Influence of Treg cells and HBV genotype on sustained response and drug resistance in the treatment with nucleoside drugs

Abstract

We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X 2=4.239, P=0.040; t=2.015, P=0.044; X 2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to lamivudine were closely correlated with baseline factors; the same cannot be found for entecavir.

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

“…However, in contrast to this opinion, Zhang et al argue that Tregs (CD4 + CD25 + ) levels were lower in the group that responded to lamivudine treatment than in the group that did not respond. No significant change of Tregs was observed in the entecavir treatment group [112], which may be due to the difference in the specific markers selected for Tregs. Th17 cells mediate non-specific inflammation, and the Th17/Treg imbalance is associated with disease progression in patients with CHB infection [113].…”

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

“…Nevertheless, Zhang et al contended that the levels of Tregs identified as CD4 + CD25 + were reduced in the cohort displaying a positive response to lamivudine treatment compared to the non‐responsive group. No significant change in Tregs was observed in the entecavir treatment group [98], possibly due to the difference in the specific markers selected for Tregs. Th17 cells mediate nonspecific inflammation, and the Th17/Treg imbalance is associated with disease progression in patients with CHB infection [99].…”