Cystic fibrosis-related liver disease in children- A vascular or a biliary disease?

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.