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中华肝脏外科手术学电子杂志 ›› 2025, Vol. 14 ›› Issue (01) : 18 -24. doi: 10.3877/cma.j.issn.2095-3232.2025006

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脂肪变性供肝脱脂策略的研究
徐涵治1, 邱洵1, 汪恺2, 徐骁1,2,()   
  1. 1.310058 杭州,浙江大学转化医学研究院
    2.310059 杭州,杭州医学院临床医学院
  • 收稿日期:2024-10-24 出版日期:2025-02-10
  • 通信作者: 徐骁
  • 基金资助:
    国家重点研发计划(2021YFA1100500)国家自然科学基金重点项目(81930016)

Study of defatting strategy for steatotic donor livers

Hanzhi Xu1, Xun Qiu1, Kai Wang2, Xiao Xu1,2,()   

  1. 1.Institute of Translational Medicine, Zhejiang University School of Medicine,Hangzhou 310058, China
    2.School of Clinical Medicine, Hangzhou Medical College, Hangzhou 310059, China
  • Received:2024-10-24 Published:2025-02-10
  • Corresponding author: Xiao Xu
引用本文:

徐涵治, 邱洵, 汪恺, 徐骁. 脂肪变性供肝脱脂策略的研究[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(01): 18-24.

Hanzhi Xu, Xun Qiu, Kai Wang, Xiao Xu. Study of defatting strategy for steatotic donor livers[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2025, 14(01): 18-24.

肝移植是治疗终末期肝病的最有效手段,但供肝短缺问题严重制约了肝移植的发展。因此,扩大标准供肝逐渐被用于肝移植,而脂肪变性供肝是其重要组成部分。然而,脂肪变性是降低供肝质量,影响移植预后的重要原因,故供肝脱脂策略亟待进一步的研究。随着对肝脏脂质代谢机制的不断深入探索,越来越多的药物被用于降低肝脏脂质的过度蓄积。此外,机械灌注技术的发展为供肝脱脂提供了崭新途径。脱脂药物可以通过加入到灌注液来发挥其作用,最终降低供肝脂肪变性程度,减轻组织损伤,使更多脂肪变性肝脏用于临床肝移植。本文将综合现有研究成果,就肝脏降脂药物和机械灌注在供肝脱脂方面的应用进行综述。

Liver transplantation is the most effective treatment for end-stage liver disease.However, the shortage of donor liver severely restricts the development of liver transplantation.Therefore,the extended standard donor liver has been gradually applied in liver transplantation, and steatotic donor liver is an important part.However, steatosis is a critical factor lowering the quality of donor liver allografts and affecting clinical prognosis of liver transplantation.Hence, the defatting strategies for donor liver allografts remain to be investigated.With deepening exploration of the mechanism of hepatic lipid metabolism, an increasing amount of medicines have been adopted to reduce excessive accumulation of liver lipids.In addition, the development of mechanical perfusion strategies provides a novel defatting technology for donor liver allografts.Defatting drugs can function when added into the perfusion solution, and ultimately alleviate the degree of steatosis of donor livers, mitigate tissue injuries, and enable the application of more steatotic donor livers in clinical liver transplantation.In this article, recent research progress in the application of liver lipid-lowering drugs and mechanical perfusion in defatting for donor liver allografts were reviewed.

表1 肝脏降脂药物疗效汇总
作者 药物 功效
Loomba等[6] GS-0976 20 mg组血酰基肉碱、金属属蛋白酶抑制因子1下调
Calle等[7] PF-05221304 ≥10 mg组肝脏质子密度脂肪分数剂量依赖性下调,血TG上调
Calle等[7] PF-05221304、PF-06865571 肝脏质子密度脂肪分数和血TG均下调
Syed-Abdul等[8] TVB-2640 脂肪从头合成能力、血ALT水平下调
Ratziu等[9] Aramchol 600 mg组肝内TG、血ALT下调,改善肝脏纤维化程度
Loomba等[10] IONIS-DGAT2Rx 肝脏质子密度脂肪分数下调
Harrison等[14] NGM282 肝脏质子密度脂肪分数下调
Sanyal等[15] Pegbelfermin(BMS-986036) 肝脏质子密度脂肪分数下调
Harrison等[22] Resmetirom(MGL-3196) 肝脏质子密度脂肪分数下调
Francque等[24] Lanifibranor 脂肪变性、炎症活动度和纤维化评分下调
Ratziu等[25] Elafibranor 120 mg组肝酶、血脂、和全身性炎症标志物下调,NAFLD评分降低
Gawrieh等[26] Saroglitazar 4 mg组肝酶、肝脏质子密度脂肪分数、胰岛素抗性和血脂改善
Kazierad等[27] PF-06835919 300 mg组肝脏质子密度脂肪分数、炎症指标下调
Newsome等[30] Semaglutide 0.4 mg组脂肪变性、炎症活动度和纤维化评分下调
Cusi等[31] Canagliflozin 肝脏质子密度脂肪分数下调
Younossi等[32] 奥贝胆酸 肝脏纤维化程度改善
Harrison等[33] MET409 肝脏质子密度脂肪分数下调,肝酶等肝功能指标改善
Patel等[34] Cilofexor(GS-9674) 100 mg组肝脏质子密度脂肪分数下调,30和100 mg组肝酶、胆汁生成等肝功能指标均改善
表2 肝脏降脂药物联合机械灌注疗效汇总
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