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肝移植患者非酒精性脂肪性肝病发生过程中的肝外器官

Extrahepatic organs in the development of non-alcoholic fatty liver disease in liver transplant patients.

作者信息

Su Renyi, Wei Xuyong, Wei Qiang, Lu Di, Lin Zuyuan, Wang Shuo, Shao Chuxiao, Xu Xiao

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China.

出版信息

Hepatobiliary Surg Nutr. 2022 Jun;11(3):400-411. doi: 10.21037/hbsn-20-568.

Abstract

BACKGROUND AND OBJECTIVE

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients who undergo liver transplantation (LT). Whereas there is huge data on NAFLD, little is known about NAFLD in LT. In this review, we aim to explore extrahepatic organs and their potential mechanisms in the development of NAFLD in LT patients and discuss current limitations in preclinical and clinical scenarios with suggestions for future study.

METHODS

The following keywords, such as NAFLD, NASH, liver transplant, therapy, pathogenesis and biomarkers, were set for literature retrieval. The articles which were published articles in English till 25th June 2020 in PubMed database were included, and there is no limit for the study design type.

KEY CONTENT AND FINDINGS

Following LT, there are significant shifts in the microbiota and farnesoid X receptor may be a potential therapeutic target for NAFLD in LT settings. The roles of probiotics and diet on NALFD remain inconclusive in LT background. Nevertheless, the adipokines and cytokines disorder and local insulin resistance of adipose tissue may contribute to NAFLD process. Bariatric surgeries are promising in controlling de novo and recurrent NAFLD with significant reduction in abdominal adipose tissue, despite the optimal timing is inconclusive in LT cases. Furthermore, circumstantial evidence indicates that miRNA-33a may function as a mediator bridging sarcopenia and NAFLD of post-LT. β-Hydroxy-β-Methyl-Butyrate treatment could improve muscle status in graft recipients and shows protective potential for NAFLD in LT settings.

CONCLUSIONS

Gut, adipose tissue and muscle are intricately intertwined in promoting NAFLD in LT cases. Further animal studies are needed to deepen our understanding of mechanisms in multi-organ crosstalk. High quality clinical trials are warrant for making guidelines and developing management strategies on NAFLD after LT.

摘要

背景与目的

非酒精性脂肪性肝病(NAFLD)在肝移植(LT)患者中极为普遍。尽管关于NAFLD的数据众多,但对于LT中的NAFLD却知之甚少。在本综述中,我们旨在探讨肝外器官及其在LT患者NAFLD发生发展中的潜在机制,并讨论临床前和临床场景中的当前局限性以及对未来研究的建议。

方法

设置以下关键词进行文献检索,如NAFLD、NASH、肝移植、治疗、发病机制和生物标志物。纳入截至2020年6月25日在PubMed数据库中发表的英文文章,研究设计类型不限。

关键内容与发现

LT后,微生物群发生显著变化,法尼酯X受体可能是LT背景下NAFLD的潜在治疗靶点。在LT背景下,益生菌和饮食对NAFLD的作用尚无定论。然而,脂肪因子和细胞因子紊乱以及脂肪组织的局部胰岛素抵抗可能有助于NAFLD进程。减肥手术在控制新发和复发性NAFLD方面前景广阔,可显著减少腹部脂肪组织,尽管LT病例的最佳时机尚无定论。此外,间接证据表明,miRNA - 33a可能作为连接LT后肌肉减少症和NAFLD的介质发挥作用。β-羟基-β-甲基丁酸治疗可改善移植受者的肌肉状态,并在LT背景下显示出对NAFLD的保护潜力。

结论

在LT病例中,肠道、脂肪组织和肌肉在促进NAFLD方面错综复杂地相互关联。需要进一步的动物研究来加深我们对多器官相互作用机制的理解。高质量的临床试验对于制定LT后NAFLD的指南和管理策略是必要的。

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本文引用的文献

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Sarcopenia in nonalcoholic fatty liver disease: new challenges for clinical practice.非酒精性脂肪性肝病中的肌肉减少症:临床实践的新挑战。
Expert Rev Gastroenterol Hepatol. 2020 Mar;14(3):197-205. doi: 10.1080/17474124.2020.1731303. Epub 2020 Feb 23.

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