The Study Of Progressive Familial Intrahepatic Cholestasis Related With ABCB11/BSEP Gene Mutation

Objective: To study and summarize the clinical features and diagnosis of progressivefamilial intrahepatic cholestasis type2, as to distinguish the type ofprogressive familial intrahepatic cholestasis at the first, then to treat it in timeand improve the prognosis.Method: Collect and analyse clinical manifestations, laboratory examinations, liverhistopathology findings, other examination findings and molecular studies ofthe three cases of progressive familial intrahepatic cholestasis type2andreview the related literature.Result: Of the three progressive familial intrahepatic cholestasis type2(PFIC2)patients, there were one male and two female infants.The age at onset wasduring the first three months of life, and the earliest was the third day of life.The main clinical features of the patients included cholestasis ofhepatocellular origin, severe pruritus and jaundice. Hepatosplenomegaly withor without liver texture changed was the main physical sign. Some patientshowed hydroperitoneum. The patients all showed elevated levels of serumtotal bilirubin, especially conjugated bilirubin, very high serum bile saltsconcentration, and high serum alkaline phosphatase (ALP) level, but low ornormal levels of serum gamma-glutamyl transpeptidase(GGT) and normalserum cholesterol level. Two patients who underwent the operation of liverbiopsy showed mild to severe hydropic degeneration of most liver cells,cholestasis of hepatocytes and canaliculus, and periportal and lobular fibrosismay seen; the electron microscopy findings included bile pigment granulesand Kupffer’s cells distribution. The three patients all had a heterozygousmutation in exon13of the ABCB11gene. Medication with UDCA and supplement of fat-soluble vitamins were considered during the initialtherapeutic management, and partial external biliary diversion had been usedaccording to disease course. The resultant liver cirrhosis in PFIC2patientsstill required liver transplantation. The outcomes of follow-up includedjaundice cleared away entirely or slightly, or death of cirrhosis and liverfunction failure.Conclusion: The diagnosis of progressive familial intrahepatic cholestasis type2is on thebasis of clinical presentations, liver histopathology findings and geneticanalysis, excluding other causes of childhood cholestatic disorders. PFIC2iscaused by impaired bile secretion due to defect in ABCB11gene encodingthe bile salt export pump protein (BSEP), but the disease mechanism is stillunclear. Progressive familial intrahepatic cholestasis shows disease onsetearly, progression rapid of the natural course, and difficult differentialdiagnosis, but unknown mechanisms. It is very important to identify the typeand severity of the disease according to clinical and molecular analysis ofProgressive familial intrahepatic cholestasis for management and prognosis.