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

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. 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 b e t w e e n t h e l e ve l s o f C D 3 + a n d C D 4 + c e l l s a n d 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. RESULTS 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.

Direct role of antibody‐secreting B cells in the severity of chronic hepatitis B

“…Chronic hepatitis B is responsible for the death of millions of people all over the world. Many studies have shown that cellular immune response against HBV virus is important in controlling the infection with this virus [Lavanchy, ; You et al, ]. T lymphocytes subgroups such as CD4 + and CD8 + cells are known to respond to this virus and directly affect on the severity of chronic hepatitis B.…”

“…Many investigators suggested the chronicity of HBV infection was caused by a deficient cellular immune function [Michalak et al, ; Khettry et al, ; Tülek et al, ]. Thus, T‐cell dysfunction might contribute towards viral persistence [You et al, ]. A significant decreasing trend in CD3 + and CD4 + cells and CD4 + /CD8 + ratio with increasing severity of hepatocyte damage with advancing age has been observed during HBV infection [You et al, ; Salih et al, ].…”

“…Thus, T‐cell dysfunction might contribute towards viral persistence [You et al, ]. A significant decreasing trend in CD3 + and CD4 + cells and CD4 + /CD8 + ratio with increasing severity of hepatocyte damage with advancing age has been observed during HBV infection [You et al, ; Salih et al, ]. For a non‐cytopathic virus like HBV to persist, it must either overwhelm or not induce an effective antiviral immune response, or it must be able to evade it.…”

Public awareness of three major infectious diseases in rural Zhejiang province, China: a cross-sectional study

“…In China, approximately 780,000 people live with HIV; 26,000 died from Acquired Immune Deficiency Syndrome (AIDS) in 2009 [1], while 4.5 million Chinese have been infected with active pulmonary TB, 1.5 million of whom are smear-positive [2]; meanwhile 120 million people have been chronically infected with HBV [3], and more than 300,000 people die from HBV-related diseases every year [4]. According to the 6 th national population census, over 0.67 billion people live in rural areas and account for 50.32% of the entire population.…”

Substance Abuse, HIV-1 and Hepatitis

“…Similarly, efforts are under way to determine the effects of chronic HBV infection on the function of the peripheral immune system. A study involving 206 individuals with chronic HBV infection demonstrated that T-cell dysfunction in these individuals was extensive and persisted with a significant decrease in CD3 + T cells, which translated into a loss of competent cells that were immunologically capable of challenging the infection [79]. In fact, there have been reports that antiviral treatment can increase CD4 + [80] and CD8 + [81, 82] T-cell responsiveness to chronic HBV infection, suggesting that these cell populations were present but suppressed by HBV infection.…”