Published on Aug 30, 2022 and last reviewed on Feb 14, 2023 - 7 min read
Progressive familial intrahepatic cholestasis is when the liver does not produce bile sufficiently. This condition is hereditary and runs in the family.
Progressive familial intrahepatic cholestasis is a genetically acquired condition from the parents. It causes continuous damage to the liver cells and eventually leads to liver failure. It is commonly seen in children and young adults. The patients with this condition have itching, jaundice (yellowish discoloration of the skin and eyes), and no weight gain. A few blood tests and imaging techniques help find the disease. Progressive familial intrahepatic cholestasis is treated symptomatically by providing nutritional supplements to promote growth, medications like antihistamines (medicines for allergy), and liver transplantation.
This condition runs in the family and leads to liver failure. It is caused by mutations in a gene that is responsible for the bile (a greenish liquid that is a waste product formed during the processing of hemoglobin) flow in the bile duct. The bile duct is a pipe-like structure that transports bile from the liver to the intestine. Hemoglobin is a protein in the blood that carries oxygen to all body parts.
In the presence of defective genes, the bile duct secretion is not carried out properly, and the liver cells are stocked up with bile. This leads to liver damage and failure.
Mutations (interchange of DNA position) in the genes ATP8B1, ABCB11, and ABCB4 cause progressive familial intrahepatic cholestasis. The genes that change are adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1), adenosine triphosphate binding cassette subfamily B member 11 (ABC11), and adenosine triphosphate binding cassette subfamily B member 4 (ABCB4).
The gene adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1) is responsible for producing proteins that balance the bile acids. As a result, bile acids promote fat absorption from the food ingested. The adenosine triphosphate binding cassette subfamily B member 11 (ABC11) is responsible for producing a protein bile salt export pump (BSEP). It is found in the liver, and it acts by removing the bile salts from the body. When there is a defect in the functioning of the gene, the bile salt export pump (BSEP) does not function properly, leading to a build-up of the bile salts in the liver, causing damage to the liver cells and ultimately leading to liver diseases.
The gene adenosine triphosphate binding cassette subfamily B member 4 (ABCB4) takes the role of producing a protein that transfers certain fats like phospholipids in the cell membrane. These phospholipids join with the bile salts in the outer part of the liver. Mutations in this gene cause decreased production of phospholipids. As a result, the bile salts without the phospholipid-binding accumulate in the liver leading to liver damage.
Progressive Familial Intrahepatic Cholestasis I (PFICI): The gene adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1) causes progressive Familial Intrahepatic Cholestasis I (PFIC I).
Stunted growth (being shorter than average height).
Deafness (unable to hear).
Diarrhea (severe episodes of loose stools).
Pancreas dysfunction (issues in the functioning of the pancreas).
Partial External Biliary Diversion: This surgical procedure removes the abnormally stored bile outside the body. The bile is removed from the bile duct by connecting the gallbladder and the stomach wall.
Ileal Bypass: This procedure involves connecting the gastric pouch (a part of the stomach where the food consumed is received) and the jejunum (middle part of the small intestine) without involving the stomach and duodenum (first part of the small intestine).
Partial Internal Biliary Bypass: This surgical procedure involves connecting the gallbladder and the cecum (the first part of the large intestine that looks like a sac) with a part of the jejunum as a graft (a part of healthy skin or bone replaced on a diseased or damaged part).
Liver Transplant: A part or whole liver from a healthy donor is replaced in a patient with liver disease or failure.
Progressive Familial Intrahepatic Cholestasis II (PFICII): Adenosine triphosphate binding cassette subfamily B member 11 (ABC11) causes progressive Familial Intrahepatic Cholestasis II (PFIC II).
Low nutritional absorption.
Decreased fat absorption and poor absorption of vitamins A, D, E, and K.
Poor growth and development.
Increased pressure in the vein that supplies the liver (portal hypertension).
Nutritional supplements like vitamins and minerals.
Reduce the itching by giving medications.
Biliary diversion, a surgical procedure that removes the accumulated bile by connecting the gallbladder and the stomach.
Progressive Familial Intrahepatic Cholestasis III (PFICIII): Adenosine triphosphate binding cassette subfamily B member 4 (ABCB4) causes progressive Familial Intrahepatic Cholestasis III (PFIC III). This condition occurs in early adolescence or late adulthood.
The symptoms appear depending on the severity of the disease.
A liver transplant is considered depending on the severity of the condition.
The patients with progressive familial intrahepatic cholestasis have the following symptoms in common:
Jaundice (the skin and eyes become yellow).
Failure in average growth and development of the child.
Hepatomegaly (enlargement of the liver).
Splenomegaly (spleen enlargement).
Portal hypertension (the blood pressure is elevated in the blood vessel that supplies the liver).
Liver Function Test: Liver function tests (LFT) screen the liver enzymes and proteins. Enzymes like alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), and proteins like albumin, globulin, and fibrinogen are screened. Serum bilirubin levels are also checked. The levels of serum bilirubin and alkaline phosphatase are elevated. The gamma-glutamyl transferase levels are below the normal range in progressive familial intrahepatic cholestasis.
Serum Bile Salt Concentration: The bile salts are formed in the liver and stored in the gallbladder for the time being. The elevated levels of bile salts confirm the disease.
Serum Cholesterol: Cholesterol is body fat. This test reveals the amount of cholesterol present in the body. The levels of HDL(high-density lipoprotein) are elevated in this disease. The high-density lipoprotein is called good cholesterol. The levels of cholesterol are in the normal range in this condition.
Genetic Testing: Genetic testing is performed to find the changes in the genes adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1), adenosine triphosphate binding cassette subfamily B member 11 (ABC11), and adenosine triphosphate binding cassette subfamily B member 4 (ABCB4).
Ultrasound: Ultrasound techniques are performed to find out the problem in the organ internally. This technique is done in the presence of a sound wave to generate pictures of the internal organ.
CT Scan: Computed tomography (CT) scan is done to get detailed information about the targeted organ. This technique is performed with the help of X-ray images captured with computer-aided technology. This gives a clear picture of the bones, muscles, blood vessels, and the organ that causes trouble.
MRI Scan: Magnetic resonance imaging (MRI) technique captures the images of the structure and the function performed by the organ. This technique is performed in a strong magnetic field and radio waves. This gives a very detailed picture of the organ's functioning level also.
Liver Biopsy: In a liver biopsy, a tiny portion of the liver is removed to view the pathological changes at a microscopic level to find the cause of the disease. This is a confirmatory test and reveals the type of the disease.
Ursodeoxycholic Acid: This medication is used to disrupt the accumulated bile. It manages the bile acid movement in the liver and keeps the cholesterol within the normal range.
Cholestyramine: This medication reduces and resolves skin discomfort and itching. It also prevents bile acids from entering the liver. This boosts liver enzyme activity and increases the removal of bilirubin.
Rifampicin: It is an antibiotic (fights against infection-causing organisms). This acts by promoting the action of detoxifying enzymes and removing the bile acids from the body.
Phenobarbital: It is an anti-seizure drug. It also reduces anxiety.
Antihistamine: Antihistamine treats allergic reactions.
Ondansetron: Ondansetron is used to prevent vomiting and relieve nausea.
Steroids: These medications are artificial hormonal medications used to treat inflammation.
Propofol: Propofol is a medication used to relieve anxiety and makes them feel relaxed. This also has a sedative property (causing sleep and less memory of events).
Carbamazepine: This medication is used to treat seizures and facial nerve pain.
Vitamins: Fat-soluble vitamin supplements A, D, E, and K will be prescribed.
Partial external biliary diversion.
Partial internal biliary diversion.
Fibrosis of the liver (abnormal accumulation of extracellular matrix proteins like collagen, gelatin, fibrin, etc.).
Cirrhosis (scar formation in the healthy liver tissues).
Liver failure (liver dysfunction).
Liver cancer in children with progressive familial intrahepatic cholestasis II.
The term itself says the disease is progressive, which means it will keep growing. The prognosis is moderate to poor depending on the severity of the condition.
The progressive familial intrahepatic cholestasis is a genetically inherited condition. It occurs commonly in children and the younger population. Itching, skin discomfort, jaundice, and retarted growth and development are a few signs and symptoms of the disease. A few blood tests, imaging techniques, and biopsies are performed to rule out the disease. The kids with this condition are treated with medications that relieve their symptoms, and a few surgical procedures are performed to find a way to drain the accumulated bile out of the body. In severe cases, a liver transplant will be recommended. Though this is a growing disease that leads to liver failure, detecting the disease earlier if one has this condition running in the family will help start the treatment without delay to improve the patient's lifespan.
Last reviewed at:
14 Feb 2023 - 7 min read
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