A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis.

摘要: OBJECTIVES: Troglitazone is a thiazolidinedione and peroxisome proliferator–activated receptor gamma (PPARγ) ligand used to treat diabetes mellitus type II. Because hyperinsulinemia may be factor in nonalcoholic steatohepatitis (NASH), we postulated that troglitazone could have beneficial effects this disorder. Our study was initiated before reports of idiosyncratic hepatitis induced by agent completed 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 2 diabetes, three well-compensated cirrhosis Troglitazone given at dose 400 mg/day for ≤6 months. Responders (defined as normal ALT end treatment) rebiopsied. Paired specimens compared blinded fashion. Mitochondria quantitated using ultrathin electron microscopy. RESULTS: Seven ten responded treatment. nonresponders initially normalized returned pretreatment level 3 In patient, therapy stopped, has remained baseline no other clinical or laboratory findings. responders, fell 87 39 9 treatment (p 0.01), AST decreased 77 23 30 8 0.002). Biopsy comparisons after showed persistent all cases, although four seven one-point improvement necroinflammatory grade. Electron microscopy revealed elongation mitochondria therapy. CONCLUSIONS: Normal seen 70% NASH treatment, biochemical response associated only mild improvement, follow-up biopsies evidence Normalization liver enzymes who are treated thiazolidinediones should viewed reservation. Follow-up biopsy essential evaluate efficacy these agents, which, level, appears relatively modest.