Distinct T-cell receptor profiles associated with hepatitis B e antigen seroconversion during entecavir treatment.

Background & Aims: T-cell receptor (TCR) repertoire is ambiguously changed in chronic hepatitis B (CHB) patients during antivirus therapy. We tried to assess TCR repertoire dynamics and its clinical significance upon HBeAg seroconversion in CHB patients.

Methods: Twenty CHB patients undergoing 1-year entecavir (ETV) treatment were enrolled, including 10 complete response (CR) vs 10 non-complete response (NCR) patients based on HBeAg seroconversion at week 48. The TCRβ complementarity-determining region 3 (CDR3) of peripheral CD4 and CD8 T cells at weeks 0, 12 and 48 was analyzed by unbiased high-throughput sequencing. The TCR repertoire profiles and their correlations with serological parameters were analyzed.

Results: The diversity of TCRβ repertoires was decreasing in CR patients but increasing in NCR patients. The distribution pattern of TCR repertoires stratified according to clonotype frequencies changed in the opposite direction between CR and NCR patients. Narrow amounts of newly appearing clonotypes in CR patients experienced a more intensive and robust expansion and this phenomenon could occur as early as week 12 for the CD4 subset but later at week 48 for the CD8 subset. There existed some CR-exclusive clonotypes with a relatively low but increasing frequency at week 48. The number of unique TCRβ clonotypes was positively correlated with the ALT or HBV DNA level in CR patients but showed no or negative correlation in NCR patients.

Conclusion: Distinct TCR profiles contribute to predicting HBeAg seroconversion in CHB patients during ETV treatment and certain TCRβ CDR3 motif may be utilized for CHB immunotherapy in the future.