Emerging and future therapies for nonalcoholic steatohepatitis in adults

Nonalcoholic steatohepatitis (NASH) is a disease of increasing prevalence with morbidity and mortality closely related to cardiovascular disease, malignancies and cirrhosis. Despite the need for pharmacological treatment and intense research in the field, there is currently no approved agent for NASH.

There are medications shown to improve hepatic steatosis, including thiazolidinediones, vitamin E and pentoxifylline. However, hepatic fibrosis, the hard prognostic end-point for NASH, has shown little improvement with pharmaceutical intervention. Long-term use of thiazolidinediones has provided a marginal effect on fibrosis, whereas obeticholic acid, a farnesoid X receptor, showed to improve fibrosis, but further data are needed. There are currently many novel agents under investigation, including glucagon-like peptide-1 analogs, sodium glucose co-transporters and peroxisome proliferator-activated receptor-γ selective modulators, whose preliminary results have been promising.

Given the multifactorial pathogenesis of NASH, it is rational to consider multiple treatments rather than monotherapy as a more promising approach. Although, it remains to be shown, targeting more than one pathogenetic 'hit' of the disease may provide more efficacious management. Furthermore, the establishment of a noninvasive index for long-term follow-up of NASH patients will facilitate treatment guidance by reducing the need for multiple liver biopsies.