Diagnosis of Congenital Hepatic Fibrosis in Adulthood

A Multidisciplinary Approach

Mohammed I. Alsomali, MD; Martha M. Yearsley, MD; Douglas M. Levin, MD; Wei Chen, MD, PhD


Am J Clin Pathol. 2019;153(1):119-125. 

In This Article


Here we describe five cases of CHF diagnosed in adult patients (summarized in Table 1).

Case 1

Our index case is a 36-year-old woman who has carried the diagnosis of "cirrhosis" of unknown etiology since childhood, and she also has a known history of Joubert syndrome and Ehlers-Danlos syndrome. She was referred to gastroenterology and hematology clinics for further evaluation of signs of portal hypertension, including splenomegaly, esophageal varices without bleeding, and thrombocytopenia. The liver biochemical profile revealed elevated alkaline phosphatase (ALK) of 478 U/L (reference range, 38–126 U/L), alanine aminotransferase (ALT) of 112 U/L (reference range, 10–40 U/L), and aspartate aminotransferase (AST) of 140 U/L (reference range, 5–34 U/L). The autoimmune and viral hepatitis serologies were negative. The endoscopic retrograde cholangiopancreatography revealed increased density of the intrahepatic biliary tree and was negative for strictures or abnormality of the extrahepatic biliary system. A pathology review of her liver biopsy specimen performed 5 years ago demonstrated bile duct proliferations accompanied by portal, periportal, and bridging fibrosis, suggestive of CHF. Histologic features of primary biliary cholangitis, sclerosing cholangitis, or significant inflammation were absent.

Case 2

A 56-year-old woman initially sought treatment from the gastroenterology clinic after an incidental finding of abnormal liver tests (AST, 54 U/L; ALT, 86 U/L; ALK, 410 U/L). Total and direct bilirubin levels were within normal limits. The initial manifestations were fatigue and pruritus for a 1-year duration but controlled with bile acid binding agent. Per report only (slides not available for review), liver biopsy specimen at that time demonstrated portal fibrosis and bile duct proliferations suggestive of chronic biliary disease. The clinical concern was primary biliary cholangitis or autoimmune hepatitis, but the autoimmune serologies for antinuclear, antimitochondrial, and anti–smooth muscle antibodies were negative. Magnetic resonance cholangiopancreatography (MRCP), magnetic resonance imaging (MRI), and ultrasound studies of the liver were unremarkable. The subsequent liver biopsy specimen revealed features of CHF and lacked features of primary biliary cholangitis or autoimmune hepatitis. No family history of CHF or related fibrocystic diseases was reported.

Case 3

A 69-year-old man with a history of Caroli disease with liver cirrhosis and polycystic kidney disease sought treatment for altered mental status and fatigue attributed to hepatic encephalopathy and chronic renal insufficiency. He had been evaluated for liver/renal transplantation. A liver biopsy was performed and demonstrated features of CHF with portal and periportal fibrosis. The patient's clinical condition was stable on follow-up visits until he developed bacteremia and Clostridium difficile colitis. Multiple bouts of various infections had been reported. Paraesophageal and perisplenic varices were noted on a computed tomography (CT) imaging study; in addition, dilatations of intrahepatic bile ducts also were observed on ultrasound and MRI studies. However, the liver parenchymal heterogeneity seen on the ultrasound imaging study appeared noncirrhotic by MRI. The patient's hepatic encephalopathy worsened but was controlled by an additional dose of lactulose, and he was discharged in stable condition. He eventually died with comfort care.

Case 4

A 30-year-old man came to our hospital for a liver transplantation evaluation. His prothrombin time (PT) was slightly prolonged (PT, 15.2 seconds; international normalized ratio, 1.2), platelet count was decreased (50,000/μL), and liver biochemistry was unremarkable (AST, 18 U/L; ALT, 33 U/L; ALK, 71 U/L). MRCP revealed a nodular and shrunken liver. Abdominal CT scan demonstrated macronodular "cirrhotic" parenchyma with atrophy of the right lobe, regenerative changes in the left hepatic lobe, and massive splenomegaly of 24.5 cm. CT angiogram demonstrated a patent main portal vein but with changes suggesting prior thrombosis. Upper endoscopy showed large gastric varices suggesting portal hypertension. Transjugular liver biopsy specimen yielded results consistent with CHF with focal portal and periportal fibrosis. Unequivocal evidence of advanced fibrosis was not seen despite the radiologic appearance of cirrhosis. Upon further investigation, the patient had been diagnosed with Caroli disease, CHF, and ARPKD at age 7 years. He underwent combined orthotopic liver and renal transplantation. Comprehensive evaluation of the explanted liver demonstrated findings supportive of the patient's original diagnosis of CHF and only portal/periportal fibrosis with no evidence of advanced fibrosis on gross and microscopic examination. His postoperative course was complicated by moderately acute cellular rejection, recurrent biliary strictures, cholangitis, and bacteremia, for which he was treated and recovered.

Case 5

A 52-year-old man sought treatment for lower gastrointestinal bleeding and ascites, concerning for hepatic cirrhosis. MRI study revealed macronodular liver cirrhosis. A liver biopsy specimen showed features consistent with CHF. Since then, he has had multiple episodes of gastrointestinal bleeding secondary to esophageal varices. His medical history was also significant for monoclonal gammopathy of undetermined significance and chronic kidney disease. His disease course was further complicated by hepatic encephalopathy, significant ascites, and pulmonary hypertension. He underwent combined orthotopic liver and renal transplantation with no significant events postoperatively. The explanted liver demonstrated well-established biliary-type liver cirrhosis and features of CHF. He continues to follow up with the hepatology team with no significant complaints.

Histopathologic Findings

Histologic sections of all cases (features summarized in Table 2) demonstrated bile duct proliferations with open lumina in expanded and fibrotic portal tracts. Some of the bile ducts contained bile plugs. There was no significant bile duct epithelial damage, bile duct loss, portal granuloma, or significant portal inflammation. In 80% (4/5) of the cases, the portal vein branches were inconspicuous due to reduced numbers or hypoplasia. The hepatic artery branches were intact and unremarkable. The hepatic lobules showed no significant pathologic changes. Regarding hepatic fibrosis, cases 2, 3, and 4 showed portal/periportal fibrosis as highlighted by trichrome stain (case 3 shown in Image 1A and Image 1B). The liver biopsy specimen in case 1 demonstrated bridging fibrosis. The liver explant in case 5 revealed established biliary-type cirrhosis Image 1C, Image 1D, Image 1E and Image 1F.

Image 1.

Histomorphology of congenital hepatic fibrosis. A, B, Liver biopsy specimen from a 69-year-old man (case 3) with known history of Caroli disease and polycystic renal disease who initially sought treatment for manifestations of hepatic encephalopathy. H&E-stained section (A, ×100) shows irregular bile duct proliferations and inconspicuous portal vein branches; trichrome stain (B, ×100) showing portal and focal periportal fibrosis. C-F, Liver explant from a 52-year-old man (case 5) who developed manifestations of portal hypertension. H&E-stained section (C, ×40) demonstrates prominent, irregular, and occasionally anastomosing biliary channels and biliary-type cirrhosis confirmed by trichrome stain (D, ×40). E, F, Higher-power view of septal/portal areas featuring prominent and irregular bile ducts with occasional inspissated bile plugs, embedded in fibrotic stroma (E, H&E, ×200; F, trichrome, ×200).