Dynamic Characteristics of Serum Hepatitis B Surface Antigen in Chinese Chronic Hepatitis B Patients Receiving 7 Years of Entecavir Therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The ultimate goal of hepatitis B treatment is hepatitis B surface antigen (HBsAg) seroclearance. Several factors have been suggested to be associated with the rate of HBsAg reduction in antiviral-naive or lamivudine therapy cohorts. However, there are few studies evaluating the factors during long-term entecavir (ETV) therapy. In the present study, we aimed to evaluate the factors to predict the outcome of ETV therapy for 7 years.</p><p><b>METHODS</b>A total of 47 chronic hepatitis B (CHB) patients treated with ETV monotherapy were included in this study. Liver biochemistry, hepatitis B virus (HBV) serological markers, serum HBV DNA, and HBsAg titers were tested at baseline, 3 months, 6 months, and yearly from 1 to 7. The associations between factors and HBsAg reduction were assessed using multivariate tests with repeated measure analysis of variance.</p><p><b>RESULTS</b>At baseline, serum HBsAg levels showed a positive correlation with baseline HBV DNA levels (r = 0.625, P < 0.001). The mean HBsAg titers after ETV treatment were significantly lower than the baseline titers (P ranges from 0.025 to 0.000,000,6). The HBsAg reduction rate during the 1st year was greater compared to after 1 year of treatment (P < 0.05). Multivariate test showed that hepatitis B e antigen (HBeAg) seroclearance and/or HBsAg reduction ≥0.5 log10 IU/ml at 6 months had a high negative predictive value (96.77%) for HBsAg seroclearance (P = 0.002, P = 0.012, respectively).</p><p><b>CONCLUSIONS</b>The HBsAg reduction rate during the 1st year was greater than that after 1 year of treatment. Further, HBeAg status and HBsAg levels at month 6 are the optimal factors for the early prediction of HBsAg seroclearance after long-term ETV therapy in CHB patients.</p>

Antiviral nucleotide-induced dynamic change of HBV DNA and HBsAg and significance of quarterly and annual quantitative measurements over 5-year follow-up of chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the dynamic changes in hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) levels in chronic hepatitis B (CHB) patients following treatment by antiviral nucleotide drugs over a 5-year follow-up period and to assess the clinical significance of quarterly and annual quantitative measurements.</p><p><b>METHODS</b>One-hundred-and-ten patients with CHB were enrolled in the study and administered on-going standard mono-therapy with various antiviral nucleotide drugs. Over a 5-year period, the HBV DNA level was measured by quantitative PCR every three months and the HBsAg levels were measured by chemiluminescence once a year. The dynamic changes in HBV DNA and HBsAg levels were assessed by Chi-squared test and ANOVA.</p><p><b>RESULTS</b>Only 90 of the CHB patients completed the 5-year follow-up and were included in the analysis. The patients who showed HBeAg-positivity at baseline (study start) had higher levels of HBV DNA and HBsAg than the patients showing HBeAg-negativity. In general, the antiviral nucleotide drug therapy induced downward trends in HBsAg and HBV DNA level over time (F = 17.1, 151.53, all P less than 0.05). However, the most robust reduction in HBV DNA occurred during the first year. The HBsAg level followed an opposite trend, with the most robust reductions occurring in the 3rd, 4th and 5th years of treatment.</p><p><b>CONCLUSION</b>Long-term antiviral nucleotide mono-therapies induced decreases in HBV DNA and HBsAg levels in CHB patients, with the former being most reduced in the short-term and the latter in the long-term.</p>

Study of phenotypes and functions of cord blood dendritic cells from fetuses whose mothers had chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the phenotypes and functions of cord blood dendritic cells of fetuses whose mothers are patients with chronic hepatitis B.</p><p><b>METHODS</b>Peripheral blood and cord blood mononuclear cells (PBMC) were isolated from whole blood by density gradient centrifugation with Ficoll-Hypaque. The adherent cells were cultured in AIM-V medium containing recombinant human IL-4, TNF-alpha and GM-CSF. On day 9, mature DCs (mDC) were harvested and used for phenotype analysis. The amounts of IL-12 which dendritic cells produced were measured. The dendritic cells that were studied and compared were from cord blood of fetuses of both CHB positive and negative mothers and from CHC adult peripheral blood.</p><p><b>RESULTS</b>The expression rate of CD80 and CD83 of chronic hepatitis B mother cord blood dendritic cells was low compared with that of the healthy cord blood, healthy adult peripheral blood, and chronic hepatitis B adult peripheral blood, P < 0.05. The amount of IL-12 produced by chronic hepatitis B mother cord blood dendritic cells was lower than that of healthy cord blood, healthy adult peripheral blood, chronic hepatitis B adult peripheral blood (P < 0.05). The T lymphocyte proliferation inducing ability of dendritic cells of healthy adult peripheral blood was higher in inducing cord blood T lymphocytes proliferation, which was greater than that of the healthy adult peripheral blood in inducing adult T lymphocytes and was greater than that of the healthy cord blood dendritic cells in inducing cord blood T lymphocytes, which was greater than that of the healthy cord blood in inducing adult T lymphocytes, which was greater than that of chronic hepatitis B mothers in inducing cord blood T lymphocytes, which was greater than that of chronic hepatitis B mother cord blood in inducing adult T lymphocytes.</p><p><b>CONCLUSION</b>The maturation and functioning of CHB mother cord blood dendritic cells were lower than those of healthy cord blood, healthy adult peripheral blood and CHB adult peripheral blood.</p>

Dynamic expression of hepatitis B virus covalently closed circular DNA in 2.2.15 cell / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To determine the presence of covalently closed circular DNA (cccDNA), and to investigate the expression kinetics of HBV DNA, HBsAg and HBeAg in 2.2.15 cell.</p><p><b>METHODS</b>HBV cccDNA was assessed by polymerase chain reaction, HBV DNA was measured by Taqman quantitative PCR and HBsAg and HBeAg was measured by EIA.</p><p><b>RESULTS</b>HBV cccDNA was found in both intracellular and extracellular space. There was a good correlation between HBsAg, HBeAg and HBV DNA in the supernatant of 2.2.15 cell (r= 0.833, P < 0.05 and r= 0.939, P < 0.01 for HBsAg and HBeAg, respectively), whereas there was no significant correlation between intracellular HBV DNA levels and virus antigen levels (r= 0.024, P= 0.955 and r= 0.177; P= 0.625 for HBsAg and HBeAg, respectively).</p><p><b>CONCLUSION</b>HBV cccDNA was detectable in the culture medium and intracellularly in 2.2.15 cells, and these data provided an indication of HBV replication in 2.2.15 cell.</p>

Effects of oxymatrine on serum levels of Th1/Th2 type cytokines in HBsAg transgenic mice / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the effects of oxymatrine on serum levels of Th1/Th2 cytokines in HBsAg transgenic mice.</p><p><b>METHODS</b>HBsAg transgenic mice were divided into oxymatrine group and control group. Each mouse was injected with either oxymatrine 200 mg/kg 0.2 ml or 0.9% NaCl 0.2 ml intraperitoneally once a day for 30 days. Serum IFN-gamma, IL-2 and IL-4, IL-10 were quantitated before and after different treatment.</p><p><b>RESULTS</b>There was no significant difference on the levels of IFN-gamma and IL-4 before and after treatment in control group. While in oxymatrine group, the levels of IFN-gamma before and after treatment were (3.108+/-3.172) pg/ml and (11.059+/-6.971) pg/ml; those of IL-4 were (29.045+/-13.235) pg/ml and (13.024+/-9.002) pg/ml (both P less than 0.001). After treatment, the levels of IL-2 in control and oxymatrine group were (1.070+/-0.447) pg/ml and (5.537+/-2.887) pg/ml (P less than 0.000 1); and those of IL-10 were (97.226+/-73.306) pg/ml and (33.607+/-23.154) pg/ml (P less than 0.01).</p><p><b>CONCLUSION</b>After injection of oxymatrine to HBsAg transgenic mice, the serum concentration of Th1 cytokines increased while the Th2 cytokines decreased. This can help us understand more better on the mechanisms of anti-HBV effect of oxymatrine.</p>