Abstract: Objective To investigate the dynamic changes of intrahepatic T cell receptor (TCR) repertoires before and after nucleos(t)ide analogues (NUCs) antiviral therapy in chronic hepatitis B (CHB) patients. Methods A total of ten CHB patients with tebivudine (LDT) based therapy were subdivided to two groups on HBeAg status after 104 treatment. The TCRβ complementarity determining region 3 (CDR3) of liver biopsies before and after 2-year NUCs treatment was analyzed by high-throughput sequencing. The TCR repertoire profiles and their correlations with serological parameters were analyzed. Results After LDT-based treatment for 104 weeks, the diversity of intrahepatic TCR repertoires in patients with HBeAg seroconversion decreased significantly on the number of unique VJ combinations (151.0 比 71.0, P=0.043), CDR3 clonotypes (223.0 比 109.0, P=0.043), and the values of normalized Shannon diversity entropy (0.58 比 0.17, P=0.045). The decline of HBsAg levels in these patients was positively correlated with the elevation of ablated clonetype frequency (r=0.9, P=0.037). Conclusion NUCs antiviral therapy may induce changes of intrahepatic TCR repertoires. T cell clone expansion plays an important role in HBeAg seroconversion, suggesting that oral antiviral therapy combined with immunotherapy may be more conducive to the control of HBV.

Key words: Chronic hepatitis B, T cell receptor β, High throughput sequencing