Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

Table 1 Baseline characteristics

	‘DSA-positive’ group 1 (n = 54)	‘DSA-negative’ group 2 (n = 69)
Age
At LT (yr)	3.3 (1 mo-17 yr)	4.0 (1 mo-17.8 yr)
At follow-up (yr)	13.8 (2-23)	12.6 (1-24)
Gender
Female	n = 21	n = 35
Male	n = 33	n = 35
Main diagnosis
Biliary atresia	n = 20	n = 20
Alagille syndrome	n = 1	n = 8
Acute liver failure	n = 6	n = 4
Metabolic disorders1	n = 14	n = 26
Others2	n = 13	n = 11
Donor source
Ldlt	n = 9	n = 11
Ddlt	n = 45	n = 58
Full-graft	n = 8	n = 12
Split size	n = 30	n = 43
Reduced size	n = 7	n = 3
Cold ischemic time (min)	543.3 (122-949)	572.5 (145-943)
Relt	n = 22	n = 14
Graft loss due to
Cr	n = 23	n = 7
Alv	n = 7	n = 3
Thrombosis	n = 3	n = 3
Rond	n = 2	n = 0
Ssc	n = 2	n = 0
Time to DSA-testing
Years after current LT	9.75 (1-19)	7.98 (1-19)
Anti-HLA antibodies	n = 54	n = 32
Previous episodes
Of acute rejection	n = 12	n = 7
Of chronic rejection	n = 10	n = 3

¹Such as carbamoyl phosphate synthetase defects, ornithine transcarbamylase deficiency, primary hyperoxaluria, alpha1-antitrypsin-deficiency, glycogen storage disease, maple syrup urine disease, citrullinemia, Wilson disease, others.

²Such as idiopathic cirrhosis, autosomal recessive polycystic kidney disease, Crijgler-Najar syndrome, progressive familiar intrahepatic cholestasis, malignancies, vascular dysfunction, neonatal hepatitis, primary sclerosing cholangitis, autoimmune hepatitis.

LDLT: Living donor liver transplantation; DDLT: Dead donor liver transplantation; relt: Retransplantation; HLA: Human leucocyte antigen; DSA: Donor-specific antibodies; CR: Chronic rejection; ALV: Acute liver failure; ROND: Recurrence of native disease; SSC: Secondary sclerosing cholangitis.

Table 2 Biopsy characteristics

	Group 1: ‘DSA-positive’ (n = 38)	Group 2: ‘DSA-negative’ (n = 34)	P value
Fibrosis1	n = 24	n = 6
Low-grade	n = 23	n = 6	< 0.001
High-grade	n = 1	n = 0	0.5
Cirrhosis	n = 3	n = 0	0.5
Steatosis	n = 6	n = 6	0.8
Portal inflammation	n = 28	n = 18	0.005
Perivenular/perisinusoidal inflammation	n = 11	n = 2	0.011
Ductular inflammation	n = 13	n = 3	0.004
Endothelitis	n = 6	n = 2	0.1
Biliary lesions/ductulopenia	n = 6	n = 0	0.009
Ductular cholestasis	n = 12	n = 4	0.01
Biliary tract strictures	n = 9	n = 6	0.03
Single cell necrosis	n = 5	n = 0	0.02
Chronic rejection2	n = 7	n = 0	0.009
Possible camr3	n = 9	n = 0	0.002

¹Fibrosis grading according to Desmet et al.

²Chronic rejection according to Banff criteria.

³Chronic antibody-mediated rejection (camr) according to Banff 2016 criteria, with absent C4d staining.

DSA: Donor-specific antibodies.

Table 3 Immunosuppressive therapy

Group 1 ‘DSA-positive’		Group 2 ‘DSA-negative’
Monotherapy	n = 29	n = 39
CSA	n = 17	n = 20
Trough level	109.5 µg/L (23-674 µg/L) median 73 µg/L	58.0 µg/L (29-106 µg/L)
TAC	n = 10	n = 17
Trough level	4.4µg/L (1.0-7.3 µg/L)	5.5 µg/L (2.6-7.7 µg/L)
EVE		n = 1
Trough level		10.3 µg/L
SIR	n = 1
Trough level	5.2 µg/L
MMF	n = 1	n = 1
Combined therapy	n = 25	n = 30
CSA
+ EVE	n = 3	n = 4
+ MMF	n = 3	n = 3
+ PRED	n = 2	n = 1
+ EVE + PRED		n = 1
+ MMF + PRED	n = 2
Trough level	54.7µg/L (11-89 µg/L)	72.7 µg/L (23-137 µg/L)
TAC
+ EVE	n = 3	n = 6
+ MMF	n = 5	n = 7
+ PRED	n = 5	n = 3
+ MMF + PRED	n = 1	n = 3
Trough level	6.1 µg/L (3.0-9.9 µg/L)	6.3 µg/L (2.1-15.1 µg/L)
EVE
+ MMF		n = 1
+ MMF + PRED	n = 1
Trough level	3.7 µg/L (1.0-5.0 µg/L)	4.3 µg/L (1.8-7.8 µg/L)
SIR
+ MMF		n = 1 (trough levels, NA)
Adherence rates
CSA	81.5%	72.4%
TAC	87.5%	88.9%
EVE	75%	84.9%
SIR	100%	100%

Trough levels given as mean (and range). MMF: Mycophenolate mofetil; CSA: Cyclosporin A; TAC: Tacrolimus; EVE: Everolimus; PRED: Prednisolone; SIR: Sirolimus; NA: Not available; DSA: Donor-specific antibodies.