摘要
AIM: To investigate peripheral T-lymphocyte sub-population profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).METHODS: Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR). The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS: CHB patients had significantly decreased CD3+ and CD4+ cells and CD4+/CD8+ ratio, and increased CD8+ cells compared with uninfected controls (55.44 ± 12.39 vs 71.07 ± 4.76, 30.92 ± 7.48 vs 38.94 ± 3.39, 1.01 ± 0.49 vs 1.67 ± 0.33, and 34.39 ± 9.22 vs 24.02 ± 4.35; P < 0.001, respectively). Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen (HBeAg) expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P < 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P < 0.001). There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r = -0.68, -0.65 and -0.75, all P < 0.0001), and a positive correlation between CD8+ cells and viral load (r = 0.70, P < 0.0001). There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P < 0.01). In multiple regression (after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations, and was the strongest predictor of variation in CD3+, CD4+, CD8+ cells and CD4+/CD8+ ratio. However, the effect of HBeAg was not significant.CONCLUSION: T-lymphocyte failure was signifi-cantly associated with viral replication level. The substantial linear dose-response relationship and strong independent predictive effect of viral load on T-lymphocyte subpopulations suggests the possibility of a causal relationship between them, and indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients.
AIM： To investigate peripheral T-lymphocyte sub-population profile and its correlation with hepatitis B virus （HBV） replication in patients with chronic hepatitis B （CHB）.METHODS： Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction （PCR）. The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS： CHB patients had significantly decreased CD3^＋ and CD4^＋ cells and CD4^＋/CD8^＋ ratio, and increased CD8^＋ cells compared with uninfected controls （55.44 ± 12.39 vs 71.07 ± 4.76, 30.92 ± 7.48 vs 38.94 ± 3.39, 1.01 ± 0.49 vs 1.67 ± 0.33, and 34.39 ± 9.22 vs 24.02 ± 4.35; P 〈 0.001, respectively）. Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen （HBeAg） expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P 〈 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations （linear trend test P 〈 0.001）. There was a negative correlation between the levels of CD3＋ and CD4＋ cells and CD4^＋/CD8^＋ ratio and serum level of viral load in CHB patients （r = -0.68, -0.65 and -0.75, all P 〈 0.0001）, and a positive correlation between CD8^＋ cells and viral load （r = 0.70, P 〈 0.0001）. There was a significant decreasing trend in CD3^＋ and CD4^＋ cells and CD4^＋/CD8^＋ ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection （linear trend test P 〈 0.01）. In multiple regression （after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity） log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations, and was the strongest predictor of variation in CD3^＋, CD4^＋, CD8^＋ cells and CD4^＋/CD8^＋ ratio. However, the effect of HBeAg was not significant.CONCLUSION： T-lymphocyte failure was signifi-cantly associated with viral replication level. The substantial linear dose-response relationship and strong independent predictive effect of viral load on T-lymphocyte subpopulations suggests the possibility of a causal relationship between them, and indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients.
