Baseline seroepidemiology of hepatitis B virus infection in children in Taipei, 1984: a study just before mass hepatitis B vaccination program in Taiwan

Hepatitis B virus (HBV) markers were studied by radioimmunoassays in serum samples of 1,200 (647 male, 553 female) apparently healthy children under 15 years of age in Taipei between June and October 1984. The prevalence rate of hepatitis B surface antigen (HBsAg) was 5.1% in infancy, increased to 10.7% between 1 and 2 years of age, and then remained constant at about 10% thereafter. The prevalence rate of surface antibody (anti-HBs), core antibody (anti-HBc), and seropositivity (at least one marker of hepatitis B detectable) were 39.0, 30.5, and 52.5%, respectively, in infancy, then decreased to 10.7, 14.3, and 17.9%, respectively, between 1 and 2 years of age. Thereafter, the antibody prevalence increased in parallel with age. By the age of 13-14 years, nearly half of the children were infected by HBV. The results suggested that in our children, most HBsAg carriers resulted from infections before 3 years of age, and HBV infections after 3 years of age infrequently resulted in a carrier state. One hundred (83.3%) of the 120 HBsAg-positive children had hepatitis B e antigen (HBeAg), indicating high prevalence in young asymptomatic HBsAg carriers. The prevalence rate of HBeAg tended to decrease with age and a reversed trend was observed with anti-HBe. Our study, just before our government extends mass hepatitis B vaccination program from newborns to children, provides background seroepidemiologic data of HBV infections in the healthy children in Taiwan.     

Antibody responses of adults, adolescents, and children to a plasma-derived hepatitis B vaccine in a rural African setting

A field trial of a plasma-derived hepatitis B vaccine in five rural villages in Zambia was analyzed to determine if adults in a rural African setting respond to this vaccine as well as adults in Western countries and to determine the immunogenicity of fewer than the recommended three doses; 255 residents, including 171 who were susceptible to hepatitis B, were vaccinated. Among those who received three vaccine doses, protective levels of antibody to hepatitis B surface antigen (anti-HBs) developed in 67% of adults (ages 21 to 70 years), 87% of adolescents (ages 12 to 19 years), and 100% of children (ages 0 to 11 years). The 67% of vaccinated adults who developed anti-HBs at the protective level was lower than the 96% reported among adults receiving the same vaccine at the same dose and dosage schedule in studies in Western countries. No difference was seen in the response of those receiving two doses compared with those receiving three doses among adults and adolescents, suggesting that a two-dose regimen may be acceptable in these age groups in developing countries to reduce costs and improve compliance. Use of hepatitis B vaccine in a region where prevaccination hepatitis B serologic screening was not available did not appear to increase the number of severity of adverse reactions.     

The role of the hepatitis B virus infection in patients with chronic hepatitis in argentina

Over a seven-year period, we monitored 221 patients with chronic hepatitis from two medical centers. By using the counterelectrophoresis (CEP) test to detect the presence of HBsAg and anti-HBc, or both, we established that 87.7% of them had hepatitis B infection. Serum specimens originally found negative for HBsAg by CEP were further tested by reversed passive hemagglutination (RPH), and those originally found negative for anti-HBc by CEP were further tested by radioimmunoassay (RIA). Five patients were anti-HBc-positive and HBsAg-negative. No sex predominance was observed, but HBsAg incidence increased with increasing age. The HBeAg antigen was detected in 46.8% of the 161 cases tested for it; the most frequent subtype found was adw (63.7%). The present findings indicate that HBV infection largely contributes to the development of chronic hepatitis in Argentinian patients.     

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.     

Perinatal transmission of hepatitis B virus: role of maternal HBeAg and anti-HBc IgM

The development of hepatitis B surface antigen (HBsAg) carrier states in newborns of HBsAg-positive mothers was correlated to the presence of anti-HBc IgM and HBeAg in the mothers. There was a positive correlation between infection of the newborn and the presence of HBeAg, as shown previously, but no correlation with anti-HBc IgM.     

Increased expression of transforming growth factor alpha after transfection of a human hepatoblastoma cell line with the hepatitis B virus.

The expression of transforming growth factor alpha (TGF-alpha) was examined in a human hepatoblastoma cell line, Hep G2, which does not contain hepatitis B virus (HBV) DNA, and in the cell line 2.2.15, which was formed by the transfection of Hep G2 cells with the complete HBV DNA, to study the possibility that HBV and TGF-alpha could function as co-factors in hepatocarcinogenesis. Northern blot hybridization of RNA extracted from these cell lines, with densitometric analysis, revealed expression of the TGF-alpha gene in the transfected cells at a level three times higher than in the nontransfected cells. Staining of the cells using a monoclonal antibody to TGF-alpha and the avidin-biotin-peroxidase immunohistochemical method revealed a much higher intensity of TGF-alpha staining in the transfected cell line. These findings show that the presence of HBV DNA appears to cause a significant up-regulation of the TGF-alpha gene. This effect on the TGF-alpha gene may be a mechanism by which HBV contributes to the etiology of hepatocellular carcinoma in some patients.     

Occult hepatitis B virus and hepatitis C virus infections

Occult HBV infection is a well-recognised clinical entity characterised by the detection of HBV-DNA in serum and/or in liver in the absence of detectable hepatitis B surface antigen (HBsAg). Occult HBV infection has been described not only in patients who have resolved an acute or chronic HBV infection but also in patients without any serological markers of a past HBV infection. Occult HBV infection in patients with chronic HCV infection may induce more severe liver disease and lower response rate to interferon treatment. The existence of occult HCV infections has been also reported more recently. Occult HCV infection is characterised by the presence of HCV-RNA in liver and peripheral blood mononuclear cells in the absence of detectable serum HCV-RNA. Occult HCV infection may occur under two different clinical situations: in hepatitis C antibody-(anti-HCV) negative and serum HCV-RNA-negative patients with abnormal liver function tests and in anti-HCV-positive patients who have no detectable serum HCV-RNA and who have normal liver enzymes. The clinical relevance of occult HCV infections is still under investigation.     

Comparative studies of the immunogenic activity of hepatitis B surface antigen (HBsAg) and HBsAg polypeptides

Three hepatitis B surface antigen (HBsAg) preparations were compared: purified intact 22-nm HBsAg particles; HBsAg-derived, sodium dodecyl sulfate (SDS)-denatured P25 + GP30 polypeptide pool; and nondenatured P25 + GP30 micelles. The micelles had the same polypeptide composition as the P25 + GP30 pool. The immunogenicity in mice of each preparation, administered either in saline suspension or adsorbed to aluminum gel, was compared. The SDS-denatured polypeptides were less immunogenic than intact HBsAg particles, whereas the micelles were more immunogenic. High anti-HBs titers were observed in mice immunized with micelle preparations in either saline suspension or adsorbed to aluminum gel for as long as 200 days after a booster inoculation, administered 26 days after the primary dose.     

A pilot model of vaccination against hepatitis B virus suitable for mass vaccination campaigns in hyperendemic areas.

A hepatitis B vaccination campaign was carried out in a town of 60,000 inhabitants, Afragola, Campania, Italy, a hyperendemic area for hepatitis B where HBsAg prevalence was 13.4% and anti-HBc prevalence was 64.7%. This experimental pilot project aimed to reduce the incidence of both acute and asymptomatic viral hepatitis B and of related chronic liver complications. From 1983-1989, 8,400 subjects were vaccinated: 6,900 children up to 10 years of age and 1,500 subjects from 11-60 years of age. High seroconversion rates were observed: 99.0% in all children under one year of age, 96.0% in the older children, and 86.7% in adults. The rate of infection in Afragola has diminished from 63/100,000 in 1983 to 10/100,000 in 1989. Carriers of HBsAg decreased in the general population (7.3% compared to 13.4%), especially in children up to 10 years of age (1.0% compared to 9.0%). In babies who received hepatitis B vaccine at the same time as compulsory vaccinations compliance was 98% while it was 80% in babies who were vaccinated separately. In June 1991 the Italian Parliament promulgated a decree which imposes hepatitis B vaccination for all newborn babies at 3, 5, and 11 months of age, at the same times as the mandatory childhood vaccinations (diphtheria, tetanus, and polio) according to a new protocol (Piazza scheme) which has been in use since January 1987 in our pilot vaccination campaign in Afragola.     

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.     

Detection of hepatitis B virus DNA in serum and relation with the IgM class anti-HBc titers in hepatitis B virus infection

Sera from four groups of patients wtih different serologic markers of HBV infection were examined for HBV DNA using molecular hybridization technique and for IgM class anti-HBc using an ELISA based on the antibody capture principle. Results of HBV DNA assay were generally in good agreement with the presence of HBeAg. However, HBV DNA was found in 13% of anti-HBe+ sera and in one patient with anti-HBc as a sole marker. IgM anti-HBc was detected at high titers in acute hepatitis B patients and was also present during the "window-period." This marker was also found, though less frequently when other markers for HBV infectivity were absent, in chronic hepatitis B patients and healthy carriers. From these findings we conclude that the HBV DNA assay provides a reliable method of detecting the infectious agent, particularly in anti-HBe+ sera and sera with anti-HBc as a sole marker. The assay for IgM anti-HBc is useful for establishing the diagnosis of recent infection in patient with anti-HBc as a sole marker, and during acute hepatitis with very high aminotransferase values, a condition in which HBV DNA may be undetectable.     

MICA and recovery from hepatitis C virus and hepatitis B virus infections

The polymorphic MHC class I chain-related A (MICA) gene encodes a ligand that has different binding affinities for the NKG2D activating receptor of CD8+ T cells and natural killer (NK) cells. We hypothesized that MICA heterogeneity would affect recovery from hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. To test the hypothesis, we initially typed known MICA polymorphisms for 228 persons who cleared HCV infection and 442 persons with persistent hepatitis C matched on other factors affecting viral persistence. Although MICA(*)015 was detected more than two-fold more often in persons with viral clearance (odds ratio 0.36, 95% confidence interval=0.19, 0.80), it occurred in fewer than 5% of the study population. In a similar analysis of 442 persons with chronic hepatitis B and 768 matched controls who recovered, MICA(*)015 was detected in 2.0% of persons with chronic hepatitis B and only 0.9% of controls. No significant associations were detected with other MICA polymorphisms. While further investigation may reveal a structural basis of the MICA(*)015 associations, these data provide little support for the hypothesis that differential distribution of MICA alleles substantially affects recovery from HCV and HBV infections.     

Intrafamilial transmission of hepatitis C virus in Japan.

To clarify the intrafamilial transmission of hepatitis C virus (HCV), the prevalence of antibody to HCV (anti-HCV) in 107 index patients with type C chronic liver disease was studied and compared with the prevalence of anti-HCV antibody in their 296 family members. Of the 85 index patients who were positive for anti-HCV, 15 (8%) of 196 of their family members were also HCV antibody positive, whereas of the 22 index patients who were anti-HCV antibody negative, none of the family members of the 100 evaluated was positive for anti-HCV antibody, a statistically significant difference between groups (P less than 0.02). No specific relative (spouse, child, parent, and sibling) was linked to HCV positivity in the index cases making it difficult to identify the route of infection that is believed to occur via the parenteral route in the home or community.     

Hepatitis B virus DNA is frequently found in liver biopsy samples from hepatitis C virus-infected chronic hepatitis patients

Human hepatitis B virus (HBV) and hepatitis C virus (HCV) are two major etiologic agents of chronic hepatitis, which is closely related to the development of hepatocellular carcinoma (HCC). A possible involvement of HBV co-infection was investigated in ongoing HCV-related liver diseases in HCV-infected patients. A prevalence of anti-HBc in anti-HCV–positive/HBsAg-negative chronic hepatitis patients and a low copy number of HBV DNA were found in most of the liver biopsy samples of anti-HCV–positive/HBsAg-negative patients. The present data suggest that HBV co-infects frequently with HCV and may play an important role in the development of HCC in the anti-HCV–positive/HBsAg-negative patients with chronic hepatitis. J. Med. Virol. 54:249–255, 1998. © 1998 Wiley-Liss, Inc.     

Intrafamilial transmission of hepatitis C virus in hemodialysis patients

The prevalence of hepatitis C virus (HCV) infection in chronic hemodialysis patients ranges from 20 to 50% and these patients may serve as a reservoir of infection for their household contacts. The aim of this study was to investigate the prevalence of anti-HCV in hemodialysis patients and their families, and to evaluate possible routes of infection. One hundred eighty-six family members of 84 hemodialysis patients and 529 healthy adults were enrolled. The family members consisted of 50 spouses, 96 children, 11 parents, 29 siblings, and other relatives living together with the patients. Serum samples were collected for testing anti-HCV. Exposure to risk factors was obtained by a questionnaire and an interview. The results showed that prevalence of anti-HCV in hemodialysis patients was 44%, whereas in family members it was 5.4%, not significantly different from that of age-matched healthy adults (standardized morbidity rate = 1.51, P = 0.390). The anti-HCV rate in family members tended to increase with age, and a spouse of an infected hemodialysis patient had a higher risk of HCV infection than other family members (15% vs. 2.6%, odds ratio 6.6, P = 0.058). Except for the age factor, no difference was found between seropositive and se-ronegative family members with respect to risk factors such as blood transfusion, surgery, frequent injections, dental procedures, or acupuncture. It was concluded that, although the anti-HCV positivity of hemodialysis patients is high, the risk of HCV infection for their family members is not higher than that of the general population. Among family members, spouses of seropositive hemodialysis patients have the highest risk of HCV infection. These data imply that long-term intimate contact between spouses plays a key role in the intrafamilial transmission of HCV. © 1995 Wiley-Liss, inc.     

Significance of maternal and infant serum antibodies to hepatitis B core antigen in hepatitis B virus infection of infancy

The significance of IgM and IgG class antibodies to hepatitis B virus (HBV) core component (anti-HBc) was investigated in a study of maternal-fetal HBV transmission. An IgM anti-HBc response was lacking in the majority (49/53) of HBV-infected infants. This antibody thus cannot be used as an indicator of transplacental infection. However, most infants who became HBsAg positive during the first 6 months of life acquire infection in the perinatal period rather than transplacentally. Passively transferred maternal IgG anti-HBc in the infant and additional IgM anti-HBc positively in the carrier mother have no modulating influence on HBV infection of infants born to HBV carrier women.     

Antibody to hepatitis C virus in cryptogenic chronic liver disease.

The prevalence of antibody to hepatitis C virus (HCV) was studied in 207 patients with chronic liver disease of unknown etiology, in relation to clinical, epidemiological and histological features. Serum antibody to C-100 epitope of HCV was detected by ELISA in 82.6% of patients, with a significant difference compared with a group of patients with primary biliary cirrhosis (10%). The presence of anti-HCV antibody in serum did not correlate with age, sex, histological diagnosis, and activity and duration of the disease, nor with serum anti-HBc, used as a marker of exposure to hepatitis B virus infection. These results strongly support the view that most cases that were previously defined as cryptogenic forms of chronic liver disease are in fact related to HCV infection. There was a correlation between serum anti-HCV antibody and history of risk for parenteral exposure or of acute hepatitis. This correlation was particularly evident for transmission by parenteral route, suggesting that HCV infection may be transmitted often by this route (36.8% among anti-HCV antibody-positive patients and 11.1% among anti-HCV-negative patients). Liver disease in patients without risk factors for parenteral transmission and with lower prevalence of anti-HCV antibody may be caused by other as yet unidentified non-A, non-B (non-C) agents or may be of nonviral origin.     

Analysis of a pregnancy-screening and neonatal-immunization program for hepatitis B in Hamilton, Ontario, Canada, 1977-1988

During the 12 years from January, 1977, to December, 1988, the Hamilton Centre of the Canadian Red Cross Society (CRCS) Blood Transfusion Service screened 98,712 pregnant patients for hepatitis B surface antigen (HBsAg) and identified 120 positives (0.12%). The number of positives ranged from six to 16 per year. We were able to trace and enroll 65 mothers (54%) and 96 of their children in the follow-up study. The majority of the women were between 20 and 30 years of age (95.4%) and married (86%), and about one-half were employed outside the home. Sixty-five percent were white and 34% Asian, and 20 countries were listed as their places of origin. Hepatitis B immune globulin (HBIG) was available for neonatal immunization since 1977 and combined with vaccine since 1982. Of the 96 candidates for HBIG, 60 (63%) received HBIG within 24 hr, one after 3 months, four unknown, and 31 did not receive it. Of the 56 candidates for vaccination from 1982 to 1989, 26 (46%) received three doses, seven had two doses, eight had one dose, one was unknown, and 14 had none. HBsAg tests were performed on 69 children (71.8%) and anti-HBs on 61 (63.5%). Four of the children are HBsAg positive, 31 have anti-HBs, and 31 have no detectable antibodies. All four HBsAg positives had not received vaccine, and only one had received HBIG. Of the children positive for hepatitis B surface antibodies, five had received no immunization and therefore had been subclinically infected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low prevalence of antibody to hepatitis C virus in north east England

The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied in North East England in blood donors, local multiply transfused patients, local high risk individuals, and chronic liver disease patients. Anti-HCV was detected by enzyme-linked immunosorbent assay (ELISA) in 2/1120 (0.18%) blood donors; 1/84 chronic renal failure patients on haemodialysis who had received 1,992 units of blood (seroconversion rate of 0.05% per unit transfused), 1/207 cardiac patients 6 months post cardiac surgery transfused with 1,403 units of blood (1 anti-HCV pre-operatively, seroconversion rate 0.07%), 40/50 haemophilia A patients treated with commercial factor VIII, and 38/100 intravenous drug users. In addition anti-HCV was detected by ELISA in 5/35 cryptogenic chronic liver disease patients, 5/5 confirmed by recombinant immunoblot assay (RIBA) (14%); 3/30 patients with autoimmune chronic active hepatitis, 2/3 by RIBA (7%); 2/50 primary biliary cirrhosis patients, 1/2 by RIBA (2%); 0/30 alcoholic cirrhosis patients; and 2/9 patients with hepatocellular carcinoma, 1/2 by RIBA (11%). HCV is uncommon in North East England; it may be implicated in the aetiology of a minority of cases of cryptogenic liver disease and less than 5% of autoimmune chronic active hepatitis and primary biliary cirrhosis.     

Intrauterine transmission of hepatitis B virus is closely related to placental leakage

Hepatitis B virus (HBV), transmitted by hepatitis B e antigen (HBeAg)-positive mothers by intrauterine infection, infecting newborns, is closely related to signs and symptoms associated with miscarriage. However, no correlation was observed between intrauterine infection of infants and the presence of antibodies of immunoglobulin M (IgM) class antibodies against hepatitis B core antigen (anti-HBc) in maternal blood, nor was HBeAg found in maternal or cord sera. These results indicate that contamination by the mother's blood, through placental leakage, plays an important role in HBV infection in utero. Without placental leakage, maternal blood could not pass through the placenta and enter fetal circulation, and so intrauterine infection would not occur, even if very high titers of hepatitis B surface antigen (HBsAg) and HBeAg were present in maternal blood.