Profiling of Peripheral TRBV and CD4+CD25+ Treg in CHB Patients with HBeAg SC during TDF Treatment

Abstract

Background. It is lacking that markers could predict the prognosis of chronic hepatitis B (CHB) subjects during antiviral treatment, and the related cellular immune mechanism is not fully evaluated. Aim. To explore the comprehensive profile of T cell receptor β-chain (TRBV) and CD4+CD25+ regulatory T cell (Treg) in peripheral blood of CHB patients with HBeAg seroconverting (SC) during tenofovir disoproxil fumarate (TDF) treatment. Methods. The frequency of CD4+CD25high+ Treg and number of skewed TRBV in 20 HBeAg positive patients were determined at baseline and following every 12 weeks during 96-week TDF treatment. The relationship among serum alanine aminotransferase (ALT) level, HBV DNA load, Treg frequency, and the number of skewed TRBV, respectively, was analyzed for CHB patients. Receiver operative characteristic curve was applied to analyze their diagnostic value for HBeAg SC. Results. The number of skewed TRBV at week 48, Treg frequency at week 72, and ALT level at baseline could predict the HBeAg SC or non-SC in CHB patients during 96-week TDF treatment. Moreover, the positive correlation between ALT or HBV DNA and Treg levels or skewed TRBVs was significant in the SC group, but not in non-SC. Conclusions. The predictive cutoff value of ALT for HBeAg SC was 178 U/L at baseline. Moreover, the ALT, Treg, and TRBV families would be associated with the prognosis and pathogenesis of CHB patients during TDF treatment.

Therapeutic effectiveness analysis of tenofovir alafenamide and tenofovir disoproxil fumarate on the treatment for chronic hepatitis B

“…Multiple research results suggest that TDF and TAF have good efficacy and safety for CHB, compared with other NAs, they also have certain advantages in terms of resistance. [15][16][17][18][19][20][21][22][23] The mechanism of action of TAF and TDF is the same, both are new antiviral drugs for the treatment of CHB. After oral administration, they are converted to the diphosphate form of tenofovir, which can bind to deoxynucleoside substrates, inhibit the activity of the viral polymerase, and subsequently exert an inhibitory effect on the extension of HBV-DNA, blocking the replication of hepatitis B virus and achieving the therapeutic effect.…”

“…Multiple research results suggest that TDF and TAF have good efficacy and safety for CHB, compared with other NAs, they also have certain advantages in terms of resistance. [15–23]…”

The dual role of regulatory T cells in hepatitis B virus infection and related hepatocellular carcinoma

“…Pan et al conducted a 96 week follow-up of the HBV-infected patients undergoing antiviral therapy and found that patients with a high HBV viral load had higher levels of Tregs before antiviral therapy than after antiviral therapy [102]. Other studies also showed that timely and effective antiviral therapy can continuously inhibit viral replication and antigen production, resulting in a reduction in Tregs and a resumption of the immune response [103,104]. In summary, these findings suggest that Tregs inhibit the HBV-specific T cell responses in patients with CHB.…”