Progressive Familial Intrahepatic Cholestasis 1

Synonyms

5

Overview

Progressive Familial Intrahepatic Cholestasis-1 (PFIC) refers to a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. PFIC1 is the less frequent type of PFIC. The clinical presentation usually occurs first in childhood with progressive cholestasis. This usually leads to failure to thrive, hepatic failure, and the need for liver transplantation.

Symptoms

The list of signs and symptoms mentioned in various sources for Progressive Familial Intrahepatic Cholestasis 1 (PFIC-1) includes the symptoms listed below:

  • punctate corneal dystrophy
  • jaundice
  • epistaxis
  • pruritus
  • foul-smelling stool
  • short stature
  • deafness
  • diarrhe
  • inflammation of the pancreas (pancreatitis)
  • low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood
  • development of liver failure before adulthood
  • jaundice
  • steatorrhoea
  • reduced growth
  • a relatively low to normal serum γ-glutamyltranspeptidase (γGT) activity despite an elevated alkaline phosphatase

Causes

ATP8B1 gene mutations (18q21-22) cause PFIC1. The ATP8B1 gene provides instructions for making a protein that helps to maintain an appropriate balance of bile acids, a component of bile. This process, known as bile acid homeostasis, is critical for the normal secretion of bile and the proper functioning of liver cells. In its role in maintaining bile acid homeostasis, some researchers believe that the ATP8B1 protein is involved in moving certain fats across cell membranes. Mutations in the ATP8B1 gene result in the buildup of bile acids in liver cells, damaging these cells and causing liver disease. The ATP8B1 protein is found throughout the body, but it is unclear how a lack of this protein causes short stature, deafness, and other signs and symptoms of PFIC1.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Treatment

Initial treatment is supportive, with the use of agents to treat cholestasis and pruritus, including the following: 

  • Ursodeoxycholic acid therapy (UDCA) should be initiated in all patients to prevent liver damage but is not fully effective.
  • Cholestyramine
  • Rifampin is helpful to control pruritus.
  • Naloxone
  • Soluble vitamins in refractory cases as supplement
  • Medium-chain triglycerides in order to improve growth (occasionally).
  • Nasobiliary drainage may help to select potential responders to biliary diversion.
  • However, because of severe cholestasis, half of patients are ultimately candidates for liver transplantation (LT). Diarrhea often worsens after LT and might be favorably managed by bile adsorptive resin treatment. LT does not prevent extrahepatic progression of the disease, and does not lead to catch-up growth. Furthermore, severe steatohepatitis of the liver graft has been reported. Specialized follow-up is mandatory lifelong.