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

Disclosures

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

In This Article

Abstract and Introduction

Abstract

Objectives: We studied clinicopathologic features of congenital hepatic fibrosis (CHF) that could aid the diagnosis of this relatively rare condition during adulthood.

Methods: Five consecutive adult CHF cases were identified in a single institution.

Results: Clinical manifestations of CHF varied from asymptomatic to requiring liver transplantation. Three of five cases had other disease associations, including Joubert syndrome, Caroli disease, polycystic kidney disease, and congenital anomaly of hepatic vasculature. No unique common radiologic findings were found. Histologically, all cases showed characteristic abnormal interlobular bile ducts embedded in fibrotic portal stroma, with varying degrees of liver fibrosis.

Conclusions: While other disease associations and characteristic liver histomorphology are helpful clues to suspect the diagnosis of CHF in adult patients, other differential diagnoses should be excluded clinically and radiologically. This study highlights the importance of a multidisciplinary diagnostic approach by pathologists, radiologists, and hepatologists for the accurate diagnosis of CHF during adulthood.

Introduction

Congenital hepatic fibrosis (CHF) is a rare condition that can be easily overlooked when evaluating adult patients with liver fibrosis, due to the nonspecific clinical manifestations and failure to include CHF in the differential diagnosis of liver fibrosis for adult patients.

CHF is a rare fibropolycystic disease of the liver with a predominantly autosomal recessive pattern of inheritance. Isolated CHF is rare; it is usually associated with other syndromes. The total prevalence of syndromes that include CHF as a feature is estimated to be 1 in 10,000 to 20,000.[1] Patients with autosomal recessive polycystic kidney disease (ARPKD) are invariably affected by CHF,[2] caused by mutation of the PKHD1 (polycystic kidney and hepatic disease 1) gene that encodes the fibrocystin/polycystin protein—a component of primary cilia.[3] Other "ciliopathies" that have protein defects in primary cilia may be associated with CHF, including Meckel-Gruber syndrome, Joubert syndrome, Bardet-Biedl syndrome, and, rarely, autosomal dominant polycystic kidney disease.[4–10]

Hepatic presentation of CHF was initially reported by Bristowe in 1856.[11] In 1961, the varied clinical findings of CHF were described by Kerr et al,[12] including hepatosplenomegaly, hematemesis, and melena among 13 patients. CHF is usually diagnosed in early infancy or during childhood (median and mean age, 2 and 11.2 years, respectively),[2] with the most common presentations of portal hypertension including splenomegaly and variceal bleeding;[1] however, some of these patients can be asymptomatic for many years, resulting in an unexpected CHF diagnosis in adulthood.[5]

Ductal plate malformation, secondary to abnormal remodeling of the biliary system, appears to be the main mechanism of CHF pathogenesis.[13–16] Ductal plate gives origin to the biliary system, and its defect causes excess of the embryologic bile ducts and abnormalities of portal vein branches.[16] The combined clinical and pathologic characteristics are largely determined by the stage of biliary malformations during fetal development. In typical CHF, the ductal plate defect is at the level of the smaller interlobular bile ducts. In contrast, the larger intrahepatic bile ducts are affected in patients with Caroli disease. Many cases with combined features of Caroli disease and CHF were reported and can be explained by ductal plate malformation affecting different segments of intrahepatic bile ducts. The associations between CHF and related ductal plate malformation entities such as Caroli disease, Von Meyenburg complex (bile duct hamartoma), and choledochal cysts are well established in the literature.[17,18] These can drive heterogeneity in the clinical and pathologic manifestations, rendering difficulties for diagnosis. CHF is most commonly associated with ARPKD, which results in additional clinical ramifications and worse outcome.[4]

When CHF is not manifested/diagnosed during childhood, it often falls to the bottom of the differential list of liver fibrosis when working up cirrhosis in an adult patient, leading to delayed or missed diagnosis. Most of reported English literature had focused on studying CHF in the pediatric population. In this study, we aim to assess the clinical, radiologic, and pathologic features of this rare entity diagnosed in the adult age group.

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