Emerging and future therapies for nonalcoholic steatohepatitis in adults

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• Fibrosis
• inflammation
• insulin resistance
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis
• thiazolidinediones
• treatment
• vitamin E
• steatosis

Article highlights

• Despite its high prevalence and intense research in the field, there is currently no approved treatment for NASH.

• There are medications shown to improve hepatic steatosis, including thiazolidinediones, vitamin E and pentoxifylline.

• Hepatic fibrosis, the hard prognostic end-point for NASH, was hardly shown to pharmaceutically improve.

• There are many agents under investigation, including obeticholic acid and PPAR-γ selective modulators, with a promising potential for NASH treatment.

• Given that NASH is a multiple-hit disease, multiple-treatment rather than monotherapy may be a more promising approach.

This box summarizes key points contained in the article.

Declaration of interest

S.A. Polyzos has received consulting fees from InteKrin Therapeutics Inc. However, InteKrin Therapeutics Inc. had no role in the design, data collection, data interpretation or writing of this manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.