Abstract
Introduction: Acute rejection is one of the most serious complications following liver transplantation. At the same time, elevated liver enzymes raise suspicion of the onset of acute graft rejection. Immunological markers, such as donor-specific antibodies and a panel of reactive antibodies, are key immunological indicators contributing to antibody-mediated graft rejection.
Objective: To evaluate clinical, biochemical, and immunological markers associated with acute liver transplant rejection using modern statistical methods of survival analysis.
Materials and Methods: A retrospective cohort of 50 liver transplant recipients was analyzed. The primary endpoint of the study was clinically diagnosed acute liver transplant rejection during the perioperative period. Time-to-event was calculated in days. Kaplan-Meier survival analysis with the log-rank test was performed for individual markers. Due to the low number of events, multivariate analysis was performed using Cox penalized regression.
Results: There were three cases of acute graft rejection (6%). In exploratory analysis, differences in rejection-free survival were observed for Donor Specific Antibody and Panel Reactivity Antibody positivity (log-rank p ≈ 9.6 × 10⁻⁷), although positive groups were small (n = 2). A higher MELD (Model for End-Stage Liver Disease) score (>22) was associated with an increased risk of failure (log-rank p ≈ 0.035). Cox penalized regression identified MELD, Alkaline Phosphatase, and immunological markers, donor-specific antibody and panel reactive antibody, as exploratory predictors of graft rejection.
Conclusions: Immunological sensitization and initial disease severity may contribute to acute liver transplant rejection. Generally, Cox regression models for survival analysis are useful for small cohorts with rare events.