Study of defatting strategy for steatotic donor livers

doi:10.3877/cma.j.issn.2095-3232.2025006

Abstract

Abstract:

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.

Key words: Liver transplantation, Defatting, Pharmacotherapy, Machine perfusion, Nonalcoholic steatohepatitis (NASH), Nonalcoholic fatty liver disease (NAFLD)

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

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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

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

作者	药物联合体外机械灌注	功效
Nagrath等^[21]	GW501516、GW7647、金丝桃素、滨蒿内脂、毛喉素、内脂素	大鼠肝脏脂肪含量下降50%；人肝内TG含量降低38%，大泡性脂肪变性降低40%，线粒体和胆汁分泌功能改善
Raigani等^[42]和Boteon等^[43]	GW501516、GW7647、金丝桃素、滨蒿内脂、毛喉素、内脂素、左旋肉碱	大鼠肝脏胆汁生成、脂肪酸氧化等肝功能指标改善，炎症水平下调；人肝内TG含量降低38%，大泡性脂肪变性降低40%，线粒体和胆汁分泌功能改善
Taba等^[45]	GDNF	肝脏脂肪含量均降低
Banan等^[46]	唾液素4和左旋肉碱	大泡性脂肪变性降低10%，肝脏组织结构和功能改善
Sousa Da Silva等^[47]	非诺贝特、左旋肉碱	50%肝脏脂肪含量和器官功能显著改善

作者	药物联合体外机械灌注	功效
Nagrath等^[21]	GW501516、GW7647、金丝桃素、滨蒿内脂、毛喉素、内脂素	大鼠肝脏脂肪含量下降50%；人肝内TG含量降低38%，大泡性脂肪变性降低40%，线粒体和胆汁分泌功能改善
Raigani等^[42]和Boteon等^[43]	GW501516、GW7647、金丝桃素、滨蒿内脂、毛喉素、内脂素、左旋肉碱	大鼠肝脏胆汁生成、脂肪酸氧化等肝功能指标改善，炎症水平下调；人肝内TG含量降低38%，大泡性脂肪变性降低40%，线粒体和胆汁分泌功能改善
Taba等^[45]	GDNF	肝脏脂肪含量均降低
Banan等^[46]	唾液素4和左旋肉碱	大泡性脂肪变性降低10%，肝脏组织结构和功能改善
Sousa Da Silva等^[47]	非诺贝特、左旋肉碱	50%肝脏脂肪含量和器官功能显著改善

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