Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steatohepatitis: Relationship to histological improvement
Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steatohepatitis: Relationship to histological improvement
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DOI：
10.1016/j.cgh.2006.05.005
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发表时间：
2006-08-01
影响因子：
12.6
通讯作者：
Hoofnagle, Jay H.
中科院分区：
文献类型：
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作者：
Lutchman, Glen;Promrat, Kittichai;Hoofnagle, Jay H.
背景和目的：噻唑烷二酮 (TZD) 疗法通过可能与其胰岛素增敏或抗炎活性相关的机制改善非酒精性脂肪性肝炎 (NASH) 的肝脏组织学。本研究旨在评估选定脂肪因子和促炎细胞因子的血清水平变化，并将这些变化与吡格列酮治疗 NASH 所导致的肝脏组织学改善联系起来。方法：在吡格列酮开放标签研究中，对 18 名 NASH 患者在治疗第 0 天和第 48 周采集的血清样本进行了脂联素、瘦素、白细胞介素 (IL)-1a、IL-6 和肿瘤坏死因子 (TNF)-α 水平的检测。对配对肝活检标本的脂肪变性、实质炎症、细胞损伤和纤维化进行评分（0-4）。结果：第 48 周脂联素水平从 3.7 增加至 10.3 μg/mL（全部 P < .05）。吡格列酮治疗与脂肪变性（2.5 vs 1.0）、实质炎症（3.3 vs 2.1）、细胞损伤（2.2 vs 0.9）和纤维化（2.0 vs 1.4）的改善相关。脂联素水平的变化与脂肪变性的改善（P = 0.03）以及 NASH 活动指数总分（P = 0.01）的改善相关。 IL-1、IL-6、TNF-α 和瘦素水平的变化与组织学特征的改善无关。结论：TZD 治疗期间肝脏组织学的改善可能是通过脂联素介导的胰岛素敏感性和肝脂肪酸代谢作用来调节的，而不是通过促炎细胞因子的变化来调节。
Background & Aims: Thiazolidinedione (TZD) therapy improves liver histology in nonalcoholic steatohepatitis (NASH) through a mechanism possibly related to its insulin-sensitizing or anti-inflammatory activity. This study was conducted to assess changes in serum levels of selected adipokines and proinflammatory cytokines and to relate these changes to the improved liver histology resulting from pioglitazone therapy for NASH. Methods: Serum samples from 18 patients with NASH obtained at day 0 and week 48 of therapy during an open-label study of pioglitazone were tested for adiponectin, leptin, interleukin (IL)-1a, IL-6, and tumor necrosis factor (TNF)-alpha levels. Paired liver biopsy specimens were scored (0-4) for steatosis, parenchymal inflammation, cell injury, and fibrosis. Results: Adiponectin levels increased from 3.7 to 10.3 mu g/mL at week 48 (P .05 for all). Pioglitazone therapy was associated with improvements in steatosis (2.5 vs 1.0), parenchymal inflammation (3.3 vs 2.1), cell injury (2.2 vs 0.9), and fibrosis (2.0 vs 1.4). The change in adiponectin level was associated with the improvement in steatosis (P =.03) as well as in a summary NASH activity index score (P =.01). Changes in IL-1, IL-6, TNF-alpha, and leptin levels did not correlate with improvements in the histological features. Conclusions: Improvements in liver histology during TZD therapy may be modulated by an adiponectin-mediated effect on insulin sensitivity and hepatic fatty acid metabolism rather than by changes in proinflammatory cytokines.