Abstract: Objective To compare the clinical features, transporters and genotypes of PFIC types 1, 2 and 3. Methods From 2014 to 2018, PFIC patients were diagnosed in Beijing Friendship Hospital, Capital Medical University. The clinical, biochemical, pathological and genetic sequencing results were collected. Results 19 patients met the diagnostic criteria for PFIC. The mean age was 10.6 ± 22.7 months, 52% were male. 3 cases were type 1 (15.7%), 13 cases were type 2 (68.4%), 3 cases were type 3 (15.7%). There were 15 cases (78.9%) with onset within 1 year, 12 cases (63.1%) received liver transplantation. The onset of PFIC type 2 was the earliest (2.9 ± 3.37 months). Type 3 had the latest onset (48 ± 39.1 months) and the least hepatic impairment. The most common clinical manifestations were splenomegaly in 84.2% (16/19), jaundice in 78.9% (15/19), ascites in 52.6% (10/19), pruritus in 52.6% (10/19), portal hypertension in 47.3% (9/19), hepatomegaly, portal systemic shunt and gallbladder secondary changes in 42.1% (8/19). As compared to non-cirrhotic patients, direct bilirubin [ 270.6 (59.9, 390.3) vs 79.1 (10.4, 96.5)μmol/L, > 3-fold, P=0.02], indirect bilirubin[236.4(54.9,319.5)vs 65.6(11.6,85.5)μmol/L,>4-fold,P=0.041]prothrombin time [ (22.24 ± 9.93) vs (13.83 ± 2.93)s, P=0.034] and international normalized ratio [ 1.7 (1.2, 2.4) vs 1.1 (1.0, 1.3), P=0.034] were significantly higher in patients with cirrhosis. Alkaline phosphatase [ (417.2 ± 240.3) vs (214.5 ± 58.34)U/L, approximately 2-fold, P=0.049] and leukocytes [(12.1 ± 9.7 ) vs(4.14 ± 3.56)×10⁹/L, > 2-fold, P=0.049] were significantly elevated in the normal GGT group compared to the elevated GGT group. From the perspective of liver pathology, type 1 the degree of cholestasis was the most severe, without BSEP, MDR3 and MRP2 protein loss. Decreased or complete loss of BSEP protein in type 2; MDR3 protein is completely absent in type 3 with minimal cholestasis. Conclusion The results of this study showed that PFIC 3 had mild clinical severity and GGT was significantly increased, which could be used as an important clue to differentiate the types of PFIC. In addition, gene sequencing and loss of the corresponding transporter in liver histology suggest their role for PFIC diagnosis and classification.

Key words: Progressive familiar intrahepatic cholestasis, Bile acid export pump, Gene test, Hereditary genetic liver disease