Elimination Of HBsAg Research Articles

Loss of HBsAg in Patients with High Levels of HBV-DNA During Treatment with Nucleoside or Nucleotide Analogs

Background: HBsAg is synthesized in the endoplasmic reticulum and is necessary for the formation of complete HBV particles. A decreased synthesis of this antigen leads to an intracellular inhibition of virus production. Methods: The study aimed to assess the incidence of HBsAg elimination among 1,290 patients who suffered from chronic HBV infection undergoing an antiviral treatment with nucleoside or nucleotide analogs (NAs). Furthermore, possible predictive factors for this elimination were analyzed. Results: A permanent HBsAg loss was confirmed in 3% of the patients, which was more frequent in men than in women (4.4% vs. 1.9%; P = 0.009). The HBsAg elimination occurred in 5% of HBeAg (+) patients and 2.8% of HBeAg (-) patients. The age of patients whose HBsAg was eliminated was higher than the age of the remaining patients (60 vs. 51 y/o). The effect of initially used pegylated interferon alfa (PEG-IFN) therapy on the HBsAg elimination was not observed. It occurred with the use of entecavir (ETV) and tenofovir (TDF); however, among patients treated with ETV, HBsAg was significantly more often eliminated in HBeAg (+) patients. Conclusions: The HBsAg elimination in patients undergoing antiviral treatment occurs more often in men, patients with positive HBeAg before treatment, individuals above 60 years, and patients treated with ETV.

Polymorphism of IL28B gene and response to pegylated interferon α2a in chronic hepatitis B

<b>Introduction: </b>Because of its worldwide prevalence, chronic hepatitis B constitutes a significant global health issue. Chronic hepatitis B virus (HBV) infection affects about 350 million people, with 1 million deaths annually due to its sequelae. The unique way of replication makes HBV difficult to eradicate with the available treatment. Interferon is currently the only option offering a “curative treatment strategy”. Predictors of a sustained response to interferon are desired. The aim of this study was to assess the efficacy of chronic hepatitis B treatment with pegylated interferon 2a in relation to the polymorphisms of the interleukin 28B gene.<br /> <b>Material and methods</b>: Eighty-six patients were included in the study. They were treated with PegIFN2a in the dose of 180 µg weekly for 48 weeks and were followed up for at least 1 year after the end of therapy (EOT). Treatment efficacy was defined as HBsAg clearance or HBV viral load ≤ 2000 IU/ml at the end of therapy and at the end of 12 consecutive months. Two polymorphisms of IL28B at loci rs12979860 and rs809997 were examined in every patient.<br /> <b>Results</b>: No associations between any of the IL28B polymorphisms and HBsAg elimination were found. However, a weak but statistically significant association between persistent HBV-DNA decrease and a TT variant (C/T) of IL28B was found (Spearman’s correlation coefficient 0.236, p < 0.001). Patients having this polymorphism also had significantly lower HBV-DNA loads after EOT (Spearman’s correlation coefficient 0.27, p = 0.02). The weak associations and small number of patients do not allow us to draw firm conclusions. <br /> <b>Conclusions</b>: We discovered no associations between any of the IL28B polymorphisms and HBsAg loss, IL28B polymorphisms do not seem to play an important role as predictors of treatment efficacy in the treatment of chronic B hepatitis with pegylated interferon.

The dynamics of HCV DNA and HBsAg levels in acute hepatitis B patients in monoinfection and coinfection of other hepatitis viruses

Introduction Changes in the levels of DNA of hepatitis B virus (HBV) infection and the quantitative content of the surface antigen (HBsAg) in acute hepatitis B, as well as the concomitant co-injection of other hepatitis viruses have been insufficiently studied so far. Materials and Methods In 21 patients with acute HBV monoinfection and 27 patients with co-infection of HBV + HCV and/ or HDV three to four serum samples were withdrawn with interval of 6-10 days and the dynamics of HBV viral load and concentration of HBsAg was examined. Results Logarithm of the concentration of DNA HBV was established to decrease from 4.0 ± 0.65 to 3.0 ± 0.59, to 2.5 ± 0.47, to 1.9 ± 0.65 (IU /ml, M ± s), the half-life of DNA HBV was increased from 1.6 days at baseline to 4 days to the end of the study. The decline of the HBsA concentration proceeded much slower: from 38 to 23, 12, 3.8 pg/ml. Half-life period of HBsAg accounted of 8 days at the beginning and 5.7 days at the end of the study, however, in 11 patients there was observed rapid elimination of HBsAg and disappearance of HBV DNA. Conclusion The fact of co-infection with hepatitis C virus (HCV) had no significant effect on the dynamics of HBV DNA and HBsAg levels. In patients infected with Hepatitis D virus (HDV) HBV viral load was significantly lower, and the concentration of HBsAg, by contrast, is significantly higher than in acute monoinfection with HBV. Thus, in acute hepatitis B DNA elimination occurs much faster than the elimination of HBsAg. In addition, in co-infection HDV inhibits replication of HBV, but at the same time stimulates the expression of HBsAg. The obtained data should be considered in the interpretation of laboratory tests in patients with acute hepatitis B, both in the earlier period, and at follow-up.

HBSAG level at time of olt determines hepatitis B immunoglobulin dose required for elimination of HBSAG after olt in patients with HBV cirrhosis

HBSAG level at time of olt determines hepatitis B immunoglobulin dose required for elimination of HBSAG after olt in patients with HBV cirrhosis

Elimination of HBsAg and HBeAg after alpha-interferon treatment

Elimination of HBsAg and HBeAg after alpha-interferon treatment

Acute hepatitis C virus superinfection followed by spontaneous HBeAg seroconversion and HBsAg elimination

Acute hepatitis C virus superinfection followed by spontaneous hepatitis B e antigen seroconversion and hepatitis B surface antigen clearance in a patient with chronic type B hepatitis is described. The observations suggests that HCV may exert a suppressive effect on hepatitis B virus.

Serum pregnancy‐associated α2‐glycoprotein levels in the evolution of Hepatitis B virus infection

Serum pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) levels were evaluated in a follow-up study of patients with hepatitis B virus (HBV) infection and compared with biochemical and virological parameters. In a study of 25 patients with acute hepatitis, an association was found between high alpha 2-PAG values, ALT levels, and HBsAg in 20 patients (80%) (P less than 0.05), 18 recovered completely, and 2 had a protracted course. In five patients serum alpha 2-PAG levels were similar to those in the control group. On the other hand, eight (100%) chronic persistent HBV patients showed high levels of alpha 2-PAG (P less than 0.05) during the study period, and these levels correlated well with inflammatory activity and failure of HBsAg elimination. There were no significant differences in alpha 2-PAG values between asymptomatic HBsAg carriers and controls. Serial analysis of alpha 2-PAG, in correlation with viral markers, biochemical parameters, and histological data, would contribute to the ability to predict the final outcome of HBV infection.

Modification of Hepatitis B Virus Infection by Recombinant Leukocyte Alpha A Interferon

A defect in alpha interferon production in patients with chronic type B hepatitis offers a rationale principle for treating this disease with interferon. Two trials with interferon in chronic type B hepatitis indicate that this therapy achieves an elimination of HBsAg and HBeAg significantly higher than spontaneous. Our study and that of others indicate, however, that the response to interferon therapy is dependent on many variables including: the type of interferon, the interferon dose, duration of interferon treatment, sex, sexual preference in men and coinfection with other viruses. As of the multiple modes of action of interferon, a better understanding of viral replication, of the antiviral action of interferon in hepatitis B virus (HBV) infection and of the immunomodulatory action of interferon in HBV infection will help to improve the treatment of chronic HBV infection with interferon.

Hepatitis B virus pre-S gene-encoded antigenic specificity and anti-pre-S antibody: Relationship between anti-pre-S response and recovery

A solid-phase radioimmunoassay involving specific antibody was developed for determination of the pre-S gene-encoded epitopes of hepatitis B virus and anti-pre-S antibody in sera of hepatitis B patients. The reaction for pre-S determinants associated with HBsAg was quantitatively inhibited by soluble, polymerized human serum albumin, and the lower limit of the assay was about 1.6 ng of HBsAg per ml. Continuous expression of pre-S-coded antigenic sites on HBsAg particles in chronic hepatitis B patients seropositive for HBeAg or anti-HBe shows that these determinants may be considered as a marker of chronicity during hepatitis B virus infection. The anti-pre-S antibody was determined by inhibition of the reaction for pre-S determinants. This antibody, different from anti-HBs, was detected during HBsAg antigenemia in patients recovering from acute type B hepatitis, before anti-HBs response. Kinetics of synthesis of anti-pre-S antibody in the course of acute type B hepatitis, followed by elimination of HBsAg and recovery, suggest the possible role of this antibody in the immunological clearance of infective hepatitis B virus particles.

Detection of antibodies directed against the pre-S gene product of hepatitis B virus: Relationship between anti-pre-S response and recovery

A haemagglutination test and a radioimmunoassay were developed for determination of the pre-S-gene-encoded antigenic specificity of hepatitis B virus. The reaction for pre-S-coded determinants was specifically inhibited by the antibody produced in patients recovering from acute type B hepatitis. Kinetics of synthesis of anti-pre-S antibody in the course of acute type hepatitis followed by elimination of HBsAg and recovery suggest the important role of this antibody in immunological neutralization and clearance of infective HBV particles. The possible protective role of anti-pre-S antibody and the use of pre-S-determinant-positive HBsAg particles in HBV vaccines should be considered.

Immunopathologic aspects of the HBsAg carrier state in chimpanzees.

The tissue distribution of hepatitis B virus antigens was correlated with the distribution of immunoglobulins and complement and with histopathological changes. Although no circulating antibody was detected, the participation of humoral immune mechanisms in the elimination of HBsAg from the circulation was suggested by presence of HBsAg, immunoglobulins, and C'3 in germinal centers of mesenteric lymph nodes and HBsAg mixed with immunoglobulins in the mesangium of kidney glomeruli. The results support the hypothesis that the immune status of HBV chimpanzee carriers is associated with hyporesponsiveness rather than tolerance.

Hepatitis B in children: II. Study of children born to chronic HBsAg carrier mothers

A survey of 4,452 pregnant women taken to find hepatitis B surface antigen revealed 28 asymptomatic chronic carriers. At birth, 16 of 17 infants studied were negative for HBsAg, whereas anti-HBc was present in all patients at a titer similar to that of the mother. Twelve children were followed for 6 to 18 months. In four of them, HBsAg remained negative and anti-HBc titers progressively decreased and were undetectable when tested after the age of 6 months. In eight infants, HBsAg became positive after an average time of 48 days. Elimination of HBsAg occurred in seven infants; five of them had clinical and biological manifestations of mild hepatitis. Sequential determinations of total complement and C components in three patients of the latter group showed dperession of complement at the time of appearance of clinical manifestations. In the patient who became an HBsAg carrier as well as in three infants who remained HBsAg negative, no decrease in complement titers was observed. These results indicate that vertical transmission from carrier mothers can occur in a low prevalence area and that neonatally infected children are capable of active elimination of HBV.