Liver transplantation (LT) is the definitive treatment for end-stage liver disease. It significantly enhances patient survival and quality of life. However long-term graft survival remains a challenge. Key factors influencing these outcomes include human leukocyte antigen (HLA) mismatches and the presence of donor-specific anti-HLA antibodies (DSA). The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) score is novel computational tool that predicts indirectly recognizable HLA-derived donor peptides presented by recipient HLA It potentially impacts the graft's immune recognition. This score has shown utility in predicting outcomes in kidney and lung transplants. Its role in liver transplantation remains unexplored.
This study aims to investigate the relationship between PIRCHE-II scores and clinical outcomes such as patient and graft survival. It also examines the incidence of rejection episodes and post- transplant complications within the Swiss Transplant Cohort Study (STCS).
We conducted retrospective analysis of 331 liver transplants from the STCS. This included those who underwent transplantation between January 2014 and December 2016 from whom we had a complete HLA typing data. PIRCHE-II scores were calculated for each donor-recipient pair. This was done using standardized algorithm. Clinical outcomes assessed included patient survival at 1- and 5-years post-transplantation. We also assessed graft survival at the same intervals. Occurrence of acute and chronic rejection episodes was documented as well as the incidence of post-transplant complication such as vascular, biliary and infectious issues. Statistical analyses involved univariate and multivariate Cox regression models. We also used competing risk analysis to account for potential confounders.
Of the 331 liver transplants analyzed 245 cases had complete HLA typing data necessary for calculating PIRCHE-II scores. The mean PIRCHE-II score in this cohort was 92.8 ± 41.9. Analysis revealed no significant association between PIRCHE-II scores and any of the outcomes. Patient or graft survival at 1-year and 5-year follow-ups were unaffected. Furthermore, no significant correlation was observed between PIRCHE-II scores and the frequency of rejection episodes. Also, the incidence of post-transplant complications, including vascular, biliary and infectious complications was not significant.
The PIRCHE-II score did not demonstrate predictive value for key clinical outcomes such as patient and graft survival, rejection episodes or post-transplant complications in liver transplant recipients within the STCS cohort. These findings suggest that while the PIRCHE-II score effectively reflects the degree of HLA mismatch, it may not serve as standalone predictor for clinical outcomes in liver transplantation.
This study highlights limitations of relying solely on computational matching algorithms. The results demonstrate the necessity for comprehensive multifactorial approaches to improve long- term graft and patient survival in liver transplantation. Although the PIRCHE-II score offers valuable insights into HLA mismatches, its application in clinical practice requires further validation and integration with other predictive factors.