Ascites and variceal bleeding occurring in a 20-year-old with cystic fibrosis
Authors: Isabel M. Fiel, Thomas Schiano
Journal: Hepatology (2009)

A 20-year-old woman was first diagnosed with cystic fibrosis (CF) at age 12 during a workup for frequent pneumonias. Bronchiectasis was eventually diagnosed, as was exocrine pancreatic insufficiency. The patient was known to have hepatosplenomegaly with intermittent mild elevations in alanine aminotransferase (ALT) and alkaline phosphatase. Over the last 3 years, the alkaline phosphatase level was elevated to 200-260 IU/mL and the ALT and aspartate aminotransferase levels were elevated to 55-65 IU/mL. The serum albumin was 2.1 mg/dL, bilirubin was 2.0 mg/dL, and international normalized ratio was 1.4 with a platelet count of 106,000. She suffered three episodes of esophageal bleeding that were treated endoscopically and with beta-blockade. Appreciable muscle wasting developed as well as ascites refractory to diuretics and paracentesis. She successfully underwent live donor liver transplantation. ALT, alanine aminotransferase; CF, cystic fibrosis. Figure 1 is a section of the native liver showing irregular yellow-tan nodules of different sizes forming map-like areas with intervening deep clefts of fibrosis. Within these clefts are entrapped small hepatic lobules (arrows). The cut surface has a glistening mucoid appearance. Also present is a large bile duct filled with mucinous material. In Figure 2, there is inspissated bile-tinged mucus within dilated bile ductules. The two portal areas depicted (arrows) are densely fibrotic (focal biliary fibrosis) with minimal inflammation (original magnification, 40×). Figure 3 is from another portal tract with adjacent parenchyma showing steatosis (original magnification, 100×). Figure 4 demonstrates delicate acellular fibrous septa (arrows) bridging two portal tracts, as well as a patchy distribution of steatosis. Note the absence of inspissated mucus in this section (original magnification, 100×). All of the above features are typical of CF liver disease. Liver disease in patients with CF can often be subclinical but may be complicated by portal hypertension and malnutrition in the setting of minimal liver chemistry test abnormalities and in the absence of appreciable hepatic synthetic compromise.1 Typical histological changes include steatosis, periportal fibrosis with dilated bile ductules, inspissated mucoid secretions, focal biliary fibrosis, and multinodular biliary cirrhosis. These changes are unevenly distributed, and so not all may be present in a needle liver biopsy. Focal biliary lesions may coalesce with extension of fibrosis, atrophy of intervening parenchyma, and entrapment of groups of hepatic lobules. Grossly, large irregular nodules are seen with deep intervening clefts.2 Ultrastructural cholangiocyte abnormalities have been demonstrated in patients with CF suggesting that injury to bile duct cells may represent a primary event in the pathogenesis of CF liver disease and may represent long-standing impairment in ductular bile flow.2, 3 Macrovesicular steatosis is commonly found, located most frequently in periportal hepatocytes, but is unevenly distributed throughout the lobule. The inspissated secretions in bile ductules stain intensely with periodic acid-Schiff stain. Periportal fibrosis may occur even in the absence of bile ductular proliferation and inspissation of secretions. Rarely, cholangiographic and liver biopsy findings in CF may resemble those of sclerosing cholangitis.2, 4 Therefore, CF should be included in the differential diagnosis of young patients having histologic evidence of fatty liver and/or chronic biliary tract disease.