Case report: progressive familial intrahepatic cholestasis type 3 with compound heterozygous ABCB4 variants diagnosed 15 years after liver transplantation

Abstract

Background Progressive familial intrahepatic cholestasis (PFIC) type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene. This gene encodes multidrug resistance protein-3 (MDR3) that acts as a hepatocanalicular floppase that transports phosphatidylcholine from the inner to the outer canalicular membrane. In the absence of phosphatidylcholine, the detergent activity of bile salts is amplified and this leads to cholangiopathy, bile duct loss and biliary cirrhosis. Patients usually present in infancy or childhood and often progress to end-stage liver disease before adulthood. Case presentation We report a 32-year-old female who required cadaveric liver transplantation at the age of 17 for cryptogenic cirrhosis. When the patient developed chronic ductopenia in the allograft 15 years later, we hypothesized that the patient’s original disease was due to a deficiency of a biliary transport protein and the ductopenia could be explained by an autoimmune response to neoantigen that was not previously encountered by the immune system. We therefore performed genetic analyses and immunohistochemistry of the native liver, which led to a diagnosis of PFIC3. However, there was no evidence of humoral immune response to the MDR3 and therefore, we assumed that the ductopenia observed in the allograft was likely due to chronic rejection rather than autoimmune disease in the allograft. Conclusions Teenage patients referred for liver transplantation with cryptogenic liver disease should undergo work up for PFIC3. An accurate diagnosis of PFIC 3 is key for optimal management, therapeutic intervention, and avoidance of complications before the onset of end-stage liver disease.

Biliary atresia combined Wilson disease identified by whole exome sequencing in Vietnamese patient with severe liver failure

“…Based on clinical symptoms, laboratory tests, and genetic analysis, the patient shows a combination of 2 rare hepatobiliary diseases, BA and Wilson disease. The combination of 2 hepatobiliary diseases in the same patient has also been reported in recent studies [10–12] …”

Type 3 of progressive familial intrahepatic cholestasis (PFIC‐3): Case report

“…Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of genetic autosomal recessive disorders which cause defects in the formation and secretion of bile components and bile acids. 1 PFIC consists of five different variant forms numbered 1 through 5 based on the gene involved. 2 Most of these disorders present in infancy and early childhood as signs of growth failure vitamin K deficiency (i.e., easy bruising, epistaxis, coagulopathies) due to impaired vitamin K absorption and progressive liver disease leading to cirrhosis before adulthood.…”

“…Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of genetic autosomal recessive disorders which cause defects in the formation and secretion of bile components and bile acids 1 . PFIC consists of five different variant forms numbered 1 through 5 based on the gene involved 2 .…”

Type 3 of progressive familial intrahepatic cholestasis (PFIC-3): Case report

“…Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of genetic autosomal recessive disorders which cause defects in the formation and secretion of bile components and bile acids [1]. Progressive Familial Intrahepatic Cholestasis consists of five different variant forms numbered 1 through 5 based on the gene involved [2].…”