Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

AIM: To investigate peripheral T-lymphocyte subpopulation 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 significantly 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. (c) 2008 WJG. All rights reserved.