A DISTINCTIVE TYPE OF BILIARY CIRRHOSIS OF THE LIVER ASSOCIATED WITH CYSTIC FIBROSIS OF THE PANCREAS
Authors: di Sant'Agnese Paul A. , Blanc William A. 
Published: December 2021

Review of the literature shows that foci of biliary fibrosis and even more extensive cirrhotic changes had occasionally been found at necropsy for many years in the livers of patients with cystic fibrosis of the pancreas. By 1952 it was recognized by Bodian that localized fibrotic lesions are found at necropsy examination in a large proportion of such cases. In this paper it is shown that in patients with cystic fibrosis of the pancreas the initial hepatic lesions may progress to severe and at times fatal clinical manifestations due to a distinctive type of multilobular biliary cirrhosis.
Seven patients are presented, all of whom had cirrhosis of the liver and the symptoms of portal hypertension. Detailed laboratory findings are listed for all seven and the clinical histories are given for five. Five patients had liver biopsy; in four the portal pressure was measured, found to be increased and surgical shunting procedures were performed. Of the seven, three are dead, two of progressive pulmonary disease and one of uncontrollable gastrointestinal bleeding. The absence, or slight degree, of icterus in all patients is stressed and the lack of consistency of the so-called liver function tests is emphasized.
Tests of liver function performed in 25 additional patients with cystic fibrosis of the pancreas, but with no clinical evidence of liver involvement, gave normal results.
The probable evolution of hepatic lesions from the early foci of biliary fibrosis with concretions to the diffuse cirrhotic changes leading to portal hypertension is described, based on a review of all necropsy material of Babies Hospital and of biopsy and necropsy findings in four of the patients listed in this paper. The name multilobular biliary cirrhosis with concretions was given to the advanced hepatic process to emphasize the distinctive character of the cirrhosis in cystic fibrosis of the pancreas. It is emphasized that this is focal in origin and that enough relatively normal hepatic parenchyma remains to account for the normal values of the "liver function" tests, at times even after the condition has become clinically manifest. The histologic appearance suggests that the cycle is initiated by primary mechanical obstruction of bile ductules by what appear to be inspissated secretions; but a trigger mechanism is presumed to account for the spreading of the localized lesions. It is postulated that an added infection (e.g., infectious hepatitis) or nutritional insult may cause adverse response on the part of a liver which may already be basically abnormal.
The sequence of clinical events is related and it is stressed that symptoms appear only when portal hypertension develops, leading to ascites, hypersplenism, or gastrointestinal bleeding. It is possible that symptoms due to failure of liver function may appear subsequently after prolonged survival.
Seven out of 325 patients with cystic fibrosis of the pancreas have progressed to this syndrome. While the total number, therefore, is not large, a survey of the diagnostic files shows that it accounts in this hospital for one-third of pediatric patients with cirrhosis of the liver from all causes and for a much greater proportion of children with portal hypertension secondary to hepatic fibrosis. Operative shunting procedures may be needed, as gastrointestinal bleeding may be the greatest immediate danger to the patient.
It is concluded that another major area, the hepatic, must be added to the ones frequently involved in cystic fibrosis of the pancreas, and that this disease must be included among the important causes of portal hypertension secondary to cirrhosis of the liver in the pediatric age group.