Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers. (1/743)

Virus load and liver damage, as measured by quantitative polymerase chain reaction and histology activity index, were related to genotype and core promoter mutations in 43 chronic hepatitis B virus (HBV) carriers of East Asian origin. T-1762 mutants were more frequent in genotype C strains and were associated with more inflammation (P=.0036) and fibrosis (P=.0088) of the liver but not with hepatitis B e antigen (HBeAg) status or virus load. Conversely, precore mutations were associated with less liver inflammation (P=. 08), which was linked to HBeAg negativity and lower viral replication. Carriers with genotype C were more often HBeAg positive (P=.03) with precore wild type strains and more-severe liver inflammation (P=.009) than were those with genotype B. These findings suggest that pathogenic differences between genotypes may exist and that the T-1762 mutation may be useful as a marker for progressive liver damage but seem to contradict that down-regulation of HBeAg production is the major effect of this mutation.  (+info)

Hepatitis B vaccination in high-risk infants: 10-year follow-up. (2/743)

The long-term efficacy of hepatitis B vaccination among high-risk infants was determined in 805 vaccine responders, immunized at birth in Taiwan during 1981-1984 and followed to age 10 years, via life table survival and Cox multivariate analyses. At 10 years, cumulative persistence of antibody to hepatitis B surface antigen (anti-HBs) was 85%, and cumulative incidence of hepatitis B virus (HBV) infection was 15%. Three children became carriers. Twelve-month anti-HBs titer was the strongest predictor of efficacy. The higher the initial titer, the lower the risk of anti-HBs loss (relative risk [RR], 0.26 for titer of 100-999 mIU/mL; RR, 0.08 for titer >1000 mIU/mL; P<.001) and HBV infection (RR, 0.55 and 0.27; P<.05). Maternal hepatitis B e antigen positivity but not hepatitis B immunoglobulin dose or gender predicted greater antibody persistence to age 10 years. Because the level of antibody persistence remained high and few became carriers, booster revaccination within 10 years seems unnecessary.  (+info)

Quantitative analysis of hepatitis B virus precore mutant in hepatitis type B. (3/743)

Active liver disease has been detected in chronic hepatitis B after seroconversion from positive HBe antigen to positive anti-HBe antibody. Active replication of HB virus (HBV) containing a precore stop-codon mutation has been implicated in this condition. The usual methods, such as direct sequencing, to characterize the responsible mutant of HBV are not suitable for routine clinical use. Here we employed the competitive mutation site specific assay (CMSSA) to detect precore mutant HBV-DNA in patients with positive HB surface antigen. In patients with HBe antigen, precore mutant HBV-DNA was significantly higher than in patients with HBe antibody. The level of precore mutant HBV-DNA in patients with elevated serum ALT was significantly higher than in patients with normal serum ALT. Sex, age and the level of serum HBV-associated DNA polymerase levels were not correlated with levels of precore mutant HBV-DNA. Ten of 11 negative patients for the precore mutant by polymerase chain reaction followed by restriction fragment length polymorphism assay (PCRRFLP) were positive for the precore mutant by CMSSA. These results suggest that the precore mutant has already emerged in the HBeAg-positive phase as determined by CMSSA, which is more sensitive than PCR-RFLP and is useful for evaluating the clinical course of patients with chronic hepatitis B.  (+info)

Hepatitis B surface antigen disappearance and hepatitis B surface antigen subtype: a prospective, long-term, follow-up study of Japanese residents of Okinawa, Japan with chronic hepatitis B virus infection. (4/743)

To determine the natural course of hepatitis B surface antigen (HBsAg) disappearance in chronic hepatitis B virus (HBV) infection and the factors related to its disappearance, 946 HBsAg carriers in Okinawa, Japan were prospectively followed for up to 19 years (mean = 9.2 years). The disappearance of HBsAg, as determined by radioimmunoassay (RIA), was observed in 62 (6.6%) and the overall annual disappearance rate was 0.79%/year. Its disappearance was more frequent in 60 (7.4%) of 815 serum samples negative for hepatitis B e antigen (HBeAg) by RIA at entry compared with only two (1.5%) of 131 serum samples that were HBeAg positive by RIA at entry (P < 0.05). Stepwise logistic regression analysis showed that age and HBsAg subtype were significantly associated with HBsAg disappearance (both P < 0.05), and that carriers with subtype adr (odds ratio = 2.87) had an increased probability of clearing HBsAg compared with carriers with subtype adw. Conversely, HBeAg disappearance was earlier in those with the adw subtype than in those with adr. Hepatitis B virus DNA was not detected by the polymerase chain reaction after HBsAg disappearance in any of the 62 from whom it had disappeared. The HBsAg titer, as measured by reverse passive hemagglutination, was related to the time to its disappearance; the higher the titer, the longer the time to disappearance. These findings suggest that HBeAg negativity, a more advanced age, and low titers of HBsAg are favorable factors for HBsAg disappearance in the natural course of chronic HBV infection. Moreover, HBsAg subtype adr was a predictive factor for HBsAg disappearance, whereas subtype adw was predictive of early HBeAg disappearance.  (+info)

Specific vaccine therapy in chronic hepatitis B: induction of T cell proliferative responses specific for envelope antigens. (5/743)

In a pilot study, it was established that specific therapy by standard anti-hepatitis B virus (HBV) vaccination may be effective in reducing HBV replication and canceling the immune tolerance to hepatitis B surface antigen (HBsAg) particles in about 50% of persons with chronic active HBV replication. In the present study, the vaccine-induced immune responses were analyzed during an ongoing controlled multicenter vaccine trial. Vaccination elicited peripheral blood mononuclear cell proliferative responses specific for envelope antigen in 7 of 27 subjects given HBsAg. The responses induced by the vaccines were mediated by CD4+ T lymphocytes, and at least three different epitopes were recognized. HBV-specific CD4+ T lymphocytes produced high levels of interferon-gamma [corrected] and belonged to a T helper 1 subset. Reduction of serum HBV DNA in some of these persons suggests that induction of CD4+ T cell responses could be important in controlling viremia during vaccine therapy of chronic HBV carriers.  (+info)

Combinatorial screening and intracellular antiviral activity of hairpin ribozymes directed against hepatitis B virus. (6/743)

A combinatorial screening method has been used to identify hairpin ribozymes that inhibit hepatitis B virus (HBV) replication in transfected human hepatocellular carcinoma (HCC) cells. A hairpin ribozyme library (5 x 10(5) variants) containing a randomized substrate-binding domain was used to identify accessible target sites within 3.3 kb of full-length in vitro-transcribed HBV pregenomic RNA. Forty potential target sites were found within the HBV pregenomic RNA, and 17 sites conserved in all four subtypes of HBV were chosen for intracellular inhibition experiments. Polymerase II and III promoter expression constructs for corresponding hairpin ribozymes were generated and cotransfected into HCC cells together with a replication-competent dimer of HBV DNA. Four ribozymes inhibited HBV replication by 80, 69, 66, and 49%, respectively, while catalytically inactive mutant forms of these ribozymes affected HBV replication by 36, 28, 0, and 0%. These findings indicate that the inhibitory effects on HBV replication were largely mediated by the catalytic activity of the ribozymes. In conclusion, we have identified catalytically active RNAs by combinatorial screening that mediate intracellular antiviral effects on HBV.  (+info)

Markedly high seroprevalence of hepatitis B virus infection in comparison to hepatitis C virus and human T lymphotropic virus type-1 infections in selected Solomon Islands populations. (7/743)

To determine the prevalences of hepatitis B virus (HBV), hepatitis C virus (HCV), and human T lymphotropic virus type-1 (HTLV-1) infections in residents of the Solomon Islands, we surveyed 1,610 serum samples from 1,113 outpatients and 497 healthy volunteer blood donors at the Central Hospital in Honiara, the Solomon Islands. The prevalence of hepatitis B surface antigen (HBsAg) by radioimmunoassay (RIA) (n = 315, 19.6%) was significantly different from that of antibody to HCV (anti-HCV) by a second-generation enzyme immunoassay (EIA) (n = 4, 0.2%) and antibody to HTLV-1 (anti-HTLV-1) by an ELISA with Western blot analysis to verify the positivity (n = 49, 3.0%) (P < 0.0001, respectively). There were no significant differences in the prevalences of these markers between outpatients and blood donors. Hepatitis B e antigen (HBeAg) was detected by RIA in 130 (41.3%) of 315 HBsAg-positive samples. The distribution of HBsAg subtypes by EIA was 190 adr (60.3%), 111 ayw (35.2%), and 14 (0.4%) other subtypes. The HBeAg prevalence decreased with age in all groups for each subtype. There were no significant differences in the prevalence of HBeAg among HBsAg subtypes. We conclude that HBV infection is highly endemic in selected Solomon Islands populations, and that the high prevalence of HBeAg may be associated with the spread of HBV infection there.  (+info)

Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized, controlled study (CAESAR). The CAESAR Coordinating Committee. (8/743)

The efficacy and safety of lamivudine in persons coinfected with human immunodeficiency virus (HIV) type 1 and hepatitis B virus (HBV) were examined in the CAESAR study, a randomized placebo-controlled trial assessing the addition of lamivudine (150 mg 2x/day) or lamivudine (150 mg 2x/day) plus loviride (100 mg 3x/day) to zidovudine-containing background antiretroviral treatment. Baseline hepatitis B surface antigen (HBsAg) results were available for 1790 study subjects, of whom 122 (6.8%) tested positive. Retrospective analyses for serial HBV DNA, HBsAg, and hepatitis B e antigen (HBeAg) were performed on stored sera from 118 HBsAg-positive subjects. HBV DNA and HBeAg were present in 83% and 63%, respectively. At weeks 12 and 52, median log10 HBV DNA change was -2.0 and -2.7, respectively, in the lamivudine arms, compared with no reduction among placebo recipients (P<.001). A trend to lower alanine transferase level, and delayed progression of HIV-1 disease (relative hazard, 0.26; 95% confidence interval, 0.08-0.80) were also seen in the lamivudine arms, compared with the placebo group.  (+info)