On August 27, 2024, the team led by Dr. Chuanlong Zhu from the Infectious Diseases Department at Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University) published a case report in the Electronic Gastro Curbside Consult section of Gastroenterology, a prestigious journal in the field of digestive diseases. The report detailed a rare case of liver function injury caused by hypercholanemia resulting from a homozygous mutation of the SLC10A1 gene. The first author of the report is Zixing Dai, a master's student at Nanjing Medical University, with Dr. Chuanlong Zhu serving as the corresponding author.Three pathogenic mutation sites in the SLC10A1 gene have been reported, among which c.800C＞T (p.Ser267Phe) is the most common mutation in China. This mutation significantly reduces the expression of sodium taurocholate co-transporting polypeptide (NTCP), a protein responsible for bile acid metabolism. While adults with this mutation may not show obvious clinical symptoms, children might experience jaundice and developmental delays. The disease follows an autosomal recessive inheritance pattern and can only be diagnosed through persistently elevated bile acid levels and genetic testing, making misdiagnosis or missed diagnosis common.
The patient in this case is a 29-year-old male. In 2015, an abnormal liver function was discovered during a routine physical exam. Since there were no clinical symptoms, no further examination or treatment was pursued. In 2021, he sought treatment at another hospital after experiencing “abnormal liver function for 7 years, accompanied by fatigue and poor appetite for one month.” Tests for hepatitis B (HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc) and immune markers were normal, and antibodies for hepatitis A and E were negative. Ultrasound showed no significant abnormalities in the liver, gallbladder, or pancreas. After receiving liver-protecting treatment with ursodeoxycholic acid, his liver function returned to normal, but his bile acid levels remained elevated. In June 2022, he was hospitalized again due to abnormal liver function. Liver biopsy results showed no significant abnormalities, and liver-protecting treatment continued, but the underlying cause of his abnormal liver function remained unclear.
In December 2023, the patient sought treatment at Jiangsu Province Hospital in the Infectious Diseases Department. After ruling out viral hepatitis, fatty liver, drug-induced liver injury, and alcoholic liver disease, Professor Chuanlong Zhu’s team conducted genetic testing for metabolic liver disease. The testing revealed a homozygous mutation in the SLC10A1 gene at the c.800C＞T site, and further genetic testing of his parents showed a heterozygous mutation at the same site. His parents were asymptomatic, consistent with the autosomal recessive inheritance pattern.
Dr. Zhu’s team further performed fluorescent staining of the patient’s liver biopsy, which showed a significant decrease in NTCP expression. Hypercholanemia can be toxic to liver cells over time, and persistent elevation of bile acids can lead to abnormal liver function. Ultimately, the patient was diagnosed with hypercholanemia caused by NTCP deficiency.
Bile acid circulation consists of three main processes: bile acids are absorbed into liver cells, secreted into bile ducts, and then enter the intestines through bile. They are reabsorbed into the liver through the portal vein. Any genetic abnormalities in this process can disrupt bile acid circulation, leading to clinical symptoms.
Dr. Chuanlong Zhu emphasized that the uniqueness of this case lies in the fact that the patient showed no symptoms during infancy but developed liver function abnormalities and elevated bile acid levels in adulthood. Genetic testing can accurately pinpoint the mutation gene and site, and when necessary, additional experiments to verify expression can further confirm the diagnosis.
