Liver & intrahepatic bile ducts

Developmental anomalies / cysts

Congenital hepatic fibrosis

Editorial Board Member: Monika Vyas, M.D.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Irene Y. Chen, M.D.
Xiaoyan Liao, M.D., Ph.D.

Last author update: 6 August 2021
Last staff update: 9 August 2021

Copyright: 2002-2024,, Inc.

PubMed Search: Congenital hepatic fibrosis[TI] free full text[sb]

Irene Y. Chen, M.D.
Xiaoyan Liao, M.D., Ph.D.
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Cite this page: Chen IY, Liao X. Congenital hepatic fibrosis. website. Accessed July 13th, 2024.
Definition / general
Essential features
  • Commonly presents with portal hypertension and hepatosplenomegaly in children or young adults
  • Classic histological triad with evolution
    • Abnormal bile duct profile
      • Small bile ductal structures lining at the limiting plate or embedded at the center of the portal tracts
      • Bile ducts are often dilated, ectatic or have entrapped fibrous stroma
      • May or may not contain inspissated bile in the lumen
    • Hypoplastic portal vein radicles and prominent portal arteries
    • Expansile portal fibrosis progresses to bridging with broad septa separating hepatocytes into islands but lacking the nodular regeneration of hepatocytes seen in cirrhosis
  • Ductal plate malformation, fibrocystic liver disease
ICD coding
  • ICD-10: Q44.7 - other congenital malformations of liver
  • ICD-11: LB20.0 - structural developmental anomalies of liver
  • Primary location: liver
  • Organs involved in syndromic manifestation: kidney, pancreas, lungs and brain (J Med Genet 2003;40:311)
  • Normal bile duct morphogenesis is a timely regulated process (see Diagrams / tables) (J Med Genet 2003;40:311, Mech Dev 2003;120:81)
    • Embryonic day 13.5 - 14.5: precursor cells express biliary specific cytokeratins and migrate closer to the portal mesenchyme
    • Embryonic day 15.5: portal vein and the surrounding mesenchyme induce the precursor cells to form a continuous ring called ductal plate
    • Embryonic day 16.5: ductal plate becomes partially bilayered
    • Embryonic day 17.5: focal dilation between the 2 layers leads to bile duct formation starting from the hilum to the periphery, followed by progressive regression of the remaining ductal plate
  • Hereditary / sporadic genetic mutations lead to imbalanced proliferation and apoptosis during ductal plate remodeling, resulting in persistence of embryonic duct profile in ductal plate configuration (J Med Genet 2003;40:311, Hepatology 1992;16:1069, Clin Res Hepatol Gastroenterol 2014;38:407)
  • Postnatal pathologic changes
    • Variable fibrosis as a consequence of ductal plate malformation or stimulation of the matrix forming cells (Clin Res Hepatol Gastroenterol 2014;38:407)
    • Generally, minimal inflammation except when complicated by cholangitis
    • Recurrent cholangitis can lead to progressive fibrosis with functional impairment similar to cirrhosis
Diagrams / tables

Contributed by Xiaoyan Liao, M.D., Ph.D.
Embryogenesis of intrahepatic bile duct

Embryogenesis of intrahepatic bile duct

Clinical features
  • Wide range of presentations, depending on age of disease onset and concomitant kidney involvement (J Pak Med Assoc 2016;66:984, Am J Clin Pathol 2020;153:119)
    • In children or young adults with early disease onset, disease is progressive and may require liver or kidney transplant
      • Portal hypertension and related symptoms
      • Hepatosplenomegaly
      • Recurrent cholangitis if presents as Caroli syndrome (Cureus 2020;12:e11029)
      • Portopulmonary hypertension
      • Hepatocellular carcinoma or cholangiocarcinoma, though rare, can be present
    • May spontaneously regress or "burn out" in some patients
    • Adults may be asymptomatic or with only mild disease
  • Clinical suspicion of concurrent portal hypertension and chronic kidney disease in teenager or young adult
  • Imaging: integrated use of ultrasound and abdominal MRI at baseline and follow ups; CT may be helpful (Pediatr Radiol 2009;39:100)
  • Diagnostic liver biopsy showing classic histology
Radiology description
  • Ultrasound (Pediatr Radiol 2009;39:100)
    • Diffusely increased and coarsened liver echogenicity, splenomegaly and intra and extrahepatic biliary cysts / dilatations
    • Periportal thickening
    • Macroscopic cystic or fusiform dilatations of the intra and extrahepatic bile ducts
  • Magnetic resonance imaging (MRI) (Pediatr Radiol 2009;39:100)
    • Enlarged, nodular and misshapen liver with disproportionately hypertrophic left and caudate lobes
    • Cystic dilatation of intrahepatic bile ducts; periportal hepatic fibrosis
Radiology images

Contributed by Irene Y. Chen, M.D.
Intrahepatic biliary cysts

Intrahepatic biliary cysts

MR abdomen in a patient with Caroli syndrome MR abdomen in a patient with Caroli syndrome MR abdomen in a patient with Caroli syndrome

MR abdomen in a patient with Caroli syndrome

Prognostic factors
Case reports
  • Manage complications related to portal hypertension (J Pak Med Assoc 2016;66:984)
    • Varices: medical management followed by sclerotherapy or band ligation
    • Transjugular intrahepatic portosystemic shunts
  • Antibiotics for cholangitis
  • Liver transplant is the only curative treatment
Gross description
  • Enlarged and firm liver with variable nodularity
  • Cyst formation and duct dilatation is more common in Caroli syndrome
Microscopic (histologic) description
  • Classic histological triad
    • Abnormal bile duct profile
      • Small ductal structure at the periphery of the fibrous septa
      • May or may not contain inspissated bile in the lumen
    • Hypoplastic portal vein branches
    • Progressive fibrosis: bridging fibrosis with broad septa separating hepatocytes into islands
      • Lack of nodular regenerative hepatocytes
  • Evolution of the lesion as patients age
    • Infant: circumferential arrangement of ectatic and anastamosing ductal structures surrounding the hypoplastic portal veins
    • Ductal structures decrease in size and number with increased fibrosis
    • Fully evolved lesion is described in classic histological triad
Microscopic (histologic) images

Contributed by Xiaoyan Liao, M.D., Ph.D.
Abnormal duct profile

Abnormal duct profile

Aberrant bile duct profile

Aberrant bile duct profile

Congenital hepatic fibrosis

Congenital hepatic fibrosis

Fibrosis Fibrosis


Positive stains
  • Trichrome: highlights fibrosis and fibrous septa
  • CK7 and CK19: stain ductal plate cells
Negative stains
  • Iron: lack of intracytoplasmic iron deposition
  • PAS / PASD: lack of intracytoplasmic inclusions
  • Reticulin: lack of regenerative nodules
Molecular / cytogenetics description
Sample pathology report
  • Liver, biopsy:
    • Ductal plate malformation consistent with congenital hepatic fibrosis (see comment)
    • Comment: The biopsy is adequate for evaluation. Portal tracts diffusely demonstrate ductal plate malformations consisting of bile duct structures with irregular contours and regions of mild dilatation. Portal tracts / fibrous septa are without significant inflammation, interface activity or portal edema. Inspissated bile is noted in small ductal structures at the interface of fibrous septa and hepatic parenchyma. No lobular inflammation or steatosis is noted. Portal expansion by fibrosis is highlighted on trichrome stain. There is no evidence of cirrhosis. Iron and PASD stains show no additional pathologic findings.
    • Overall, the histology of this biopsy demonstrates diffuse ductal plate malformation, consistent with congenital hepatic fibrosis (fibrous bands account for 50% of the biopsy volume). Ductal plate malformation disease in the liver is often associated with polycystic renal disease or other cystic abnormalities of tubules. In the present case, the overall features are those of congenital hepatic fibrosis but there may be overlap with other fibropolycystic conditions such as Caroli syndrome. A clinical evaluation to assess the presence or absence of portal hypertension in the setting of these liver biopsy changes warrants consideration.
Differential diagnosis
  • Von Meyenburg complex:
    • Also known as biliary duct hamartoma or bile duct microhamartoma
    • Incidental small nodular lesion consists of mildly dilated ductal structures lined by flat epithelium in hyalinized stroma
    • Typically small and may present as multiple lesions
  • Autosomal dominant polycystic liver disease:
    • Often becomes symptomatic in adulthood because liver cysts increase in number and size with age
    • Mutations in hepatocystin (PRKCSH) on chromosome 19
    • Mutations in SEC63 protein (SEC63) on chromosome 6
    • Mutations in low density lipoprotein receptor related protein 5 (LRP5) on chromosome 11
  • Solitary bile duct cyst:
    • Incidental solitary unilocular cyst containing clear fluid
    • Simple cuboidal / columnar epithelium with bland fibrovascular stroma
    • No portal hypertension
  • Choledochal cysts:
    • Triad of abdominal mass, colicky pain and jaundice
    • May present with cirrhosis and portal hypertension due to secondary biliary cirrhosis
    • May be associated with colonic or duodenal atresia, anomalies of pancreas or congenital heart defects
    • Thick wall cyst with variable inflammation and fibrosis
    • Epithelium is usually denuded but can demonstrate metaplastic changes
  • Cirrhosis:
    • Diffuse nodular regeneration of hepatocyte and remodeling of hepatic architecture
    • May show prominent bile ductular proliferation
    • Varying degree of inflammation
    • Compromised liver function
    • No association with polycystic kidney disease
  • Hepatoportal sclerosis (Hepat Med 2016;8:81):
    • Under the term idiopathic noncirrhotic portal hypertension
    • Multifactorial (infection, autoimmune, etc.)
    • In young patient with portal hypertension and concurrent kidney disease, clinically mimics congenital hepatic fibrosis
    • Portal fibrosis and portal vein with medial hypertrophy and venular dilatation
    • Liver biopsy may show nodular regenerative hyperplasia and focal bile duct abnormality
  • Recurrent pyogenic cholangitis:
    • Associated with liver flukes or bile duct stones
    • Dilation and fibrosis of bile ducts with acute inflammation and intraductal abscesses
    • Other features include secondary sclerosing cholangitis
    • Increased risk of developing cholangiocarcinoma
Board review style question #1

A 2 year old boy was found to have portal hypertension while being evaluated in the hospital. A liver biopsy was performed. Which of the following findings is true regarding this disease entity?

  1. Adults experience much more severe symptom than pediatric patients
  2. Commonly associated with hepatobiliary cancer
  3. Liver transplant is the only curative treatment
  4. Symptoms resolve completely with no intervention
Board review style answer #1
C. Liver transplant is the only curative treatment

Comment Here

Reference: Congenital hepatic fibrosis
Board review style question #2

A 59 year woman with a history of diabetes presented with elevated liver enzymes and positive antimitochondrial antibody concerning for primary biliary cholangitis. A liver biopsy was performed. What is the most appropriate diagnosis?

  1. Bile duct malformation consistent with congenital hepatic fibrosis
  2. Primary biliary cholangitis
  3. Primary sclerosing cholangitis
  4. Steatosis and steatohepatitis with bridging fibrosis
Board review style answer #2
A. Bile duct malformation consistent with congenital hepatic fibrosis. This patient has undiagnosed congenital hepatic fibrosis. Adult onset congenital hepatic fibrosis may be asymptomatic or experience minor symptoms compared with pediatric patients.

Comment Here

Reference: Congenital hepatic fibrosis
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