Title: Cystic fibrosis-related liver disease in children – A vascular or a biliary disease?
Source: Journal of Cystic Fibrosis 2025, Sep 28. [E–publication]
Date of publication: September 2025
Publication type: Article
Abstract: Background: Cystic fibrosis-related liver disease(CFLD) has long been thought to be secondary to CFTR dysfunction in the biliary epithelial cells causing hepatobiliary complications, eventually progressing to cirrhosis. However, in more recent studies, non-cirrhotic portal hypertension(NCPH) has been postulated as a possible alternative mechanism contributing to CFLD.
Methods: We collected clinical information pertaining to the status of their liver disease from children with CFLD who underwent liver transplant at the 3 paediatric liver transplant centres in Australia- Melbourne, Sydney and Brisbane. Explant histopathology slides were independently reviewed by 2 experienced pathologists based at two different anatomical pathology centres.
Results: Data was collected from 18 children (including 10 females, median age 13 years) making this the largest paediatric series reported. Pre-transplant, all had evidence of portal hypertension with splenomegaly and thrombocytopenia. Median bilirubin, ALT, ALP, GGT levels and PELD/MELD, aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores were recorded to ascertain pre-transplant status. All explanted livers had evidence of variable degree of biliary cholestasis/cirrhosis as the predominant histopathological feature, whereas 11 out of the 18 explants (61%) also had patchy/focal areas of NCPH, mostly within the less fibrous or macro nodular areas.
Conclusions: Data from this series reinstates the longstanding observation that focal biliary fibrosis/biliary cirrhosis seems to be the predominant pathophysiology in this condition, and NCPH, if present, is mostly focal, representing overlap features in a percentage of these patients. As such, NCPH may represent an early feature in CFLD before progressing to biliary stasis and cirrhosis.
