Kirpich Irina A, McClain Craig J, Vatsalya Vatsalya, Schwandt Melanie, Phillips Monte, Falkner Keith Cameron, Zhang Lucy, Harwell Catey, George David T, Umhau John C
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky.
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky.
Alcohol Clin Exp Res. 2017 Apr;41(4):747-757. doi: 10.1111/acer.13346. Epub 2017 Mar 2.
Interactions between the liver, the gut, and the immune system are critical components of alcoholic liver disease (ALD). The aim of this study was to explore the associations between alcohol-induced liver injury, endotoxemia, and inflammation at admission and over time during abstinence, as well as to examine the sex-related differences in these parameters in alcohol-dependent individuals admitted to an alcohol treatment program.
A cohort of 48 otherwise healthy participants with alcohol use disorder, but no clinical signs of alcoholic liver injury (34 males [M]/14 females [F]) admitted to an alcohol detoxification program, was stratified into 2 groups based on baseline plasma alanine aminotransferase (ALT) levels (as a marker of liver injury). Group 1 (ALT < 40 U/l, 7M/8F) and Group 2 (ALT ≥ 40 U/l, 27M/6F) were identified. Plasma biomarkers of liver damage, endotoxemia, and inflammation were examined at baseline, day 8, and day 15 of the admission. The drinking history was also evaluated.
Sixty-nine percent of patients had elevated ALT and other markers of liver damage, including aspartate aminotransferase and cytokeratin 18 (CK18 M65 and CK M30) at baseline, indicating the presence of mild ALD. Elevated CK18 M65:M30 ratio suggested a greater contribution of necrotic rather than apoptotic hepatocyte cell death in the liver injury observed in these individuals. Females showed greater elevations of liver injury markers compared to males, although they had fewer drinks per day and shorter lifetime duration of heavy drinking. Liver injury was associated with systemic inflammation, specifically, elevated plasma tumor necrosis factor-alpha levels. Compared to patients without liver injury, patients with mild ALD had greater endotoxemia (increased serum lipopolysaccharide levels), which decreased with abstinence and this decrease preceded the drop in CK18 M65 levels.
The study documented the association of mild alcohol-induced liver injury and endotoxemia, which improved with 2 weeks of abstinence, in a subset of individuals admitted to an alcohol detoxification program.
肝脏、肠道和免疫系统之间的相互作用是酒精性肝病（ALD）的关键组成部分。本研究的目的是探讨戒酒期间入院时及随时间推移酒精性肝损伤、内毒素血症和炎症之间的关联，并研究酒精依赖个体在这些参数上的性别差异，这些个体被纳入酒精治疗项目。
48名无其他健康问题但患有酒精使用障碍且无酒精性肝损伤临床体征的参与者（34名男性[M]/14名女性[F]）被纳入酒精解毒项目，根据基线血浆丙氨酸氨基转移酶（ALT）水平（作为肝损伤的标志物）分为两组。确定了第1组（ALT < 40 U/l，7名男性/8名女性）和第2组（ALT≥40 U/l，27名男性/6名女性）。在入院的基线、第8天和第15天检测肝损伤、内毒素血症和炎症的血浆生物标志物。还评估了饮酒史。
69%的患者在基线时ALT及其他肝损伤标志物升高，包括天冬氨酸氨基转移酶和细胞角蛋白18（CK18 M65和CK M30），表明存在轻度ALD。CK18 M65:M30比值升高表明在这些个体中观察到的肝损伤中坏死性而非凋亡性肝细胞死亡的贡献更大。与男性相比，女性的肝损伤标志物升高更为明显，尽管她们每天饮酒量较少且重度饮酒的终生时长较短。肝损伤与全身炎症相关，具体而言，血浆肿瘤坏死因子-α水平升高。与无肝损伤的患者相比，轻度ALD患者的内毒素血症更严重（血清脂多糖水平升高），随着戒酒其降低，且这种降低先于CK18 M65水平的下降。
该研究记录了在一部分纳入酒精解毒项目的个体中，轻度酒精性肝损伤与内毒素血症之间的关联，这种关联在戒酒2周后有所改善。
