Guideline on the clinical application of ex situ liver machine perfusion

doi:10.3877/cma.j.issn.1674-3903.2024.06.002

Abstract

Abstract:

Organ transplantation is the standard treatment for end-stage organ failure, yet severe shortages of organs persist worldwide, necessitating the use of organs from extended criteria donor.Traditional static cold storage has limitations in evaluating organ function and mitigating ischemia-reperfusion injury.Consequently, various ex situ machine perfusion techniques have been developed, including hypothermic machine perfusion, hypothermic oxygenated perfusion, normothermic machine perfusion, ischemia-free liver transplantation, and sub-normothermic machine perfusion.Recent studies demonstrate that these technologies can extend preservation time, enable liver quality assessment, reduce ischemia-reperfusion injury, and improve transplantation prognosis.This guideline aims to promote the clinical application of ex situ liver machine perfusion in China.Based on evidencebased medicine principles and recent studies, recommendations are provided on graft procurement,preservation, quality evaluation, and transplantation prognosis.

Key words: Liver transplantation, Ex situ machine perfusion, Extended criteria donor, Ischemia-reperfusion injury, Transplantation prognosis

of Organ Transplantation of Chinese Medical Association Branch. Guideline on the clinical application of ex situ liver machine perfusion[J]. Chinese Journal of Transplantation(Electronic Edition), 2024, 18(06): 334-345.

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URL: https://zhyzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3903.2024.06.002

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证据级别	定义
Ⅰ	同质RCT 的系统评价
	单个RCT(可信区间窄)
	“全或无”病案系列研究
Ⅱ	同质队列研究的系统评价
	单个队列研究(包括低质量RCT,如随访率<80%)
	结果研究,生态学研究
Ⅲ	同质病例对照研究的系统评价
	单个病例对照研究
Ⅳ	病例系列研究(包括低质量队列及病例对照研究)
Ⅴ	基于经验未严格论证的专家意见

证据级别	定义
Ⅰ	同质RCT 的系统评价
	单个RCT(可信区间窄)
	“全或无”病案系列研究
Ⅱ	同质队列研究的系统评价
	单个队列研究(包括低质量RCT,如随访率<80%)
	结果研究,生态学研究
Ⅲ	同质病例对照研究的系统评价
	单个病例对照研究
Ⅳ	病例系列研究(包括低质量队列及病例对照研究)
Ⅴ	基于经验未严格论证的专家意见

序号	推荐意见	证据级别	推荐强度
	HMP
1	无氧供HMP/ HMP-O₂ 的灌注液温度推荐控制在4 ～8 ℃	Ⅱ	强
2	无氧供HMP/ HMP-O₂ 的灌注流速推荐为0. 66 mL·min ^-1 ·g ^-1 (肝脏)	Ⅲ	强
3	HMP-O₂ 灌注前,推荐以10 L/ min 的速度预充纯氧至少20 min	Ⅲ	强
4	HOPE/ DHOPE 的灌注液温度推荐控制在8 ～10 ℃	Ⅱ	强
5	HOPE/ DHOPE 的门静脉灌注压力推荐为2 ～5 mmHg,灌注流速推荐为100 ～ 400 mL/ min;肝动脉的灌注压力推荐为20 ～30 mmHg,灌注流速推荐为50 ～ 150 mL/ min;灌注液氧分压推荐为60 ～ 100 kPa,氧流速推荐为500 ～1 000 mL/ min	Ⅲ	强
6	FMN 对HOPE 评估供肝质量具有潜在价值	Ⅲ	强
7	DHOPE-COR-NMP 序贯机械灌注有利于评估高风险供肝	Ⅱ	强
8	无氧供HMP 有助于降低DNDD 供肝术后早期移植物功能不全发生率,增加边缘性供肝使用率	Ⅳ	弱
9	HMP-O₂ 有助于降低术后早期移植物功能不全发生率	Ⅲ	弱
10	HMP-O₂ 有助于降低术后胆道并发症发生率	Ⅳ	弱
11	HOPE/ DHOPE 能提高肝移植术后1 年移植物生存率	Ⅰ	强
12	HOPE/ DHOPE 能降低术后严重并发症(Clavien-Dindo 分级≥Ⅲb)发生率,且能降低ECD-DNDD 供肝术后胆道非吻合口狭窄发生率	Ⅱ	强
13	HOPE/ DHOPE 能降低术后早期移植物功能不全发生率,且能降低DCDD 供肝术后胆道非吻合口狭窄发生率	Ⅰ	强
14	HOPE/ DHOPE 能提高ECD-DNDD 供肝术后5 年移植物生存率	Ⅲ	强
15	HOPE/ DHOPE 能降低术后再移植率	Ⅲ	强
16	HOPE/ DHOPE 能降低DCDD 供肝术后急性排斥反应发生率	Ⅲ	弱
17	供肝体外劈离可在HOPE 的支持下进行,有助于减轻劈离肝缺血损伤	Ⅳ	弱
	NMP
18	NMP 的灌注液温度推荐控制在34 ～37 ℃;肝动脉的灌注流速推荐为150 ～400 mL/ min,灌注压力推荐为45 ～75 mmHg;门静脉的灌注流速推荐为700 ～1 700 mL/ min,灌注压力推荐为4 ～10 mmHg	Ⅱ	强
19	NMP 的灌注液推荐采用胶体溶液替代血浆,采用洗涤红细胞或者人造血红蛋白作为携氧载体,在此基础上加入抗生素、肝素、碳酸氢钠缓冲液和静脉营养剂等成分	Ⅱ	强
20	采用COR 衔接DHOPE 和NMP 时,推荐采用人造血红蛋白作为灌注液的携氧载体,亦可采用洗涤红细胞,并加入抗生素、肝素等NMP 所需的灌注液成分	Ⅱ	强
21	DHOPE-COR-NMP 的复温阶段,推荐以每2 min 提升1 ℃的速度逐渐提高灌注液的温度,同时逐渐增加门静脉和肝动脉的灌注压力至NMP 的合适范围内	Ⅲ	强
22	灌注液中的肝脏代谢相关指标对NMP 下评估供肝质量有重要价值,推荐采用灌注液乳酸水平、pH 值、葡萄糖、胆汁生成、胆汁pH 值以及肝动脉和门静脉流速等指标评估肝脏质量	Ⅱ	强
23	NMP 能减轻移植物早期损伤	Ⅰ	强
24	NMP 有助于降低术后严重并发症(Clavien-Dindo 分级≥Ⅲb)发生率,并降低缺血性胆道病变发生率	Ⅳ	弱
25	NMP 能降低DCDD 供肝术后早期移植物功能不全发生率,增加边缘性供肝使用率	Ⅲ	强
26	NMP 能降低复流后综合征发生率	Ⅲ	弱
	IFLT
27	IFLT 能够减轻供肝IRI,降低DNDD 供肝移植术后早期移植物功能不全发生率	Ⅱ	强
28	IFLT 能降低DNDD 供肝移植术后综合并发症评分,减少移植术中复流后综合征和术后胆道非吻合口狭窄发生率	Ⅲ	强
29	IFLT 能降低DNDD 供肝移植术后肝细胞癌复发率	Ⅲ	弱
30	IFLT 技术能减少肝移植术后ICU 住院时间	Ⅲ	强
31	IFLT 有助于提高边缘性供肝使用率	Ⅲ	强
32	IFLT 技术能有效减少灌注液病原微生物污染	Ⅲ	强
	临床试验开展
33	开展NMP 灌注边缘性供肝的RCT 和体外药物干预的临床试验	/	/
34	开展序贯机械灌注的临床RCT	/	/
35	建立统一的机械灌注下供肝质量评估标准	/	/

序号	推荐意见	证据级别	推荐强度
	HMP
1	无氧供HMP/ HMP-O₂ 的灌注液温度推荐控制在4 ～8 ℃	Ⅱ	强
2	无氧供HMP/ HMP-O₂ 的灌注流速推荐为0. 66 mL·min ^-1 ·g ^-1 (肝脏)	Ⅲ	强
3	HMP-O₂ 灌注前,推荐以10 L/ min 的速度预充纯氧至少20 min	Ⅲ	强
4	HOPE/ DHOPE 的灌注液温度推荐控制在8 ～10 ℃	Ⅱ	强
5	HOPE/ DHOPE 的门静脉灌注压力推荐为2 ～5 mmHg,灌注流速推荐为100 ～ 400 mL/ min;肝动脉的灌注压力推荐为20 ～30 mmHg,灌注流速推荐为50 ～ 150 mL/ min;灌注液氧分压推荐为60 ～ 100 kPa,氧流速推荐为500 ～1 000 mL/ min	Ⅲ	强
6	FMN 对HOPE 评估供肝质量具有潜在价值	Ⅲ	强
7	DHOPE-COR-NMP 序贯机械灌注有利于评估高风险供肝	Ⅱ	强
8	无氧供HMP 有助于降低DNDD 供肝术后早期移植物功能不全发生率,增加边缘性供肝使用率	Ⅳ	弱
9	HMP-O₂ 有助于降低术后早期移植物功能不全发生率	Ⅲ	弱
10	HMP-O₂ 有助于降低术后胆道并发症发生率	Ⅳ	弱
11	HOPE/ DHOPE 能提高肝移植术后1 年移植物生存率	Ⅰ	强
12	HOPE/ DHOPE 能降低术后严重并发症(Clavien-Dindo 分级≥Ⅲb)发生率,且能降低ECD-DNDD 供肝术后胆道非吻合口狭窄发生率	Ⅱ	强
13	HOPE/ DHOPE 能降低术后早期移植物功能不全发生率,且能降低DCDD 供肝术后胆道非吻合口狭窄发生率	Ⅰ	强
14	HOPE/ DHOPE 能提高ECD-DNDD 供肝术后5 年移植物生存率	Ⅲ	强
15	HOPE/ DHOPE 能降低术后再移植率	Ⅲ	强
16	HOPE/ DHOPE 能降低DCDD 供肝术后急性排斥反应发生率	Ⅲ	弱
17	供肝体外劈离可在HOPE 的支持下进行,有助于减轻劈离肝缺血损伤	Ⅳ	弱
	NMP
18	NMP 的灌注液温度推荐控制在34 ～37 ℃;肝动脉的灌注流速推荐为150 ～400 mL/ min,灌注压力推荐为45 ～75 mmHg;门静脉的灌注流速推荐为700 ～1 700 mL/ min,灌注压力推荐为4 ～10 mmHg	Ⅱ	强
19	NMP 的灌注液推荐采用胶体溶液替代血浆,采用洗涤红细胞或者人造血红蛋白作为携氧载体,在此基础上加入抗生素、肝素、碳酸氢钠缓冲液和静脉营养剂等成分	Ⅱ	强
20	采用COR 衔接DHOPE 和NMP 时,推荐采用人造血红蛋白作为灌注液的携氧载体,亦可采用洗涤红细胞,并加入抗生素、肝素等NMP 所需的灌注液成分	Ⅱ	强
21	DHOPE-COR-NMP 的复温阶段,推荐以每2 min 提升1 ℃的速度逐渐提高灌注液的温度,同时逐渐增加门静脉和肝动脉的灌注压力至NMP 的合适范围内	Ⅲ	强
22	灌注液中的肝脏代谢相关指标对NMP 下评估供肝质量有重要价值,推荐采用灌注液乳酸水平、pH 值、葡萄糖、胆汁生成、胆汁pH 值以及肝动脉和门静脉流速等指标评估肝脏质量	Ⅱ	强
23	NMP 能减轻移植物早期损伤	Ⅰ	强
24	NMP 有助于降低术后严重并发症(Clavien-Dindo 分级≥Ⅲb)发生率,并降低缺血性胆道病变发生率	Ⅳ	弱
25	NMP 能降低DCDD 供肝术后早期移植物功能不全发生率,增加边缘性供肝使用率	Ⅲ	强
26	NMP 能降低复流后综合征发生率	Ⅲ	弱
	IFLT
27	IFLT 能够减轻供肝IRI,降低DNDD 供肝移植术后早期移植物功能不全发生率	Ⅱ	强
28	IFLT 能降低DNDD 供肝移植术后综合并发症评分,减少移植术中复流后综合征和术后胆道非吻合口狭窄发生率	Ⅲ	强
29	IFLT 能降低DNDD 供肝移植术后肝细胞癌复发率	Ⅲ	弱
30	IFLT 技术能减少肝移植术后ICU 住院时间	Ⅲ	强
31	IFLT 有助于提高边缘性供肝使用率	Ⅲ	强
32	IFLT 技术能有效减少灌注液病原微生物污染	Ⅲ	强
	临床试验开展
33	开展NMP 灌注边缘性供肝的RCT 和体外药物干预的临床试验	/	/
34	开展序贯机械灌注的临床RCT	/	/
35	建立统一的机械灌注下供肝质量评估标准	/	/

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