Long-Term Efficacy of Rosiglitazone in Nonalcoholic Steatohepatitis: Results of the Fatty Liver Improvement by Rosiglitazone Therapy (FLIRT 2) Extension Trial
Long-Term Efficacy of Rosiglitazone in Nonalcoholic Steatohepatitis: Results of the Fatty Liver Improvement by Rosiglitazone Therapy (FLIRT 2) Extension Trial
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DOI：
10.1002/hep.23270
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发表时间：
2010-02-01
期刊：
影响因子：
13.5
通讯作者：
Poynard, Thierry
中科院分区：
文献类型：
--
作者：
Ratziu, Vlad;Charlotte, Frederic;Poynard, Thierry
格列酮治疗非酒精性脂肪性肝炎（NASH）的短期试验产生了有争议的组织学结果。更长的治疗时间可能会导致额外的改善。经过1年的随机试验，53例患者接受了对照肝活检，并参加了罗格列酮（RSG）的开放标签扩展试验，8 mg/天，为期2年。总共有44名患者完成了扩展期，其中40名患者进行了第三次肝活检。其中，22名患者在随机化阶段（PLB-RSG）接受安慰剂（PLB），18名患者接受RSG（RSG-RSG）。在2年的扩展阶段，血清胰岛素下降了26%，稳态模型评估（HOMA）下降了30%，丙氨酸氨基转移酶（ALT）下降了24%。然而，平均NASH活性评分（NAS）（3.8 +/- 2.11 vs 3.68 +/- 1.8）、气球样变评分、纤维化分期（1.76 +/- 1.18 vs 1.85 +/- 1.19）或显微形态测定法纤维化面积（4.43% +/- 0.68至5.54% +/- 0.68）无显著变化。在PLB-RSG组中，脂肪变性在RSG治疗2年后显著下降（中位数下降15%）;在RSG-RSG组中，在第一年最初下降20%后，再治疗2年RSG并未导致进一步改善。同样，在RSG-RSG组中，NAS评分、气球样变、小叶内炎症、纤维化分期或纤维化面积在额外2年的RSG中没有改善。结论：罗格列酮在治疗的第一年有显著的抗脂肪生成作用，尽管对胰岛素敏感性和转氨酶水平有维持作用，但长期治疗没有额外获益。这表明改善胰岛素敏感性可能不足以治疗NASH，应探索其他肝损伤治疗靶点。（《肝脏学》2010年;51：445-453）
Short-term trials of glitazones in nonalcoholic steatohepatitis (NASH) yielded controversial histological results. Longer treatment might result in additional improvement. After a 1-year randomized trial, 53 patients underwent a control liver biopsy and were enrolled in an open-label extension trial of rosiglitazone (RSG), 8 mg/day for 2 additional years. In all, 44 completed the extension phase including 40 with a third liver biopsy. Of these, 22 received placebo (PLB) in the randomized phase (PLB-RSG), and 18 RSG (RSG-RSG). During the 2-year extension phase serum insulin decreased by 26%, homeostasis model assessment (HOMA) by 30%, and alanine aminotransferase (ALT) by 24%. However, there was no significant change in the mean NASH activity score (NAS) (3.8 +/- 2.11 versus 3.68 +/- 1.8), ballooning score, fibrosis stage (1.76 +/- 1.18 versus 1.85 +/- 1.19), or area of fibrosis by micromorphometry (4.43% +/- 0.68 to 5.54% +/- 0.68). In the PLB-RSG group steatosis significantly decreased after 2 years of RSG (median decrease of 15%); in the RSG-RSG group, after an initial decline in the first year of 20%, 2 additional years of RSG did not result in further improvement. Likewise, there was no improvement in the NAS score, ballooning, intralobular inflammation, fibrosis stage, or area of fibrosis with 2 additional years of RSG in the RSG-RSG group. Conclusion: Rosiglitazone has a substantial antisteatogenic effect in the first year of treatment without additional benefit with longer therapy despite a maintained effect on insulin sensitivity and transaminase levels. This suggests that improving insulin sensitivity might not be sufficient in NASH and that additional targets of therapy for liver injury should be explored. (HEPATOLOGY 2010;51:445-453.)