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Published on: May 10, 2022
CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during
Jiezuan Yang1, Shaoyan Xu2, Jinlin Cheng1
1The First Affiliated Hospital, Zhejiang University School of Medicine, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Hangzhou, China.
Insights
Serum levels of C-X-C motif ligand-10 (CXCL10) and CXCR3 predict hepatitis B outcomes. A decrease in CXCL10 during tenofovir disoproxil fumarate (TDF) therapy indicates a higher chance of hepatitis B e antigen seroconversion.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Serum C-X-C motif ligand-10 (CXCL10) and its receptor CXCR3 may predict outcomes in chronic hepatitis B (CHB) patients on tenofovir disoproxil fumarate (TDF).
- Limited data exists on CXCL10/CXCR3 profiles and clinical utility in HBeAg-positive CHB patients during TDF treatment.
Purpose of the Study:
- To investigate the profile and clinical application of CXCL10 and CXCR3 in HBeAg-positive CHB patients receiving TDF.
- To explore the association between CXCL10/CXCR3 dynamics and HBeAg seroconversion (SC).
Main Methods:
- CXCL10 and CXCR3 levels were measured in 118 CHB patients treated with TDF for at least 96 weeks.
- Gene set enrichment analysis explored gene sets linked to HBeAg SC.
- Immunohistochemical analysis assessed CXCL10/CXCR3 protein in liver tissues before and after TDF treatment.
Main Results:
- Changes in CXCL10 (ΔCXCL10) and CXCR3 (ΔCXCR3) correlated with HBeAg SC possibility.
- Liver tissue CXCL10/CXCR3 showed significant differences post-successful TDF treatment.
- Multivariate Cox analysis identified ΔCXCL10 as an independent predictor of HBeAg SC (AUC=0.8867).
Conclusions:
- Lower descending CXCL10 levels are associated with increased HBeAg SC probability in CHB patients on TDF.
- Liver tissue CXCL10 may play a role in the immunological process of HBeAg SC.
Abstract:
The serum chemokine C-X-C motif ligand-10 (CXCL10) and its unique receptor (CXCR3) may predict the prognosis of patients with chronic hepatitis B (CHB) treated with tenofovir disoproxil fumarate (TDF). Nevertheless, there are few reports on the profile of CXCL10 and CXCR3 and their clinical application in HBeAg (+) CHB patients during TDF antiviral therapy. CXCL10 and CXCR3 were determined in 118 CHB patients naively treated with TDF for at least 96 weeks at baseline and at treatment weeks 12 and 24. In addition, gene set enrichment analysis was used to examine the associated dataset from Gene Expression Omnibus and explore the gene sets associated with HBeAg seroconversion (SC). The change of CXCL10 (ΔCXCL10, baseline to 48-week TDF treatment) and CXCR3 (ΔCXCR3) is closely related to the possibility of HBeAg SC of CHB patients under TDF treatment. Immunohistochemical analysis of CXCL10/CXCR3 protein in liver tissue shows that there is a significant difference between paired liver biopsy samples taken before and after 96 weeks of successful TDF treatment of CHB patients (11 pairs) but no significance for unsuccessful TDF treatment (14 pairs). Multivariate Cox analysis suggests that the ΔCXCL10 is an independent predictive indicator of HBeAg SC, and the area under the receiver operating characteristic curve of the ΔCXCL10 in CHB patients is 0.8867 (p < 0.0001). Our results suggest that a lower descending CXCL10 level is associated with an increased probability of HBeAg SC of CHB patients during TDF therapy. Moreover, liver tissue CXCL10 might be involved in the immunological process of HBeAg SC.
