Sirolimus to treat chronic and steroid‐resistant allograft rejection‐related fibrosis in pediatric liver transplantation

This study aimed to report our experience with the use of Sirolimus (SRL) in pediatric liver transplant patients with chronic rejection or steroid‐resistant rejection with hepatic fibrosis, focusing on their histological evolution. All pediatric liver transplant recipients who received off‐label treatment with SRL for chronic ductopenic rejection or cortico‐resistant rejection between July 2003 and July 2022 were included in the study. All nine patients included in the study showed improvement in liver enzymes and cholestasis parameters as soon as 1‐month after post‐SRL introduction. A decrease in fibrosis stage was observed in 7/9 (77.7%) patients at 36 months. All but one patient experienced an improvement in the Rejection Activity Index and ductopenia at 12 months. A single patient had to discontinue SRL treatment owing to nephrotic proteinuria. In conclusion, SRL may be a safe and effective treatment for chronic and steroid‐resistant rejection and may improve allograft rejection‐related fibrosis and ductal damage. What is Known Fibrosis and ductopenia are two of the most common features of chronic steroid‐resistant liver rejection. However, the reversibility of these injuries remains controversial. Sirolimus (SRL) is an immunosuppressant that exerts dual effects on cell growth and angiogenesis. These properties make SRL particularly attractive for the treatment of chronic and steroid‐resistant rejection. What is New In our series, 77.7% of the patients presented fibrosis improvement and 100% improved ductopenia at 1 year after SRL introduction. Four of nine patients presented with normal histology (neither fibrosis nor ductopenia) at 36 months post‐SRL. The histological findings were followed liver stiffness and liver function tests improvement.