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 3 RESOLVE-IT study. In a post hoc analysis of a previous 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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