Author information
1
Department of Medicine and Betty and Guy Beatty Center for Integrated Research, Claude Moore, Inova Health Systems, Falls Church, VA.
2
Department of Gastroenterology, University of California at San Diego, La Jolla, CA.
3
Department of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, IL.
4
Department of Medical Sciences, University of Torino, Torino, Italy.
5
Department of Medicine, Università di Bologna, Bologna, Italy.
6
Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, MO.
7
Saint-Antoine Hospital, Paris, France.
8
Department of Gastroenterology, University Hospitals of Geneva, Geneva, Switzerland.
9
Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, 22908.
10
Institute of Cardiometabolim and Nutrition (ICAN) and Hospital Pitié Salpêtrière, de L'Hopital, Paris, France.
11
Division of Gastroenterology, Massachusetts General Hospital, Cambridge, MA.
12
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
13
Division of Gastroenterology and Hepatology, Duke University, Durham, NC.
14
Pinnacle Clinical Research, San Antonio, Texas, 78233.
15
Division of Gastroenterology, Virginia Commonwealth University, Richmond, VA.
16
Department of Pediatrics, Columbia College of Physicians and Surgeons, New York, NY.
17
Hôpital Claude Huriez Rue Michel Polonowski, Lille, France.
18
Department of Medicine, University of Chicago, Chicago, IL.
19
Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN.
20
Institute of Cellular Medicine, Newcastle University, New Castle, UK.
21
Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, WA.
22
Department of Gastroenterology & Hepatology, Westmead Hospital and Sydney West Local Health District, Sydney, Australia.
23
College of Health Solutions, Arizona State University, Phoenix, Arizona.
Abstract
NASH/NAFLD is rapidly becoming one of top causes of cirrhosis, hepatocellular carcinoma and indication for liver transplantation. Except for life style modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is hard to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD and has been shown to improve liver histology. In order to have approved regimens for treatment of NASH/NAFLD, a number of issues that must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced stage of fibrosis, it is not an independent predictor of long term mortality. In contrast, there is significant data to suggest that stage of fibrosis is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, a number of important secondary endpoints, including non-invasive biomarkers, long term outcomes, and patient reported outcomes, must be considered. In 2017, a few phase 3 clinical trials for treatment of NASH are in progress. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH enriches the pipeline of emerging therapies.
CONCLUSION:
Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD.