Arsene Diana, Farooq Omar, Bataller Ramon
Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, 7340.A Medical Biomolecular Research Building, Chapel Hill, NC, 27599, USA.
Department of Nutrition, University of North Carolina, Chapel Hill, USA.
Hepatol Int. 2016 Jul;10(4):538-52. doi: 10.1007/s12072-015-9701-6. Epub 2016 Apr 12.
Alcoholic liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. ALD encompasses a spectrum of disorders including asymptomatic steatosis, steatohepatitis, fibrosis, cirrhosis and its related complications, and the acute-on-chronic state of alcoholic hepatitis. While multidisciplinary efforts continue to be aimed at curbing progression of this spectrum of disorders, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of ALD. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with severe AH is very high (20-50 % at 3 months). The current therapeutic regimens are limited. The development of new therapies requires translational studies in human samples and suitable animal models that reproduce clinical and histological features of human AH. This review article summarizes the clinical syndrome, pre-clinical translational tools, and pathogenesis of AH at a molecular and cellular level, with the aim of identifying new targets of potential therapeutic intervention.
酒精性肝病（ALD）是全球肝脏相关发病和死亡的主要原因。ALD涵盖一系列疾病，包括无症状脂肪变性、脂肪性肝炎、纤维化、肝硬化及其相关并发症，以及酒精性肝炎的慢加急性状态。尽管多学科努力仍致力于遏制这一系列疾病的进展，但迫切需要将精力集中在针对酒精性肝炎（AH）（ALD最严重的形式）的有效治疗干预措施上。AH的特征是大量饮酒的患者突然出现黄疸以及与肝功能不全和门静脉高压相关的并发症。重症AH患者的死亡率非常高（3个月时为20%-50%）。目前的治疗方案有限。新疗法的开发需要在人类样本和能够重现人类AH临床和组织学特征的合适动物模型中进行转化研究。这篇综述文章总结了AH的临床综合征、临床前转化工具以及分子和细胞水平的发病机制，旨在确定潜在治疗干预的新靶点。
