Stratification of risk of death in severe acute alcoholic hepatitis using a panel of adipokines and cytokines.
Stratification of risk of death in severe acute alcoholic hepatitis using a panel of adipokines and cytokines.
复制标题
使用一组脂肪因子和细胞因子对严重急性酒精性肝炎的死亡风险进行分层。
DOI：
10.1111/acer.12558
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Behari,Jaideep
中科院分区：
文献类型：
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作者：
Rachakonda,Vikrant;Gabbert,Charles;Raina,Amit;Li,Huanan;Malik,Shahid;DeLany,JamesP;Behari,Jaideep
研究背景在小鼠模型中，脂肪组织代谢失调与酒精性肝病的发病机制有关。我们的目的是描述血清标志物的脂肪组织代谢和炎症严重急性酒精性肝炎（AAH）患者，并确定其效用，以预测生存严重AAH.MethodsA前瞻性，病例对照研究设计。纳入76例重度AAH住院患者和25例酒精性肝硬化非卧床患者作为对照。采集血清样本进行生化分析。患者进行了为期180天的随访后登记，以确定survival.ResultsAAH患者表现出较高的血清甘油和游离脂肪酸水平，这表明增强脂肪组织甘油三酯水解。与酒精性肝硬化相比，AAH患者表现出不同的血清脂质组学特征，但在全身性和脂肪特异性胰岛素抵抗方面没有表现出这种特征。AAH患者血清瘦素和纤溶酶激活抑制剂-1水平较高，而血清瘦素水平降低。AAH患者的促脂解细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-8和IL-15的血清水平显著升高。只有53%的AAH患者在入院后存活了180天，而所有的AAH患者在研究结束时都存活了。在重度AAH患者中，白色血细胞计数、血红蛋白、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）与180天生存率相关，所有5种标志物均通过受试者-操作者曲线分析显示准确性。血清IL-6水平≥38.66 pg/ml是重度AAH中最精确识别的死亡。IL-6 ≥ 38.66 pg/ml患者的平均生存率显著降低，与那些较低level.ConclusionsAAH患者表现出的证据相比，酒精性肝硬化患者脂肪组织脂解增加和血清脂质谱改变。IL-6可能是一种有用的生物标志物，可对死亡风险最高的重度AAH患者进行风险分层。
BackgroundDysregulated adipose tissue metabolism has been implicated in the pathogenesis of alcoholic liver disease in murine models. We aimed to characterize serum markers of adipose tissue metabolism and inflammation in patients with severe acute alcoholic hepatitis (AAH) and determine their utility to predict survival in severe AAH.MethodsA prospective, case–control study design was used. Seventy‐six patients hospitalized with severe AAH and 25 ambulatory patients with alcoholic cirrhosis as controls were included. Serum samples were collected for biochemical analyses. Patients were followed for 180 days after enrollment to determine the survival.ResultsAAH patients exhibited higher serum glycerol and free fatty acid levels, suggesting enhanced adipose tissue triglyceride hydrolysis. Patients with AAH demonstrated a distinct serum lipidomic profile compared with alcoholic cirrhosis but not in systemic and adipose‐specific insulin resistance. AAH patients had higher serum resistin and plasmin activation inhibitor‐1 levels, while serum leptin was decreased. Serum levels of the prolipolytic cytokines tumor necrosis factor‐α(TNF‐α), interleukin (IL)‐6, IL‐8, and IL‐15 were significantly higher in AAH patients. Only 53% of AAH patients survived 180 days after admission, while all cirrhotic patients were alive at the end of the study period. Among patients with severe AAH, white blood cell count, hemoglobin, resistin, IL‐6 and TNF‐αwere associated with 180‐day survival, and all 5 markers demonstrated accuracy by area under receiver–operator curve analysis. Serum IL‐6 levels ≥38.66 pg/ml most precisely identified deaths in severe AAH. Patients with IL‐6 ≥ 38.66 pg/ml had significantly decreased mean survival compared to those with lower levels.ConclusionsAAH patients demonstrate evidence of increased adipose tissue lipolysis and altered serum lipidomic profile compared with alcoholic cirrhosis patients. IL‐6 may be a useful biomarker to risk stratify severe AAH patients at the highest risk of mortality.