title: Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Epidemiology Unit, Faculty of Medicine, Prince of Songkhla University, Hat Yai, Songkhla 90110, Thailand. jingyoukm@126.com
authors.forename: Jing
authors.initials: J
authors.lastname: You
authors.forename: Hutcha
authors.initials: H
authors.lastname: Sriplung
authors.forename: Alan
authors.initials: A
authors.lastname: Geater
authors.forename: Virasakdi
authors.initials: V
authors.lastname: Chongsuvivatwong
authors.forename: Lin
authors.initials: L
authors.lastname: Zhuang
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Chen
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.forename: Bao-Zhang
authors.initials: BZ
authors.lastname: Tang
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Huang
mesh_terms: D000328:Adult; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006515:Hepatitis B virus / Q000302:isolation & purification / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology*; D006801:Humans; D016014:Linear Models; D008297:Male; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000821:virology; D014779:Virus Replication
chemical_list: D004279:DNA, Viral