Copyright ©The Author(s) 2020.
World J Gastroenterol. Dec 21, 2020; 26(47): 7470-7484
Published online Dec 21, 2020. doi: 10.3748/wjg.v26.i47.7470
Table 1 Overview of progressive familial intrahepatic cholestasis subtypes

PFICAssociated with MYO5B defects
Molecular findingsImpaired hepatocyte bile salt secretion; canalicular cholestasis; giant cell transformation; portal and lobular fibrosis; lack of ductular proliferationIncreased intracellular bile salt concentrations; canalicular cholestasis; lobular and portal fibrosis; hepatocellular necrosisAbsence of PC from the biliary canaliculi; increased free bile salts in canaliculi; cholangiocyte damage; increased cholesterol crystallization nonspecific portal inflammation; portal fibrosis; giant cell hepatitisAbnormal CLDN1 localization; normal CLDN2 localization; compromised tight junctions; bile salt leakage into the paracellular space; hepatocyte and cholangiocyte damage; giant cell transformationUndetectable expression of BSEP in the bile canaliculi; intralobular cholestasis with ductular reaction; hepatocellular ballooning; giant cell transformationPossibly mislocalized BSEP and MDR3 upon staining; portal and lobular fibrosis; giant cell transformation. Intestinal MVID findings (mislocalized apical brush border proteins, villus atrophy, presence of microvillus inclusion bodies)
Clinical findingsLow GGT cholestasis; jaundice caused by hyperbilirubinemia; pruritus; hepatosplenomegaly; diarrhea; stunted growth; exocrine pancreatic insufficiency; progressive sensorineural hearing loss; fat-soluble vitamin deficiencies; can lead to cirrhosis and end stage liver diseaseLow GGT cholestasis; elevated transaminases; elevated serum bilirubin; elevated AFP; jaundice; pruritus; scleral icterus; hepatomegaly; chronic skin picking; reduced growthElevated GGT cholestasis; pruritus; hepatosplenomegaly; variceal bleeding; portal hypertension; jaundice; acholic stools; stunted growth; reduced bone density; learning disabilities; elevated transaminases; elevated bilirubin; elevated APLow GGT cholestasis; neurological and respiratory symptomsNeonatal onset of normal GGT associated cholestasis; elevated serum bilirubin; elevated serum AFP; vitamin K independent coagulopathy; fibrosis progressing into micronodular cirrhosisNormal GGT cholestasis; jaundice; pruritus; mildly elevated ALT and AST; elevated serum BS; hepatomegaly
Clinical outcomesMedical management is the first line of defense, but if it is insufficient, surgical is next. Bilary diversion has been effective in around 80% of patients. The last resort is LT in patients who develop cirrhosis and liver failure. Extrahepatic symptoms can persist (or worsen) after LTThere is a 15% chance of cirrhosis developing into HCC or cholangiocarcinoma. Genetic defect(s) can aid in determination of success of biliary diversion. LT in PFIC 2 patients might lead to development of BSEP specific allo-reactive antibodies (in approximately 8% of PFIC 2 patients who undergo LT). In these cases, a second LT may be needed if BSEP deficiency develops in the new liverHCC and cholangiocarcinoma have been associated with PFIC 3. The severity varies, with those retaining MDR3 expression responding better to medical treatment. Biliary diversion procedures aren’t as effective due to severity upon presentation, but LT is curativeThere have been some reports of HCC occurrence in PFIC 4 patients, though not much is known about the mechanism. LT has been successful, with no reported recurrence of the PFIC 4 phenotype after LTPFIC 5 is very rare (only 8 cases reported in the literature so far). LT has been used, but steatosis in the transplanted liver has been reported in some casesMVID has been associated with MYO5B defects. Lifelong TPN is required but is associated with increased risk of sepsis and small bowel transplant. Combined bowel-liver transplants may reduce the risk of post transplant onset of cholestasis
TreatmentsMedical: Vitamin supplementation; UDCA; Rifampin; Cholestyramine; CFTR folding correctorsMedical: 4PBA. Surgical: Biliary diversion procedures; LT (might need increased immunosuppression)Medical: UDCA; Rifampin. Surgical: Biliary diversion; LTSurgical: LTMedical: UDCA; Rifampin; ASBT inhibitors; OCA. Surgical: LTMedical: UDCA; rifampin; Cholestyramine. Surgical: PEBD; isolated or Combined liver-bowel transplant