Graft Fibrosis Over 10 to 15 Years in Pediatric Liver Transplant Recipients: Multicenter Study of Paired, Longitudinal Surveillance Biopsies.

Abstract

Previous single-center, cross-sectional studies have reported a steep increase in the prevalence and severity of fibrosis through 10 to 15years after pediatric liver transplantation. We report a multicenter study of paired surveillance biopsies in a contemporary cohort. Children who underwent liver transplant when younger than 6years old and had paired surveillance liver biopsies were enrolled (n=78, 35% girls, median 1.2years old at transplant). A central pathologist graded inflammation, assessed rejection activity index, and staged fibrosis in the portal, sinusoidal, and perivenular compartments, allowing for calculation of the Liver Allograft Fibrosis Score (LAFSc). Analysis of variance tested associations between fibrosis progression and clinical parameters. The first biopsy, at a median 8.2 years (interquartile range, 5.9-11.6 years) after transplantation, showed absent to mild fibrosis (LAFSc 0-2) in 29%, moderate (LAFSc 3-5) in 56%, and severe (LAFSc 6-7) in 14% of patients. The second biopsy, at a median 4.7 years (IQR, 4.3-5.1 years) later, showed fibrosis progression (LAFSc increased by ≥3) in 10 (13%) and regression (LAFSc decreased by ≥3) in 4 (5%) patients. After adjusting for baseline LAFSc, younger age at transplant was the only risk factor for fibrosis progression. Although fibrosis prevalence and severity 6 to 12years after transplant was similar to previous reports, fibrosis trajectory during the next 4 to 5years was stable. Our data may be reassuring for children with consistently normal liver tests. A comprehensive understanding of factors determining allograft health during the very long term is essential to optimizing allograft and patient health.