*Purpose: Anti-HLA donor specific antibodies (dnDSA) after liver transplantation (LT) are currently under investigation. Recent studies show an incidence of dnDSA after LT ranging from 10-25%. However, the prevalence of dnDSA in LT recipients with alloimmune injury (ALO) and non-aloimmune liver injury (non-ALO) is unknown.

*Methods: Case-control cross-sectional study to investigate the prevalence of dnDSA in LT recipients with ALO and non-ALO compared to LT recipients without liver injury (control group, CONT). ALO: biopsy-proven T-cell mediated rejection or antibody-mediated rejection lesions, including nodular regenerative hyperplasia. Non-ALO: active liver injury other than ALO. CONTROL: LT recipients with normal liver tests, normal elastography and no rejection within 6 months. Screening Luminex was performed in all patients and Single Antigen Luminex Assay was performed in those with positive screening. Results are expressed as median (IQR).

*Results: The cohort consisted of 83 LT recipients: 20 ALO, 16 non-ALO and 37 CONT. The overall cohort was screened for dnDSA at a median of 30 (300) months after LT (32% < 1year, 43% 1-5 years, 25% > 5 years). The median age was 57 (47) and 29% were female with previous pregnancy in 46%. The pretransplant liver disease was alcohol-related (33%), viral (29%), cholestasic/autoimmune (21%) or other. The immunosupression at DSA assessment was calcineurin inhibitor ± MMF/steroids in 95% of patients and 37% patients had experienced previous episodes of rejection. There were no significant differences regarding age, gender and time since LT between the three groups. ALO patients had previous rejection more frequently than non-ALO and CONT patients (61% vs 45% vs 20%, p=0.11, respectively), higher values of ALT (168 (426) vs 138 (471) vs 23 (20) UI/ml), p= 0.025) and higher liver stiffness [and 8.2 (12) vs 4.9(8) vs 5.5(8) kPa; p=0.010). The prevalence of positive dnDSA class II was 55% vs 20% vs 8% in ALO vs non-ALO vs CONT patients (p= 0.015). All dnDSA in the ALO group targeted the DQ locus. The median MFI tended to be higher in ALO patients [9445 (23026)] compared to non-ALO and CONT patients [6026 (19978) vs 1500 (16840, p=0.067)]. Of note, three patients had nodular regenerative hyperplasia and focal C4d deposition with high titers of dnDSA class II anti-DQ (median MFI 23500). The prevalence of and dnDSA class I was 0% vs 5 vs 6.3% % in ALO vs non-ALO vs CONT. We did not find histological differences between ALO patients with negative vs. positive dnDSA class II.

*Conclusions: High titers of class II dnDSA are common in LT recipients with active alloinmune injury. A larger cohort is needed to further investigate the clinical and histological implications of positive dnDSA in LT recipients with rejection.

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