A Pilot Study of A Thiazolidinedione, Troglitazone, in Nonalcoholic Steatohepatitis

作者：Stephen Hugh Caldwell, Elizabeth Erickson Hespenheide, Jan A. Redick, Julia C. Iezzoni, Emily H. Battle, Bonnie L. Sheppard · 发表于：The American Journal of Gastroenterology · 年份：2001 · DOI：10.1111/j.1572-0241.2001.03553.x · 被引用次数：395 · 研究领域：Liver Disease Diagnosis and Treatment、Peroxisome Proliferator-Activated Receptors、Diabetes, Cardiovascular Risks, and Lipoproteins

OBJECTIVES: Troglitazone is a thiazolidinedione and peroxisome proliferator-activated receptor gamma (PPARgamma) ligand used to treat diabetes mellitus type II. Because hyperinsulinemia may be a factor in nonalcoholic steatohepatitis (NASH), we postulated that troglitazone could have beneficial effects in this disorder. Our study was initiated before reports of idiosyncratic hepatitis induced by this agent and was completed before its recent withdrawal from the market. METHODS: We studied 10 female patients (age 44 +/- 16) with histological NASH. All but two were obese (mean body mass index, BMI = 38 +/- 6). One had type 2 diabetes, and three had well-compensated cirrhosis with NASH. Troglitazone was given at a dose of 400 mg/day for < or = 6 months. Responders (defined as normal ALT at the end of treatment) were rebiopsied. Paired specimens were compared in blinded fashion. Mitochondria were quantitated using ultrathin electron microscopy. RESULTS: Seven of ten patients responded with normal ALT at the end of treatment. One of three nonresponders initially normalized ALT but returned to pretreatment level at 3 months. In this patient, therapy was stopped, and the ALT has remained at the baseline level with no other clinical or laboratory findings. In the responders, ALT fell from 87 +/- 38 before to 39 +/- 9 at the end of treatment (p = 0.01), and AST decreased from 77 +/- 23 to 30 +/- 8 (p = 0.002). Biopsy comparisons before and after therapy showed persistent steatohepatit...