Serum hepatitis B surface antigen levels correlate with high serum HBV DNA levels in patients with chronic hepatitis B: a cross-sectional study

Purpose: The hallmark of chronic hepatitis B (CHB) infection is the presence of hepatitis B surface antigen (HBsAg) positivity for at least 6 months. Recently, serum levels of HBsAg have been compared with serum HBV DNA as a surrogate marker to monitor CHB patients. However, data correlating these two markers are scarce. Hence, the present study was done to correlate HBV DNA with HBsAg in CHB patients. Materials and Methods: Consecutive patients of CHB were included. HBV DNA was measured by real-time polymerase chain reaction (PCR). Serum HBsAg was measured by Architect HBsAg. Results: Of the 198 patients enrolled, 166 fulfilled the inclusion criteria (mean age 43 ± 14 years, 87% males) and the median HBV DNA was 1.7 × 10³ (range 6.0–1.1 × 10⁸) IU/ml. Median HBsAg was 8.7 × 10³ (range 5.0–3.2 × 10⁵) IU/ml. Overall correlation between HBV DNA and HBsAg was weak but significant (Spearman ρ = 0.443, P < 0.01). Correlation in HBe antigen-positive group was better (ρ = 0.402, P < 0.01) in comparison to HBe antigen-negative group (ρ = 0.193 P = 0.05). Good correlation existed in treatment-naïve group (ρ = 0.538, P < 0.01). Correlation was regardless of normal or raised alanine transaminase (ALT). Eighty (48%) patients had high HBV DNA (≥2000 IU/ml). Correlation in high DNA group was significant (P < 0.01). The best cut-off of HBsAg for diagnosing high DNA is 3.36 ×10³ IU/ml. Conclusions: Serum HBsAg correlates with HBV DNA in CHB patients, especially in high serum HBV DNA, HBe antigen-positive and treatment-naïve group. HBsAg levels can be used for predicting high serum HBV DNA levels.     

Treatment with lamivudine and entecavir in severe acute hepatitis B

Background: Severe acute hepatitis B (SAHB) is an insufficiently described clinical entity, with relatively scarce data on anti-viral therapy available in field literature. Methods: We performed an open-label study to evaluate specific anti-viral therapy in SAHB in Bucharest, Romania, during 2005–2009. Patients were allocated to two treatment groups and one control group: Group 1 – lamivudine 100 mg/day, Group 2 – entecavir 0.5 mg/day and Group 3 – standard of care, without anti-viral therapy. The primary endpoint was hepatitis B surface antigen (HBsAg) to hepatitis B surface antibody (anti-HBs) seroconversion by 24 weeks. Additional analyses included assessment of HBsAg clearance and hepatitis B e antigen (HBeAg) to hepatitis B e antibody (anti-HBe) seroconversion. Results: In Group 1, 7/69 patients (10.14%, P = 0.032) reached HBsAg/Ab seroconversion by 24 weeks, compared with 9/21 (42.85%, P = 0.053) in Group 2 and 25/110 (22.72%) in Group 3. HBsAg clearance by 24 weeks: 16/69 patients (23.18%, P = 0.027) in Group 1, 11/21 (52.38%, P = 0.256) in Group 2 and 43/110 (39.09%) in Group 3. HBeAg/Ab seroconversion: 46/61 (75.40%, P = 0.399) in Group 1, 9/19 (47.36%, P = 0.001) in Group 2 and 74/100 (74.00%) in Group 3. Conclusion: Anti-viral therapy can be considered for managing selected cases of SAHB. Biochemical as well as virological parameters need to orient the choice of the anti-viral agent. Lamivudine displayed a greater decrease in viral load compared to controls, but it was associated with lower levels of HBsAg to anti-HBs seroconversion. Patients treated with entecavir showed a better response in terms of HBs seroconversion by 24 weeks.     

High rate of seroconversion following administration of a single supplementary dose of recombinant hepatitis B vaccine in Iranian healthy nonresponder neonates

Forty-nine Iranian neonates who failed to develop a protective anti hepatitis B surface antigen (HBs) response following primary vaccination with triple doses of recombinant hepatitis B vaccine, were classified as hypo-responders (anti-HBs > 1 < 10 IU/l) or non-responders (anti-HBs < 1 IU/l) and subsequently challenged with a single supplementary vaccine dose. A protective and anamnestic type of response was observed in 90% (44/49) of the neonates. The mean titer of anti-HBs antibody was significantly higher following supplementary vaccination, compared to that achieved after primary vaccination. This was more evident in the primary hypo-responder neonates (P < 0.00001) than the non-responder group (P < 0.002). The results indicate that a significant proportion of the non-responder neonates to HBs antigen can be induced to develop a protective and long-lasting antibody response by administration of a single additional vaccine dose. Received: 24 September 1996     

Correlation between two chemiluminescence based assays for quantification of hepatitis B surface antigen in patients with chronic hepatitis B infection

Purpose: Hepatitis B surface Antigen (HBsAg) is the hallmark in diagnosing hepatitis B virus (HBV) infection. In India many commercial assays are available for detection of HBsAg but very few can measure it quantitatively. The present study presents the comparative evaluation of two methods and their correlation with serum HBsAg in chronic hepatitis B (CHB) patients. Materials and Methods: Consecutive patients of CHB were included and there HBsAg levels were measured by two methods: (i) Elecsys, Roche Diagnostics, a qualitative assay and (ii) Architect, Abbott Diagnostics, a quantitative assay. The HBV DNA was measured by real-time polymerase chain reaction (qPCR). Results: Total of 136 patients were included in the study and there was a significant overall correlation between both the assays (correlation coefficient [r] = 0.83; P < 0.001). Assays correlated well with each other across all subgroups of CHB: treatment naïve (r = 0.73; P < 0.001, n = 32), on treatment (r = 0.56; P < 0.05, n = 104), hepatitis Be (HBe) antigen positive (r = 0.67; P < 0.001, n = 62) and anti-HBe positive (r = 0.61; P < 0.05, n = 74) group. On correlation with serum HBV DNA, Architect assay demonstrated good correlation (r = 0.73; P < 0.001, n = 136) as compared to the Elecsys assay (r = 0.27; P = 0.068, n = 136). Architect HBsAg QT assay (A1) also correlated well with HBV DNA in the treatment naïve group (r = 0.69; P < 0.001, n = 32). Conclusions: Our study hence proved that both the assays are comparable and a simple qualitative assay with in-house modification can be used easily for quatitation of HBsAg in clinical samples.     

In vitro immune responses to hepatitis B surface antigen (pre-S2 and S) following remote infection by hepatitis B virus in humans

In this report we evaluate the human immune response to hepatitis B surface antigen (HBsAg) following remote infection with hepatitis B virus (HBV). HBsAg-reactive lymphocytes can be readily demonstrated in the peripheral blood of individuals with established immunity following infection with HBV.In vitro stimulation with small doses of plasma-derived HBsAg, yeast-derived HBsAg (S region) or pre-S2 peptide will induce specific IgG to HBsAg (anti-HBs) in the absence of a polyclonal increase in total IgG. The pre-S2 peptide will stimulate, in a T cell-dependent fashion, thein vitro production of anti-HBs with specificity for the S domain. This anti-HBs production is mediated by pre-S2-stimulated soluble T-cell factors. Peripheral blood mononuclear cells from individuals with established immunity proliferate to the yeast-derived HBsAg but not to the plasma-derived HBsAg or pre-S2 peptide. The chronic HBsAg carriers do not produce anti-HBs following stimulation with HBsAg regardless of the source or component of antigen used. Different study protocols failed to demonstrate HBsAg-specific responses in the peripheral blood mononuclear cells of chronic carriers.     

Serum hepatitis B surface antigen is correlated with intrahepatic total HBV DNA and cccDNA in treatment‐naïve patients with chronic hepatitis B but not in patients with HBV related hepatocellular carcinoma

The aim of the study was to investigate correlations between intrahepatic hepatitis B virus total DNA, covalently closed circular DNA (cccDNA), and serum HBsAg in treatment‐naïve chronic hepatitis B and HBV related hepatocellular carcinoma (HCC). Liver tissues were taken from 42 HBV related HCC and 36 patients with chronic hepatitis B. A fraction of DNA extracted from liver tissue was digested with a plasmid‐safe ATP‐dependent DNase and used for HBV cccDNA detection. The remaining DNA was used for the detection of HBV total DNA and β‐globin, the latter of which is a housekeeping gene and quantified for normalization by real‐time PCR. Quantitation of serum HBsAg was performed by a chemiluminescence assay. Serum HBsAg had positive correlations with serum HBV DNA (r = 0.636, P < 0.001), intrahepatic HBV total DNA (r = 0.519, P = 0.001) and cccDNA (r = 0.733, P < 0.001) in 36 treatment‐naïve chronic hepatitis B, while HBsAg correlated poorly with DNA (r = 0.224, P = 0.210), intrahepatic total DNA and cccDNA in the tumor (r = 0.351, P = 0.031; r = 0.164, P = 0.324, respectively) and non‐tumor (r = 0.237, P = 0.152; r = 0.072, P = 0.667, respectively) liver tissues of 42 HCC. HBV cccDNA and total DNA were significantly higher in liver tissue from chronic hepatitis B than in tumor and non‐tumor of HCC (P < 0.001). Serum HBsAg and HBV DNA were also higher in chronic hepatitis B than in HCC (P < 0.001). It was concluded that levels of serum HBsAg and intrahepatic cccDNA and total DNA were significantly higher in chronic hepatitis B than in HCC, and significant correlations among them were observed in treatment‐naïve chronic hepatitis B but not in HCC. J. Med. Virol. 85:219–227, 2013. © 2012 Wiley Periodicals, Inc.     

Anti-hepatitis B surface antigen IgG1 subclass is predominant in individuals who have recovered from hepatitis B virus infection, chronic carriers and vaccinees

Patterns of each IgG-specific subclass for hepatitis B virus (HBV) core antigen (anti-HBc) are remarkably different among individuals with different infection status, i.e., completely recovered or chronic carrier. Each of the IgG-specific subclasses of HBV surface antigen (anti-HBs) was tested for ELISA sensitivity using four commercially available hepatitis B surface antigen (HBsAg) kits and one self-prepared plate. The specificity in 18 serum samples obtained from chronic HBV carriers, recovered individuals, vaccinees and non-infected individuals was investigated. Differences in absorbance values were obtained by comparing results from these different plates. Data on the absorbance values of anti-HBs IgG subclasses obtained indicated that one to four subjects had a false-negative or false-positive result using the four commercial plates. Only the self-prepared plate demonstrated 100% specificity and sensitivity for anti-HBs subclasses. Moreover, the results indicate that anti-HBs subclass IgG1 was predominant in cured patients, chronic carriers and vaccinees. The samples from both chronic carriers and vaccinees exhibited a significantly higher concentration of total IgG and IgG1 than samples in recovered individuals (P<0.05).     

Effects of hepatitis C and B viruses infection on the development of hepatocellular carcinoma

A case control study consisting of 102 patients with HCC, 102 sex-matched and age-matched patients with nonhepatic disease, and 204 matched healthy controls was carried out to investigate the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC). The prevalence of antibody to HCV (anti-HCV) in HCC (34.3%) was higher than in nonhepatic disease (10.7%, P< 0.001) or in healthy controls (2.4%, P< 0.001). The prevalence of hepatitis B surface antigen (HBsAg) in HCC (77.4%) was higher than in nonhepatic disease (16.6%, P< 0.001) or in healthy controls (19.6%, P< 0.001). Anti-HCV positivity in nonhepatic disease was higher than in healthy controls (P<0.01). Using patients with nonhepatic disease as controls, stepwise logistic regression analysis indicated that both anti-HCV (odds ratio, 3.4; 95% confidence interval, 2.1-5.6) and HBsAg (odds ratio, 5.6; 95% confidence interval, 3.6–8.5) are independent risk factors for HCC. Using healthy controls, the development of HCC was also strongly associated with anti-HCV (odds ratio, 8.0; 95% confidence interval, 4.3–14.6) and HBsAg (odds ratio, 5.5; 95% confidence interval, 3.7–8.2). Calculation of incremental odds ratio indicated that there is no interaction between HBV and HCV. In conclusion, HBV and HCV are risk factors of HCC. They act independently and without interaction. © 1994 Wiley-Liss, Inc.     

Hepatitis B and hepatitis C among institutionalized psychiatric patients in Taiwan

To investigate the seroprevalence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) in a psychiatric institution in Taiwan, where hepatitis B virus (HBV) is hyperendemic, a total of 780 patients with psychiatric disorders were studied. Enzyme-linked immunosorbent assays (ELISA) were used for testing HBsAg and anti-HCV. The prevalence of HBsAg was higher than that of anti-HCV among these patients (18.1% vs. 6.8%, P < 0.0001). The HBsAg carrier rate in these patients was consistent with that of the general population, with a trend for HBsAg carrier rate to be lower in the aged and in females. In contrast, the prevalence of anti-HCV was higher in these patients than in general population. Anti-HCV positivity was found more frequently in patients who had received blood transfusion previously (24% vs. 6.4%, P < 0.05). The majority (92%) of patients with positive anti-HCV did not have a history of apparent parenteral exposure. The prevalence of anti-HCV increased significantly with duration of the psychiatric disorder. The prevalence of anti-HCV also tended to increase with duration of hospitalization but without reaching statistical significance. These findings suggest that these institutionalized psychiatric patients contract hepatitis B, as does the general population in Taiwan, and they should be considered as a specific risk group for hepatitis C infection. © 1993 Wiley-Liss, Inc.     

Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg‐negative patients

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg‐negative chronic hepatitis B patients. Thirty‐three treatment‐naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/10⁶ cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg‐negative chronic hepatitis B. J. Med. Virol. 82:1494–1500, 2010. © 2010 Wiley‐Liss, Inc.     

Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection

Antibody to hepatitis B surface antigen (HBsAg) (anti‐HBs) can exist in patients with chronic hepatitis B virus (HBV) infection. To date, little is known about the association of concurrent HBsAg and anti‐HBs (concurrent HBsAg/ anti‐HBs) with hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical relevance of concurrent HBsAg/anti‐HBs with preS deletion mutations and HCC in chronic HBV infection. A total of 755 patients with chronic HBV infection were included consecutively at a tertiary center. Logistic regression analysis was used to identify risk factors for HCC, and serum HBV DNA was amplified, followed by direct sequencing to detect preS deletions. The prevalence of concurrent HBsAg/anti‐HBs was 6.4% (48/755) and all HBVs tested were genotype C. HCC occurred more frequently in the concurrent HBsAg/anti‐HBs group than in the HBsAg only group [22.9% (11/48) vs. 7.9% (56/707), P = 0.002]. In multivariate analyses, age >40 years [odds ratio (OR), 14.712; 95% confidence interval (CI), 4.365–49.579; P < 0.001], male gender (OR 2.431; 95% CI, 1.226–4.820; P = 0.011), decompensated cirrhosis (OR, 3.642; 95% CI, 1.788–7.421; P < 0.001) and concurrent HBsAg/anti‐HBs (OR, 4.336; 95% CI, 1.956–9.613; P < 0.001) were associated independently with HCC. In molecular analysis, preS deletion mutations were more frequent in the concurrent HBsAg/anti‐HBs and HCC groups than in the HBsAg without HCC group (42.3% and 32.5% vs. 11.3%; P = 0.002 and 0.012, respectively). In conclusion, concurrent HBsAg/anti‐HBs is associated with preS deletion mutations and may be one of the risk factors for HCC in chronic HBV infection with genotype C. J. Med. Virol. 81:1531–1538, 2009. © 2009 Wiley‐Liss, Inc.     

Circulating microRNA‐122 levels are important predictor of hepatitis B virus surface antigen seroclearance

It is currently unclear what impact serum microRNA‐122 (miR‐122) levels have on clearance of hepatitis B virus (HBV) surface antigen (HBsAg) in HBV‐infected patients who had not received antiviral therapy. The current study evaluated the impact of serum miR‐122 levels on HBsAg seroclearance in 367 consecutive HBV‐infected patients who had not received antiviral therapy between their initial and last visit, and investigated the predictive factors of HBsAg seroclearance. Cumulative HBsAg seroclearance rates were 13.5%, 32.0%, and 37.4% after 10, 20, and 30 years, respectively. The yearly incidence of HBsAg seroclearance over the investigated 30‐year period was 1.25%. A significant and strong correlation was observed between serum miR‐122 and HBsAg levels. Moreover, there was a significant correlation between serum miR‐122 levels and the levels of HBV DNA, hepatitis B e‐antigen, and HBV core‐related antigen. The HBsAg seroclearance rate in patients with a <1.0‐fold change of serum miR‐122 levels was significantly higher than in those with a ≥1.0‐fold change. Multivariate analysis identified age (≥30 years), HBV DNA levels (<2.2 log U/mL), HBV genotype (non‐C), and serum miR‐122 levels (<1.0‐fold change) as significant predictors of HBsAg seroclearance. Our results indicated that serum miR‐122 level is an important predictor of HBsAg seroclearance in Japanese patients who do not receive antiviral therapy. Understanding the complexity of the interactions among various virus‐related and host‐related factors could potentially help in the design of new therapies that enhance HBsAg seroclearance.     

Immunogenicity in chimpanzees of experimental hepatitis B vaccines prepared from intact hepatitis B virus,purified polypeptides,or polypeptide micelles

The immunogenicity of three experimental hepatitis B vaccines was evaluated in chimpanzees. Although no antibody to hepatitis B surface antigen (anti-HBs) was detected in two chimpanzees that received an aqueous polypeptide vaccine subcutaneously, a strong anti-HBs response was observed two and ten weeks, respectively, following challenge with hepatitis B virus. Inoculation of two additional chimpanzees with a micellar preparation of these polypeptides by the intravenous route resulted in anti-HBs production in one of the chimpanzees. Two chimpanzees inoculated subcutaneously with an aqueous vaccine of formalin-inactivated intact hepatitis B virus developed anti-HBs in low titers, but the development of antibody to the hepatitis B core antigen following challenge inoculations suggested that subclinical HBV infections may have occurred despite prior vaccination.     

Hepatitis B virus surface gene mutants in immunoprophylaxis-failed infants from Southern China

Hepatitis B virus (HBV) vaccination was considered the most powerful tool for prevention of HBV transmission from mother to infant. In 1992, a universal HBV vaccination program for infants was launched in China. The aim of this study was to investigate the HBV surface antigen (HBsAg) variations in immunoprophylaxis-failed infants, vaccine free infant patients and adult chronic hepatitis B (CHB) patients (without nucleoside analog treatment). Immunoprophylaxis-failed infants were recruited from two centers (Guangdong and Chongqing, representing Southern China). HBV serum markers, including HBsAg, hepatitis e antigen (HBeAg), and core antigen, were detected by the enzyme-linked immunosorbent assay. HBV DNA load was detected by quantitative polymerase chain reaction. Nucleotide sequences encoding HBsAg were amplified and analyzed. Frequencies of amino acid substitutions within the second loop of “a” determinant (region with greater local hydrophilicity) in immunoprophylaxis-failed infants were clearly higher than the unvaccinated infant patients and adult CHB patients (9.6% vs 0% vs 3.8%; χ ² = 7.454; P = 0.024). More than 50% (52.8%) aa substitutions in immunoprophylaxis-failed infants were located in B cell epitopes, while 64.6% aa substitutions in adult CHB patients were located in CTL cell epitopes. HBeAg negative patients had higher substitution frequency in CTL and Th cell epitopes, and in immunoprophylaxis-failed infant patients with substitution in major hydrophilic region region had a higher alanine aminotransferase level (68.6 ± 111.5 vs 62.1 ± 132.2; P = 0.026), and lower DNA load (7.03 ± 1.72 vs 7.82 ± 1.73; P < 0.001). In conclusion, our results observed vaccine-induced immune selection pressure in vaccine failed infants, substitutions in “a” determinant, especially the G145 substitution was still the most stable and remarkable site of vaccine escape.     

Seroepidemiological associations between tuberculosis,malaria, hepatitis B,and AIDS in West Africa

Serum samples from 51 patients with malaria, 35 patients with hepatitis B virus infection, 111 patients with tuberculosis, and 166 healthy controls were studied to determine any associations between tuberculosis, malaria, hepatitis B, and AIDS in Nigeria, West Africa. All serum samples were examined for the presence of HIV-1/HIV-2, hepatitis B virus surface antigen (HBsAg), and malaria antibodies. Only one patient was HIV-1 antibody-positive and none HIV-2 antibody-positive. Statistical associations were found between the presence of malaria antibody litres on the one hand and a diagnosis of hepatitis B virus infection (P < 0.05) or tuberculosis (P < 0.05). A stronger association (P < 0.001) was found between the presence of HBsAg and tuberculosis suggesting that HBsAg carriers are at higher risk of contracting tuberculosis. © 1994 Wiley-Liss, Inc.     

Occult hepatitis B virus infection in patients with leprosy

Leprosy patients may present with immune system impairment and have a higher hepatitis B virus (HBV) seroprevalence, justifying the investigation of occult HBV infection in these individuals. The aim of this study was to verify the frequency and the clinical factors associated with occult HBV infection in leprosy patients. Between 2015 and 2016, leprosy patients from a reference center in Brazil were interviewed to assess clinical data. Blood samples were collected for the screening of HBV serological markers using enzyme-linked immunosorbent assay. Patients with negative hepatitis B surface antigen (HBsAg) that had positive anti-HBc and/or anti-HBs were selected for HBV DNA detection using real-time polymerase chain reaction. SPSS was used for data analysis. Among 114 selected patients, six were identified with occult infection (5.3%) and five of them with multibacillary leprosy. Three patients with occult infection had a history of a type 2 reaction (P = 0.072; OR, 4.97; 95% CI, 0.87-28.52). Only two patients with occult infection had isolated anti-HBc, while three had isolated anti-HBs, including those with the highest HBV DNA titers. In conclusion, in leprosy patients with negative HBsAg and positive anti-HBc and/or anti-HBs, occult HBV infection occurs in 5.3% and can be found even in patients with isolated anti-HBs.     

Seroprevalence of hepatitis B virus among health care workers in Korea

We studied the seroprevalence of HBsAg, anti-HBs and anti-HBc and the vaccination histories among health care workers (HCWs) at a large suburban referral hospital in Korea. The purpose of this study was to determine the immune status of HCWs against hepatitis B virus and we also wanted to prepare a practical guideline to protect HCWs from occupational exposure. During December, 2003, 571 HCWs (56 physicians, 289 nurses, 113 technicians and 113 aid-nurses) aged between 21 and 74 yr were included in the surveillance. The positive rates of HBsAg and anti-HBs were 2.4% (14/571) and 76.9% (439/571), respectively. The positive rate of anti-HBs was lower in the physician group, and this was associated with the male gender and older age. Of the 439 anti-HBs positive cases, 320 cases (73.1%) were anti-HBc negative and this was significantly associated with a past history of HBV vaccination. The distribution of the anti-HBs levels was not associated with age (except for HCWs in their sixties), gender or occupation. Our study revealed that the seroprevalence rates of HBsAg and anti-HBs in HCWs in Korea were not different from those of the general population. Based on this surveillance, we can make reasonable decisions in case of occupational exposure to hepatitis B virus.     

Detection of hepatitis B surface antigen (HBsAg) in peripheral blood mononuclear cells of patients with acute and chronic active hepatitis B

Seventy five patients with acute and chronic active hepatitis (CAH) were studied by indirect immunofluorescence with monoclonal antibodies for the presence of hepatitis B surface antigen (HBsAg) on peripheral blood mononuclear cells (PBMC). The viral surface antigen was detected in the PBMC of all the patients with hepatitis B virus (HBV)-induced CAH and in acute patients with more than 2 months of evolution. No HBsAg was detected in the samples obtained from 12 normal controls or from 14 non-A, non-B CAH patients. Analysis of PBMC subsets revealed that HBsAg was present in non-T cells; dual fluorescence studies showed HBsAg on surface Ig-positive lymphocytes. The binding of anti-HBs monoclonal antibodies was higher than that of a goat anti-HBs serum, and the highest reactivity was observed with an antibody against the pre-S(2)-region sequence. Both HBsAg and hepatitis B core antigen (HBcAg) were also detected in lysates of PBMC by dot blot analysis.     

Hepatitis B and D virus infection among drug abusers in Taiwan

Approximately 15 to 20% of the general population in Taiwan are chronic hepatitis B surface antigen (HBsAg) carriers. However, the incidence of hepatitis D virus (HDV) infection is low (5-8%) in patients with HBsAg-positive chronic liver diseases in this area. To evaluate the prevalence of hepatitis B virus (HBV) and HDV infection among drug abusers in Taiwan, serum samples were collected from 152 drug abusers at the Taipei Municipal Anti-Narcotic Institute and test for HBV and HDV markers. Of these, 24 (15.8%) were HBsAg positive, and only 15 (9.9%) were seronegative for all HBV markers. Of the 115 intravenous drug abusers, serum antibody to hepatitis D antigen (anti-HD) was positive in 78.9% of 19 persons who were HBsAg positive, and in 7.5% of 80 persons who were positive for antibody to HBsAg (anti-HBs). Anti-HD was not detected in the sera from all 37 nonintravenous drug abusers regardless of the status of their HBV markers. Also, none of 63 asymptomatic HBsAg carrier pregnant women or 23 patients with acute type B viral hepatitis had measurable anti-HD in their sera. Thus, the high frequency of HDV detected among Chinese HBsAg carrier intravenous drug abusers in Taiwan is similar to that reported in Western countries.     

Mutations in hepatitis B virus DNA from patients with coexisting HBsAg and anti-HBs

Background

The serological markers with coexistence of hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) of hepatitis B virus (HBV) infection were rare pattern. The virological significance, immune response and clinical outcome of these patients remain largely unknown.

Objectives

This research explores the relationship between this serological profile and HBV genome variants.

Study design

We studied 35 patients both carrying HBsAg and anti-HBs (group I), and 70 patients with HBsAg positive but anti-HBs negative (group II, served as control). The HBV genome sequences were obtained by direct sequencing of polymerase chain reaction (PCR) products.

Results

The amino acid (aa) variation within major hydrophilic region (MHR), especially in the first loop (aa124-137) of “a” determinant in group I is significantly higher than those in group II. The aa variation of cytotoxic lymphocyte (CTL) epitope in HBsAg (aa87–aa95) in group I is also significantly higher than that in group II. Interestingly, the basal core promoter (BCP) double mutations (A1762T/G1764A) in group I is significantly higher than those in group II as well.

Conclusions

In patients with HBV infection, the coexistence of HBsAg and anti-HBs is associated with an increased aa variability in several key areas of HBV genome. The molecular characteristic of HBV in HBsAg and anti-HBs positive patients is distinct and worth further studies.