Kim Moon-Sun, Ong Madeleine, Qu Xianqin
Moon-Sun Kim, Madeleine Ong, XianQin Qu, School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, NSW 2007, Australia.
World J Gastroenterol. 2016 Jan 7;22(1):8-23. doi: 10.3748/wjg.v22.i1.8.
Alcohol consumption is the principal factor in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and liver failure. As one of the oldest forms of liver injury known to humans, ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide. Although the biological mechanisms, including increasing of acetaldehyde, oxidative stress with induction of cytochrome p450 2E1, inflammatory cytokine release, abnormal lipid metabolism and induction of hepatocyte apoptosis, by which chronic alcohol consumption triggers serious complex progression of ALD is well established, there is no universally accepted therapy to prevent or reverse. In this article, we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies. This review is focused on current therapeutic strategies for ALD, including lifestyle modification with nutrition supplements, available pharmacological drugs and new agents that are under development, liver transplantation, application of complementary medicines, and their combination. The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature. We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD. Through a system review, this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications. It is worthwhile to conduct large-scale, multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD.
饮酒是慢性肝病发病机制中的主要因素。酒精性肝病(ALD)由肝脏的组织学病变定义,其范围可从单纯性肝脂肪变性到更晚期阶段,如酒精性脂肪性肝炎、肝硬化、肝细胞癌和肝衰竭。作为人类已知的最古老的肝损伤形式之一,ALD仍然是肝脏相关发病率和死亡率的主要原因,并且随着全球住院和管理成本不断上升,这一负担正施加于医疗系统。尽管长期饮酒引发ALD严重复杂进展的生物学机制,包括乙醛增加、细胞色素p450 2E1诱导的氧化应激、炎性细胞因子释放、异常脂质代谢和肝细胞凋亡诱导等已得到充分证实,但尚无普遍接受的预防或逆转疗法。在本文中,我们简要回顾了ALD的发病机制以及新型疗法开发的分子靶点。本综述聚焦于ALD的当前治疗策略,包括通过营养补充剂进行生活方式改变、可用的药物、正在研发的新药、肝移植、补充药物的应用及其联合使用。已根据文献中当前可得的知识对每种传统药物和天然药物的相关分子机制进行了综述。我们还总结了专门用于预防和治疗ALD的传统药物和草药的疗效与安全性。通过系统综述,本文强调药物与天然制剂联合使用可能为ALD及其并发症提供最佳管理。开展大规模、多中心临床试验以进一步证明综合治疗ALD的安全性和益处是值得的。