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World J Gastroenterol. Feb 21, 2008; 14(7): 1112-1119
Published online Feb 21, 2008. doi: 10.3748/wjg.14.1112
Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B
Jing You, Hutcha Sriplung, Alan Geater, Virasakdi Chongsuvivatwong, Lin Zhuang, Hong-Ying Chen, Lan Yu, Bao-Zhang Tang, Jun-Hua Huang
Jing You, Hutcha Sriplung, Alan Geater, Virasakdi Chongsuvivatwong, Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
Lin Zhuang, Department of Hepatopathy, Third Municipal People’s Hospital of Kunming, Kunming 650041, Yunnan Province, China
Hong-Ying Chen, Lan Yu, Bao-Zhang Tang, Department of Infectious Diseases, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
Jun-Hua Huang, Department of Infectious Diseases, Yunnan General Hospital of the Chinese People’s Armed Police Forces, Kunming 650111, Yunnan Province, China
Correspondence to: Dr. Jing You, Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. jingyoukm@126.com
Telephone: +66-84-6320906
Received: August 21, 2007
Revised: October 23, 2007
Published online: February 21, 2008
Abstract

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.

Keywords: Hepatitis B virus; Chronic hepatitis B virus infection; Hepatitis B virus DNA; T lymphocyte subpopulation; Immune function