Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy.

Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy.
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DOI:
10.1016/j.toxrep.2021.02.010
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发表时间:
2021
期刊:
影响因子:
--
通讯作者:
Das A
Das A
中科院分区:
其他
文献类型:
--
作者:
Subramaniyan V;Chakravarthi S;Jegasothy R;Seng WY;Fuloria NK;Fuloria S;Hazarika I;Das A

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长期摄入酒精会引发致病过程,涉及蛋白质-醛加合物的产生和细胞因子的释放。涉及的基因多态性可能包括乙醇脱氢酶、细胞色素 P4502E1 以及与酒精中毒相关的基因多态性。酒精摄入可能与早产风险相关,但没有确切的剂量反应关系。口服己酮可可碱药物可降低酗酒患者脂肪性肝炎的严重程度。全球医疗保健负担之一是酒精相关性肝病(ALD)和因急性或慢性饮酒而引起的肝脏相关死亡。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、粘膜免疫细胞,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。治疗的基础始于戒酒。皮质类固醇用于治疗 ALD,但由于接受度差、持续死亡以及肿瘤坏死因子-α 被确定为发病机制中不可或缺的组成部分,最近的研究重点是己酮可可碱和抗肿瘤坏死因子抗体来中和细胞因子,用于治疗严重酒精性肝炎。抗氧化剂在治疗中也发挥着重要作用,但迄今为止,还没有针对 ALD 任何阶段的普遍接受的治疗方法。治疗方面需要恢复肠道功能,需要以营养为主的治疗来调节肠道系统的功能,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引起的代谢功能障碍的机制、对肝脏发病机制的贡献、妊娠的影响以及ALD的靶向治疗。
Chronic intake of alcohol initiates a pathogenic process that involves the production of protein-aldehyde adducts, and release of cytokines. Involved gene polymorphisms may include alcohol dehydrogenase, cytochrome P4502E1, and those associated with alcoholism. Alcohol ingestion could be correlated to the risk of preterm births, there is no exact dose-response relationship. Oral drugs of pentoxifylline have reduced the severity of steatohepatitis in alcohol-use patients. 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.
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