Subramaniyan Vetriselvan, Chakravarthi Srikumar, Jegasothy Ravindran, Seng Wu Yuan, Fuloria Neeraj Kumar, Fuloria Shivkanya, Hazarika Iswar, Das Anju
Department of Pharmacology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia.
Department of Pathology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia.
Toxicol Rep. 2021 Feb 19;8:376-385. doi: 10.1016/j.toxrep.2021.02.010. eCollection 2021.
One of the global burdens of health care is an alcohol-associated liver disease (ALD) and liver-related death which is caused due to acute or chronic consumption of alcohol. Chronic consumption of alcohol damage the normal defense mechanism of the liver and likely to disturb the gut barrier system, mucosal immune cells, which leads to decreased nutrient absorption. Therapy of ALD depends upon the spectrum of liver injury that causes fatty liver, hepatitis, and cirrhosis. The foundation of therapy starts with abstinence from alcohol. Corticosteroids are used for the treatment of ALD but due to poor acceptance, continuing mortality, and identification of tumor necrosis factor-alpha as an integral component in pathogenesis, recent studies focus on pentoxifylline and, antitumor necrosis factor antibody to neutralize cytokines in the therapy of severe alcoholic hepatitis. Antioxidants also play a significant role in the treatment but till today there is no universally accepted therapy available for any stage of ALD. The treatment aspects need to restore the gut functions and require nutrient-based treatments to regulate the functions of the gut system and prevent liver injury. The vital action of saturated fatty acids greatly controls the gut barrier. Overall, this review mainly focuses on the mechanism of alcohol-induced metabolic dysfunction, contribution to liver pathogenesis, the effect of pregnancy, and targeted therapy of ALD.
医疗保健的全球负担之一是酒精性肝病(ALD)以及因急性或慢性饮酒导致的肝脏相关死亡。长期饮酒会损害肝脏的正常防御机制,并可能扰乱肠道屏障系统、黏膜免疫细胞,从而导致营养吸收减少。ALD的治疗取决于导致脂肪肝、肝炎和肝硬化的肝损伤范围。治疗的基础是戒酒。皮质类固醇用于治疗ALD,但由于接受度低、持续死亡率以及肿瘤坏死因子-α被确定为发病机制中的一个重要组成部分,最近的研究集中在己酮可可碱以及抗肿瘤坏死因子抗体,以在重症酒精性肝炎的治疗中中和细胞因子。抗氧化剂在治疗中也起着重要作用,但直到今天,对于ALD的任何阶段都没有普遍接受的治疗方法。治疗方面需要恢复肠道功能,并需要基于营养的治疗来调节肠道系统的功能并预防肝损伤。饱和脂肪酸的重要作用极大地控制着肠道屏障。总体而言,本综述主要关注酒精诱导的代谢功能障碍机制、对肝脏发病机制的影响、妊娠的影响以及ALD的靶向治疗。