HBsAg Group Research Articles

Molecular analysis on chronic hepatitis B patients with low-level HBsAg

Objective To investigate the molecular characteristics and epidemiological signification of patients with low-level HBsAg. Methods PCR and gene sequencing were used to detect HBV DNA and Tyr-Met-Asp-Asp(YMDD) mutant in 136 serum samples with low-level HBsAg and 44 sernm samples with high-level HBsAg. Genotyping was performed in 47 cases with HBV DNA 105 copies/L by concentration method and 37 cases with high-level HBsAg. S gene sequences and serotypes were analyzed in 14 cases with HBV DNA 105 copies/L and 29 cases with high-level HBsAg. S gene sequences were compared with the consensus sequence of Chinese strain by BioEdit software. Results The HBV DNA-positive rate, YMDD mutation rate and HBV DNA load (logarithm) in low-level and high-level HBsAg group were 34.6% (47/136), 0% (0/136), 6.5±1.4 and 84.1% (37/44), 9.1% (4/44), 8.9±1.8, respectively. There was statistically significant differences between two groups (for concentration method,χ2 = 30.8, P 0.05). S gene sequencing results showed no S gnne variation was detected, but there were 6 single nucleotide polymorphisms in 16 cases, which would not result in the alternation of amino acid. Conclusions Low-replication phenomenon of HBV DNA was present in patients with low-level HBsAg. The major genotyps and serotype was type B and adw/ayw, respectively. Polymorphic variants have been found in the S gene. The existence of low-level HBsAg might be related with its own molecular characteristics resulting in low expression of HBsAg or immune tolerance induced by low-level HBsAg after HBV infection. Key words: Hepatitis B; chronic; Hepatitis B surface antigen; Polymerase chain reaction; Genotype

Study on liver damage caused by anti-TB drug intermittent treatment on patients with HBV-TB co-infection

To study the features of liver damage caused by anti-TB medicines among patients with TB-HBV co-infection, in order to complement and improve the implementation of DOTs strategy in the region. A historical cohort study was conducted including the process of reviewing and analyzing files of the 781 naive TB patients hospitalized from June 2004 to October 2005. Cases were divided into HBsAg (+) group and HBsAg (-) group. The overall damage rate among the 781 investigation cases was 20.74%, including 121 cases (74.69%) in HBsAg (+) group and 41 cases (25.31%) in HBsAg (-) group. Data showed that liver damage rate and average value of ALT and AST of HBsAg (+) group were higher than those in HBsAg (-) group. First case with liver damage in HBsAg (+) group happened on the 7th day of the treatment, while the first liver damage case happened in HBsAg (-) group was on the 16th day. The average onset in HBsAg (+) group was earlier than HBsAg (-) group for 18.09 days. The average time of liver function recovery in HBsAg (+) group was 57.02 days and in HBsAg (-) group it was 27.56 days while the appearance among HBsAg (+) group was 29.46 days later than in HBsAg (-) group. The incidence rate of liver damage caused by anti-TB medicines was higher among HBV positive patients than those HBV negative patients. Patients co-infected with HBV infection appeared to be more serious, with higher incidence on liver damage and earlier onset, as well as with the degree of damage to the liver.

IMP321 (sLAG-3), an immunopotentiator for T cell responses against a HBsAg antigen in healthy adults: a single blind randomised controlled phase I study

BackgroundLAG-3 (CD223) is a natural high affinity ligand for MHC class II. The soluble form (sLAG-3) induces maturation of monocyte-derived dendritic cells in vitro and is used as a potent Th1-like immune enhancer with many antigens in animal models. To extend this observation to human, a proof of concept study was conducted with a clinical-grade sLAG-3, termed IMP321, coinjected with alum-non-absorbed recombinant hepatitis B surface antigen.MethodsIn a randomised, single blind controlled phase I dose escalation study, 48 seronegative healthy volunteers aged 18–55 years were vaccinated at 0, 4 and 8 weeks by subcutaneous injection with 10 μg HBsAg mixed with saline (control) or with IMP321 at one of four doses (3, 10, 30 and 100 μg). To evaluate the efficacy of this three injections over 2 months immunization protocol, an additional control group was injected with the commercial vaccine Engerix-B®.ResultsIMP321 was very well tolerated. Indeed, a lower incidence of adverse events was reported from the HBsAg plus IMP321 groups than from the Engerix-B® group. HBsAg-specific antibody responses (anti-HBs) appeared sooner and were higher at 8 and 12 weeks in IMP321 recipients compared to HBsAg control subjects. More importantly, increased numbers of responders to HBsAg were found in IMP321 recipients compared HBsAg group, as revealed by higher post-vaccination frequencies of CD4 Th1 or CD8 Tc1 antigen specific T cells. IMP321 induced CD4 Th1 antigen-specific T cells in some of these naïve individuals after only one injection, especially in the 10 and 30 μg dose groups.ConclusionIMP321 as an adjuvant to HBsAg was well-tolerated and enhanced T cell response vaccine immunogenicity (i.e. induced both CD4 Th1 and CD8 Tc1 antigen-specific T cells). This latter property has allowed the development of IMP321 as an immunopotentiator for therapeutic vaccines.

At least three epitopes are recognized by the human repertoire in the hepatitis B virus group a antigen inducing protection; possible consequences for seroprevention and serodiagnosis

Many recent investigations have shown that both HBV and anti-HBs antibodies coexist in the same patient, and HBV can be found in individuals with anti-HBc antibodies in the absence of immunologically detectable HBsAg. In most cases, mutant forms of HBV affecting the region of the envelope gene coding for the group a determinant recognized by human antibodies have been found. The nature of the group a determinant was revisited with an ELISA involving dissociated, but not alkylated, envelope subunits. No antibody recognizing a continuous epitope of the major S envelope protein could be found in humans; the full activity of human anti-HBs antibodies appeared to be focused on the discontinuous group a determinant. The immunological human repertoire against the HBsAg group a determinant was analysed by competitive inhibition of three mouse monoclonal antibodies (mAbs) selected as recognizing three distinct specificities on the group a determinant. Antibodies to specificities #1 and 3 were found in 52/70 anti-HBs human sera and generally predominated over specificity #2, which was lacking in some sera. The heterogeneity of the group a determinant suggested by these data argue for the use of more than one type of anti-HBs mAb for seroprevention of recurrence after liver transplantation and HBs serodiagnosis. Provided all three types of mAbs characterized here recognize HBV variants with mutations in the a determinant and are virus-neutralizing, it may be helpful, after association of such mAbs, to use them for diagnosis and to devise new immunotherapeutic strategies to prevent emergence of HBsAg escape mutants.

Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis. Lack of correlation with hepatitis C and D virus superinfection.

We investigated the frequency of HBsAg clearance and the possible role of viral superinfection in a long-term follow-up of 184 patients with chronic hepatitis B (CHB). Our subjects were 184 patients with chronic hepatitis B and the follow-up was 12-216 months (mean 66.2 +/- 53.7 months). The investigative methods used were: immunoenzymatic assays for HBV, HCV, HDV, and HIV markers; polymerase chain reaction (PCR) for HBV DNA; and liver biopsy and immunoperoxidase. During the follow-up, 20 of the 184 patients cleared serum HBsAg. A comparison of patients with persistent HBsAg(group I) and of those who cleared this marker (group II) showed a significant difference in mortality (P = 0.002) between the two groups and a tendency to a more severe exacerbation (flare) in group II (P = 0.07). Antibodies to hepatitis C and D virus as well as antibodies to HIV were equally distributed in both groups. Thirteen patients (7.9%) from group I, but none from group II, subsequently developed hepatocellular carcinoma. These results suggest that the frequency of spontaneous clearance of HBsAg during chronic HBV infection is low. No determinant factor for the clearance was found, including the presence of liver cirrhosis. Serum HBV DNA was undetectable by PCR after clearance in 16 out of 17 patients.

Significance of measurement of pre‐S2 antigen for the prevention of vertical transmission of hepatitis B virus in infants born to HBsAg carrier mothers

The significance of pre-S2 antigen (pre-S2 Ag) as a marker of hepatitis B virus (HBV) infection, especially in infants born to HBsAg carrier mothers who are HBeAg-negative or HBeAg-positive, was evaluated. Pre-S2 Ag was measured by enzyme immunoassay. HBsAg carrier mothers who were HBeAg-negative and HBeAb-positive were divided into two groups: group A, mothers whose infants were not infected with HBV (n = 10) and group B, mothers whose infants were infected with HBV (n = 13). Absorption rates of pre-S2 Ag in group A and B were 0.09 +/- 0.04 and 1.36 +/- 0.95, respectively. The values for pre-S2 Ag in group B were significantly higher than those in group A. Values for pre-S2 Ag among HBsAg carrier mothers who were HBeAg-positive and HBeAb-negative were also measured by reverse passive hemagglutination. In the same way, HBsAg carrier mothers who were HBeAg-positive and HBeAb-negative were divided into two groups: group C, mothers whose infants did not become HBsAg carriers (n = 15) and group D, mothers whose infants became HBsAg carriers (n = 11). The titers of pre-S2 Ag (reverse passive hemagglutination) in group C and D were 2(5.75) +/- 1.68 and 2(10.45 +/- 1.69), respectively. The values for pre-S2 Ag in group D were significantly higher than those in group C. The values for pre-S2 Ag as markers of infectivity became higher with increasing amounts of HBV-DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Transmission of Hepatitis B Virus Infection in Ethiopia with Emphasis on the Importance of Vertical Transmission

This two-year controlled study was conducted to define the mode of transmission of hepatitis B infection in Ethiopia. Twenty-five of 500 (5%) expectant mothers were identified as HbsAg positive (Group A). A control group of 29 mothers negative for HBsAg (Group B) was randomly selected. These 54 mothers and their families (husbands, infants and the infants' older siblings) were followed for two years with determinations of serological markers of ongoing or past hepatitis B virus infection at 6, 12 and 24 months. Social and clinical data as well as possible factors contributing to the spread of HBV (ie tattoos, circumcision, etc.) were compiled from questionnaires. Twenty-one of the 25 (84%) HBsAg positive mothers had anti-HBe and none had HBeAg. One case of vertical hepatitis B virus transmission was seen while horizontal transmission during the study period occurred in two infants and in two older siblings. Potential risk factors for non-perinatal transmission were highly prevalent in both groups and may represent the main route of transmitting the infection, while, as shown in the present study, the vertical transmission of HBV infection only plays a minor role in the maintenance of the high infection rate in Ethiopia. Vaccinating all babies soon after birth would, therefore, be an effective means of eradicating or reducing the hepatitis B virus infection and its sequelae.