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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Liver transplantation in precirrhotic biliary tract disease: Portal hypertension is frequently associated with nodular regenerative hyperplasia and obliterative portal venopathy.

Chronic biliary tract disease is the third most common indication for orthotopic liver transplantation (OLT) in the United States. Most patients undergoing OLT for chronic biliary tract disease have end-stage liver disease associated with cirrhosis, but a minority are transplanted in the precirrhotic stage for indications that can include poor quality of life (eg, intractable pruritus or fatigue), recurrent ascending cholangitis, or cholangiocarcinoma. A smaller subset of these patients suffer from severe noncirrhotic portal hypertension that can be associated with histologic features of nodular regenerative hyperplasia (NRH) and/or obliterative portal venopathy. We reviewed 306 liver explants performed for chronic biliary tract disease at 2 institutions during 1995 to 2003 to identify patients who were transplanted in the precirrhotic stage. The following clinical data were recorded: age, sex, type of biliary tract disease, radiology, clinical symptoms, signs of portal hypertension, pretransplant shunting procedures, time between diagnosis and OLT, and primary indication for OLT. Histopathologic data included: explant weight, gross appearance, fibrosis stage (1 to 4), cholangitis, bile duct dysplasia, malignancy, portal vein thrombi, presence of NRH, and presence of obliterative portal venopathy. Twenty-six of 306 (8.5%) patients underwent OLT in the precirrhotic stage (12 females: 14 males, mean age of 46 y, age range 12 to 68 y). At explant, fibrosis stage ranged from 1 to 2 (portal and periportal fibrosis) to 3 (multiple bridging fibrosis). Underlying biliary tract disease included primary sclerosing cholangitis (18 cases), primary biliary cirrhosis (5 cases), autoimmune cholangitis (2 cases), and secondary sclerosing cholangitis (1 case). Primary indications for OLT were recurrent cholangitis and/or decreased quality of life (11 cases), complications of portal hypertension (6 cases), portal hypertension plus cholangitis/decreased quality of life (5 cases), and malignancy (4 cases). Of the 11 patients with portal hypertension as a major indication for transplant, 2 had undergone transjugular intrahepatic portal-systemic shunting and 3 others had portal vein thrombi. Histopathologically, NRH was prominent in 8 of these 11 patients (73%) and obliterative portal venopathy in 6 (55%). NRH was also present in 4 of the 15 (27%) patients who were transplanted for other indications. These results indicate that precirrhotic portal hypertension is a predominant or major contributing factor to OLT in a significant minority (11 of 306, 3.3%) of patients with chronic biliary tract disease. The occurrence of NRH in some patients transplanted for other indications suggests it is a histologic pattern that can precede the development of clinically significant portal hypertension.[1]


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