Hepatic steatosis after pediatric liver transplant

Abstract

Hepatic steatosis develops after liver transplantation (LT) in 30% of adults, and nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in nontransplanted children. However, posttransplant steatosis has been minimally studied in pediatric LT recipients. We explored the prevalence, persistence, and association with chronic liver damage of hepatic steatosis in these children. In this single-center study of pediatric patients transplanted 1988-2015 (n = 318), 31% of those with any posttransplant biopsy (n = 271) had ≥ 1 biopsy with steatosis. Median time from transplant to first biopsy with steatosis was 0.8 months (interquartile range [IQR], 0.3-6.5 months) and to last biopsy with steatosis was 5.5 months (IQR, 1.0-24.5 months); 85% of patients with steatosis also had for-cause biopsies without steatosis. All available for-cause biopsies were re-evaluated (n = 104). Of 9 biopsies that could be interpreted as nonalcoholic steatohepatitis (NASH)/borderline NASH, with steatosis plus inflammation or ballooning, 8 also had features of cholestasis or rejection. Among 70 patients with surveillance biopsies 3.6-20.0 years after transplant, only 1 overweight adolescent had a biopsy with NAFLD (grade 1 steatosis, mild inflammation, no ballooning or fibrosis)-despite a 30% prevalence of overweight/obesity in the cohort and 27% with steatosis on previous for-cause biopsy. Steatosis on preceding for-cause biopsy was not associated with portal (P = 0.49) or perivenular fibrosis (P = 0.85) on surveillance biopsy. Hepatic steatosis commonly develops early after transplant in children and adolescents, but it rarely persists. Biopsies that did have steatosis with NASH characteristics were all for-cause, mostly in patients with NAFLD risk factors and/or confounding causes of liver damage. Prospective studies that follow children into adulthood will be needed to evaluate if and when hepatic steatosis presents a longterm risk for pediatric LT recipients. Liver Transplantation 23 957-967 2017 AASLD.

FIGURE 1

Retrospective analysis of hepatic steatosis in post-transplant liver biopsies of pediatric liver transplant recipients, detailing samples available for evaluation and histologic outcomes for patients in the cohort. Surveillance biopsies are shaded grey; all other biopsies described were for-cause. Characteristics of patients with biopsies that met criteria for NASH are detailed in Table 2. *Eleven biopsies were not available for review, primarily because they had been returned to a referring center. An additional 24 were not assessable due to faded stains. 22 of 24 were performed before 1996.

FIGURE 2

Post-transplant time course of for-cause biopsies with steatosis in pediatric liver transplant recipients. Each horizontal gray line corresponds to one of the 84 patients with any for-cause steatotic biopsy, and each X represents one biopsy with steatosis. Each patient’s biopsies are connected by a black line. The grey dashed vertical line marks 2 months post-transplant; the majority of biopsies with steatosis occurred early after transplant, and few patients had persistent steatosis long-term.