283 Tracing the Dynamics of T-Cell Subsets in Different Phases of Hbeag Negative Chronic HBV Infection (original) (raw)
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Viral Immunology, 2015
Hepatitis B virus (HBV) is a leading cause of liver cirrhosis and hepatocellular carcinoma. The outcome of HBV infection is largely determined by the host immune response, with virus-specific cytotoxic T cells being able to mediate immunity against HBV as well as causing liver pathology. cd T cells are reported to be depleted in patients with HBV-associated liver disease. However, it is not known if these cells control HBV infection in patients with asymptomatic chronic HBV infection. In this study, the frequencies, phenotypes, and interferon-c production were examined by circulating cd T cell subsets in a group of asymptomatic HBV carriers with low viral loads and little evidence of liver disease. It is shown that cd T cells expressing Vd1 and Vd2 T cell receptors and effector-memory phenotypes are found at higher frequencies in these patients compared to controls. Vd2 T cells from the patients expressed interferon-c significantly more frequently than Vd2 T cells from healthy donors in the absence of ex vivo stimulation. These data suggest that effector-memory IFN-cproducing Vd2 T cells may contribute to the control of HBV in patients with asymptomatic infection, without mediating liver pathology.
Acute phase HBV-specific T cell responses associated with HBV persistence after HBV/HCV coinfection
Hepatology, 2005
A cute symptomatic hepatitis B virus (HBV) infections acquired in adult life are self-limited in virtually all cases. For this reason, HBV-specific T cell responses mounted in the infected host at the early acute stage of infection have been characterized only in self-limited cases of acute hepatitis B when both CD4and CD8-mediated responses are generally vigorous, multispecific, and Th1 oriented. 1-8 In contrast, HBV-specific T cell responses are deeply depressed in patients with an established and long-lasting condition of chronic HBV infection, 1-3,9-11 but the behavior of these responses early after infection when the virus subsequently persists is totally unknown. Therefore, whether the impairment of T cell responses typical of chronic hepatitis B is a cause of virus persistence or rather represents an effect of chronic infection remains undefined.
PLoS ONE, 2013
Background & Aims: The immune impairment characterizing chronic hepatitis B (cHBV) infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV. Methods: Peripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis) of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNc ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay. Results: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients. Conclusions: Different clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.
Biomedicines
HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206–1945]PEIU/mL) and declines in chronic hepatitis (481[28–1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = −0.66, p = 0.006) and chronic hepatitis (Rho = −0.35; p = 0.05). Interestingly, qHBeAg st...
World Journal of Gastroenterology, 2009
To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection. A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages: immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time polymerase chain reaction. CD8(+) T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages (36.87 +/- 7.58 vs 34.37 +/- 9.07, 36.87 +/- 7.58 vs 28.09 +/- 5.64, P < 0.001). The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8(+) T-cells than CD4(+) T-cells (36.87 +/- 7.58 vs 30.23 +/- 6.35, 34.37 +/- 9.07 vs 30.92 +/- 7.40, P < 0.01), whereas the peripheral blood in patients at the immune-inactive carrier stage and in normal controls contained less CD8(+) T-cells than CD4(+) T-cells (28.09 +/- 5.64 vs 36.85 +/- 6.06, 24.02 +/- 4.35 vs 38.94 +/- 3.39, P < 0.01). ANOVA linear trend test showed that CD8(+) T-cells were significantly increased in patients with a high viral load (39.41 +/- 7.36, 33.83 +/- 7.50, 31.81 +/- 5.95 and 26.89 +/- 5.71, P < 0.001), while CD4(+) T-cells were significantly increased in patients with a low HBV DNA load (37.45 +/- 6.14, 33.33 +/- 5.61, 31.58 +/- 6.99 and 27.56 +/- 5.49, P < 0.001). Multiple regression analysis displayed that log copies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3(+), CD4(+) and CD8(+) cells and CD4(+)/CD8(+) ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation. Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load.
The Cytokine IP-10 in Chronic HBV and HCV Infection
Journal of IMAB - Annual Proceeding (Scientific Papers), 2013
Introduction: IP-10 it has been studied as a predictor of treatment response in chronic HCV infected patients. The data for the HBV infection are not enough. Aim: To compare IP-10 levels in patients with chronic HBV /CHB/ and HCV infection /CHC/ and their relation to liver disease and treatment response. Material and methods: 20 patients-with CHC genotype 1 infection /on standard bi-therapy/ and 32 patients with CHB /21 pts-NUC; 11 pts-IFN/. Results: The IP-10 did not correlate with sex, age, ALT and liver fibrosis. The basal IP-10 were lower in patients with CHB (p=0,017). There was a difference in IP-10 baseline levels among the HCV patients with or without RVR (p=0,007). A negative correlation was found between basal IP-10 and RVR (r=-0,508; p=0,008). Conclusion: IP-10 could predict virological response in patients with CHC on standard bi-therapy, but not in HBV infected patients on standard therapy.