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Nonalcoholic Steatohepatitis & Pioglitazone Treatment

Ann Intern Med; ePub 2016 Jun 21; Cusi, Orsak, et al

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The long-term use of pioglitazone for patients with prediabetes or type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis (NASH) is safe and effective, according to a randomized, controlled trial in which 101 patients with prediabetes or T2DM and biopsy-proven NASH were prescribed a hypocaloric diet and then randomly assigned to pioglitazone (45 mg/d) or placebo for 18 months, followed by an 18-month, open-label phase with pioglitazone treatment. Primary outcome was a reduction of at least 2 points in the nonalcoholic fatty liver disease activity score (NAS) without worsening of fibrosis. Researchers found:

• 58% of patients in the pioglitazone group achieved the primary outcome vs 17% in the placebo group and 51% had resolution of NASH vs. 19% in the placebo group.

• Pioglitazone treatment was associated with improvement in individual histologic scores, including the fibrosis score; reduced hepatic triglyceride content from 19% to 7%; and improved adipose tissue, hepatic, and muscle insulin sensitivity.

• Overall rate of adverse events did not differ between groups; however, weight gain was greater with pioglitazone.

Citation: Cusi K, Orsak B, Bril F, et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: A randomized, controlled trial. [Published online ahead of print June 21, 2016]. Ann Intern Med. doi:10.7326/M15-1774.

Commentary: Nonalcoholic fatty liver disease (NAFLD) can occur with isolated steatosis without inflammation, or can have inflammation associated with fatty infiltration of the liver, called nonalcoholic steatohepatitis (NASH). It is estimated that 20% of the population has NAFLD, and 3% to 5% have NASH. In patients with diabetes, 50 to 70% have NAFLD. To date, other than sustained weight loss, no intervention has been consistently shown to benefit patients with NASH.1,2 This study shows impressive improvement with pioglitazone in patients with NASH and diabetes or prediabetes and suggests that pioglitazone is both worthy of further study and worth considering in patients with type 2 diabetes and NASH. —Neil Skolnik, MD

1. Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142:711-725. doi:10.1053/j.gastro.2012.02.003.

2. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005-2023. doi:10.1002/hep.25762.

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