A 17-year-old boy presented with jaundice, white clay stool, nausea, and loss of appetite for 1 month. There was no history of rash 3 months before admission. Chinese medicine was externally applied, and the patient took anti-allergy drugs orally. Later, the rash improved, and fever occurred intermittently. The patient was a student with no history of other drug use, blood transfusions, allergies, smoking, or alcohol. His parents are in good health. Physical examination found that his skin and sclera were yellow. No other abnormalities were noted upon physical examination. The liver-related laboratory examination revealed cholestasis, and GGT levels were normal. Aspartate aminotransferase (AST), 36 U/L; alanine aminotransferase (ALT), 35 U/L; alkaline phosphatase (ALP), 157 U/L; Total bile acid (TBA), 150 mumol/L; total bilirubin (TBIL), 298.4 mumol/L; and direct bilirubin (DBIL), 227.4 mumol/L. Serological and laboratory results excluded autoimmune hepatitis, primary biliary cholangitis (PBC), viral hepatitis, Wilson disease and a1-antitrypsin deficiency (Table 1). Ultrasound examination showed no cholelithiasis or bile duct dilatation. The liver stiffness measurement was 11.4 kPa. Computed tomography (CT) shows no abnormality in the liver, and the gallbladder is collapsed without bile filling. Magnetic resonance cholangiopancreatography (MRCP) shows suspected stenosis at the beginning of the common hepatic duct. Endoscopic ultrasonography showed that the extrahepatic bile duct was normal without dilation, and no definite obstruction was observed. Gastroscopy showed the size and morphology of the duodenal papilla were normal (Figure 1).
To clarify the cause of cholestasis, liver biopsy was performed and sections stained with hematoxylin-eosin (HE), Masson, mesh, PAS, DPAS, iron, CK7, CK19, CD10 and bile salt export pump (BSEP). Liver biopsy revealed a clear lobular structure. The main lesions were cholestasis with hepatocytes in central lobules II and III, bile embolism of capillary bile ducts and cholestasis with Kupffer cells, and positive staining for CK7 in some hepatocytes in the lobule (Figure 2). Pathological-clinical diagnosis is simple cholestasis. Genetic testing was performed on the patient and his parents. The patient's genetic test revealed a rare missense mutation ATP8B1 rs540027832 (chr18-55328450 c.2663C > A p. T888K NM_00560 3.4) (Supplementary Table 1), and genetic tests on his parents showed that the mutation was inherited from his father (Supplementary Figure 1).
The patient's clinical manifestations and related examination results conformed to BRIC1. Drug-induced liver injury cannot be excluded. The patient was treated with glycyrrhizin, ursodeoxycholic acid (UDCA), glucocorticoids and haemofiltration. After 5 rounds of haemofiltration, the patient's symptoms gradually improved, and the bilirubin index gradually decreased. After follow-up, bilirubin gradually decreased to normal within 3 months.