Identification of liver transplant biopsy phenotypes associated with distinct liver biological markers and allograft survival.

The intricate association between histological lesions and circulating anti-HLA donor-specific antibodies (DSA) in liver transplantation (LT) requires further clarification. We conducted a probabilistic unsupervised approach in a comprehensively well-annotated LT cohort to identify clinically relevant archetypes. We evaluated 490 pairs of LT biopsies with DSA testing from 325 recipients transplanted between 2010-2020 across three French centers, and an external cohort of 202 biopsies from 128 recipients. Unsupervised archetypal analysis integrated all clinico-immuno-histological parameters of each biopsy to identify biopsy archetypes. The median time post-LT was 1.17 years (IQR:0.38-2.38). We identified 7 archetypes distinguished by clinico-immuno-histological parameters: Archetype #1: severe T cell-mediated rejection (TCMR) (15.9%); #2: chronic rejection with ductopenia (1.8%); #3: architectural and microvascular damages (3.5%); #4: (sub)normal (55.9%); #5: mild TCMR (4.9%); #6: acute antibody-mediated rejection (6.5%); #7: chronic rejection with DSA (11.4%). Cell infiltrates varied by archetypes. These archetypes were associated with distinct liver biological markers, and allograft outcomes. These findings remained consistent when stratified on patient's age or indications for LT, with good performance in the external cohort (mean highest probability assignment=0.58, SD±0.17). In conclusion, we have identified clinically meaningful archetypes, providing valuable insights into the intricate DSA-histology association, which may help for standardizing liver-allograft pathology classification.

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Copyright © 2023. Published by Elsevier Inc.