The Role of Humoral Alloreactivity in Liver Transplantation: Lessons Learned and New Perspectives

Table 1

Summary of recent studies of de novo DSA on clinical outcomes ABO-compatible liver transplantation.

Reference	Study design	Sample size	Prevalence of; de novo DSA	Study findings
Kaneku et al. (2013) [13]	Retrospective	749 adult	8.1% at 1 year	(i) Presence of DSA associated with inferior patient and graft survival; (ii) Almost all de novo DSA were against HLA class II antigens (majority DQ); (iii) Risk of de novo DSA formation increased by low calcineurin inhibitor levels and the use of cyclosporine (versus tacrolimus)
Grabhorn et al. (2015) [17]	Retrospective	43 pediatric	33% in stable recipients; 68% in chronic rejectors	(i) Higher rate of de novo DSA among pediatric LT recipients with chronic rejection; (ii) Antibodies predominantly against HLA class II antigens
O’Leary et al. (2015) [15]	Retrospective	749 adult	8% at 1 year	(i) IgG3 subclass DSA-positive patients at highest risk for death; (ii) IgG3-negative, DSA-positive patients still had inferior outcomes compared to DSA-negative patients
Wozniak et al. (2015) [16]	Cross-sectional	50 pediatric	54%	(i) Younger age associated with presence of DSA; (ii) Nontolerant patients more likely to have DQ DSA (61%) compared with stable (20%) and tolerant (29%) patients; (iii) DQ DSA associated with de novo autoimmune hepatitis and late acute rejection
Del Bello et al. (2015) [18]	Prospective	152 adult	14%	(i) Younger age, low exposure to calcineurin inhibitors, and noncompliance were risk factors for de novo DSA emergence; (ii) Nine of 21 (43%) DSA-positive recipients developed acute rejection; (iii) No differences in patient or graft survival with DSA presence
Levitsky et al. (2016) [19]	Retrospective analysis of an observational cohort study	195 adult (129 LDLT,; 66 DDLT)	5.4% in LDLT; 6.1% in DDLT	(i) No differences in the prevalence of de novo DSA between LDLT and DDLT recipients; (ii) Presence of DSA was an independent risk factor for graft failure in LDLT and DDLT

LDLT, living donor liver transplantation; DDLT, deceased donor liver transplantation.