progressive familial intrahepatic 3 Cholestasis

A hereditary autsomal recessive form of intrahepatic cholestasis characterized by childhood onset of CHOLESTASIS that progresses to hepatic FIBROSIS, cirrhosis, and END-STAGE LIVER DISEASE before adulthood. Mutations in the ABCB4 gene have been identified. OMIM: 602347

Also Known As:

Cholestasis, progressive familial intrahepatic 3; Abcb4-Related Intrahepatic Cholestasis; Cholestasis, Progressive Familial Intrahepatic, 3; Cholestasis, Progressive Familial Intrahepatic, with Elevated Serum Gamma-Glutamyltransferase; Low gamma-GT Familial Intrahepatic Cholestasis; MDR3 Deficiency; PFIC3 Progressive familial intrahepatic cholestasis type 3; Progressive Familial Intrahepatic Cholestasis 3 (PFIC 3); Progressive Familial Intrahepatic Cholestasis 3 (PFIC3); Progressive familial intrahepatic cholestasis with elevated serum gamma-glutamyltransferase

Networked: 14 relevant articles (0 outcomes, 1 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Cholestasis
2.	Fibrosis (Cirrhosis)
3.	Cholelithiasis
4.	Liver Failure
5.	Liver Diseases (Liver Disease)

Experts

1.	Rela, Mohamed: 2 articles (05/2019 - 10/2015)
2.	Vij, Mukul: 2 articles (05/2019 - 10/2015)
3.	Baussan, Christiane: 2 articles (05/2010 - 01/2009)
4.	Davit-Spraul, Anne: 2 articles (05/2010 - 01/2009)
5.	Gonzales, Emmanuel: 2 articles (05/2010 - 01/2009)
6.	Jacquemin, Emmanuel: 2 articles (05/2010 - 01/2009)
7.	Bhardwaj, Ravi: 1 article (03/2022)
8.	Goyal, Neerav: 1 article (03/2022)
9.	Kumar, Karunesh: 1 article (03/2022)
10.	Malhotra, Smita: 1 article (03/2022)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to progressive familial intrahepatic 3 Cholestasis:

1.	Ursodeoxycholic Acid (Urso)FDA LinkGeneric 10/01/2023 - "In this study, data show that genotype and response to ursodeoxycholic acid therapy predicted native liver survival in patients with PFIC3 (progressive familial intrahepatic cholestasis type 3). " 05/01/2010 - "Most patients with MDR3 deficiency have a favorable outcome with ursodeoxycholic acid (UDCA) therapy, but some PFIC3 patients who do not respond to UDCA treatment still require liver transplantation. " 11/01/2001 - "Patients with PFIC3 due to MDR3 deficiency may benefit from ursodeoxycholic acid therapy and could be good candidates for cell therapy in the future." 01/01/2009 - " is evidence that biallelic or monoallelic MDR3 defect causes or predisposes to 6 human liver diseases (PFIC3, adult biliary cirrhosis, low phospholipid associated cholelithiasis syndrome, transient neonatal cholestasis, intrahepatic cholestasis of pregnancy, drug induced cholestasis).Some patients with MDR3 deficiency may benefit from ursodeoxycholic acid therapy and could be good candidates to a targeted pharmacological approach and/or to cell therapy in the future."
2.	Phospholipids (Phosphatides)FDA LinkGeneric 04/01/2006 - "We will emphasize autoimmune cholangitis and (Low Phospholipid Associated Cholelithiasis) LPAC with MDR3 deficiency. " 03/01/2000 - "In contrast, in children with cholestasis and high serum bile acid concentrations, a high serum gamma glutamyltranspeptidase value would indicate MDR3 deficiency, which should be excluded through biliary phospholipid determination and genetic analysis of PGY3 gene. " 01/01/2009 - " is evidence that biallelic or monoallelic MDR3 defect causes or predisposes to 6 human liver diseases (PFIC3, adult biliary cirrhosis, low phospholipid associated cholelithiasis syndrome, transient neonatal cholestasis, intrahepatic cholestasis of pregnancy, drug induced cholestasis).Some patients with MDR3 deficiency may benefit from ursodeoxycholic acid therapy and could be good candidates to a targeted pharmacological approach and/or to cell therapy in the future."
3.	Proteins (Proteins, Gene)FDA Link 09/01/2015 - "These data indicate that fibrosis associated with MDR3 deficiency can be reversed by long-term treatment with UDCA, at least when there is residual expression of the protein." 03/01/2022 - "There were 13 identified PFIC cases (familial intrahepatic cholestasis 1 [FIC1] deficiency-4, bile salt export pump (BSEP) deficiency-3, tight junction protein [TJP2] deficiency 3, multidrug-resistant protein 3 [MDR3] deficiency 2 and farnesoid X receptor deficiency-1). "
4.	Bile Acids and Salts (Bile Acids)IBA 02/01/2011 - "The currently preferred nomenclature for the three PFIC disorders that have been characterized to date is FIC1 deficiency, BSEP deficiency, and MDR3 deficiency, relating to mutations in the specific genes involved in bile acid formation and transport. " 03/01/2000 - "In contrast, in children with cholestasis and high serum bile acid concentrations, a high serum gamma glutamyltranspeptidase value would indicate MDR3 deficiency, which should be excluded through biliary phospholipid determination and genetic analysis of PGY3 gene. "
5.	Tight Junction ProteinsIBA 03/01/2022 - "There were 13 identified PFIC cases (familial intrahepatic cholestasis 1 [FIC1] deficiency-4, bile salt export pump (BSEP) deficiency-3, tight junction protein [TJP2] deficiency 3, multidrug-resistant protein 3 [MDR3] deficiency 2 and farnesoid X receptor deficiency-1). "
6.	Member 1 Subfamily B ATP Binding Cassette TransporterIBA 05/01/2019 - "Paucity of Interlobular Bile Ducts in Multidrug-Resistant P-Glycoprotein 3 (MDR3) Deficiency."
7.	Phenobarbital (Luminal)FDA Link 09/01/2015 - "MDR3 deficiency results in a disbalanced bile which may damage the luminal membrane of cells of the hepatobiliary system. "
8.	ParaffinIBA 10/01/2015 - "We conclude that MDR3 immunostaining on formalin-fixed and paraffin-embedded sections is a useful tool to diagnose severe MDR3 deficiency in pediatric liver cholestatic disease cases where genetic testing is not available. "
9.	Membrane Proteins (Integral Membrane Proteins)IBA 10/01/2015 - "Multidrug resistance protein 3 (MDR3) is a hepatocyte canalicular membrane protein encoded by the ABCB4/MDR3 gene located on chromosome 7. Several liver diseases are known to be associated with MDR3 deficiency. "
10.	gamma-Glutamyltransferase (gamma-Glutamyl Transpeptidase)IBA 04/01/2003 - "The present case, which accumulates the 3 clinical disorders assocaited with MDR3 deficiency, shows that this condition should be suspected not only in children or young people with high gamma-glutamyl transpeptidase cholestasis but also in middle-aged or older patients with chronic idiopathic cholestasis, especially when there is a previous history of cholestasis of pregnancy or juvenile cholelithiasis."

Therapies and Procedures

1.	Therapeutics 10/01/2023 - "In this study, data show that genotype and response to ursodeoxycholic acid therapy predicted native liver survival in patients with PFIC3 (progressive familial intrahepatic cholestasis type 3). " 05/01/2010 - "Most patients with MDR3 deficiency have a favorable outcome with ursodeoxycholic acid (UDCA) therapy, but some PFIC3 patients who do not respond to UDCA treatment still require liver transplantation. " 11/01/2001 - "Patients with PFIC3 due to MDR3 deficiency may benefit from ursodeoxycholic acid therapy and could be good candidates for cell therapy in the future." 01/01/2009 - " is evidence that biallelic or monoallelic MDR3 defect causes or predisposes to 6 human liver diseases (PFIC3, adult biliary cirrhosis, low phospholipid associated cholelithiasis syndrome, transient neonatal cholestasis, intrahepatic cholestasis of pregnancy, drug induced cholestasis).Some patients with MDR3 deficiency may benefit from ursodeoxycholic acid therapy and could be good candidates to a targeted pharmacological approach and/or to cell therapy in the future."
2.	Liver Transplantation 01/22/2015 - "If untreated, MDR3 deficiency can lead to progressive liver failure requiring liver transplantation. " 05/01/2019 - "Severe MDR3 deficiency typically occurs during childhood with progressive cholestasis evolving to cirrhosis and liver failure, requiring liver transplantation. " 10/01/2015 - "Severe MDR3 deficiency typically presents during the first year of life or early childhood, often progressing to chronic liver disease with cirrhosis and portal hypertension, requiring liver transplantation. " 05/01/2010 - "Most patients with MDR3 deficiency have a favorable outcome with ursodeoxycholic acid (UDCA) therapy, but some PFIC3 patients who do not respond to UDCA treatment still require liver transplantation. "
3.	Cell- and Tissue-Based Therapy (Cell Therapy) 11/01/2001 - "Patients with PFIC3 due to MDR3 deficiency may benefit from ursodeoxycholic acid therapy and could be good candidates for cell therapy in the future." 01/01/2009 - " is evidence that biallelic or monoallelic MDR3 defect causes or predisposes to 6 human liver diseases (PFIC3, adult biliary cirrhosis, low phospholipid associated cholelithiasis syndrome, transient neonatal cholestasis, intrahepatic cholestasis of pregnancy, drug induced cholestasis).Some patients with MDR3 deficiency may benefit from ursodeoxycholic acid therapy and could be good candidates to a targeted pharmacological approach and/or to cell therapy in the future."