Liver Safety of Statins in Prediabetes or T2DM and Nonalcoholic Steatohepatitis: Post-hoc Analysis of a Randomized Trial.

Abstract Patients with NAFLD have a high cardiovascular risk, but statins are rarely prescribed due to fear of hepatotoxicity. To perform a prospective assessment of the long-term safety of statins in patients with prediabetes/T2DM and NASH. Post-hoc analysis of statin use during a randomized, controlled trial (RCT) assessing pioglitazone vs. placebo in patients with NASH. A total of 101 subjects (86 on statins) with biopsy-proven NASH and prediabetes/T2DM were followed for up to 36 months. Oral glucose tolerance test and percutaneous liver biopsy (baseline, month 18, and 36). Liver 1H-MRS and euglycemic insulin clamp with measurement of glucose turnover (baseline and month 18). Histological (liver biopsy) and biochemical (plasma ALT) safety of statin use among patients with NASH. Only 37% of patients were on statins at enrollment despite their high cardiovascular risk. Non-statin users had higher plasma ALT levels, but similar histologic severity of liver disease at baseline. In both statin users and non-users, the same number of subjects (n=4) had a ≥2-fold increase in plasma aminotransferases during follow-up. One non-statin user was discontinued because of this elevation. Values returned to normal without any active measure in all other cases. No changes on liver histology or hepatic insulin resistance were observed in patients with NASH newly started on a statin and receiving placebo during the main RCT. Statin therapy is safe in patients with prediabetes/T2DM and biopsy-proven NASH. Given their high cardiovascular risk, statin therapy should be encouraged in this population.