Differential distribution of hepatitis B surface antigen and hepatitis B core antigen in the liver of hepatitis B patients.

One hundred liver biopsies from 100 patients with clinical presumptive diagnosis of hepatitis were examined by immunofluorescence for the presence of hepatitis B surface antigen (HBSAg) and hepatitis B core antigen (HBcAg). Of the 60 HBsAg-positive livers, 51 were diagnosed as chronic hepatitis on histological grounds, 6 as acute hepatitis, and 3 as "near-normal liver." From the 60 tissue-positive cases, 3 subjects were HBsAg seronegative. HBcAg was detected in 44 livers, all of which also had HBcAg in the localized in the cytoplasm and the membranes of the hepatocytes, and HBcAg in the nuclei and in 4 cases also in the cytoplasm. Predominant HBsAg expression in the cytoplasm was observed in near-normal liver, chronic persistent hepatitis, and cirrhosis with little activity. This correlated with the amount of ground glass hepatocytes in the biopsies. HBcAg and membrane-localized HBsAg were minimal in those conditions. HBcAg was most prevalent in patients with chronic aggressive hepatitis and active cirrhosis treated with immunosuppressive drugs, whereas the amounts of HBsAg and HBcAg in nontreated patients of those two groups and in acute hepatitis with signs of transition to chronicity were almost equal. HBsAg expression in liver cell membranes was most prominent in active forms of chronic hepatitis (chronic aggressive hepatitis and in active cirrhosis) and in acute hepatitis with signs of transition to chronicity. This observation correlated in the presence of HBcAg in the biopsies of those patients. In acute hepatitis both HBsAg and HBcAg were detected rarely and no membrane expression of HBsAg was observed. The over-all results show a significant relationship between the different degrees of accumulation of HBsAg and HBcAg in the liver and the various histological types of hepatitis and further suggest an interplay of both hepatitis B virus and host immune response in the development and pathogenesis of hepatitis B.     

Comparison of hepatitis B surface antigen and e antigen in predicting liver histology in hepatitis B e antigen-positive chronic hepatitis B patients

Background/Aim

The purpose of this study was to determine the relationship between hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels and liver histology in HBeAg-positive patients with chronic hepatitis B virus (CHB) infection.

Methods

Serum HBsAg and HBeAg levels were analyzed, and liver biopsies were obtained from 203 HBeAg-positive CHB patients (62.6 % males; median age 31.3 years). The upper limit of normal (ULN) for ALT in this study was 30 and 19 U/L for males and females, respectively. Histologic assessment was based on Scheuer classification.

Results

ALT <2 × ULN, fibrosis stage <S2, and necro-inflammation grade <G2 were noted in 70 (34.5 %), 141 (69.5 %), and 105 (51.7 %) patients, respectively. Patients with significant histology (fibrosis stage ≥S2 and/or fibrosis stage of 1 plus inflammation grade ≥2) had significantly lower median HBsAg (13,998.4 and 42,186.5 IU/mL, respectively, p < 0.001) and HBeAg levels (540.5 and 1,206.8 S/CO, respectively, p < 0.001) than patients with insignificant histology. Among patients with ALT <2 × ULN, the area under the ROC curve for serum HBsAg and HBeAg levels was 0.76 and 0.70, respectively. Using a cutoff value of 17,558 IU/mL for HBsAg and 875.6 S/CO for HBeAg in patients with ALT <2×ULN, positive predictive values for insignificant histology were 87 and 86.8 %, respectively, whereas the negative predictive values were 50 and 47.1 %, respectively.

Conclusions

Among HBeAg-positive patients with ALT <2 × ULN, high-serum HBsAg and HBeAg levels can equally accurately predict insignificant histology.     

Serum hepatitis B surface antigen (HBsAg) kinetics in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B

Background

We investigated the differences in HBsAg kinetics at different levels of viremia in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB).

Methods

We compared HBsAg levels among HBeAg-negative CHB patients with persistently undetectable HBV DNA (≤20 IU/mL; Group A, n = 100), HBV DNA 20–2,000 IU/mL (Group B, n = 100), and HBV DNA >2,000 IU/mL (Group C, n = 100). HBsAg and HBV DNA levels were measured at three consecutive time points during follow-up (median 21.4 months).

Results

Median HBsAg levels were significantly lower in Group A than in Groups B and C at all time points (p < 0.001). HBV DNA and HBsAg levels were weakly correlated (r = 0.180 and 0.151 for Groups B and C, respectively). Among patients with HBsAg <100 IU/mL, Group A patients had the greatest median serum HBsAg reduction (0.341 log IU/mL/year; Group B, 0.122 log IU/mL/year; Group C, 0.057 log IU/mL/year; p = 0.002). Among Group A patients with HBsAg <100 IU/mL, baseline HBsAg achieved an AUROC of 0.876 in predicting >1 log annual HBsAg reduction; 10–100 IU/mL HBsAg was the optimal level for prediction (sensitivity 90 %; specificity 74.6 %). Serum HBsAg/HBV DNA ratios were significantly higher in Group B than in Groups A and C (p < 0.05).

Conclusions

HBV DNA and HBsAg were weakly correlated. Only patients with undetectable HBV DNA showed decline in HBsAg levels during follow-up. The greatest reduction in HBsAg levels occurred in patients with baseline HBsAg <100 IU/mL.     

乙型肝炎病毒前S1抗原对判断病毒复制和乙型肝炎预后的价值

目的探讨乙型肝炎病毒前S1抗原与HBVM和HBV DNA的相关性,评价前S1抗原与病毒复制和在判断乙型肝炎预后中的作用。方法采用ELISA法检测前S1抗原;采用时间分辨免疫荧光法检测HBVM;采用酶学速率法检测肝功能;采用荧光定量PCR方法检测HBV DNA。结果在HBeAg阳性的141例患者中,HBV DNA和前S1抗原的检出率分别为97.2%和92.9%,抗-HBe阳性的183例中,分别为39.9%和37.2%;在HB-sAg阳性/抗-HBc阳性的59例中分别为62.7%和54.2%;慢性乙型肝炎轻度159例,中度132例,重度96例,其血清前S1抗原阳性率分别为56.6%、73.5%和61.5%,三组之间无显著性相差。结论检测前S1抗原可以较好地反映HBV的存在和复制,其在乙型肝炎发病中的临床意义还有待探讨。     

Determinants for hepatitis B e antigen clearance in chronic type B hepatitis

A 6-year (mean 24.5 months) longitudinal study has been undertaken in 237 HBeAg-positive patients with clinicopathologically verified chronic hepatitis. HBeAg clearance occurred in 74 patients at a rate of 16% per year, and a cumulative probability of 67% at the end of a 5-year follow-up. HBeAg clearance was preceded by a temporary "exacerbation" with SGPT greater than 300 IU/L in 62% of the patients. On the other hand, irrespective of the level of SGPT elevation, only 23% of such exacerbations were followed by HBeAg clearance. Further analysis indicates that alphafetoprotein greater than 100 ng/ml, frequently associated with bridging hepatic necrosis, during "exacerbation" predicts HBeAg clearance. In addition, patients with chronic lobular hepatitis and chronic active hepatitis have a higher annual HBeAg clearance rate than patients with chronic persistent hepatitis and nonspecific histologic changes (greater than 15% vs less than 8%, P less than 0.03). Short-term immunosuppressive treatment did not delay HBeAg seroconversion. Male patients had a higher annual HBeAg clearance rate than female patients (18.2% vs 8.7%, P less than 0.05). It was concluded that, in addition to the time factor, the nature of chronic hepatitis, the extent of hepatic damage during "exacerbation", and the sex of the patients are important determinants for HBeAg clearance.     

Clinical importance of serum hepatitis B surface antigen levels in chronic hepatitis B

Quantitative serology for hepatitis B surface antigen (HBsAg) is a new candidate marker for prediction of clinical outcome. The aim of this study was to investigate the clinical significance of quantifying HBsAg in patients with hepatitis B virus (HBV) infection. A total of 424 patients who tested positive for HBsAg and were referred to Chiba University Hospital between January 1985 and April 2008 were included in the study, and the following characteristics were analyzed: age, gender, status of hepatitis B e antigen (HBeAg), alanine aminotransferase level (ALT), HBV DNA level, number of platelets and development of hepatocellular carcinoma. Measurement of HBsAg was performed using the chemiluminescent enzyme immunoassay method. The study group consisted of 239 men and 185 women, and their average age was 40.6 ± 14.0 years. HBsAg showed a positive correlation with HBV DNA level (Pearson's product moment correlation, r = 0.586, P < 0.001) and a weak inverse correlation with age (r = 0.3325, P < 0.001). A control study, matched with age and sex, was performed between two groups with and without HBeAg seroconversion during follow-up period. Compared with the age and sex-matched controls, the change in HBsAg levels per year showed a significant decrease 2 years before seroconversion (paired t-test, P < 0.05). The serial measurement of quantitative HBsAg level has the possibility of predicting the occurrence of HBeAg seroconversion.     

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen-positive [HBeAg(+)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/mL), and 1.71 Paul Ehrlich (PE) IU/mL (-0.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(+) patients, baseline alanine aminotransferase (P = 0.013), HBV DNA (P = 0.040), and qHBsAg levels (P = 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(+) group versus the SR(-) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(+) patients. CONCLUSION: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(+) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated.