Pediatric liver transplantation (pLT) relies on immunosuppression, yet maintaining the right balance remains a major challenge. Excessive suppression increases susceptibility to infections, while insufficient control favors rejection. Moreover, immune-mediated disorders can disrupt the balance of immune homeostasis, adding complexity to post-transplant immune management.
The aim of this Privat-Docent thesis is to explore the mechanisms underlying immune tolerance, to present my work on key aspects of this delicate balance in pLT, and outline future perspectives in the field.
Beyond pharmacological immunosuppression, two major concepts shape immunity in pLT: the immaturity of the child’s immune system and the liver’s role as an immune organ. Rejection is further influenced by donor-specific antibodies, nutritional status, and graft characteristics. For example, one of the included publications demonstrated an association between rejection and vitamin D deficiency. Over-immunosuppression and the consequent risk of infection remain major concerns in solid organ transplantation, leading to substantial morbidity and mortality. Two of the presented publications focus on infections after pLT. Within the Swiss Transplant Cohort Study (STCS), we analyzed pediatric patients and highlighted the significant burden of infections during the first post-transplant year, with differences according to time, age, and organ type. Another study examined infections following post-transplant cholangiography in pLT. Infection can also trigger immunological dysregulation such as PTLD. In this thesis, we present our PTLD cohort together with a diagnostic and management algorithm based on local experience. Finally, immune-mediated disorders may arise from either under- or over-immunosuppression; our work on hemolytic anemia illustrates such rare complications after pLT.
This Privat-Docent thesis highlights the multifaceted nature of immune imbalance in pLT. Understanding the interplay between immunosuppression, infection, rejection, and immune-mediated disorders is key to improving outcomes and guiding personalized strategies.
