RESUMEN
The intricate association between histologic lesions and circulating antihuman leucocyte antigen 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 and 2020 across 3 French centers and an external cohort of 202 biopsies from 128 recipients. Unsupervised archetypal analysis integrated all clinico-immuno-histologic parameters of each biopsy to identify biopsy archetypes. The median time after LT was 1.17 (interquartile range, 0.38-2.38) years. We identified 7 archetypes distinguished by clinico-immuno-histologic parameters: archetype #1: severe T cell-mediated rejection (15.9%); #2: chronic rejection with ductopenia (1.8%); #3: architectural and microvascular damages (3.5%); #4: (sub)normal (55.9%); #5: mild T cell-mediated rejection (4.9%); #6: acute antibody-mediated rejection (6.5%); and #7: chronic rejection with DSA (11.4%). Cell infiltrates vary in the archetype. These archetypes were associated with distinct liver biological markers and allograft outcomes. These findings remained consistent when stratified using the patient's age or indications for LT, with good performance in the external cohort (mean highest probability assignment = 0.58, standard deviation ± 0.17). In conclusion, we have identified clinically meaningful archetypes, providing valuable insights into the intricate DSA-histology association, which may help standardize liver allograft pathology classification.
Asunto(s)
Biomarcadores , Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Rechazo de Injerto/patología , Rechazo de Injerto/etiología , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Masculino , Femenino , Persona de Mediana Edad , Supervivencia de Injerto/inmunología , Estudios de Seguimiento , Biopsia , Biomarcadores/análisis , Biomarcadores/metabolismo , Pronóstico , Isoanticuerpos/inmunología , Isoanticuerpos/sangre , Fenotipo , Donantes de Tejidos , Factores de Riesgo , Adulto , Antígenos HLA/inmunología , Aloinjertos , Estudios RetrospectivosRESUMEN
The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.
Asunto(s)
Rechazo de Injerto , Trasplante de Hígado , Humanos , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Supervivencia de Injerto , AloinjertosRESUMEN
En contraste con el adenocarcinoma primario biliar o colangiocarcinoma, otros tumores derivados de la vía biliar son difíciles de diagnosticar preoperatoriamente, debido principalmente a su baja incidencia y el difícil proceso diagnóstico que requieren. Sin embargo, dado que los colangiocarcinomas suponen alrededor del 80% de todas las neoplasias biliares primarias, cuando se trata de un paciente con un tumor biliar con características anormales, es importante pensar en otras opciones, a pesar de su baja frecuencia. En este trabajo presentamos un caso clínico de un tumor neuroendocrino primario de la vía biliar, y una revisión de la literatura acerca de esta rara enfermedad (AU)
In contrast to the primary biliary carcinoma or cholangiocarcinoma, other tumors derived from the bile duct are difficult to diagnose preoperatively, mainly because of its low incidence and difficult diagnostic process. However, since cholangiocarcinomas account for about 80% of all primary biliary tumors, it is important to think about other options despite their low frequency when a patient presents with abnormal characteristics. We present a case of a primary neuroendocrine tumor of the bile duct, and a review of the literature on this rare disease (AU)