Promising therapies for treatment of nonalcoholic steatohepatitis

ABSTRACT

Introduction: Non-alcoholic fatty liver disease (NAFLD) has become the most common etiology for abnormal aminotransferase levels and chronic liver disease. Its growing prevalence is largely linked to the presence of metabolic syndrome, particularly diabetes and insulin resistance. It is estimated that 60–80% of the type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). A subset of patients with hepatic steatosis progress to NASH, while 15–20% of patients with NASH develop cirrhosis. This progression is thought to be multifactorial, and there are currently no FDA-approved medications for the treatment of NASH.

Areas covered: We review drugs currently in Phase II and III clinical trials for treatment of NAFLD and NASH, including their mechanisms of action, relationship to the pathophysiology of NASH, and rationale for their development.

Expert opinion: The treatment of NASH is complex and necessitates targeting a number of different pathways. Combination therapy, preferably tailored toward the disease stage and severity, will be needed to achieve maximum therapeutic effect. With multiple agents currently being developed, there may soon be an ability to effectively slow or even reverse the disease process in many NAFLD/NASH patients.

KEYWORDS:

• Non-alcoholic fatty liver disease
• non-alcoholic steatohepatitis
• treatment for non-alcoholic fatty liver disease
• treatment for non-alcoholic steatohepatitis

Acknowledgements

The study was conducted at the Clinical and Translational Research Institute, University of California at San Diego.

Declaration of interest

R Loomba has served as a consultant to Gilead Sciences, Galmed, Arrowhead, Tobira, Alnylam, Zafgen, Metacrine, Viking, Celgene, Metacrine, Bristol-Myers Squibb, Intercept, Shire, Boehringer Ingelheim, Eli Lily, DeutRx, Genkyotex, Nimbus, RuiYi, Enanta, Isis, Conatus, Scholar Rock, Merck, Profil Institute, Janssen, Corgenix, Roivant, and Adheron. He has received research grant support from Daiichi Sankyo, Gilead Sciences, Merck, Promedior, Galectin, Immuron, Galmed, Tobira, Seimens, Bristol-Myers Sqibb, NGM Biopharmaceuticals, GE Pharmaceuticals and Kinemed. M Noureddin is a consultant for Owlpharma and has served on the advisory board for Abbott. 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

R Loomba is supported in part by the American Gastroenterological Association (AGA) Foundation –Sucampo –ASP Designated Research Award in Geriatric Gastroenterology and by a T. Franklin Williams Scholarship Award; Funding provided by: Atlantic Philanthropies, Inc, the John A. Hartford Foundation, the Association of Specialty Professors, and the American Gastroenterological Association and grant K23-DK090303 and R01-DK106419-01.