Cystic fibrosis-related liver disease in children- A vascular or a biliary disease?
Amit Saha1, Michael Stormon2, Peter Lewindon3
1The Royal Children's Hospital, Melbourne, Australia; St John of God Midland Public Hospital, Perth, Australia; Curtin Medical School, Faculty of Health Sciences, Curtin University, Australia.
Insights
Cystic fibrosis-related liver disease (CFLD) predominantly shows biliary cirrhosis, with non-cirrhotic portal hypertension (NCPH) appearing as focal, possibly early, features. This study analyzed pediatric liver transplant cases to understand CFLD pathophysiology.
Area of Science:
- Pediatric Hepatology
- Gastroenterology
- Transplant Surgery
Background:
- Cystic fibrosis-related liver disease (CFLD) was traditionally attributed to CFTR dysfunction leading to biliary complications and cirrhosis.
- Non-cirrhotic portal hypertension (NCPH) has emerged as a potential alternative mechanism in CFLD pathogenesis.
Purpose of the Study:
- To investigate the histopathological features of CFLD in pediatric liver transplant recipients.
- To evaluate the prevalence and characteristics of NCPH in conjunction with biliary pathology in CFLD.
Main Methods:
- Retrospective analysis of clinical data from 18 pediatric CFLD patients undergoing liver transplant in Australia.
- Independent histopathological review of explanted liver tissues by experienced pathologists.
Main Results:
- The largest pediatric series reported, with a median age of 13 years; all patients exhibited signs of portal hypertension pre-transplant.
- Biliary cholestasis/cirrhosis was the predominant histopathological finding in explanted livers.
- Focal NCPH was observed in 61% of explants, often in less fibrous or macronodular areas.
Conclusions:
- Biliary fibrosis/cirrhosis remains the primary pathology in CFLD.
- NCPH, when present, is typically focal and may represent an early stage of CFLD preceding biliary stasis and cirrhosis.
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.
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