Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

AIM: To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection.METHODS: A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages: immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. SerumHBV DNA load was assessed by quantitative real-time polymerase chain reaction.RESULTS: CD8+ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages (36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P < 0.001). The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8+ T-cells than CD4+ T-cells (36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P < 0.01), whereas the peripheral blood in patients at the immune-inactive carrier stage and in normal controls contained less CD8+ T-cells than CD4+ T-cells (28.09 ± 5.64 vs 36.85 ± 6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P < 0.01). ANOVA linear trend test showed that CD8+ T-cells were signif icantly increased in patients with a high viral load (39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P < 0.001), while CD4+ T-cells were signif icantly increased in patients with a low HBV DNA load (37.45 ± 6.14, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P < 0.001). Multiple regression analysis displayed that log copies of HBV DNA still maintained its highly signif icant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3+, CD4+ and CD8+ cells and CD4+/CD8+ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.CONCLUSION: Differences in peripheral T-cell subpopulation profi les can be found in different clinical stages of chronic HBV infection. T-cell impairment is signifi cantly associated with HBV load.

AIM： To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus （HBV） replication in different dinical stages of chronic HBV infection. METHODS： A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages： immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time poiymerase chain reaction. RESULTS： CD8^＋ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages （36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P 〈 0.001）. The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8^＋ T-cells than CD4^＋ T-cells （36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P 〈 0.01）, whereas the peripheral blood in patients at the immune- inactive carrier stage and in normal controls contained less CD8^＋ T-cells than CD4^＋ T-cells （28.09 ± 5.64 vs 36.85 ±6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P 〈 0.01）. ANOVA linear trend test showed that CD8^＋ T-cells were significantly increased in patients with a high viral load （39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P 〈 0.001）, while CD4^＋ T-cells were significantly increased in patients with a low HBV DNA load （37.45 ± 6.24, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P 〈 0.001）. Nultiple regression analysis displayed that log copies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3^＋, CD4^＋ and CD8^＋ cells and CD4^＋/CD8^＋ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation. CONCLUSION： Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load.