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


When the diagnosis of CHF is not established during childhood, it can be easily missed or underrecognized in adult patients with cirrhotic or noncirrhotic portal hypertension. This point is exemplified by case 1, in which the correct diagnosis of CHF was finally made when the patient was 36 years old and had been carrying a diagnosis of cirrhosis since childhood. Please note that this case was correctly diagnosed using all the data from before her last reevaluation with confirmatory studies only including pathology review of the outside liver biopsy specimen itself. The failure to correct the diagnosis that did not follow the natural history of cirrhosis presenting in childhood reflects the classic error of logic called "anchoring." Because imaging and laboratory values were attributed to the first, no thought was made to challenge the diagnosis of cirrhosis of unknown etiology. In a relatively rare condition with overlapping features shared with a much more common disease, one must reconsider a diagnosis when the course is unusual.

In the absence of specific clinical or radiologic findings, liver biopsy with characteristic histomorphology of ductal plate malformation remains the most helpful diagnostic tool to suggest the diagnosis of CHF in adult patients. In addition to the bile duct abnormalities, we also observed inconspicuous portal vein branches in most (80%) cases in this study. This is in keeping with prior description[19] and likely associated with the embryologic relation of the portal structures during ductal plate formation. The ductal plate begins to develop between the sixth and seventh weeks of gestation,[8] and the bile ducts originate from the mesenchyme around the portal veins. The portal vein branches are important in determining the three-dimensional domain of the intrahepatic biliary system, and abnormalities are typically seen in conjunction with bile duct anomalies.[16]

While liver biopsy specimens may provide the first clue of CHF in an adult patient, CHF is a clinicopathologic diagnosis. Correlation with clinical and radiologic evaluation is essential to exclude other diseases, especially the ones with bile ductular proliferation on biopsy specimens. Radiologic studies are helpful to exclude other more common biliary tract abnormalities, especially in our targeted adult population, such as bile duct stricture, bile duct dilatation, choledocholithiasis, and primary sclerosing cholangitis. Helpful histologic clues that can pinpoint toward CHF diagnosis include bile duct proliferations with open lumina in fibrotic portal tracts, as opposed to bile ductular proliferations with narrow/occluded lumina commonly seen in other biliary processes, as well as no significant portal inflammation and absence of significant bile duct damage unless associated with ascending cholangitis. Von Meyenberg complex is a histologic mimicker of CHF, especially in a needle biopsy specimen; however, it can be distinguished from CHF when an adequate number (at least 10) of portal tracts are available for evaluation since the pathologic findings in CHF are considerably more diffuse. Knowledge of the clinical history of chronic kidney disease and other ciliopathies, such as Caroli disease, is also a good pointer to possible concomitant CHF.

Unfortunately, there is no specific clinical manifestation for CHF in adult patients. In our cohort of patients, the symptomology of CHF varies dramatically, from minimal to severe, requiring liver transplantation. The most common manifestations were signs and symptoms related to portal hypertension, such as esophageal and paraesophageal varices and splenomegaly. These striking variations in CHF presentation are similar to what have been observed by other CHF studies with adult patients.[7,20] Notably, those with combined ARPKD and CHF (as in case 4) are mostly discovered early during postnatal life due to significant oligohydramnios and enlarged kidneys with related complications such as pulmonary hypoplasia.[21] However, CHF and ARPKD are likely independent disease processes as supported by the absence of a good correlation between the glomerular filtration rate and spleen volume.[4]

Several clinical patterns of CHF have been described: portal hypertensive, cholangitic, mixed, or latent variants.[22] The portal hypertensive pattern of CHF is the most common and can be explained by thick fibrous septa and accompanying abnormalities in the portal veins. All cases except case 2 in our study were of the portal hypertensive type, presenting with esophageal/gastric varices, gastrointestinal bleeding, and hepatic encephalopathy. Recurrent cholangitis as a result of cystic biliary dilatation is relatively common and considered a second most prevalent manifestation, especially in the presence of Caroli disease.[8]

The overall prognosis and clinical outcomes are largely dictated by the stage of hepatic fibrosis and major clinical complications, most notably portal hypertension. There is a low but dreaded risk for hepatobiliary neoplasms (cholangiocarcinoma > hepatocellular carcinoma), especially in patients older than 40 years.[2,7] No hepatobiliary malignancy had been detected in all patients of this study as of the most recent follow-up.

Biochemically, liver enzymes were not significantly elevated in CHF except in cases 1 and 2 (see Table 1). This observation is not surprising since CHF typically lacks significant inflammatory activity and hepatocellular injury. In later stages of the disease, the most common laboratory abnormalities have been reported to be prolonged prothrombin time and thrombocytopenia.[4]