ABSTRACT
BACKGROUND: Cystic fibrosis (CF)-associated liver disease commonly manifests as portal hypertension and its complications. We investigated the proposal that the pathophysiology is of non-cirrhotic rather than cirrhotic portal hypertension. This distinction may have important implications for treatment. METHODS: We compared liver transplant explants from cystic fibrosis patients with explants from patients with classical cholestatic diseases, primary biliary cholangitis and primary sclerosing cholangitis. Presence of cirrhosis, fibrosis, nodular regenerative hyperplasia, biliary and portal venous pathology were recorded. Quantitation of portal venules in representative section was performed. RESULTS: Nine patients with cystic fibrosis liver disease, 7 primary biliary cholangitis (PBC) and 7 primary sclerosing cholangitis (PSC) were evaluated. Cirrhosis was present in 0/9 of CF patients and 11/14 of the PBC and PSC controls (p < 0.01). Nodular regenerative hyperplasia was present in 8/9 of the CF patients but none of the controls (p < 0.01). Portal venule numbers per 15 mm2 section were significantly lower in the CF patients 52 (20-72) compared to the primary biliary cholangitis 78 (47-110) and primary sclerosing cholangitis patients, 79 (41-134) (p < 0.05). Portal sclerotic nodules were found in all the CF patients but in only one of the controls (9/9 vs 1/14 p < 0.01). CONCLUSIONS: This study demonstrates that non-cirrhotic portal hypertension or obliterative portal venopathy is the predominant hepatic pathophysiology in adult CF patients requiring liver transplantation. It suggests that treatments directed at the hepatic portal venous system may be more effective than current treatment directed at the biliary system in cystic fibrosis.
