Evaluating the role and effectiveness of protocol liver biopsies in pediatric post-transplant care: a systematic review

INTRODUCTION: Pediatric liver transplantation has improved long-term survival, but optimal surveillance strategies for late graft injury remain uncertain. This systematic review evaluated the utility of protocol liver biopsies for detecting subclinical histopathological abnormalities after pediatric liver transplantation, particularly fibrosis, inflammation, steatosis, and rejection. METHODS: We conducted a PRISMA-compliant systematic review of PubMed and ScienceDirect, with supplementary hand-searching of references and trial registries. Eligible studies included English-language primary studies of pediatric liver transplant recipients undergoing surveillance liver biopsy. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Newcastle-Ottawa Scale. RESULTS: Fifteen studies comprising 2004 pediatric liver transplant recipients were included. Protocol biopsies frequently identified histological abnormalities despite minimal or absent clinical symptoms. Fibrosis was common and appeared to increase over time, with crude estimates suggesting any fibrosis in approximately 66.2% of patients at 1 year and 81.6% at 15 years post-transplant. Inflammation was also prevalent but tended to decline over time. Several factors were inconsistently associated with fibrosis and inflammation, including donor gender, graft type, immunosuppression regimen, donor-specific antibodies, and surgical complications. In comparative data, protocol biopsies detected more subclinical rejection than for-cause biopsies in stable recipients. CONCLUSIONS: In selected cases, repeat protocol or targeted follow-up biopsies after treatment modification may help determine whether inflammation or fibrosis is stabilizing, improving, or progressing. Protocol liver biopsies are a valuable surveillance tool in pediatric liver transplant follow-up, enabling early detection of clinically silent graft pathology and potentially informing timely immunosuppression adjustment.