Relationship between the changes in immune cells and HBeAg loss following antiviral treatment in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the changes in hepatitis B virus (HBV)-specific and non-specific cellular immunity that accompany viral load decline during adefovir dipivoxil (ADV) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, and to explore the antiviral immunity mechanism underlying the treatment response.</p><p><b>METHODS</b>Serial analysis of cellular immunological parameters was performed in HBeAg-positive patients (n = 20) throughout the 48-week course of ADV therapy (10 mg/d). HBV-specific T cell reactivity to HBV core antigen (HBcAg) was assessed by enzyme-linked immunosorbent spot assay and cell proliferation assay at pre-treatment (baseline) and post-treatment weeks 4, 12, 24, 36, and 48. Percentage of regulatory T cells (Tregs), as well as activated peripheral natural killer (NK) cells (expressing the NKG2D receptor), was measured by flow cytometry. Comparisons of means were performed by the two-tailed t-test or the Mann-Whitney rank sum test.</p><p><b>RESULTS</b>After 48 weeks of ADV therapy, HBeAg loss was observed in six of the 20 (30%) patients and 14 patients remained HBeAg-positive. In the patients with HBeAg loss, the viral load reduction was accompanied by a significantly enhanced response rate of HBV-specific interferon (IFN)-gamma-producing CD4+ T cells [measured as (spot forming cells/peripheral blood mononuclear cells); baseline: (661.25+/-281.97) *10(-6) vs. week 48: (280.75+/-104.33) *10(-6), P = 0.045]. In contrast, patients without HBeAg loss showed no significant differences in T cell response rates. The patient groups with and without HBeAg loss showed similar proportions of peripheral blood Tregs during the treatment course, which included a trend of gradual decrease from baseline to week 4 with steady levels thereafter. In addition, both groups showed a similar increase in NKG2D expression that began at week 12 and peaked at week 48.</p><p><b>CONCLUSION</b>HBV-specific T cell reactivity temporally increases in some ADV-treated chronic hepatitis B patients, and this trend is strongly associated with HBeAg loss. Furthermore, recovery of HBV-specific T cell reactivity promotes viral clearance and HBeAg seroconversion.</p>

Relation between HBsAg levels during the immune clearance phase of hepatitis B virus infection and liver pathological stages of chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>