Clinical and pathological features of progressive familial intrahepatic cholestasis type 3 / 临床肝胆病杂志

ABSTRACT

Objective To investigate the clinical and pathological features of progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods A retrospective analysis was performed for 1326 patients with unexplained liver disease who attended Nanjing Second Hospital from January 2017 to December 2019, among whom 8 patients were diagnosed with PFIC3 based on clinical/pathological manifestation and gene sequencing results (1 patient did not undergo liver biopsy due to contraindication). Clinical, laboratory, imaging, and pathological findings were analyzed and a literature review was performed for the pathology of ABCB4-related diseases to summarize the clinical and pathological features of PFIC-3. Results Among the 8 patients with PFIC3, there were 5 male patients and 3 female patients, with a median age of 29.5 years. Of all 8 patients, 4 (50%) manifested as chronic cholestasis and 4 (50%) manifested as biliary cirrhosis, among whom 3 (75%) had the manifestation of portal hypertension. As for biochemical examination, 75% (6/8) had an increase in alkaline phosphatase, and 100% (8/8) had an increase in gamma-glutamyl transpeptidase. As for imaging examination, 50% (4/8) had cholecystitis, 25% (2/8) had gallstones, 25% (2/8) had bile duct dilatation, 75% (6/8) had splenomegaly, and 25% (2/8) had liver cirrhosis. As for liver biopsy, all 7 patients manifested as bile duct injury and/or reduction, and 57.1% (5/7) had absence of the bile duct. Multidrug resistance P-glycoprotein 3 (MDR3) immunohistochemical staining showed normal expression in 42.9% (3/7) of the patients and reduced expression in 57.1% (4/7) of the patients. Literature review obtained 17 articles with a description of the bile duct or MDR3 immunohistochemistry. Among the 7 patients with low phospholipid-associated cholelithiasis, 71.4% (5/7) had normal bile duct, 14.3% (1/7) had bile duct reduction, and 14.3% (1/7) had absence of the bile duct; among the 6 patients with intrahepatic cholestasis of pregnancy, 16.7% (1/6) had normal bile duct, 50% (3/6) had bile duct reduction, and 33.3% (2/6) had absence of the bile duct; among the 8 patients with PFIC3, 25% (2/8) had bile duct reduction and 75% (6/8) had absence of bile duct; among the 21 patients with PFIC3, 9.5% (2/21) had normal expression of MDR3, 23.8% (5/21) had a reduction in the expression of MDR3, and 66.7% (14/21) had absence of the expression of MDR3. Conclusion PFIC3 mainly manifests as cholestasis, cholelithiasis, and hepatic fibrosis. Pathological manifestation includes bile duct injury and bile duct reduction or absence of the bile duct in severe cases, and the degree of injury is associated with disease severity. MDR3 immunohistochemistry may show normal expression, reduced expression, or absence of expression, and diagnosis cannot be excluded in patients with normal expression. Genetic testing can be performed for diagnosis when necessary.