Primary biliary cholangitis (PBC) is an autoimmune liver disease with strong genetic susceptibility.The genome-wide association studies and immunochip studies conducted in recent years help to reveal the pathogenesis of PBC.The susceptibility genes of PBC are classified into human leukocyte antigen gene and non-human leukocyte antigen gene,and most of the susceptibility loci are associated with immune regulation,suggesting that disorders of the immune regulatory pathways may play an important role in the pathogenesis of PBC.In addition,the weighted genetic risk score of these candidate genes may predict the risk of PBC.At present,about one third of PBC patients have suboptimal response to ursodeoxycholic acid;therefore,targeted drugs for susceptibility genes may become an effective substitutive therapy.

Objective:To investigate the expressional condition of interleukin-16 (IL-16) in the liver and serum of patients with primary biliary cholangitis (PBC).Methods:Liver biopsies samples were collected from 70 cases and 10 healthy controls, and serum samples were collected from 62 cases and 87 healthy controls. The expression of IL-16 in liver was detected by immunohistochemistry, and the serum level of IL-16 was determined by enzyme-linked immunosorbent assay. The correlation between the expression level of IL-16 and the severity of disease was determined by correlation analysis with clinical biomarker. The t-test was used for normally distributed data. Wilcoxon signed rank sum test was used for non-normally distributed data.Results:The expression level of IL-16 in the liver of PBC patients was significantly higher than that in the healthy control group ( P = 0.002 5), and it was mainly expressed in infiltrating lymphocytes in the portal area. Correlation analysis showed that the level of IL-16 in liver tissue was positively correlated with the degree of liver inflammation ( r = 0.36, P = 0.002). In addition, the serum IL-16 level of PBC patients were significantly higher than that of healthy people ( P = 0.000 5), and serum IL-16 level was correlated with the level of cholestasis biomarker γ-glutamyltransferase ( r = 0.31, P = 0.03). Conclusion:The expression level of IL-16 is significantly increased in liver and serum of PBC patients, and it is positively correlated with the severity of the disease, suggesting that IL-16 may be used as a biomarker to assess the severity of the disease.

Intestinal homeostasis depends on complex interactions between the gut microbiota and host immune system. Emerging evidence indicates that the intestinal microbiota is a key player in autoimmune liver disease (AILD). Autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and IgG4-related sclerosing cholangitis have been linked to gut dysbiosis. Diverse mechanisms contribute to disturbances in intestinal homeostasis in AILD. Bacterial translocation and molecular mimicry can lead to hepatic inflammation and immune activation. Additionally, the gut and liver are continuously exposed to microbial metabolic products, mediating variable effects on liver immune pathologies. Importantly, microbiota-specific or associated immune responses, either hepatic or systemic, are abnormal in AILD. Comprehensive knowledge about host-microbiota interactions, included but not limited to this review, facilitates novel clinical practice from a microbiome-based perspective. However, many challenges and controversies remain in the microbiota field of AILD, and there is an urgent need for future investigations.