PHILADELPHIA – While current treatment options are limited for patients with nonalcoholic steatohepatitis (NASH), a number of potential agents in clinical trials, , MPH, said here at the 6th annual Digestive Diseases: New Advances conference.
With agents currently available and those to come, the future will be focused on long-term management of NASH as a chronic disease in specialized centers, according to Dr. Younossi, chairman in the department of medicine at Inova Fairfax Hospital and vice president for research at Inova Health System, both in Falls Church, Va.
“We are not going to be able to cure NASH – we need to manage it,” Dr. Younossi said in a podium presentation. “NASH will be managed like type 2 diabetes. It’s not going to be treated like hepatitis C.”
Current treatment options are limited, with no Food and Drug Administration–approved options, and just two agents, vitamin E and pioglitazone, supported by guidance from the American Association for the Study of Liver Diseases (AASLD), Dr. Younossi said.
Public health interventions are needed to address the obesity and type 2 diabetes that are “the root of this disease,” Dr. Younossi said at the meeting, which was jointly provided by Rutgers and Global Academy for Medical Education.
Current AASLD guidance is based on studies suggesting that weight loss in the 3%-5% range may improve steatosis, and a 7%-10% weight loss can improve most histologic features of NASH, including fibrosis.
“The problem is that this is very hard to achieve,” Dr. Younossi said, adding that it is also hard to maintain. In a 2011 meta-analysis of clinical trials for reduction in nonalcoholic fatty liver disease, only a small minority of patients were able to maintain weight loss.
Bariatric surgery may be “very effective” for weight loss in the right patients, with some trials showing a proportion of patients maintaining improvement at 5-year follow-up, he said.
Exercise alone might prevent or reduce steatosis, but its effects on other aspects of liver histology, such as fibrosis, remain unknown, Dr. Younossi said.
Pioglitazone improves liver histology in patients with biopsy-proven NASH, although the benefits and risks, including potential adverse effects such as bone loss, diastolic dysfunction, or weight gain, should be discussed with each individual patient, he said.
Dr. Younossi highlighted randomized phase 3 trials for several agents that could figure into the treatment paradigm of NASH in the future by targeting different promoters of NASH and fibrosis progression. One of those was elafibranor, which targets the PPAR alpha/gamma pathways and is being evaluated versus placebo in NASH patients in the phase 3study. In a post hoc analysis of a randomized trial, the treatment resolved NASH without fibrosis worsening.
Other agents being evaluated in phase 3 trials include the CCR2/CCR5 receptor blocker cenicriviroc, the FXR agonist obeticholic acid, and the ASK-1 inhibitor selonsertib, Dr. Younossi said.
Optimal NASH care in the future may be based on targeting multiple such pathways, with patients increasingly treated at specialized centers that incorporate not only hepatologists, but also diabetes experts, dietitians, and exercise specialists.
“My own belief is that you have to treat this in the long term and also in a multidisciplinary sort of approach,” he said.
Dr. Younossi indicated that he is a consultant for Gilead, Intercept, Bristol-Myers Squibb, Novo Nordisk, Viking, Terms, Shionogi, AbbVie, Merck, and Novartis.
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