eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology
Congenital Hepatic Fibrosis
Updated: Mar 31, 2008
Introduction
Background
Congenital hepatic fibrosis (CHF) is an autosomal recessive disease that primarily affects the hepatobiliary and renal systems. It is characterized by hepatic fibrosis, portal hypertension, and renal cystic disease. CHF is one of the fibropolycystic diseases, which also include Caroli disease, autosomal dominant polycystic kidney disease (ADPKD), and autosomal recessive polycystic kidney disease (ARPKD).
CHF is associated with an impairment of renal functions, usually caused by an ARPKD, which is a severe form of polycystic kidney disease.1 The hepatic manifestations of CHF were first described in 1856.2 In 1961, the term CHF, with its varied clinical manifestations, was recognized.3
Pathophysiology
CHF results from a malformation of the ductal plate (the embryological precursor of the biliary system), secondary biliary strictures, and periportal fibrosis.4 This subsequently results in the development of portal hypertension.
The ductal plate is the cylindric layer of cells that surrounds a branch of the portal vein. It is a precursor of the intrahepatic bile ducts. Ductal plates arise around the smaller portal vein branches at a distance from the hilum. Progressive remodeling starts at 12 weeks' gestation. Both interlobular and intralobular bile ductules develop from the ductal plate. The lack of remodeling of the ductal plate results in persistence of an excess of embryonic duct structures. This abnormality has been termed the ductal plate malformation5 and consists of persistence of the ductal plate with an increase in duct elements and an increase in portal fibrous tissue.
The family of fibropolycystic diseases are characterized by varying degrees of persistent bile duct structures, fibrosis, and duct dilatation. They are all developmental anomalies of the duct plate and occurred at various stages of remodeling. CHF is a ductal plate malformation of the small interlobular bile ducts, whereas Caroli disease involves the large intrahepatic bile ducts.
The classic renal lesion associated with CHF is ARPKD, which results in an impairment of renal functions. Its association with ADPKD is also recognized, especially among adults. The relationship of ARPKD to CHF remains a controversial issue. The 2 conditions may actually be one disorder with different clinicopathological presentations.
ARPKD is caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene,6 which consists of 86 exons that are variably assembled into numerous alternatively spliced transcripts.7 Most cases of ARPKD and CHF are genetically homogeneous. However, the exact pathogenesis of association between CHF and ADPKD still requires further research and study.
In all cases of CHF-ARPKD, a hepatic lesion of ductal plate malformation of the interlobular bile ducts is found; the difference in its presentation is primarily age dependent. Gradual disappearance of bile duct profiles associated with increased periportal fibrosis results from a progressive destructive cholangiopathy that involves the immature bile duct structures.
The hepatic disease progresses to develop portal hypertension associated with splenomegaly and esophageal varices. CHF is characterized by the intrahepatic form of portal hypertension, which is caused by the intrahepatic obstruction that affects the blood supply to the liver and subsequently leads to the development of cavernous transformations of the portal vein with a rise in portal venous pressure.
CHF is also associated with cholangitis. The presence of cholangitis or its repeated occurrence may influence the status of the hepatic lesion and the prognosis of the disease. Commonly, the hepatic lesion is associated with renal involvement characterized by cystic tubular dilatations, which affect both the cortical and medullary portions of the kidney. The longer the patient survives, the less characteristic the renal pathology becomes.
Frequency
International
CHF is a rare autosomal recessive disease; the exact incidence and prevalence are not known. Only a few hundred patients with CHF have been reported in the literature. The disease appears in both sporadic (in as many as 56% of cases) and familial patterns.
Mortality/Morbidity
Most neonates and young infants with predominant renal involvement die of renal failure in early infancy. As many as 25% of patients may succumb to renal failure, according to estimates. Cholangitis significantly contributes to morbidity and mortality rates in CHF. When hepatic lesions dominate the clinical expression of the disease, children who are affected may remain asymptomatic until late childhood or even adulthood. Most patients do well. Coexisting renal lesions may also remain asymptomatic until early adulthood.
Sex
No sex predilection is observed.
Age
CHF may present in the neonatal period, but delayed presentation in late childhood or even adulthood is reported.
Clinical
History
The onset of symptoms varies in spectrum and severity. Patients usually develop nonspecific symptoms, making the initial diagnosis difficult. The age at presentation may range form early childhood to the fifth decade of life. However, most cases however are diagnosed during adolescence and early adulthood.
- Congenital hepatic fibrosis (CHF) has 4 different forms: portal hypertensive (most common), cholangitic, mixed, and latent. Patients in the portal hypertensive group often present with esophageal variceal hemorrhage. Those with the cholangitic form have characteristic cholestasis and recurrent cholangitis. Patients with the latent form present at an older age or are diagnosed as an incidental finding.
- Most patients initially manifest with symptoms and signs of portal hypertension. These include hematemesis and melena.
- When hepatic lesions dominate the clinical expression of the disease, the affected child may remain asymptomatic for years before evidence of hepatic involvement manifests as a sequela of portal hypertension with repeated episodes of GI bleeding of varying severity.
- Rarely, patients may present with abdominal pain localized to the right upper quadrant.
- If renal lesions dominate the clinical picture, the patient may die of renal failure in early infancy.
Physical
- Portal hypertension may be the initial manifestation that leads to the identification of ADPKD.
- Hepatomegaly is present in nearly all patients with predominant involvement of the left lobe. Upon palpation, the liver is firm, and its surface is smooth or finely nodular. The liver edge is sometimes irregular, suggesting cirrhosis.
- In most patients, splenomegaly is associated with evidence of hypersplenism.
- Nephromegaly is a common finding during a physical examination in patients with CHF and ARPKD.
- Abdominal pain is rare; when present, it is usually localized to the right upper quadrant.
Causes
- CHF is an autosomal recessive disorder.
- No definite cause or causative agent has been identified.
- Transforming growth factor-1 and thrombospondin-1 may play a role in the pathogenesis of liver fibrosis in patients with CHF.8
- Abundant connective tissue growth factor retained diffusely in heparan sulfate proteoglycan in the fibrous portal tracts or septa may be responsible for nonresolving hepatic fibrosis in CHF.9
More on Congenital Hepatic Fibrosis |
 Overview: Congenital Hepatic Fibrosis |
| Differential Diagnoses & Workup: Congenital Hepatic Fibrosis |
| Treatment & Medication: Congenital Hepatic Fibrosis |
| Follow-up: Congenital Hepatic Fibrosis |
| Multimedia: Congenital Hepatic Fibrosis |
| References |
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References
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Further Reading
Keywords
congenital hepatic fibrosis, CHF, biliary fibroadenomatosis, hepatic fibroangioadenomatosis, fibrous angio adenomatosis, ductal plate malformation, autosomal recessive polycystic kidney disease, ARPKD, portal hypertension, renal cystic disease, Caroli disease, autosomal dominant polycystic kidney disease, ADPKD, cholangitis, hematemesis, melena, cholestasis, hepatomegaly, cirrhosis, hypersplenism, nephromegaly
