Fernando Bril1,2, Paola Portillo Sanchez1,2, Romina Lomonaco1,2, Beverly Orsak3, Joan Hecht4, Fermin Tio5, Kenneth Cusi1,2,3,4. 1. Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610. 2. Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida 32608. 3. Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229. 4. Audie L. Murphy Veterans Affairs Medical Center, San Antonio, Texas 78229. 5. Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
Abstract
Context: Patients with nonalcoholic fatty liver disease have a high cardiovascular risk, but statins are rarely prescribed because of fear of hepatotoxicity. Objective: To prospectively assess the long-term safety of statins in patients with prediabetes/type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis (NASH). Design: Post hoc analysis of statin use during a randomized, controlled trial assessing pioglitazone vs placebo for NASH. Patients: A total of 101 patients (86 receiving statins) with biopsy-proven NASH and prediabetes/T2DM were followed for up to 36 months. Interventions: Oral glucose tolerance test and percutaneous liver biopsy (baseline, month 18, and month 36); liver magnetic resonance spectroscopy and euglycemic insulin clamp (baseline and month 18). Main Outcome Measures: Histologic and biochemical safety of statin use among patients with NASH. Results: Only 37% of patients were receiving statins at enrollment despite their high cardiovascular risk. Statin nonusers had higher plasma alanine aminotransferase levels but similar histologic severity of liver disease at baseline. In both statin users and nonusers, the same number of patients (n = 4) had a twofold or greater increase in plasma aminotransferases during follow-up. One statin nonuser was discontinued from the study 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 study. Conclusions: Statin therapy is safe in patients with prediabetes/T2DM and NASH. Given their high cardiovascular risk, statin therapy should be encouraged in this population.
Context: Patients with nonalcoholic fatty liver disease have a high cardiovascular risk, but statins are rarely prescribed because of fear of hepatotoxicity. Objective: To prospectively assess the long-term safety of statins in patients with prediabetes/type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis (NASH). Design: Post hoc analysis of statin use during a randomized, controlled trial assessing pioglitazone vs placebo for NASH. Patients: A total of 101 patients (86 receiving statins) with biopsy-proven NASH and prediabetes/T2DM were followed for up to 36 months. Interventions: Oral glucose tolerance test and percutaneous liver biopsy (baseline, month 18, and month 36); liver magnetic resonance spectroscopy and euglycemic insulin clamp (baseline and month 18). Main Outcome Measures: Histologic and biochemical safety of statin use among patients with NASH. Results: Only 37% of patients were receiving statins at enrollment despite their high cardiovascular risk. Statin nonusers had higher plasma alanine aminotransferase levels but similar histologic severity of liver disease at baseline. In both statin users and nonusers, the same number of patients (n = 4) had a twofold or greater increase in plasma aminotransferases during follow-up. One statin nonuser was discontinued from the study 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 study. Conclusions: Statin therapy is safe in patients with prediabetes/T2DM and NASH. Given their high cardiovascular risk, statin therapy should be encouraged in this population.
Authors: Jordan Fulcher; Rachel O'Connell; Merryn Voysey; Jonathan Emberson; Lisa Blackwell; Borislava Mihaylova; John Simes; Rory Collins; Adrienne Kirby; Helen Colhoun; Eugene Braunwald; John La Rosa; T R Pedersen; Andrew Tonkin; Barry Davis; Peter Sleight; Maria Grazia Franzosi; Colin Baigent; Anthony Keech Journal: Lancet Date: 2015-01-09 Impact factor: 79.321
Authors: Austin Nelson; Dawn M Torres; Ana E Morgan; Christopher Fincke; Stephen A Harrison Journal: J Clin Gastroenterol Date: 2009 Nov-Dec Impact factor: 3.062
Authors: Naga Chalasani; Hisham Aljadhey; Joe Kesterson; Michael D Murray; Stephen D Hall Journal: Gastroenterology Date: 2004-05 Impact factor: 22.682
Authors: Jason M Hui; Alex Hodge; Geoffrey C Farrell; James G Kench; Adamandia Kriketos; Jacob George Journal: Hepatology Date: 2004-07 Impact factor: 17.425
Authors: Laurie R Braun; Meghan N Feldpausch; Natalia Czerwonka; Julian Weiss; Karen Branch; Hang Lee; Edgar L Martinez-Salazar; Martin Torriani; Craig A Sponseller; Steven K Grinspoon; Takara L Stanley Journal: J Clin Endocrinol Metab Date: 2018-11-01 Impact factor: 5.958
Authors: Fasiha Kanwal; Jay H Shubrook; Leon A Adams; Kim Pfotenhauer; Vincent Wai-Sun Wong; Eugene Wright; Manal F Abdelmalek; Stephen A Harrison; Rohit Loomba; Christos S Mantzoros; Elisabetta Bugianesi; Robert H Eckel; Lee M Kaplan; Hashem B El-Serag; Kenneth Cusi Journal: Gastroenterology Date: 2021-09-20 Impact factor: 33.883