<b>OBJECTIVEb>To study the clinical and histological features of chronic hepatitis B (CHB) with negative hepatitis B e-antigen (HBeAg).

<b>METHODSb>A total of 743 in-patients with chronic hepatitis B were recruited into the study and divided into two groups according to the HBeAg status. The correlation among alanine transaminase (ALT) levels, hepatitis B virus (HBV) DNA semiquantification, and the liver histopathological data were detected.

<b>RESULTSb>Of the 743 successive in-patients, 267 (35.9%) were HBeAg-negative. The HBDAG-negative group had significantly lower serologic HBV DNA levels (63.0% of < 100 pg/ml) vs HBeAg-positive (42.6%, P < 0.001), while more sever inflammation (58.1% of inflammatory scores of histological activity index (HAIinf > or = 9) vs HBeAg-positive group (46.0%, P < 0.001) and severe fibrosis (45.3% of fibrosis scores of histological activity index (HAIfib > or = 3) vs HBeAg-positive group (27.9%, P < 0.001) of liver histology. In HBeAg-positive patients, increasing ALI levels were significantly associated with high inflammation and fibrosis scores and low HBV DNA levels. However, it was not the case in the HBeAg-negative cases. In HBeAg-positive patients, 91.3% of them had HAIinf > or = 9 and 65.7% had HAIfib > or = 3 with HBV DNA > 100 pg/ml, while 8.2% of them had HAIinf > or = 9 and 12.3% had HAIfib > or = 3 with HBV DNA < 20 pg/ml, indicating an obverse correlation between HBV DNA levels and histology scores.

<b>CONCLUSIONSb>As regards clinical and histological background, the chronic HBeAg-negative hepatitis B is a different subpopulation from the HBeAg-positive counterpart.

DNA, Viral ; Fibrosis ; pathology ; Hepatitis B ; immunology ; pathology ; Hepatitis B e Antigens ; analysis ; Hepatitis B virus ; genetics ; Hepatitis, Chronic ; Humans ; Liver ; pathology

<b>OBJECTIVEb>To investigate whether the level of hepatitis B surface antigen (HBsAg) represents the status of inflammation and stages of fibrosis in livers of patients with chronic hepatitis B (CHB) during the immune clearance phase (IC).

<b>METHODSb>Liver biopsy samples and sera were collected from 165 consecutive patients (136 males; 29 females) with CHB in IC who were treated in our hospital between March 2009 and June 2011. Routine biochemical tests were carried out to measure indicators of liver function. The relation between HBsAg level and liver pathological stages were determined by Spearman's rank correlation analysis. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of HBsAg level for liver pathological stages. Binary logistic regression was used to analyze potentially relevant indicators, and liver pathology-predicting models were built and analyzed by the ROC method.

<b>RESULTSb>The mean values of HBsAg (IU/mL) were significantly different at the different liver inflammation stages: G1, 27 716.07+/-32 870.69; G2, 34 478.75+/-40 899.55; G3, 19 408.09+/-24 881.07; G4, 14 286.31+/-28 610.14. Likewise, the mean values of HBsAg (IU/mL) were significantly different at the different liver fibrosis stages: S1, 41 337.23+/-43 236.39; S2, 27 264.32+/-32 517.29; S3, 111 541.77+/-11 538.93; S4, 11 447.37+/-22215.44. Spearman's rank correlation analysis indicated a significant correlation between HBsAg level and liver inflammation stage (rs = -0.244) and fibrosis stage (rs = -0.365). ROC curve analysis of the diagnostic value of HBsAg for inflammation stages S more than or equal to 4 revealed that the area under the curve (AUC) was 0.70. The specificity of diagnosing S more than or equal to 4 was > 95.16% when HBsAg was less than or equal to 32995 IU/mL. Binary logistic regression analysis identified age, serum albumin, cholinesterase, and HBsAg as independent predictors of liver fibrosis.

<b>CONCLUSIONb>HBsAg level is negatively correlated with liver inflammation and fibrosis stages for patients with CHB in the IC phase, and might represent a useful noninvasive marker of the degree of hepatic fibrosis.

Adult ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B, Chronic ; blood ; immunology ; pathology ; Humans ; Inflammation ; Liver ; immunology ; pathology ; Liver Cirrhosis ; immunology ; pathology ; Male ; Middle Aged ; Young Adult

Adult ; Biopsy ; Fatty Liver ; complications ; immunology ; pathology ; Female ; Hepatitis B, Chronic ; complications ; immunology ; pathology ; Humans ; Male ; T-Lymphocytes, Regulatory ; immunology

<b>BACKGROUNDb>To study characteristics of peripheral T cell subsets in 94 children with chronic hepatitis B and to elucidate its relationships with clinical status and hepatic pathology.

<b>METHODSb>Peripheral T cell subsets were detected using flow cytometric analysis with specific monoclonal antibodies staining in 94 patients with HBV infection. The authors simultaneously detected their serum ALT, markers of HBV infection and examined liver biopsy material for pathological changes.

<b>RESULTSb>In patients with serious liver lesion, the ratio of CD4+/CD8+ cells was significantly higher than those with mild lesion (1.41+/-0.54 vs 1.08+/-0.35, P less than 0.05), which seemed to be associated with the various liver lesions among the patients. In female cases, the levels of CD4+ T cells and the ratio of CD4+/CD8+ T cells were higher than their counterpart in male cases (33.1+/-5.39 vs 28.8+/-6.28, 1.28+/-0.32 vs 1.02+/-0.36, P less than 0.05), but the level of CD8+ T cells was lower than those in males (26.79+/-4.66 vs 30.51+/-7.17, P less than 0.05). There was no obvious correlation between T cell subsets and circulating HBV viral load, the size of spleen among the HBV-infected children.

<b>CONCLUSIONb>The characteristics of peripheral T cell subsets probably suggests the immune disorder occurred in these children with hepatitis B compared with healthy controls and its mechanism needs further investigation.

Child ; Child, Preschool ; Female ; Hepatitis B, Chronic ; immunology ; pathology ; Humans ; Infant ; Liver ; pathology ; Male ; T-Lymphocyte Subsets ; immunology

<b>OBJECTIVESb>To investigate the relationship between the quantity of peripheral dendritic cell (DC) and of serum HBV DNA and the inflammatory level in chronic hepatitis B (CHB).

<b>METHODSb>The myeloid DC (DC1) and plasmacytoid DC (DC2) in fresh peripheral blood were enumerated by using three-color flow cytometry in chronic hepatitis B patients and healthy donors. The hepatic inflammatory levels were evaluated by percutaneous liver biopsy. The serum HBV DNA levels were determined by real-time PCR.

<b>RESULTSb>CHB patients with serum HBV DNA < or = 10(6) copies/ml exhibited a significant increase in the percentage of circulating DC2 in comparison with those of CHB patients with serum HBV DNA > or = 10(6) and with healthy donors (P < 0.05). The two latter groups showed no significant differences between each other. There was also no significant difference in the relative quantity of peripheral blood DC1 among the three groups mentioned above (P = 0.162). No evidence was found to support that the relative quantity of peripheral blood DC2 was associated with the clinical severity of the disease or the inflammatory level in the liver (P > 0.05).

<b>CONCLUSIONb>The relative quantity of peripheral blood DC2 is associated with HBV DNA level. It is suggested that DC2 may play a pivotal role in inhibiting HBV replication in CHB patients. There was no relationship found between relative quantities of DCs and the inflammatory level in the liver.

DNA, Viral ; blood ; Dendritic Cells ; cytology ; immunology ; Female ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; immunology ; pathology ; virology ; Humans ; Liver ; pathology ; Male ; Virus Replication

<b>OBJECTIVEb>To explore Chinese medicine (CM) syndrome distribution of chronic hepatitis B virus (HBV) carriers in immunotolerant phase (ITP).

<b>METHODSb>One 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.

<b>RESULTSb>When 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.

<b>CONCLUSIONSb>Most 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

BACKGROUND/AIMS: The protective role of HBV-specific CD8+ cells is dependent on their ability to efficiently migrate to the infected liver, where they may exert an effector function. The migratory behavior of CD8+ cells is influenced by their expression of different chemokine receptors. This study was intended to analyse the pattern of chemokine receptor expression of HBV specific CD 8+ cells in chronic B viral infection. METHODS: We analysed the CCR5 and CCR3 profile of HBV-specific CD8+ cells isolated from the blood and liver of patients with different patterns of HBV infection. Purified T cells were stained directly ex vivo, or after antigen-specific stimulation, using HBV peptide-specific HLA tetramers and monoclonal antibodies to CD8, CCR5 and CCR3, with analysis by flow cytometry. RESULTS: In patients with chronic hepatitis B characterised by low levels of virus (serum HBV DNA <0.5pg/mL) and minimal liver inflammation, analysis of circulating and intrahepatic CD8+ cells demonstrated that liver infiltrating Tc18-27-specific cells were preferentially CCR5+ (up to 80% of HBV-specific CD8+ cells), in contrast to cells of the same specificity within the circulating compartment (up to 35% of HBV-specific CD8+ cells). Furthermore, CCR3 was expressed by about 10% of Tc18-27+ cells infiltrating the liver, but was absent from circulating cells. Following HBV-specific stimulation in vitro the CCR5 expression of circulating Tc18-27-specific cells was up-regulated, to levels found in liver infiltrating cells, whereas CCR3 expression was unchanged. CONCLUSIONS: The chemokine receptor profile of HBV-specific CD8+ cells is influenced by the anatomical site of these cells, and the clinical pattern of disease. The ability of circulating HBV-specific CD8+ cells of patients with low replicating virus to upregulate CCR5 suggests that these cells may respond to increases in virus replication by efficiently migrating into the infected liver.
CD8-Positive T-Lymphocytes/immunology/*metabolism ; English Abstract ; Hepatitis B Virus/immunology ; Hepatitis B, Chronic/*immunology/pathology ; Human ; Liver/pathology ; Receptors, CCR5/metabolism ; Receptors, Chemokine/*metabolism ; T-Cell Antigen Receptor Specificity

<b>OBJECTIVEb>To investigate the association of serological markers of hepatitis B virus (HBV) and alanine transaminase (ALT) with hepatic tissue pathology in patients with chronic hepatitis B.

<b>METHODSb>The serological marker of HBV, liver function and liver biopsy of 133 patients with chronic hepatitis B were measured and evaluated. The patients were divided into 4 groups according to HBeAg and HBV DNA positivity. Hepatic necrosis/inflammation grade and hepatic fibrosis were compared between the groups.

<b>RESULTSb>Hepatic histological examination of all these patients showed inflammation, necrosis and different degrees of fibrosis. In patients with normal serum ALT, liver biopsy showed different degrees of inflammation, hepatic fibrosis, and even hepatocirrhosis. In patients with abnormal serum ALT negative for HBeAg, hepatic tissue inflammation and fibrosis were more serious. Hepatic tissue pathology was not paralleled with the level of HBV replication.

<b>CONCLUSIONb>Evaluation of the liver disease can not depend solely on serum ALT and viral loading in these patients. Hepatic tissue pathology in patients with chronic hepatitis B should be served as the most reliable evidence for evaluating hepatitis conditions and making the decision on antiviral therapy.

Adolescent ; Adult ; Alanine Transaminase ; blood ; Biopsy, Needle ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Humans ; Liver ; pathology ; virology ; Male ; Middle Aged ; Viral Load

<b>OBJECTIVEb>To study the relationships among pathological and immunohistochemical changes in liver tissues, and the HBeAg, HBV DNA, ALT level in the patients with chronic hepatitis B.

<b>METHODSb>Pathological and immunohistochemical examinations of liver tissue liver function tests, serum HBV and HBV DNA detection were performed in 194 patients with chronic hepatitis B.

<b>RESULTSb>There was significant difference between the serum HBeAg positive group and the negative group in G2, G3-4 S2, S3-4 in liver tissues; The serum HBV DNA level of the groups S0 and S1-4, and the hepatic activity index between the groups G0-1 and G2-4 were significantly different. And the hepatic HBcAg positive group and HBcAg negative group were significantly different too. There was no significant difference between the HBsAg level in liver tissues as "+" group and the "++ - +++" group. The pathological diagnosis as S1 or (and) G2 is respectively 28.57%, 53.33%, 80.15%, 77.88% among the four groups with normal-mild-moderate-severe elevated serum ALT level.

<b>CONCLUSIONb>Serum HBV DNA correlated with HBcAg expression in liver tissue; the HBsAg level in liver tissues have no relationship with the serum HBV DNA level. The patients with low serum HBV DNA level may have high index of hepatic activity and hepatic fibrosis. Asymptomatic carriers and patients with low serum ALT level should be encouraged to accept liver biopsy. It can determine the degree of liver inflammation and fibrosis and timing of treatment.

Adolescent ; Adult ; Alanine Transaminase ; blood ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; immunology ; physiology ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Host-Pathogen Interactions ; Humans ; Liver ; pathology ; virology ; Male ; Middle Aged ; Young Adult

<b>OBJECTIVEb>To study the expression of HBsAg and HBcAg in hepatocytes in CHB patients, and analyze the correlation among the expression of HBsAg and HBcAg, the quantity of HBV DNA in serum, the pathology of liver tissue and the clinical manifestation.

<b>METHODSb>Quantitative polymerase chain reaction was used to assay the quantity of HBV DNA in serum in 351 CHB patients. Furthermore pathological diagnosis was performed using liver biopsy to assay the expression of HBsAg and HBcAg in hepatocytes by an immunohistochemical staining technique.

<b>RESULTSb>The positive expression rate of HBsAg and HBcAg in hepatocytes was 92.3% and 76.9% respectively. Cytoplasm-membrane HBcAg expression type (75.6%) was observed in the CHB with more active inflammation, while Nucleus HBcAg expression type (24.4%) was observed in the CHB with more sedative one (P < 0.0001). The expression of HBsAg was correlated with the quantity of HBV DNA in serum (rp = 0.24, P = 0.0129), while inversely correlated with the inflammation and the fibrillation of liver tissue (rp = -0.22, P = 0.0279; rp = -0.23, P = 0.0186). The expression of HBcAg was correlated with the quantity of HBV DNA in serum (rp = 0.52, P < 0.0001), while was inversely correlated with the inflammation and the fibrosis of liver (rp = -0.33, P < 0.0001; rp = -0.34, P < 0.0001).

<b>CONCLUSIONb>Cytoplasm-membrane HBcAg expression type was observed in the CHB with more active inflammation, while Nucleus HBcAg expression type was observed in the CHB with mild change. In the immunopathogenesis of the liver damage in CHB, HBcAg might be a main target antigen. HBsAg might be a sensitive index to screen HBV infection; HBcAg might probably be a reliable index to evaluate the replication of HBV

Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Viral ; blood ; Female ; Hepatitis B Core Antigens ; analysis ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B, Chronic ; immunology ; pathology ; virology ; Hepatocytes ; virology ; Humans ; Immunohistochemistry ; Liver ; pathology ; Male ; Middle Aged