Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant: What is the evidence?

Table 3 Clinical studies assessing the impact of normothermic machine perfusion on ischemic type biliary lesions after liver transplantation

Ref.	Study design	Intervention group (n)	Control group (n)	DBD, DCD intervention	DBD, DCD control	NMP duration1	Viability testing	Definition of ITBL	Follow u	ITBL-intervention		ITBL-control
										DCD	DBD	DCD	DBD
Markmann et al[65], 2022	RCT	NMP at source (153)	SCS (146)	125, 28	133, 13	4.5 h	NR	IBC defined as NAS or bile leaks, confirmed with ERCP or MRCP	12 mo	4/153 (2.6%) (DBD and DCD)		14/146 (9.5%) (DBD and DCD)
Nasralla et al[64], 2018	RCT	NMP at source (121)	SCS (101)	87, 34	80, 21	9.1 h	No viability testing	Protocol MRCP at 6 mo. No distinction between IC and ITBL	6 mo	3/27 (11.1%)2	4/54 (7.4%)2	5/19 (26.3%)2	3/55 (5.5%)2
Ghinolfi et al[74], 2019	RCT	NMP back-to-base (10)	SCS (10)	All DBD	All DBD	4.2 h	NR	NR	6 mo	NA	1/10 (10%)	NA	0/10
Gaurav et al[44], 2022	Cohort	NMP back to base OR at-source (67)	SCS (97); NRP (69)	All DCD	All DCD	7.6 h	Cambridge criteria	NAS defined as any BS, dilatation, or irregularity of the bile ducts and/or cast on MRCP away from the anastomosis with patent HA	6 mo minimum	12/67 (17.9%) [7/67, 10.4%3]	NA	NRP-4/69 (5.7%) [03] SCS-22/97 (22.6%) [12/97, 12.3%3]	NA
Hann et al[82], 2022	Cohort	NMP back to base (26)	SCS (56)	All DBD	All DBD	12 h	Birmingham criteria	Not reported	6 mo minimum	NA	1/26 (3.8%)	NA	6/56 (10.7%)
Fodor et al[75], 2021	Cohort	NMP back to base (59)	SCS (59)	49, 9	55, 4	15 h	Certain parameters signs of "good organ function", others considered "warning" signs	ITBL was defined as BS, dilatation or irregularity of the intra- or extrahepatic bile ducts with or without biliary cast formation in the absence of HAS or HAT	3 mo minimum	0/9	2/49 (4%)	1/4 (25%)	7/55 (12.7%)
Mohkam et al[45], 2022	Cohort	NMP at source (34)	NRP (68)	All DCDs	All DCD	8.8 h	Not applied	Refers to BS requiring a specific treatment or resulting to graft loss and/or death	23 mo	1/34 (2.9%)	NA	1/68 (1.5%)	NA
Mergental et al[71], 2020	Cohort	NMP back-to-base (22)	SCS (44)	12, 10	24, 204	9.8 h	Birmingham criteria	NR	6 mo	7/10 (70%)	0/12	NR	NR
Bral et al[83], 2019	Cohort	NMP back-to-base (26)	NMP at source (17)	20, 6	13, 4	7.8 h (back-to-base) 10.3 h (at-source)	Parameters included opening lactate level, lactate clearance, necessity of bicarbonate supplementation, and bile production	IC defined as diffuse BS in the absence of significant arterial stenosis	6 mo	0/6	0/20	0/4	0/13
Ceresa et al[62], 2019	Cohort	NMP back-to-base (31)	NMP at-source (104)	23, 8	73, 31	8.4 h (mean)	No viability criteria	NR	12 mo	0/8	0/23	NR	NR
Liu et al[84], 2019	Cohort	NMP back to base OR at-source (21)	SCS (84)	13, 8	52, 32	4 h 52	No viability testing	NR	12 mo minimum	0/8	0/13	NR	NR
Bral et al[85], 2017	Cohort	NMP at-source (9)	SCS (30)	6, 3	22, 8	11.5 h	No viability testing	NR	6 mo	0/3	0/6	NR	NR
Ravikumar et al[63], 2016	Cohort	NMP at-source (20)	SCS (40)	16, 4	32, 8	9.3 h	No viability testing	NR	30 d	0/4	0/16	NR	NR

¹Median duration unless otherwise stated.

²Numerator represents the number of patients that completed the 6 mo protocol magnetic resonance cholangiopancreatography.

³Number of clinically significant strictures, defined as those requiring intervention.

⁴Presumed based on propensity matching.

BS: Biliary strictures; DBD: Donor after Brain Death; DCD: Donated after circulatory death; ERCP: Endoscopic retrograde cholangiopancreatography; IC: Ischemic cholangiopathy; HA: Hepatic artery; HAS: Hepatic artery stenosis; HAT: Hepatic artery thrombosis; IBC: Ischemic biliary complication; ITBL: Ischemic type biliary lesions; NAS: Nonanastamotic biliary strictures; NR: Not reported; NRP: Normothermic Regional Perfusion; MRCP: Magnetic resonance cholangiopancreatography; RCT: Randomized controlled trials; NA: Not available.