Congenital Hepatic Fibrosis (CHF) is a rare disease that affects both the liver and kidneys. The patient is born with this disorder (congenital), and it is inherited as an autosomal recessive trait. The typical liver abnormalities are an enlarged liver (hepatomegaly), increased pressure in the venous system that carries blood from different organs to the liver (portal hypertension), and fiber-like connective tissue that spreads over and through the liver (hepatic fibrosis), often referred to as hepatic lesions. Gastrointestinal (stomach and intestines) bleeding is frequently an early sign of this condition. Affected individuals also have impaired renal function, usually caused, in children and teenagers, by an autosomal recessive polycystic kidney disease (ARPKD). Impaired renal function associated with CHF in adults is caused by an autosomal dominant polycystic kidney disease (ADPKD).
The relationship of ARPKD to CHF is the subject of substantial controversy. Some clinicians suggest that the two conditions represent one disorder with a range of clinical/pathological presentations.
While the onset of Congenital Hepatic Fibrosis may be noticed first in adults, it may also present in newly born babies (neonates), children and adolescents. The more obvious symptoms are a swollen abdomen, a firm, slightly enlarged liver and, most especially, vomiting blood due to bleeding from the esophagus, stomach, and intestines. Inflamed bile ducts (cholangitis) are characteristic, as well.
The main findings in this disorder are identified through diagnostic testing. Many of the following signs are present in patients with this disorder:
Portal Hypertension: increased pressure in the venous system that carries blood from multiple organs to the liver (portal system). This increased blood pressure is caused by blockage of this blood supply to the liver due to excess connective tissue growth in the liver. Portal hypertension can cause enlargement of the spleen and swollen or dilated veins of the esophagus.
Hepatic Fibrosis: a fiber-like connective tissue that spreads through the liver.
Nephromegaly: enlarged kidney.
Gastrointestinal Bleeding: bleeding from the stomach and intestines that may cause the patient to vomit red blood.
Polycystic Kidney Disease: an inherited disorder in which cysts invade both kidneys. This causes enlargement in the size of the kidney while, at the same time, reducing the amount of functional kidney tissue, by compression. (For more information on this disorder choose “Polycystic Kidney Disease” as your search term in the Rare Disease Database).
Splenomegaly: an enlarged spleen.
Liver function tests are usually normal in patients with this disease. The diagnosis of Congenital Hepatic Fibrosis is confirmed by a liver biopsy.
The gene that may be responsible for Congenital Hepatic Fibrosis may be the same gene that has been proven to be responsible for polycystic kidney disease. This idea remains much contested among researchers and clinicians. The gene in question has been mapped to Gene Map Locus 6p21.1-p12.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome, and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 6p21″ refers to band 21 on the short arm of chromosome 6. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Congenital Hepatic Fibrosis is inherited as an autosomal recessive trait. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
The cause of Congenital Hepatic Fibrosis has also been of interest to clinical scientists who study the development of the embryo. Some time before the 12th week of gestation, a layer of cells close by the portal vein transforms into a tube-like structure called the ductal plate. At the 12th week, this tube generates many, many very small bile ducts (ductules). If this transformation fails to take place, the ductal plate persists along with primitive duct elements leading to increased fibrous tissue extending from the portal vein through the liver.
Congenital Hepatic Fibrosis is rare and appears to affect males and females in equal numbers. It may present at an early neonatal stage. Normally, it is detected within the first ten years of life, but it may become apparent as early as soon after birth or as late as during late childhood or in adulthood. The disorder is rare throughout the world. According to one estimate, it occurs in one per 16,000 live births.
Treatment of Congenital Hepatic Fibrosis is symptomatic and supportive.
To prevent gastrointestinal hemorrhage, portal hypertension may need to be treated surgically. Aspirin and alcohol should be avoided.
Treatment of Polycystic Kidney Disease consists of management of urinary infections and secondary hypertension. The kidney function may deteriorate very slowly in some patients. In general, kidney function is normal or slightly impaired when congenital hepatic fibrosis is found along with polycystic kidney disease in older children. Patients eventually need dialysis in order to remove toxins from the blood.
Transplantation of a kidney or liver may be indicated.
Genetic counseling may be of benefit for patients and their families.
Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future.
Research on Autosomal Recessive Polycystic Kidney Disease (ARPKD) that affects children is being pursued by the following research team:
Lisa M. Guay-Woodford, M.D.
Norman D. Rosenblum, M.D.
Kathy L. Jabs, M.D.
William E. Harmon, M.D.
E. William Harris, Jr., M.D., Ph.D.
The Division of Nephrology
The Children’s Hospital
300 Longwood Ave.
Boston, MA 02115
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Simkes AM. Congenital Hepatic Fibrosis. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:691-92..
Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:371-72.
Stein JH, Hutton JJ, Kohler PO, et al. Eds. Internal Medicine. 4th ed. Mosby-Yearbook, Inc., St. Louis, MO. 1994:627-28.
Kaczorowski JM, Halterman JS, Spitalnik P, et al. Pathology teach and tell: congenital hepatic fibrosis and autosomal dominant polycystic kidney disease. Pediatr Pathol Mol Med. 2001;20:245-48.
Kakkar N, Vasishta RK, Lamba A, et al. Pathology teach and tell: perinatal recessive polycystic kidney disease with congenital hepatic fibrosis. Pediatr Pathol Mol Med. 2001;20:227-34.
Kikuchi Y, Matsui A, Momoi MY. A rare case of congenital hepatic fibrosis with severe pulmonary hypertension in an adolescent. Pediatr Int. 2001;43:319-22.
Sigalet DL, Mayer S, Blanchard H. Portal venous decompression with H-type mesocaval shunt using autologous vein graft: a North American experience. J Pediatr Surg. 2001;36:91-96.
De Koning TJ, Nikkels PG, Dorland L, et al. Congenital hepatic fibrosis in 3 siblings with phosphomannose isomerase deficiency. Virchows Arch. 2000;437:101-05.
Freeze HH, Aebi M. Molecular basis of carbohydrate-deficient glycoprotein syndromes type I with normal phosphomannomutase activity. Biochim Biophys Acta. 1999;1455:167-78.
De Koning TJ, Dorland L, van Berge Henegouwen GP. Phosphomannose isomerase deficiency as a cause of congenital hepatic fibrosis and protein losing enteropathy. J Hepatol. 1999;31:557-60.
Freeze HH. New diagnosis and treatment of congenital hepatic fibrosis. J Pediatr Gastroenterol Nutr. 1999;29:104-06.
FROM THE INTERNET
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 263200: Last Edit Date; 3/1/2002.
Nazer H, Nazer D. Congenital Hepatic Fibrosis. eMedicine. Last Updated: April 17, 2002. 14pp.
GPNotebook. [Congenital Hepatic Fibrosis.] nd. 1p.
Reichen J. Congenital hepatic fibrosis. August 9, 2002:5pp.
Henry Ford health System. [Med Help International.] Congenital Hepatic Fibrosis. nd. 2pp.