Biopsy-Proven Intestinal Failure-Associated Liver Disease in Pediatric Short Bowel Syndrome: Histopathological...

Background/Objectives: Intestinal failure-associated liver disease (IFALD), characterized by steatosis and/or cholestasis, may develop in patients receiving long-term parenteral nutrition (PN) for chronic intestinal failure. This study aimed to evaluate the histopathological features and clinical outcomes of IFALD in children with short bowel syndrome (SBS) enrolled in an Intestinal Rehabilitation Program (IRP) between 2015 and 2022. Methods: Data from 72 children with SBS requiring PN were retrospectively reviewed. Liver biopsy specimens were obtained during bowel-lengthening procedures or surgical exploration. Histopathological findings and clinical outcomes were analyzed. Active IFALD (phase 1) (cholestasis/inflammation; see below for full description) is diagnosed when serum direct/conjugated bilirubin is >1.0-2.0 mg/dL and >20% of total serum bilirubin in infants and children who have received PN for at least 14 days, and in whom other causes of cholestasis have been excluded. Liver histology may show cellular and canalicular cholestasis, bile ductular reaction, and portal bile plugs similar to those observed in extrahepatic biliary obstruction, variable portal inflammation, steatosis, and periportal fibrosis of all stages, as well as prominent liver macrophages. Chronic IFALD is the persistent form of intestinal failure-associated liver disease characterized by established hepatic fibrosis and/or cirrhosis resulting from prolonged intestinal failure and parenteral nutrition exposure, with or without persistent biochemical evidence of cholestasis. Results: Sixteen patients underwent diagnostic liver biopsy at a median age of 14 months (range, 3-62 months). Histopathological evaluation demonstrated cholestasis in 13 patients (81.3%) and steatosis in 2 patients (12.5%). Among patients with cholestasis, intracellular and canalicular patterns were observed in 10 (62.5%) and 6 (37.5%) patients, respectively. Fibrosis was identified in 5 patients (31.3%), including stage 1 in 3, stage 2 in 1, and stage 3 (bridging) in 1. Active IFALD and chronic IFALD were detected in 13 and 5 patients, respectively. One patient died due to IFALD-related end-stage liver disease. Conclusions: IFALD remains a significant and potentially fatal complication in children with SBS receiving long-term PN. Histopathological evidence of liver injury may precede biochemical abnormalities, emphasizing the importance of early surveillance, optimization of PN strategies, and timely achievement of enteral autonomy.