical trials, it is not clear whether patients with lower scores have a lower risk of progression to advanced fibrosis. End points for clinical trials of patients with NASH cirrhosis currently are based on model for end-stage liver disease and Child-Pugh-Turcotte scores, as well as the hepatic venous pressure gradient. Different strategies are being explored to reduce liver diseases that are linked to a sedentary lifestyle, overeating, and genetic factors. In association with insulin resistance and deregulation of the lipid metabolism (accumulation of lipotoxins that promote hepatic lipogenesis, adipose tissue lipolysis, and impaired β-oxidation), these factors could increase the risk of liver steatosis with necroinflammatory lesions and fibrosis. We review the pathogenic mechanisms of NASH and therapeutic options, as well as strategies that are being developed for the treatment of injury to the liver and other organs.