Hepatic fat loss in advanced nonalcoholic steatohepatitis: Are alterations in serum adiponectin the cause?
Hepatic fat loss in advanced nonalcoholic steatohepatitis: Are alterations in serum adiponectin the cause?
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DOI：
10.1002/hep.26072
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发表时间：
2013-06-01
期刊：
影响因子：
13.5
通讯作者：
George, Jacob
中科院分区：
文献类型：
--
作者：
van der Poorten, David;Samer, Caroline F.;George, Jacob
非酒精性脂肪性肝炎（NASH）中的晚期肝纤维化通常伴有肝脏脂肪减少至完全脂肪损失（燃耗NASH），但这种现象背后的机制尚未阐明。脂联素在任何原因的肝硬化中升高，并具有有效的抗脂肪变性活性。在这项研究中，我们检查了65例晚期活检证实的NASH患者（纤维化3-4期）和54例轻度疾病患者（纤维化0-1期），以确定脂肪变性的消失是否与血清脂联素的变化相关。所有患者在肝活检时进行空腹血液检查和人体测量。通过形态测定法准确定量肝脏脂肪。血清脂联素测定采用免疫法。与早期NASH患者相比，晚期NASH患者胰岛素抵抗、内脏肥胖和年龄更大，但肝脏脂肪含量或脂联素水平没有差异。脂联素与整个队列的肝脂百分比呈显著负相关（r =-0.28，P < 0.01），其中以晚期NASH患者为主导（r =-0.40，P < 0.01）。在晚期NASH中，脂联素每增加4 g/L，肝脏脂肪减少5%的比值比OR为2.0（95%置信区间[CI]：1.3-3.0，P < 0.01）。在多变量分析中，脂联素与几乎完全的肝脏脂肪丢失或脂肪耗尽NASH高度显著相关（12.1 vs 7.4 g/L，P = 0.001）。脂联素，胆汁酸和脂肪细胞fexaramine激活之间的关系在体内和体外证明，提示肝细胞-脂肪细胞串扰。结论：晚期NASH患者血清脂联素水平与肝脏脂肪丢失独立相关。脂联素可能是导致NASH衰竭的部分原因。（肝脏学2012）
Advanced liver fibrosis in nonalcoholic steatohepatitis (NASH) is often accompanied by a reduction in hepatic fat to the point of complete fat loss (burnt-out NASH), but the mechanisms behind this phenomenon have not been elucidated. Adiponectin is raised in cirrhosis of any cause and has potent antisteatotic activity. In this study we examined 65 patients with advanced biopsy-proven NASH (fibrosis stage 3-4) and 54 with mild disease (fibrosis stage 0-1) to determine if disappearance of steatosis correlated with changes in serum adiponectin. All patents had fasting blood tests and anthropometric measures at the time of liver biopsy. Liver fat was accurately quantitated by morphometry. Serum adiponectin was measured by immunoassay. When compared to those with early disease, patients with advanced NASH were more insulin-resistant, viscerally obese, and older, but there was no difference in liver fat content or adiponectin levels. Adiponectin had a significant negative correlation with liver fat percentage in the whole cohort (r = -0.28, P < 0.01), driven by patients with advanced NASH (r = -0.40, P < 0.01). In advanced NASH, for each 4 g/L increase in adiponectin there was an odds ratio OR of 2.0 (95% confidence interval [CI]: 1.3-3.0, P < 0.01) for a 5% reduction in hepatic fat. Adiponectin was highly and significantly associated with almost complete hepatic fat loss or burnt-out NASH (12.1 versus 7.4 g/L, P = 0.001) on multivariate analysis. A relationship between adiponectin, bile acids, and adipocyte fexaramine activation was demonstrated in vivo and in vitro, suggestive of hepatocyte-adipocyte crosstalk. Conclusion: Serum adiponectin levels in advanced NASH are independently associated with hepatic fat loss. Adiponectin may in part be responsible for the paradox of burnt-out NASH. (HEPATOLOGY 2012)