Long-term hepatitis B vaccine in infants born to hepatitis B e antigen positive mothers

Neonates of hepatitis B surface antigen (HBsAg) positive and hepatitis B encoded antigen (HBeAg) positive mothers received 10 micrograms of recombinant hepatitis B vaccine at months 0, 1, 6, or 0, 1, 2, 12, with or without immunoglobulin at birth, and were followed up to the age of 8 years for HBsAg, anti-HBc, and anti-HBs. Some were boosted at month 60. The overall vaccine protection at month 12 was 96.2%. No child became a chronic carrier beyond the age of 3 years, showing that this vaccine provides immediate protection against HBsAg carriage, and long term protection against fetally acquired HBsAg. After month 60 hepatitis B serological markers without disease, indicating re-exposure to HBV, reappeared in comparable numbers among boosted and non-boosted children (5 for a total of 167 children). This vaccine provides long-term protection against hepatitis B chronic carriage and infection in high risk neonates with or without a month 60 booster. A booster at the age of 5-6 years or 11-12 years would reduce HBV infection, viral circulation and transmission, while ensuring long-term antibody persistence.     

Passive-active immunization in infants of hepatitis Be antigen-positive mothers. Comparison of the efficacy of early and delayed active immunization

OBJECTIVE: To assess the efficacy of late active immunization against hepatitis B concomitant with diphtheria, pertussis, tetanus, and polio vaccine in high-risk infants receiving hepatitis B immune globulin at birth. DESIGN: Randomized study of infants born to mothers positive for hepatitis B surface antigen (HBsAg) and hepatitis Be antigen (HBeAg). SETTING: Three large city hospitals and one rural area providing prenatal care and obstetric services. SUBJECTS: Eighty neonates of HBsAg- and HBeAg-positive carrier mothers received 0.5 mL/kg of body weight hepatitis B immune globulin within 2 hours of birth and hepatitis B vaccine (10 micrograms) at 0, 1, 2, and 11 months of age (group A) or at 3, 4, 5, and 11 months of age concomitant with diphtheria, pertussis, tetanus, and polio immunization (group B). A second dose of hepatitis B immune globulin was given to infants on schedule B at 3 months. MAIN OUTCOME MEASURES: Blood samples were collected at 0, 3, 6, 11, and 12 months of age and tested for antibodies against hepatitis B core antigen and HBsAg. Follow-up visits were scheduled annually up to 5 years of age. RESULTS: Eight infants were excluded from analysis. During the study period, six children became HBsAg carriers, three in each group, which corresponds to a 5-year incidence of infection of 9% and 8% for groups A (three of 35) and B (three of 37), respectively. Subclinical infections (persistent anti-HBc positivity beyond month 12 or appearance of anti-HBc) were encountered in another eight infants (four in each group). CONCLUSION: Late active immunization starting at 3 months of age appears to provide similar protective efficacy as active immunization starting at birth when combined with hepatitis B immune globulin at 0 and 3 months of age.     

Prevention of hepatitis B infection: the appropriate strategy for India

Hepatitis B infection is a major global health problem with a high morbidity and mortality. With safe and effective vaccines available, it is now possible to prevent it. Many countries have started national hepatitis B control programmes but no attempt has been made to do this in our country. An analysis of the available data on the epidemiology of hepatitis B infection in India reveals that perinatal maternofoetal transmission accounts for only a minority of hepatitis B virus carriers in India. Therefore, a policy of screening pregnant mothers for the presence of hepatitis B surface antigen and selective immunization of babies born to those who are surface antigen positive will have very little effect on the hepatitis B carrier rate in our population. Universal immunization of all newborns will have a much greater impact, it will be logistically simpler and more cost-effective--the cost of preventing one hepatitis B carrier being nearly one-fourth of that with selective immunization. We recommend that hepatitis B vaccine should be included in our country's expanded programme of immunization.     

Nested polymerase chain reaction (PCR) and multiple cloned antibody capture PCR for the examination of serum hepatitis B virus DNA in negative hepatitis B surface antigen patients suffering from liver diseases

In order to find out rapidly the causes of the liver diseases suffered by patients with negative hepatitis B surface antigen (HBsAg), nested polymerase chain reaction (PCR) and multiple cloned antibody capture PCR techniques were established to examine serum hepatitis B virus (HBV) DNA. By using both techniques along with the examination of hepatitis C virus (HCV) infection, the causes of chronic liver diseases with negative HBsAg were studied. It is found that nested-PCR can increase the sensitivity of single PCR more than 1,000 fold and multiple cloned antibody capture-PCR can detect concentration of HBV DNA as low as 0.1-0.01 pg/L. HBV DNA positive patients were found in 45.5%, 30.8%, 13.3% and 100% respectively of the patients suffering from liver cirhosis with negative HBsAg (group A, 22 cases), chronic hepatitis with negative HBsAg (group B, 13 cases), normal subjects with negative HBsAg and positive hepatitis B core antibody (HBcAb, group C, 30 cases) and liver cirhosis with positive HBsAg and negative HBeAg (group D, 12 cases). HBV DNA can be also found in the serum of HBsAb positive patients and subjects supposed to be healthy, 81.8% and 53.8% of the patients were infected with HBV and/or HCV in group A and group B respectively. All these results suggest that nested-PCR and multiple cloned antibody capture-PCR are rapid and highly sensitive methods for detection of serum HBV DNA. HBV infection is an important cause of chronic liver diseases in patients with negative HBsAg. The causes of most of the HBsAg-negative chronic liver diseases are related with infection of viruses. The clinical significance of serum HBsAb in naturally infected patients should be reconsidered.     

Relation between laboratory test results and histological hepatitis activity in individuals positive for hepatitis B surface antigen and antibodies to hepatitis B e antigen

BACKGROUND: Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B e antigen (anti-HBe) commonly coexist, and laboratory tests are often requested to assess histological hepatitis activity. An optimum panel of tests has not been found and the usefulness of hepatitis B virus (HBV) DNA assays in this context has not been established. We assessed various blood tests to find which best predicted hepatitis activity. METHODS: Routine plasma biochemical liver tests and serum HBV DNA (hybridisation and PCR assays) were assessed prospectively in 123 patients positive for HBsAg and anti-HBe. We scored histological hepatitis activity (hepatitis activity index) and determined whether chronic active hepatitis (chronic hepatitis with portal and periportal lesions) was present. We analysed the relation between laboratory data and the hepatitis activity index or risk of chronic active hepatitis by multiple regression and multiple logistic regression, respectively. FINDINGS: The analyses provided models for predicting either the hepatitis activity index or the risk of chronic active hepatitis. Aspartate aminotransferase was the most important test in the two models. The contribution of HBV DNA and other assays, especially alanine-aminotransferase activity, were of no practical importance. INTERPRETATION: Because screening by aspartate-aminotransferase activity could not be improved by the addition of other assays or HBV DNA, patients positive for HBsAg and anti-HBe could be screened for chronic active hepatitis with a single assay and counselling of patients can be improved if proper reference values are used.     

The effects of a myocardial bridge on coronary atherosclerosis and ischaemia

An outbreak of acute hepatitis cases in a small community took place 6 months after the community's arrival to the Brazilian Amazon. An epidemiological investigation was performed and included residents aged more than two years. Study subjects were interviewed and bled to test for hepatitis markers by enzyme immunoassays. Around 80% of the village population was surveyed. The overall prevalence of hepatitis B virus (HBV) markers was 75.1% (281/374). The surface antigen of HBV (HBsAg) and the IgM class antibody against hepatitis B core antigen (IgM anti-HBc) were present in 10.4% and 9.6%, respectively. Evidence of HBV-HDV (Delta virus) coinfection or hepatitis C infection was not found. IgM class antibody against hepatitis A virus was uncommon (3.7%). Follow-up evaluation 6 and 12 months later were carried out to identify new HBV infections. An incidence rate of 7.2 new infections per 100 exposed subjects per month was found. Average individual risk for HBV infection among susceptible inhabitants of the village between June 1995 and June 1996 can be estimated at 57.6%. The predominant HB-sAg subtype found (ayw3) suggests that immigrants may have carried HBV from the original area. Time living in the study region was significantly associated with HBV markers in analysis for linear trend and logistic regression analysis. Environmentally related factors may have facilitated HBV transmission.     

Prevention and control of hepatitis B virus infection in Singapore

Hepatitis B virus (HBV) accounted for 24% to 54% of the reported acute viral hepatitis cases in Singapore from 1982 to 1996. The prevalence of HBV infection, as indicated by the presence of markers of HBV, increased from 9.3% in children below 5 years of age to 54.6% in adults above 55 years. The overall hepatitis B surface antigen (HBsAg) prevalence was 5.7% for males and 3.4% for females, with the highest rate among the Chinese. About 39% of the HBsAg carriers were hepatitis B 'e' antigen positive. The main mode of transmission during the first year of life was perinatal, with 43% of the babies born to HBsAg-positive mothers developing the carrier state. Horizontal transmission within the infected household was significantly associated with sharing of personal and household articles. Based on the findings of seroprevalence surveys in various population groups and clinical trials on the safety, immunogenicity and efficacy of various doses and schedules with the plasma-based and yeast-derived hepatitis B vaccines in newborn babies, a national childhood hepatitis B vaccination programme was formulated and implemented in phases, starting with babies born to carrier mothers on 1 October 1985 and finally extending to all newborns on 1 September 1987. The hepatitis B prevention and control programme has been successful. During the period 1994 to 1996, more than 90% of children completed the full schedule of immunisation by below one year of age, and 85% had evidence of vaccination at school entry at age six. Follow-up of 2 cohorts of vaccinated children showed that perinatal transmission has been reduced by 80% to 100%. Horizontal transmission has also declined through other public health measures. The efficacy of the hepatitis B vaccine and the adequacy of reduced doses in the long-term protection of chronic carrier state have been shown in children and adults. The incidence of acute hepatitis B has declined from 10.4 per 100,000 in 1985 to 4.8 per 100,000 in 1996. There is a noticeable reduction in HBsAg prevalence in selected population (school children, national servicemen and antenatal women). The age-standardised incidence rate of primary liver cancer among males had also dropped from 27.8 per 100,000 per year during 1978 to 1982 to 19.0 per 100,000 per year during 1988 to 1992.     

Differences in risk factors for being either a hepatitis B carrier or anti-hepatitis C+ in a hepatoma-hyperendemic area in rural Taiwan

This is a study of the differences in the risk factors for being either hepatitis B surface antigen positive [HBsAg(+)] or antibody to hepatitis C virus positive [Anti-HCV(+)] in A-Lein, a rural area in southern Taiwan, an area which also has a high hepatoma mortality rate. Three hundred eighty-five patients age > or =40 years participated in hepatoma screening at the A-Lein Community Health Center during 1995. Those who were HBsAg(-) and anti-HCV(-) or had coinfection of HBsAg(+) and anti-HCV(+) were excluded, leaving 293 patients: 109 HBsAg(+) and 184 anti-HCV(+). The anti-HCV(+) patients had a lower socioeconomic status (as defined by level of education and type of occupation) and were older than HBsAg(+) patients (P < 0.05). Those with higher alanine aminotransferase levels (ALT) also had a higher anti-HCV(+) to HBsAg(+) odds ratio (OR), and a dose response relationship was found, P < 0.0001. Anti-HCV(+) patients were more likely than HBsAg(+) patients to have a spouse who shared the infection, OR = 5.11; 95% CI, 2.30-11.28. Anti-HCV(+) patients were more likely than HBsAg(+) patients to have had blood transfusions (OR = 2.66; 95% CI, 1.20-5.89), frequent medical injections (OR = 2.64; 95% CI, 1.62-4.31), or injections by non-licensed medical providers (OR = 1.91; 95% CI, 1.18-3.09). Multiple logistic regression analysis showed that the significant factors for anti-HCV(+) patients vs. HBsAg(+) patients are drinking habit (OR = 3.45; 95% CI, 1.02-11.60), age (OR = 6.33; 95% CI, 2.93-13.68), and frequent medical injections (OR = 2.88; 95% CI, 1.65-5.03). The transmission of hepatitis C in A-Lein is closely related to low socioeconomic status, age, alcohol abuse, spouses being anti-HCV(+), and frequent medical injections, especially from non-licensed medical providers, including both pharmacists and those with no medical licensing whatsoever. These nonlicensed medical providers sometimes reuse needles to save money, which is a likely route of infection.     

Liver transplantation in HBsAg-positive HBV-DNA--negative cirrhotics: immunoprophylaxis and long-term outcome

The presence of a positive hepatitis B surface antigen (HBsAg) has been considered a highly questionable indication for orthotopic liver transplantation. We report our experience in the treatment of HBsAg-positive HBV-DNA-negative cirrhotics with liver transplantation, whether or not followed by passive prophylaxis with specific immunoglobulins. Of the 123 cirrhotics who received transplants at our institution since May 1986, 39 (31.7%) were HBsAg positive; of these, 1 was HBV-DNA positive, and 4 were hepatitis Be antigen (HBeAg) positive. Since April 1991, 25 HBsAg-positive HBV-DNA-negative cirrhotics have undergone an original protocol with the periodical intramuscular administration of 5,000 IU of specific immunoglobulins starting in the anhepatic phase and lasting for at least 1 year. There were no differences among cirrhotics in terms of operative mortality and long-term survival with respect to the presence of the HBsAg. Of the 35 HBsAg-positive HBV-DNA-negative patients having a follow-up of 1 month or longer, 12 (34.3%) developed HBsAg recurrence; of them, 4 (33.3%) had received a complete prophylaxis, whereas 8 (66.7%) had not. The recurrence rate was 80% (8 out of 10) in the group of patients who had not received the prophylaxis and 16% (4 out of 25) in the group who had received the prophylaxis (P = .0003). The actuarial recurrence rate in the treated patients was 20.2% and 20.2% after 1 and 3 years, respectively, whereas in the untreated group it was 60.0% and 70.0% (P < .01). The hazard of recurrence of treated patients was reduced to 24.9% compared with untreated patients. Liver transplantation can be performed in HBsAg-positive HBV DNA negative patients without an increase in the operative risk or a worsening of long-term results. Immunoglobulin prophylaxis seems to be effective in preventing hepatitis recurrence after transplantation.     

Prevalence of hepatitis B and C viruses in healthy Indonesian blood donors

Blood samples were collected from 7572 healthy volunteer blood donors from 21 of the 27 Indonesian provinces, and tested for antibodies to hepatitis C virus (anti-HCV) using the new second-generation enzyme immunosorbent assay, and also tested for hepatitis B surface antigen (HBsAg). We detected anti-HCV in 2.1% of the blood donors. No statistically significant difference was found between males and females or between locations, but there was a statistically significant increasing likelihood of anti-HCV prevalence with increasing age. HBsAg was found in 8.8% of the 3839 tested donors. There was no statistically significant difference between sexes or age groups, but there was a statistically significant higher prevalence in the islands of Sulawesi and eastern Indonesia. Only 7 individuals, from 5 locations, were both anti-HCV and HBsAg positive. Based on responses to a questionnaire, a history of surgery, blood transfusion, intravenous medication, and acupuncture were identified as risk factors for the presence of anti-HCV. No such risk factor was identified for HBsAg prevalence. The combined data suggest separate modes of transmission for the 2 viruses, and indicate the need for continued surveillance for these agents in Indonesian blood banks.     

Factors associated with intrafamilial transmission of hepatitis B virus infection in Korea

Epidemiologic and serologic data on 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls who were negative for serologic markers of hepatitis B virus (HBV) were obtained from March 1990 to August 1991. Using this data, possible routes of intrafamilial transmission of hepatitis B virus among household contacts of chronic carriers of hepatitis B surface antigen (HBsAg) were evaluated and analyzed. The HBsAg prevalence among the household contacts of carriers was 14. 1% (95% CI 7.8-24.0) compared to 0.0% (95% CI 0.0-7.0) among those of controls (P < 0.01). The offspring of carriers showed significantly higher risk of HBV infection(relative risk; 6.6). Sharing of towels and handkerchieves, and drinking vessels was associated with an increased risk of HBV infection via intrafamilial transmission in Korea (relative risk 11.5 for towel and handkerchief, 12.1 for drinking vessels).     

Estimation of the future numbers of patients with circulatory diseases in Japan based on the results of national patient surveys]

Virological response to treatment of chronic hepatitis B is defined as the loss of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The quantitative measurement of HBV DNA is useful for monitoring and predicting the response to therapy with interferon-alpha (IFN-alpha). In this study, we evaluated whether quantitative measurement of serum HBeAg and IgM antibody to hepatitis B core antigen (HBcAb) could also be used in this manner. Using a microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence rate vs HBeAg concentration was constructed to provide quantitative results. The IgM HBcAb index was also measured using a microparticle enzyme immunoassay and serum HBV DNA was measured by a solution hybridization assay. We studied 48 patients who were initially positive for HBeAg and HBV DNA and who were treated with IFN-alpha2b. Their sera were serially evaluated for HBeAg concentration, and results were compared with HBV DNA levels. In the 14 patients who responded to IFN, similar disappearance curves were observed with good intraindividual correlation between the levels of the two markers. In the 34 non-responders, HBeAg levels decreased during treatment but never became negative; HBV DNA levels also decreased during treatment and became transiently undetectable in six patients, falsely suggesting treatment success. The IgM HBcAb index paralleled changes in alanine aminotransferase (ALT) concentration and did not provide additional information. Multiple logistic regression indicated that baseline ALT and HBeAg concentrations were independent predictors of the response to treatment and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude that quantitative measurement of HBeAg provides information similar to that of HBV DNA in monitoring and predicting the response to treatment; this technique could be readily adaptable to clinical laboratories.     

Hepatitis B virus transmission in an elementary school setting

CONTEXT: The risk of transmission of hepatitis B virus (HBV) in day care centers and schools is low. OBJECTIVE: To investigate the source of HBV transmission for an elementary school teacher with acute hepatitis B. DESIGN: Serologic survey for HBV infection among elementary school students, school staff, and household members of an HBV-infected teacher and student. SETTING: General community and elementary school. PATIENTS: Elementary school students and staff members and household members of an HBV-infected teacher. MAIN OUTCOME MEASURES: Elementary school students, school staff, and household members of an HBV-infected teacher were tested for markers of HBV infection. Samples positive for hepatitis B surface antigen (HBsAg) were tested for HBsAg subtype using monoclonal antibodies and examined for HBV DNA homology by polymerase chain reaction techniques. RESULTS: An HBV-infected student and the teacher were found to have the same HBV subtype (ayw1-2) and to have identical HBV DNA sequences. The teacher reported none of the usual risk factors for acquiring HBV infection, and none of her family members had been infected prior to her illness. The specific means of HBV transmission from student to teacher was not identified. Of 108 total children in the same grade as the HBV-infected student, 102 (94%) were tested for serologic markers of HBV infection, and none was positive. CONCLUSIONS: This investigation documented transmission from an HBV-infected student to a teacher in an elementary school setting without a reported overt percutaneous or permucosal exposure to blood or infectious body fluids. Transmission of HBV to other students or staff members in the school was not observed.     

Changes in ceftazidime concentration in the CSF following overdose in acute kidney failure]

The diagnosis of liver diseases induced by hepatitis B virus (HBV) is supported by the detection of HBV surface antigen (HBsAg) in serum. The present study aimed to investigate the presence of HBV deoxyribonucleic acid (DNA) in patients with liver cirrhosis using a polymerase chain reaction (PCR) based on primers derived from the pre-S1 and pre-core regions. HBsAg was detected in 10 of 48 patients (21%), total anti-hepatitis B core antigen (HBc) antibodies in 54%, anti-hepatitis B e antigen (HBeAg) in 14.6%, anti-HBc immunoglobulin M in 8%, and anti-HBs in 26%; none had detectable HBeAg. HBV DNA was detected in 73% of the cirrhotic patients. All cirrhotic patients with HBsAg also had HBV DNA; HBV DNA was detected in 64.5% of those without HBsAg. We conclude that the clearance of HBsAg does not necessarily indicate termination of viraemia in patients with liver cirrhosis and the detection of HBV DNA using a PCR based on primers from the pre-S1 and pre-core regions should be included in the diagnosis of HBV infection.     

Neuromuscular effects of rocuronium bromide (Org 9426) during fentanyl and halothane anaesthesia

The prevalence of hepatitis B virus (HBV) infection in the South African urban obstetric population, which consists of white, black, coloured and Asian patients from different socio-economic, cultural and geographical backgrounds, is unknown. Routine screening performed in 3,469 urban pregnant women revealed that 42 patients were HBV surface antigen-positive (a prevalence of 1.21%). Only 2 patients (4.6%) were hepatitis B e antigen (HBeAg)-positive (0.06% of the entire cohort), whereas the remaining 40 were identified as hepatitis B e antibody-positive. Despite a significant increase in the numbers of black patients, there has not been an accompanying increase in the number of HBV carriers. Replicative infection was equally distributed among white and black pregnant women. Because the low prevalence of HBeAg results in lack of perinatal transmission and the prevention of a single case of neonatal hepatitis B infection is costly, we conclude that in South African urban hospitals, routine screening for hepatitis B is not cost-effective.     

Functional analysis of HBV genomes from patients with fulminant hepatitis

Two previous case reports suggest that hepatitis B virus (HBV) core promoter variants with a high replication competence contribute to the pathogenesis of fulminant hepatitis B (FHB). We recently found in HBV genomes from patients with FHB an accumulation of mutations within the core promoter region. Therefore, the aim of this study was to investigate the phenotype of these HBV variants. Replication competence and expression of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) of viral genomes from seven patients with FHB and one patient with fulminant recurrent hepatitis after liver transplantation were analyzed by transfection experiments in human hepatoma cells. Compared with wild-type virus, the HBV variants from the seven patients with FHB produced similar or slightly lower levels of intracellular replicative intermediates and extracellular viral particles. In contrast, the HBV genomes from the patient with fulminant recurrent hepatitis synthesized and secreted significantly more HBV DNA. All genomes tested expressed similar or even higher levels of HBeAg compared with wild-type virus, except for those from four patients with a precore stop codon mutation in the respective dominant viral populations. The level of HBsAg produced by all variant genomes was similar or reduced compared with wild-type virus. These data indicate that in some cases HBV variants with enhanced replication competence and/or a defect in HBeAg expression may contribute to the development of FHB. However, neither phenotype is an essential prerequisite; thus, an additional role of other viral or host factors in the pathogenesis of FHB is suggested.     

Fibrosing cholestatic hepatitis in a transplant recipient with hepatitis B virus precore mutant

A patient with hepatitis B virus (HBV) precore mutant (seropositive for hepatitis B surface antigen [HBsAg], anti-hepatitis B e antigen [HBeAg], and HBV DNA) who underwent orthotopic liver transplantation for end-stage liver disease is described. Sequencing of the HBV precore region of the pretransplant serum sample confirmed the presence of the precore stop-codon mutant (G-->A mutation in codon 1896) only. The patient received HBV immunoglobulin prophylaxis for 6 months but HBV recurred thereafter with a mild hepatitic flare, and he remained seropositive for HBsAg, anti-HBe, and HBV DNA. The initial hepatitic illness resolved in 3 months. The patient remained well for another 16 months before presenting with fibrosing cholestatic hepatitis (FCH). During his entire initial hepatitic flare, quiescent period, and final FCH phase, he remained seropositive for HBsAg, anti-HBe, and HBV DNA. Moreover, sequencing of the serum HBV DNA in final FCH phase showed the presence of the identical HBV precore mutant. Immunohistochemical staining showed extensive expression of HBsAg/pre-S1, pre-S2, and hepatitis B core antigen, but HBeAg was scarcely detectable. This case illustrates that (1) recurrence of HBV precore mutant infection can occur in liver; (2) it can give rise to FCH; and (3) hepatic accumulation of HBeAg is not essential for the development of FCH.     

The effect of i.v. enalaprilat in chronically treated hypertensive patients during cardiac surgery

In areas where hepatitis B virus (HBV) is prevalent, HBV carriers negative for hepatitis B surface antigen (HbsAg) by enzyme-linked immunosorbent assay (ELISA) have been reported. Moreover, even after screening donor blood for HbsAg and hepatitis B core antibody (HBcAb), post-transfusion hepatitis B continues to occur, though with a decreasing frequency. Therefore, screening tests far more sensitive for detecting HBsAg than those currently available are needed. We developed a highly sensitive method for HBsAg detection. It is based on the recognition of peroxidase activity through measuring the formation of stable nitroxide radical with electron spin resonance (ESR) spectroscopy in the presence of hydrogen peroxide, p-acetamidophenol (p-AP), and 4-hydrazonomethyl-1-hydroxy-2,2,5,5,-tetramethyl-3-imidazoline-3-o xide (HHTIO). A cut-off value was established by testing of 186 healthy adults and 50 HBsAg-positive individuals. The signal to noise (S/N) ratio of less than 1.488 obtained by ESR spectroscopy was considered to be negative and more than 2.181, positive. The p-AP/HHTIO method was found to be 10 times more sensitive than the standard ELISA and reproducibility was excellent. Additional investigations were made on the HBsAg levels in the serum from 26 healthy subjects, in whom cut-off index levels on ELISA were negative but relatively high (range: 0.6 to 1.0); and on 15 patients with non B non C hepatitis. Three of 26 cases and 3 of 15 with non B non C hepatitis were judged to be HBsAg positive. Of these, 5 were found to be positive for HBV DNA by polymerase chain reaction (PCR). It was shown in this study that the p-AP/HHTIO method is practical and useful in screening HBV carriers because of the sensitivity in HBsAg detection, which is comparable to PCR analysis.     

Distinguishing between acute and symptomatic chronic hepatitis B virus infection

BACKGROUND/AIMS: Differentiating between an acute hepatitis B (AH-B) infection and an acute exacerbation of a chronic hepatitis B (CH-B) infection can present a problem for the clinician. The only current serological method of distinguishing between acute and symptomatic chronic hepatitis B virus (HBV) infection is the immunoglobulin M antibody to hepatitis B core antigen (anti-HBc) assay, which can be problematic. Therefore, in an attempt to better distinguish between acute and chronic HBV infection, sera from 26 patients with AH-B and 53 patients with CH-B were compared in a variety of experimental immunoassays. METHODS: Experimental assays have been designed to detect free antibody to hepatitis B e antigen (anti-HBe), hepatitis B e antigen (HBeAg)/anti-HBe immune complexes (ICs), and hepatitis B surface antigens (HBsAg)/antibody to hepatitis B surface antigen (anti-HBs) in the presence of excess antigen. An additional assay was developed to detect a novel anti-HBc specificity, designated antibody to woodchuck hepatitis virus (anti-HBcW), which cross-reacts with the core antigen of the woodchuck hepatitis virus. RESULTS: Sera from patients with CH-B showed significantly higher levels of free anti-HBe, HBeAg/anti-HBe ICs, and HBsAg/anti-HBs ICs compared with AH-B patient sera. Furthermore, patients with CH-B consistently produced high titer anti-HBcW, whereas patients with AH-B produced little or no anti-HBcW antibody. CONCLUSIONS: The serology of AH-B infection and symptomatic CH-B infection can be distinguished using a variety of experimental immunoassays in addition to the immunoglobulin M anti-HBc assay.