Outcomes after liver transplantation in accordance with ABO compatibility: A systematic review and meta-analysis

Table 1 Characteristics of the included studies

Ref.	Publication(yr)	Study periods(yr)	Region	Arms	Samplesize	Population3	Recipient age	Donor age	UrgentIndications34	Donor type3	Prescription for ABO-I LT	Immunosuppression
Song et al[28]	2016	2008-2013	South Korea	ABO-I	235	Adult	52.8 ± 8.0	29.2 ± 9.1	No	Living	Rituximab, PE, GLI (±), Splenectomy (±), Cyclophosphamide	Steroids, Basiliximab,Tac, MMF
				ABO-C	1301		51.7 ± 5.9	28.2 ± 7.6
Kim et al[29]	2016	2010-2013	South Korea	ABO-I	472	Adult	50 (22-65)	32 (18-68)	No	Living	Rituximab, PE, GLI (±)	Steroids, Basiliximab, Tac, MMF
				ABO-C	942		51 (20-68)	30 (18-62)
Kim et al[30]	2016	2011-2014	South Korea	ABO-I	252	Adult	51.3 ± 6.7	30.1 ± 11.2	No	Living	Rituximab, PE, IVIG, Preoperative MMF	Steroids, Basiliximab, Tac, MMF
				ABO-C	752		51.1 ± 6.7	28.8 ± 11.3
Ikegami et al[31]	2016	1997-2013	Japan	ABO-I	19	Adult	47.7 ± 15.7	36.6 ± 11.3	No	Living	Rituximab3, IVIG (±), PE, GLI (±), Splenectomy (±), Preoperative MMF (±)	Steroids, Tac (or CsA), MMF
				ABO-C	389		51.7 ± 11.9	37.4 ± 10.5
Lee et al[32]	2015	2006-2013	Taiwan	ABO-I	46	Adult	53.5 (19-67)	NA	No	Living	Rituximab, Plasmapheresis (or PE)	Steroids, Tac, MMF
				ABO-C	340		54.7 (18-70)	NA
Shen et al[33]	2014	2010-2013	China	ABO-I	35	Adult	46.7 ± 12.1	NA	Yes	Deceased	Rituximab, IVIG	Steroids, Basiliximab, Tac, MMF
				ABO-C	66		42.6 ± 10.2	NA
Heffron et al[34]	2010	1998-2008	United States	ABO-I	12	Pediatric	NA	NA	Yes	Deceased	-	Steroids, Daclizumab, Tac, MMF
				ABO-C	21		NA	NA
Stewart et al[35]	2009	1990-2006	United States	ABO-I	1302	Infant	0.3	8.1	No	Deceased	NA	NA
				ABO-C	3902		0.4	8.3
				ABO-I	1162	Pediatric	9.6	23.9
				ABO-C	3482		9	16.5
				ABO-I	5852	Adult	45.7	36
				ABO-C	17552		50.3	37.9
Iwamoto et al[36]	2008	2000-2007	Japan	ABO-I	15	Adult	NA	NA	No	Living	NA	NA
				ABO-C	37		NA	NA
Toso et al[20]	2007	1991-2005	Canada	ABO-I	14	Adult	42 (17-61)	NA	Yes	Deceased	Lymphocyte-depleting antibodies5, Plasmapheresis (±)	Steroids, Daclizumab, CsA (or Tac), AZA (or MMF, Sirolimus)
				ABO-C1	29		47 (16-62)	NA
				ABO-Id	65		47 (17-66)	NA
Saito et al[37]	2007	2000-2001	Japan	ABO-I	10	All ages	NA	NA	No	Deceased,	NA	NA
				ABO-C	81		NA	NA		Living
Koukoutsis et al[19]	2007	1984-2005	United Kingdom	ABO-I	4	Adult	NA	NA	Yes	Deceased	NA	NA
				ABO-C1	73		NA	NA
				ABO-Id	203		NA	NA
Ueda et al[18]	2006	1990-2003	Japan	ABO-I	74	Pediatric	NA	NA	No	Living	Steroids pulse weekly, PGE1, CsA - > AZA (1 mo after LT)	Steroids, Tac
				ABO-C1	114		NA	NA
				ABO-Id	380		NA	NA
Heffron et al[38]	2006	1999-2005	United States	ABO-I	16	Pediatric	6.5 ± 6.2	NA	No	Deceased	Plasmapheresis (±)	Steroids, Daclizumab, Tac, MMF
				ABO-C	122		8.1 ± 6.2	NA
Bjøro et al[17]	2003	1990-2001	Nordic countries	ABO-I	10	All ages	NA	44.8 (22-55)	Yes	Deceased	NA	NA
				ABO-C†	76		NA	42.3 (12-85)
				ABO-Id	143		NA	41.0 (2-75)
Chui et al[39]	1997	1986-1996	Australia	ABO-I	7	All ages	13 (6-32)	NA	Yes	Deceased	Plasmapheresis (±), Splenectomy (±)	Steroids, CsA, AZA
				ABO-C	36		NA	NA
Cacciarelli et al[16]	1995	1988-1993	United States	ABO-I	14	Pediatric	2.2 ± 1.1	NA	No	Deceased	OKT3 (or ATG, CsA)	Steroids, ATG (or OKT3, CsA), Tac
				ABO-C†	22		4.2 ± 1.0	NA
				ABO-Id	108		3.7 ± 0.5	NA
Lo et al[40]	1994	1988-1993	United States	ABO-I	29	All ages	NA	NA	Yes	Deceased	ATG (±)	Steroids, CsA (or OKT3), AZA
				ABO-C	196		NA	NA
Sanchez et al[41]	1993	1985-1991	United States	ABO-I	182	Adult	45 (16-61)	NA	No	Deceased	NA	NA
				ABO-C	182		47 (17-59)	NA
Reding et al[15]	1992	1984-1989	Belgium	ABO-I	16	All ages	NA	NA	Yes	Deceased	OKT3 (±)	Steroids, CsA, AZA(±)
				ABO-C†	16		NA	NA
				ABO-Id	38		NA	NA
Gugenheim et al[5]	1990	1984-1988	France	ABO-I	17	All ages	30 (12-49)	NA	Yes	Deceased	-	Steroids, CsA, AZA
				ABO-C	217		NA	NA

¹Compatible, but not identical; ²Propensity or case matched patients;

³If there are minority groups that make up less than about 10%, the article is categorized as covering the majority;

⁴Such as FHF, ALF, retransplantation, and critically ill patients in the intensive care unit; ⁵Documented as "lymphocyte-depleting antibodies", but not clarified exactly. ABO-C: ABO-compatible; ABO-I: ABO-incompatible; ABO-Id: ABO-identical; ATG: anti-thymocyte globulin; AZA: Azathioprine; CsA: Cyclosporin A; GLI: Graft local infusion; IVIG: Intravenous immunoglobulin; LT: Liver transplantation; MMF: Mycophenolate mofetil; NA: Not applicable; OKT3: Muromonab-CD3; PE: Plasma exchange; Tac: Tacrolimus.

Table 2 Modified Newcastle-Ottawa quality assessment scale for cohort studies included in the meta-analysis

Ref.	Selection				Comparability1	Outcome			Overall
	Representativeness	Selection	Ascertainment	Incident disease		Assessment	Length offollow-up	Adequacy offollow-up	Quality Score (Maximum 9)
Song et al[28]	↓	↓	↓	↑	↑	↓	↓	↓	6
Kim et al[29]	↓	↓	↓	↑	↓↓	↓	↓	↓	8
Kim et al[30]	↓	↓	↓	↑	↓↓	↓	↓	↓	8
Ikegami et al[31]	↓	↓	↓	↑	↑	↓	↓	↓	6
Lee et al[32]	↓	↓	↓	↑	↑	↓	↓	↓	6
Shen et al[33]	↓	↓	↓	↑	↑	↓	↓	↓	6
Heffron et al[34]	↓	↓	↓	↑	↑	↓	↓	↓	6
Stewart et al[35]	↓	↓	↓	↑	↓↓	↓	↓	↓	8
Iwamoto et al[36]	↓	↓	↓	↑	↑	↓	↓	↓	6
Toso et al[20]	↓	↓	↓	↑	↑	↓	↓	↓	6
Saito et al[37]	↓	↓	↓	↑	↑	↓	↓	↓	6
Koukoutsis et al[19]	↓	↓	↓	↑	↑	↓	↓	↓	6
Ueda et al[18]	↓	↓	↓	↑	↑	↓	↓	↓	6
Heffron et al[38]	↓	↓	↓	↑	↑	↓	↓	↓	6
Bjøro et al[17]	↓	↓	↓	↑	↑	↓	↓	↓	6
Chui et al[39]	↓	↓	↓	↑	↑	↓	↓	↓	6
Cacciarelli et al[16]	↓	↓	↓	↑	↑	↓	↓	↓	6
Lo et al[40]	↓	↓	↓	↑	↑	↓	↓	↓	6
Sanchez et al[41]	↓	↓	↓	↑	↓↓	↓	↓	↓	8
Reding et al[15]	↓	↓	↓	↑	↑	↓	↓	↓	6
Gugenheim et al[5]	↓	↓	↓	↑	↑	↓	↓	↓	6

¹A maximum of two downward arrows (↓↓) can be given for comparability. ↓ : Consistent with criteria and low risk of bias; ↑ : Not consistent with criteria and high risk of bias.

Table 3 Sensitivity analysis and subgroup analysis

Variables	No. of studies	OR=[95%CI]	P1 value	I2 (%)
Sensitivity analysis
Overall biliary complication		1.75 [0.89-3.43]	0.10	54
Omitting Sanchez et al[41]	7	1.52 [1.01-2.28]	0.04	0
Omitting Cacciarelli et al[16]	7	1.81 [0.87-3.76]	0.11	61
Omitting Heffron et al[38]	7	1.86 [0.87-3.95]	0.11	60
Omitting Toso et al[20]	7	1.86 [0.84-4.13]	0.13	60
Omitting Iwamoto et al[36]	7	1.81 [0.84-3.92]	0.13	61
Omitting Shen et al[33]	7	1.89 [0.90-3.96]	0.09	59
Omitting Lee et al[32]	7	1.69 [0.72-3.94]	0.23	56
Omitting Kim et al[29]	7	2.07 [0.98-4.37]	0.06	50
Bile leak		1.85 [0.46-7.39]	0.39	53
Omitting Sanchez et al[41]	2	0.98 [0.38-2.49]	0.96	0
Omitting Kim et al[30]	2	2.47 [0.19-31.38]	0.49	77
Omitting Kim et al[29]	2	3.62 [0.53-24.77]	0.19	46
Biliary stricture		1.37 [0.70-2.70]	0.36	47
Omitting Sanchez et al[41]	5	1.28 [0.62-2.62]	0.51	54
Omitting Lo et al[40]	5	1.11 [0.54-2.26]	0.78	42
Omitting Ikegami et al[31]	5	1.55 [0.71-3.39]	0.27	49
Omitting Kim et al[30]	5	1.47 [0.74-2.95]	0.27	51
Omitting Kim et al[29]	5	1.72 [0.91-3.25]	0.09	28
Omitting Song et al[28]	5	1.20 [0.43-3.31]	0.73	49
Subgroup analysis
1-yr graft survival		0.66 [0.57-0.76]	< 0.001	36
Rituximab for ABO-I LT (yes/no)	4 vs 7	0.88 [0.58-1.33] vs 0.44 [0.20-0.66]	0.02	0 vs 49
Living donor (yes/no)	4 vs 12	0.79 [0.56-1.13] vs 0.64 [0.55-0.74]	0.27	0 vs 44
Urgent indication (yes/no)	8 vs 8	0.37 [0.23-0.59] vs 0.70 [0.61-0.81]	0.01	27 vs 8
Pediatric2 (yes/no)	5 vs 12	0.88 [0.68-1.15] vs 0.59 [0.50-0.69]	0.01	12 vs 45
3-yr graft survival		0.74 [0.64-0.85]	< 0.001	0
Rituximab for ABO-I LT (yes/no)	3 vs 3	0.81 [0.56-1.18] vs 0.60 [0.26-1.41]	0.53	0 vs 0
Living donor (yes/no)	2 vs 5	0.84 [0.57-1.25] vs 0.72 [0.62-0.84]	0.47	0 vs 0
Urgent indication (yes/no)	3 vs 4	0.59 [0.27-1.31] vs 0.74 [0.64-0.86]	0.58	0 vs 0
Pediatric2 (yes/no)	3 vs 5	0.95 [0.71-1.26] vs 0.67 [0.57-0.80]	0.04	0 vs 0
5-yr graft survival		0.75 [0.66-0.86]	< 0.001	0
Rituximab for ABO-I LT (yes/no)	3 vs 2	0.96 [0.66-1.39] vs 0.56 [0.33-0.96]	0.11	0 vs 0
Living donor (yes/no)	4 vs 4	0.83 [0.61-1.14] vs 0.73 [0.63-0.86]	0.46	10 vs 0
Urgent indication (yes/no)	3 vs 5	0.60 [0.26-1.39] vs 0.76 [0.66-0.87]	0.6	0 vs 0
Pediatric 2 (yes/no)	2 vs 7	0.82 [0.63-1.07] vs 0.73 [0.62-0.86]	0.44	42 vs 0
10-yr graft survival		0.80 [0.69-0.93]	0.004	69
Rituximab for ABO-I LT (yes/no)	0 vs 1	NA vs 0.51 [0.31-0.85]	NA	NA
Living donor (yes/no)	1 vs 1	0.51 [0.31-0.85] vs 0.84 [0.71-0.98]	0.07	NA vs NA
Urgent indication (yes/no)	0 vs 2	NA vs 0.70 [0.44-1.11]	NA	NA vs 69
Pediatric 2 (yes/no)	2 vs 1	0.71 [0.41-1.23] vs 0.81 [0.70-0.98]	0.65	72 vs NA
1-yr patient survival		0.88 [0.67-1.16]	0.38	0
Rituximab for ABO-I LT (yes/no)	4 vs 7	0.88 [0.59-1.31] vs 0.67 [0.44-1.04]	0.38	0 vs 0
Living donor (yes/no)	4 vs 11	0.79 [0.56-1.13] vs 1.04 [0.67-1.61]	0.35	0 vs 9
Urgent indication (yes/no)	8 vs 7	0.93 [0.56-1.52] vs 0.87 [0.62-1.20]	0.83	0 vs 21
Pediatric (yes/no)	4 vs 11	0.64 [0.38-1.09] vs 0.98 [0.71-1.35]	0.18	0 vs 5
3-yr patient survival		0.89 [0.64-1.23]	0.47	0
Rituximab for ABO-I LT (yes/no)	4 vs 3	0.90 [0.64-1.27] vs 0.80 [0.31-2.06]	0.82	0 vs 43
Living donor (yes/no)	3 vs 4	0.91 [0.64-1.32] vs 0.78 [0.38-1.62]	0.71	5 vs 15
Urgent indication (yes/no)	3 vs 4	0.81 [0.35-1.91] vs 0.90 [0.63-1.28]	0.83	43 vs 0
Pediatric (yes/no)	2 vs 5	0.46 [0.15-1.38] vs 0.94 [0.67-1.32]	0.22	18 vs 0
5-yr patient survival		0.89 [0.66-1.20]	0.45	17
Rituximab for ABO-I LT (yes/no)	2 vs 2	0.89 [0.61-1.31] vs 1.00 [0.20-5.08]	0.89	0 vs 57
Living donor (yes/no)	3 vs 3	0.79 [0.57-1.08] vs 2.38 [0.86-6.63]	0.04	0 vs 0
Urgent indication (yes/no)	3 vs 3	2.38 [0.86-6.63] vs 0.79 [0.57-1.08]	0.04	0 vs 0
Pediatric (yes/no)	1 vs 5	0.58 [0.32-1.02] vs 1.04 [0.72-1.48]	0.09	NA vs 0
10-yr patient survival		0.46 [0.28-0.78]	0.004	7
Rituximab for ABO-I LT (yes/no)	0 vs 1	NA vs 0.46 [0.28-0.78]	NA	NA
Living donor (yes/no)	1 vs 0	0.46 [0.28-0.78] vs NA	NA	NA
Urgent indication (yes/no)	0 vs 1	NA vs 0.46 [0.28-0.78]	NA	NA
Pediatric (yes/no)	1 vs 0	0.46 [0.28-0.78] vs NA	NA	NA
ACR		1.23 [0.93-1.62]	0.15	0
Rituximab for ABO-I LT (yes/no)	5 vs 5	0.86 [0.57-1.30] vs 1.61 [1.01-2.58]	0.048	0 vs 0
Living donor (yes/no)	4 vs 9	0.87 [0.58-1.32] vs 1.69 [1.14-2.50]	0.02	0 vs 0
Urgent indication (yes/no)	6 vs 7	1.56 [0.96-2.53] vs 1.08 [0.77-1.53]	0.23	0 vs 22
Pediatric (yes/no)	3 vs 10	1.64 [0.82-3.29] vs 1.16 [0.85-1.57]	0.37	0 vs 0
CR		2.28 [1.00-5.22]	0.05	42
Rituximab for ABO-I LT (yes/no)	2 vs 2	6.45 [0.13-333.04] vs 2.64 [0.83-8.44]	0.67	80 vs 0
Living donor (yes/no)	2 vs 2	6.45 [0.13-333.04] vs 2.64 [0.83-8.44]	0.67	80 vs 0
Urgent indication (yes/no)	2 vs 2	2.64 [0.83-8.44] vs 6.45 [0.13-333.04]	0.67	0 vs 80
Pediatric (yes/no)	0 vs 4	NA vs 2.28 [1.00-5.22]	NA	NA vs 42
AMR		74.21 [16.32-337.45]	< 0.001	12
Rituximab for ABO-I LT (yes/no)	2 vs 1	48.32 [ 2.31-1011.61] vs 245.87 [13.04-4636.62]	0.45	53 vs NA
Living donor (yes/no)	1 vs 3	208.48 [12.49-3479.38] vs 35.81 [6.02-212.88]	0.3	NA vs 18
Urgent indication (yes/no)	3 vs 1	35.81 [ 6.02-212.88] vs 208.48 [12.49-3479.38]	0.3	18 vs NA
Pediatric (yes/no)	0 vs 4	NA vs 74.21 [16.32-337.45]	NA	NA vs 12
Bacterial infection		0.72 [0.46-1.14]	0.16	0
Rituximab for ABO-I LT (yes/no)	4 vs 0	0.72 [0.46-1.14] vs NA	NA	0 vs NA
Living donor (yes/no)	3 vs 1	0.70 [0.42-1.15] vs 0.84 [0.29-2.45]	0.75	0 vs NA
Urgent indication (yes/no)	1 vs 3	0.84 [0.29-2.45] vs 0.70 [0.42-1.15]	0.75	NA vs 0
Pediatric (yes/no)	0 vs 4	NA vs 0.72 [0.46-1.14]	NA	NA vs 0
Fungal infection		0.66 [0.37-1.18]	0.16	0
Rituximab for ABO-I LT (yes/no)	3 vs 0	0.78 [0.42-1.44] vs NA	NA	0 vs NA
Living donor (yes/no)	2 vs 2	0.65 [0.31-1.33] vs 0.63 [0.09-4.40]	0.99	0 vs 62
Urgent indication (yes/no)	2 vs 2	0.63 [0.09-4.40] vs 0.65 [0.31-1.33]	0.99	62 vs 0
Pediatric (yes/no)	0 vs 4	NA vs 0.71 [0.39-1.28]	NA	NA vs 0
CMV infection		2.64 [1.63-4.29]	< 0.001	43
Rituximab for ABO-I LT (yes/no)	3 vs 0	2.2 [1.23-3.93] vs NA	NA	4 vs NA
Living donor (yes/no)	3 vs 2	2.25 [1.24-4.09] vs 6.43 [0.17-242.88]	0.58	4 vs 82
Urgent indication (yes/no)	1 vs 4	1.45 [0.45-4.74] vs 2.77 [1.12-6.86]	0.4	NA vs 53
Pediatric (yes/no)	0 vs 5	NA vs 2.64 [1.63-4.29]	NA	NA vs 43
Overall Biliary complication		1.75 [0.89-3.43]	0.1	54
Rituximab for ABO-I LT (yes/no)	3 vs 2	1.38 [0.62-3.07] vs 1.25 [0.35-4.51]	0.89	51 vs 0
Living donor (yes/no)	3 vs 5	1.52 [0.74-3.10] vs 2.36 [0.63-8.87]	0.57	46 vs 66
Urgent indication (yes/no)	2 vs 6	1.23 [0.48-3.21] vs 2.08 [0.85-5.07]	0.44	0 vs 66
Pediatric (yes/no)	2 vs 6	1.25 [0.35-4.51] vs 1.95 [0.85-4.46]	0.57	0 vs 67
Bile leak		1.85 [0.46-7.39]	0.39	53
Rituximab for ABO-I LT (yes/no)	2 vs 0	0.96 [0.38-2.46] vs NA	NA	0 vs NA
Living donor (yes/no)	2 vs 1	0.98 [0.38-2.49] vs 10.82 [1.17-100.44]	0.051	0 vs NA
Urgent indication (yes/no)	0 vs 3	NA vs 1.85 [0.46-7.39]	NA	NA vs 53
Pediatric (yes/no)	0 vs 3	NA vs 1.85 [0.46-7.39]	NA	NA vs 53
Biliary stricture		1.37 [0.70-2.70]	0.36	47
Rituximab for ABO-I LT (yes/no)	4 vs 1	1.00 [0.46-2.15] vs 4.32 [1.18-15.81]	0.06	52 vs NA
Living donor (yes/no)	4 vs 2	1.00 [0.46-2.15] vs 4.49 [1.36-14.87]	0.04	52 vs 0
Urgent indication (yes/no)	1 vs 5	4.32 [1.18-15.81] vs 1.44 [1.04-1.99]	0.11	NA vs 42
Pediatric (yes/no)	0 vs 6	NA vs 1.52 [1.11-2.08]	NA	NA vs 47
HV complication		1.60 [0.64-4.00]	0.32	NA
Rituximab for ABO-I LT (yes/no)	1 vs 0	1.60 [0.64-4.00] vs NA	NA	NA
Living donor (yes/no)	1 vs 0	1.60 [0.64-4.00] vs NA	NA	NA
Urgent indication (yes/no)	0 vs 1	NA vs 1.60 [0.64-4.00]	NA	NA
Pediatric (yes/no)	0 vs 1	NA vs 1.60 [0.64-4.00]	NA	NA
PV complication		1.83 [0.70-4.76]	0.22	0
Rituximab for ABO-I LT (yes/no)	3 vs 1	1.19 [0.31-4.65] vs 2.65 [0.29-24.07]	0.55	0 vs NA
Living donor (yes/no)	3 vs 2	1.19 [0.31-4.65] vs 3.27 [0.82-13.07]	0.31	0 vs 0
Urgent indication (yes/no)	2 vs 3	3.27 [0.82-13.07] vs 1.19 [0.31-4.65]	0.31	0 vs 0
Pediatric (yes/no)	0 vs 5	NA vs 1.83 [0.70-4.76]	NA	NA vs 0
HA complication		4.17 [2.26-7.67]	< 0.001	0
Rituximab for ABO-I LT (yes/no)	3 vs 3	2.52 [0.68-9.27] vs 4.43 [0.90-21.87]	0.59	0 vs 53
Living donor (yes/no)	4 vs 5	3.62 [1.20-10.91] vs 4.44 [2.13-9.25]	0.76	0 vs 10
Urgent indication (yes/no)	3 vs 6	5.50 [2.33-13.00] vs 3.30 [1.39-7.83]	0.41	0 vs 0
Pediatric (yes/no)	1 vs 8	0.47 [0.03-8.56] vs 5.26 [2.73-10.14]	0.11	NA vs 0

¹P value for overall effect or test for differences in subgroup analysis;

²Stewart et al[35] reported graft survival rates of pediatric and adults, respectively. ABO-I: ABO-Incompatible; ACR: Acute cellular rejection; AMR: Antibody-mediated rejection; CMV: Cytomegalovirus; CR: Chronic rejection; HA: Hepatic artery; HV: Hepatic vein; LT: Liver transplantation; PV: Portal vein.