BACKGROUND/AIMS: The long-term virologic and biochemical changes in patients with HBeAg negative HBV infection, especially in Asia, remain unclear. To address this issue, we conducted a 3 year- retrospective, cohort study. METHODS: A total of 157 patients with HBeAg negative HBV infection who were monitored without treatment were reviewed between January 1999 and March 2004. Those patients were followed up every 3 months with liver function tests and serologic tests. All patients were stratified into 3 groups; inactive carrier (IC), viremic carrier (VC) and chronic hepatitis (CH). Serum HBV DNA was measured by a hybridization assay (sensitivity: 1.4 x 10(5) genomes/mL, Digene Diagnostics, Silver Spring, USA). RESULTS: The median age of enrolled patients was 42.7 years (M:F=2.3:1). By single time-point observations, the 3 year-cohort prevalence of HBeAg negative CH varied from 12.7 to 35.8% (median 20.7%) HBeAg negative CH was accumulated over time (P=0.002) and transition rates among three groups after 3 years of follow-up are as follows: IC to CH, 6.0%; IC to VC, 4.1%; VC to CH, 23.2%. VC seems to be a disease state in the middle of transition from IC to CH. CONCLUSIONS: We demonstrated the dynamic changing patterns of HBeAg negative CH with time, of which the change from IC or VC to CH was dominant.
Middle Aged ; Male ; Humans ; Hepatitis B, Chronic/*immunology/virology ; Hepatitis B e Antigens/*blood ; Female ; Carrier State/immunology ; Adult

Carrier State ; immunology ; prevention & control ; China ; epidemiology ; Hepatitis B ; epidemiology ; prevention & control ; Hepatitis B Vaccines ; immunology ; Humans ; Prevalence ; Vaccination

OBJECTIVETo study of serum level of cortisol and peripheral T lymphocyte subsets state in the hepatitis B virus (HBV) carriers.

METHODSSixty chronic HBV carriers and ten healthy controls were all enrolled in this present study. Serum expression of cortisol was determined by radioimmunoassay, and also flow cytometry was performed to evaluate peripheral blood T lymphocyte subset.

RESULTSCompared with those in normal controls, the serous levels of cortisol in chronic HBV carriers were significantly elevated, while there was no distinct difference in the proportion of CD4+ T lymphocytes ( P > 0.05) with the decreased odds of CD4+/CD8+ lymphocytes( P < 0.05) and obvious higher proportion of CD8+ T lymphocytes( P < 0.05). In comparison between HBeAg positive group and HBeAg negative group, the serous levels of cortisol of the former group were significantly higher ( P < 0.05), and so proportion of CD8+ T was too ( P < 0.05). However, there is no significant differences in the proportion of CD4+ T lymphocyte ( P > 0.05).

CONCLUSIONThe elevated serum cortisol and increased CD8+ T lymphocytes subsets in the chronic HBV carriers, suggested that there was disturbance of endocrine-immune response in the chronicity of HBV infection.

Adult ; Carrier State ; immunology ; pathology ; virology ; Female ; Hepatitis B ; blood ; immunology ; metabolism ; pathology ; Hepatitis B virus ; immunology ; Humans ; Hydrocortisone ; blood ; immunology ; Male ; T-Lymphocyte Subsets ; immunology

Adult ; Carrier State ; blood ; immunology ; virology ; Female ; Hepatitis B Surface Antigens ; blood ; Humans ; Hypertension, Portal ; blood ; virology

OBJECTIVETo investigate the effect of HBV antigens and pathological mechanism of chronic HBV infection by analyzing the cellular immune function of peripheral blood mononuclear cells (PBMCs) from HBsAg carriers.

METHODSPBMCs were prepared from individuals with chronic asymptomatic HBV infection and cultured in the presence of different antigens and/ or cytokines. The levels of cytokines in culture supernatants were detected by ELISA method. The phenotype of the cells was detected by FACS.

RESULTSThe levels of IFN y secreted by PBMCs from HBsAg carriers were (48.3+/-19.8) pg/ml, significantly lower than that from healthy controls (t = 3.023, P less than 0.05); The IFN y produced by PBMCs from HBeAg positive patients due to HBsAg and HBcAg stimulation were (50.4+/-51.6) pg/ml and (63.2+/-36.9) pg/ml, significantly lower than that of HBeAg negative patients (t = 2.468 and 3.184, P less than 0.05, respectively). The IL-12p70 secreted by PBMCs from HBeAg positive patients was also significantly lower than that of HBeAg negative patients (P less than 0.05); Exogenous IL-12 promoted significantly PBMCs to secrete IFN y (P less than 0.01) and IL-12 combined with HBV antigens activated CD8+CD45RA+CCR7+ and CD8+CD45RA-CD62L+ cells. IL-12 secreted by PBMCs decreased in HBeAg positive patients, which may be the crucial reason of viral persistence in chronic HBV carriers. Exogenous IL-12 combined with specific HBV antigen could promote the central memory CD8+ T cells to produce IFN y.

Adolescent ; Adult ; Carrier State ; blood ; immunology ; virology ; Case-Control Studies ; Hepatitis B ; blood ; immunology ; Hepatitis B Antigens ; blood ; Hepatitis B virus ; immunology ; Humans ; Interferon-gamma ; blood ; Interleukin-12 ; blood ; immunology ; Leukocytes, Mononuclear ; immunology ; T-Lymphocytes ; immunology ; Young Adult

Adult ; Carrier State ; drug therapy ; Female ; Hepatitis B, Chronic ; complications ; drug therapy ; immunology ; Humans ; Immunologic Deficiency Syndromes ; complications ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Secondary Prevention

OBJECTIVETo explore Chinese medicine (CM) syndrome distribution of chronic hepatitis B virus (HBV) carriers in immunotolerant phase (ITP).

METHODSOne hundred and eighty-five chronic HBV carriers in ITP, seen in the Third Affiliated Hospital of Sun Yat-sen University from May 2009 to December 2010, were admitted in an observational study under the guidance of CM. Patients' CM symptoms and signs, demographics, liver biochemistries, and qualitative HBV DNA were recorded in the questionnaires. CM syndromes were then differentiated to 15 detailed types and analyzed by generalization. Lastly, the location, pathogenic factors and nature of the disease were also assessed.

RESULTSWhen CM syndrome patterns were differentiated to 15 types, there were 27 (15%) no syndrome cases, 94 (50%) single syndrome cases and 64 (35%) compound syndromes cases. The main detailed syndromes included Liver (Gan)-qi depression (LQD), Kidney (Shen)-qi deficiency (KQD), Spleen (Pi)-qi deficiency (SQD) and Kidney-yang deficiency (KYAD). After CM syndromes generalized to five types, their frequency was Spleen-Kidney deficiency (SKD)>LQD>inner dampness-heat retention (IDHR)>Liver-Kidney deficiency (LKD)>blood stasis blocking collateral (BSBC). SKD and LQD occupied 64%. The disease location included Liver, Gallbladder (Dan), Spleen, Stomach (Wei) and Kidney. The pathogenic factors were mainly qi stagnation, qi deficiency, yang deficiency, concurrently dampness-heat and blood stasis. The deficiency syndrome was more than excess syndrome in its nature.

CONCLUSIONSMost of chronic HBV carriers in ITP have their CM syndrome, and the most common types are SKAD, LQD. This study suggests that the natural history may be improved through breaking the state of immune tolerance or shorten the time of ITP by strengthening Spleen-Kidney and reliving Liver qi.

Adolescent ; Adult ; Biopsy ; Carrier State ; immunology ; Child ; Child, Preschool ; Female ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; immunology ; pathology ; virology ; Humans ; Immune Tolerance ; Liver ; immunology ; pathology ; virology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Syndrome ; Viscera ; pathology ; Young Adult

OBJECTIVE: To explore the effect of unmethylated CpG motif containing oligodeoxynucleotides (CpG ODN) on the function of dendritic cells (DCs) in patients with chronic hepatitis B (CHB). METHODS: DCs were obtained from peripheral blood mononuclear cells (PBMCs) of 15 CHB patients, 12 hepatitis B virus (HBV) carriers, and 10 healthy controls. The expressions of HLA-DR, CD80, and CD86 on DCs were determined by fluorescence activated cell sorting (FACS). The IL-12 level in supernatant of the culture medium was measured by ELISA, and the morphological changes of DCs were observed under transmission electron microscope. RESULTS: Compared with the controls, DCs stimulated with CpG ODN represented enrichment in cell surface protrusions and rough endoplasmic reticulum, decreased or disappeared vacuole. The expressions of HLA-DR, CD86, and CD80 were much higher in DCs stimulated with CpG ODN than those in complete medium control (P<0.05). When culturing in complete medium, the expressions of HLA-DR, CD86, and CD80 were much lower in CHB patients and HBV carriers than healthy controls (P<0.05). The expressions of HLA-DR and CD86 stimulated with CpG ODN were much lower in CHB patients than HBV carriers and healthy controls (P<0.05). The expressions of CD80 were much lower in CHB patients and HBV carriers than healthy controls (P<0.05). The levels of IL-12 were much higher in DCs stimulated with CpG ODN than that in complete medium controls (P<0.05). The levels of IL-12 in complete medium or medium added with CpG ODN were much lower in CHB patients and HBV carriers than in healthy controls (P<0.05). CONCLUSION CpG ODN could significantly promote the maturation of dendritic cells in peripheral blood in CHB patients.
Adult ; B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; Carrier State ; immunology ; Case-Control Studies ; CpG Islands ; Dendritic Cells ; drug effects ; immunology ; Female ; HLA-DR Antigens ; metabolism ; Hepatitis B, Chronic ; immunology ; Humans ; Male ; Oligodeoxyribonucleotides ; pharmacology

OBJECTIVETo better understand the duplication of hepatitis B virus (HBV) in order to improve clinical diagnoses and treatments via quantitative measurement of HBV-DNA and comparison of correlation of HBV-DNA with HBeAg and anti-HBe.

METHODSFor 883 hepatitis B patients with positive HBsAg, HBV-DNA was measured by COBAS AMPLICOR HBV MONITOR reagent and COBAS AMPLICOR quantitative PCR instrument. Microparticle enzyme immunoassay analysis (MEIA) was then carried out with fully automatic enzyme immunoassay analysis instrument made by Abbott Axsym from the U.S. to measure HBeAg and anti-HBe. Correlation was analysed by SPSS.

RESULTS(1)Positive correlation between 690 HBV-DNA positive and HBeAg positive with r= 0. 505 (P< 0.01) was found with mean values as:HBV-DNA:7.12 x 10(12) copies/ml;HBeAg:218.31 S/CO. HBV-DNA:10(4) copies/ml, HBeAg: 104 S/CO; HBV-DNA: 10(5)-10(8) copies/ml, HBeAg: 112 S/CO; HBV-DNA: 10(9)-10(15) copies/ml, HBeAg: 252 S/CO. (2) No correlation was found between 193 HBV-DNA and anti-HBe + with r= -0.052(P= 0.477> 0.05) with Mean: HBV-DNA: 8.0x 10(10) copies/ml anti-HBe: 0.18 S/CO.

CONCLUSIONHBV-DNA and HBeAg appeared to have had linear correlation, showing that HBeAg> 100 S/CO,HBV-DNA> 10(4) copies/ml and hepatitis B virus were reproduced. However, HBV-DNA did not show linear correlation with anti-HBe as HBeAg negative and anti-HBe positive, the level of hepatitis B viral replication decrease slightly. But the virus load is still high. Infectivity can not neglect.

Antibodies, Viral ; analysis ; Carrier State ; DNA, Viral ; analysis ; Hepatitis B ; diagnosis ; genetics ; immunology ; Hepatitis B e Antigens ; analysis ; Hepatitis B virus ; genetics ; immunology ; Humans ; Immunoenzyme Techniques ; Polymerase Chain Reaction ; Viral Load ; Virus Replication

OBJECTIVETo observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac).

METHODSA total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 micro g of GM-CSF plus 10 micro g of rHBvac injected intramuscularly at the same location (GM-CSF group, 14 children) or 200 IU HBIG and 10 micro g rHBvac in different muscles (HBIG group, 13 children) on a monthly four-dose schedule. HBV-DNA quantification and other HBV serological markers were tested before and after the four-dose therapy.

RESULTSTwelve children in each group completed the study. Of them, 3 children in the GM-CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment. Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM-CSF group and 10 in the HBIG group. One from each group had an HBeAg/anti-HBe seroconversion after the treatment. The quantity of HBV-DNA was significantly lower after the treatment (P = 0.023) in GM-CSF group, but was not significantly reduced in HBIG group. No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group.

CONCLUSIONCombined GM-CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis.

Carrier State ; therapy ; Child ; Child, Preschool ; Combined Modality Therapy ; DNA, Viral ; blood ; Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Hepatitis B Vaccines ; immunology ; Hepatitis B, Chronic ; therapy ; Humans ; Immunoglobulins ; therapeutic use ; Pilot Projects ; Vaccines, Synthetic ; immunology