Zhang Y R, Li B, Wang C X, Zhou N, Qi W, Li X L, Wu L Y, Wei S F, Zhang Y D
Department of Infectious Diseases, The First People's Hospital of Lanzhou, Gansu, China.
Department of Thoracic Surgery, Gansu Province Tumor Hospital, Gansu, China.
Braz J Med Biol Res. 2017 Mar 2;50(3):e5796. doi: 10.1590/1414-431X20165796.
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; X2=4.239, P=0.040; t=2.015, P=0.044; X2=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.
我们旨在研究调节性T细胞（包括CD4+CD25+、CD8+CD28-）及乙型肝炎病毒（HBV）基因型对核苷类药物持续病毒学应答及耐受性的影响。共纳入137例患者。84例患者接受拉米夫定治疗，另外53例患者接受恩替卡韦治疗。治疗前，检测生化指标、HBV DNA载量、HBV血清水平、HBV基因型、外周血CD3+、CD4+、CD8+、CD4+CD25+/CD3+以及CD8+CD28-/CD3+频率。根据治疗4周后的HBV DNA载量，将患者分为应答组和次优应答组。拉米夫定组继续治疗，之后再分为无耐药组和耐药组。与拉米夫定的次优应答组和耐药组相比，应答组和无耐药组的CD4+CD25+/CD3+水平更高（t=4.372，P=0.046；t=7.262，P=0.017）。在无耐药组中，CD8+CD28-/CD3+频率低于耐药组（t=5.527，P=0.037）。病毒载量和乙肝e抗原（HBeAg）阳性率显著低于应答组和耐药组（t=2.164，P=0.038；X2=4.239，P=0.040；t=2.015，P=0.044；X2=16.2，P=0.000）。C型病毒基因型患者的耐药发生率较高。对于恩替卡韦的病毒学应答，CD8+CD28-/CD3+水平显著低于次优应答组（t=6.283，P=0.036）。比较应答组和次优应答组的CD3+、CD4+、CD8+、CD4+CD25+/CD3+以及病毒基因型，差异无统计学意义（P>0.05）。包括CD4+CD25+/CD3+和CD8+CD28-/CD3+频率在内的基线调节性T细胞与快速病毒学应答发生率及核苷类药物耐药性有关。接受拉米夫定治疗的C型HBV基因型患者更常出现耐药。抗病毒疗效及对拉米夫定的耐药性与基线因素密切相关；恩替卡韦则未发现这种情况。
