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Congenital Hepatic Fibrosis (CHF)
Thursday, 18 March 2004
Sunday, 28 November 2004

What

Congenital hepatic fibrosis (CHF) is a rare, hereditary disorder, first described in 1856, which is characterized by fibrosis (scarring) of the liver and irregularly shaped bile ducts. Bile ducts are essential to move bile, which is necessary for the digestion and absorption of fats, from the liver to the small intestines. The scarring and irregularly shaped bile ducts may eventually lead to liver failure.

Who

Congenital hepatic fibrosis is inherited in an autosomal recessive manner; this means that each parent carries one defective gene and one normal gene and the affected child inherits one defective gene from each parent. The parents are not affected by the disease since they each have a normal gene to counterbalance the defective gene. For each child these parents have, there is a 25% chance that the child will be affected. Nevertheless, there are sporadic cases in which neither parent carries the defective gene, and by random occurrence, the child gets the disease. Since CHF is such a rare disease, the incidence and prevalence have not been determined. There has been no predisposition noted in males or females. CHF is often associated with other disorders. CHF may be linked with impaired kidney function, often due to Autosomal Recessive Polycystic Kidney Disease (ARPKD). All children with ARPKD will also have CHF; however, not everyone with CHF will have ARPKD. Of note, 75% of patients with CHF will have some kind of kidney abnormalities. The occurrence of CHF with ARPKD has been noted to be about 1 in 20,000 live births. CHF may also coexist with Caroli syndrome, which is dilatation of intrahepatic (within the liver) bile ducts. In adults, CHF may be associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Autosomal dominant means that the affected person only needs one defective copy of the gene to have the disease.

Signs and Symptoms

Patients with CHF may present with liver-related symptoms or kidney-related symptoms. The most common initial symptoms in 70% of patients are hematemesis (blood in the vomit) or melena (blood in the stool, stool may look bloody or black and tarry). If the kidneys are involved, many infants die of kidney failure in early infancy, because with early kidney failure, lungs fail to develop properly, and the infants may be unable to breathe adequately. If liver problems are the main manifestation of the disease, the patient may be without obvious symptoms for years before the disease becomes apparent. Liver function is usually normal until late in the disease. Portal hypertension may result from CHF. The portal vein transports blood into the liver and scarring of the liver makes blood flow into the liver difficult. This obstruction of blood flow causes an increase in blood pressure specifically in the portal vein. Gastrointestinal bleeding can result from portal hypertension and patients can develop blood in the vomit (hematemesis) or blood in the stool (melena). • Other signs/symptoms include: o Hepatomegaly (enlarged liver) o Splenomegaly (enlarged spleen) – this is due to increased destruction of blood cells, and may result in low platelets (increased time of blood clotting), low white blood cell count (increased susceptibility to infections), and low red blood cell count (anemia – decreased oxygen carrying capacity of the blood to tissues). o Rarely, abdominal pain is present, usually located in the right upper quadrant A serious complication of CHF is cholangitis or blockage of the bile ducts which can lead to a bacterial infection into the liver. Signs/symptoms of cholangitis include: fever, chills, abdominal pain, nausea, vomiting. Cholangitis is treated with antibiotics; however, repeated episodes may damage the liver and lead to liver failure

Possible Causes

The cause for congenital hepatic fibrosis is unknown. However, in patients with both ARPKD and CHF, a defect in the gene PKHD1 is seen in the majority of cases. This gene is found on chromosome 6, but the exact function is still unknown.

Diagnosis

The initial manifestation of this disease may be gastrointestinal bleeding. Important steps in diagnosing the disease include: • Blood tests that measure liver function. o Liver enzymes (AST and ALT) are usually normal until late in the disease process. o Alkaline phosphatase and GGT may be elevated. Elevation in these enzymes may indicate blockage of the bile ducts. o If the patient has cholangitis, she/he may have a high bilirubin level, high liver enzymes, and a high white blood cell count (indicating infection). • Physical exam may detect a large spleen • Complete blood count may show a low white blood cell count, low red blood cell count, and low platelet count • Blood tests that measure kidney function o High BUN (blood urea nitrogen - breakdown product eliminated by the kidneys), high creatinine (substance normally filtered by the kidneys), and decreased creatinine clearance (demonstrates how well creatinine is filtered by the kidneys) • Imaging studies are important to further delineate the disease o Ultrasound with Doppler studies to look for liver echogenicity, hypertension, splenomegaly, patency of portal vasculature, nephromegaly (large kidneys) with polycystic (many cysts) changes o CT scan may further help with diagnosis o Angiography (x-ray that visualizes blood flow in the veins and arteries). This test can help visualize the vascular anatomy of the liver and can help identify cholangitis. o IVP (intravenous pyleography). This x-ray test uses contrast to help visualize the urinary tract system, including the kidneys, bladder, ureters, and urethra. • Diagnostic procedures o A liver biopsy is the gold standard in diagnosing CHF. If the disease is present, the biopsy shows a specific kind of extensive overall scarring of the liver.

Treatment

The treatment of CHF is often focused on managing the complications directly resulting from the disease. Cholangitis can be a significant complication of CHF and is treated with antibiotics. Portal hypertension with bleeding needs to be treated emergently with intravenous fluids, nasogastric tube placement, and blood transfusions, if necessary. Bleeding can be treated by using a special tube placed down the throat to find the bleeding vessels and stop their bleeding. If portal hypertension is severe, surgery may be necessary to relieve the hypertension and to decrease the chance of bleeding. Medications to reduce the portal pressure are often used in children to delay the need for surgery. Liver transplantation may be seriously considered with liver failure, recurrent cholangitis, or if all other treatments fail. Some of the following medications may be used in treatment of CHF. • Sulfamethoxazole and Trimethoprim (Bactrim, Septra, Cotrim) – antibiotics used for cholangitis. • Ursodiol (Actigall, Urso) – enhances bile flow, may decrease the incidence of cholangitis • Vasopressin, Somatostatin, Propranolol – medications that reduce portal blood pressure

Prognosis

The prognosis of CHF depends on how well the complications are managed. Most patients do well if gastrointestinal bleeding is well controlled and there is no kidney failure. However, approximately 25% of patients may succumb to kidney failure. Cholangitis can be life-threatening; therefore, it is important to treat cholangitis quickly and appropriately. Kidney involvement in neonates/infants may signify a poorer prognosis.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

American Liver Foundation
This website provides information on liver transplantation and research in liver disease.

ARPKD/CHF Alliance
Great website for information about ARPKD/CHF. Provides links to research, resources, and events which support patients with ARPKD/CHF.

Google Search for Congenital Hepatic Fibrosis (CHF)

References and Sources

Kamath, BM, and Piccoli, DA. (2003) “Heritable disorders of the bile ducts.” Gastroenterology Clinics. Vol 32, No 3. WB Saunders Company. Nazer, H. and Nazer, D. “Congenital Hepatic Fibrosis.” On http://www.emedicine.com www.webmd.com www.arpkd.org