Significance of anti-hbc in the absence of other hepatitis B markers in a college-aged population.

A study of 291 college students in the Houston (Tex., USA) area was performed to determine the relationship between alanine aminotransferase (ALT) level and antibodies to the hepatitis B virus (HBV) core antigen (anti-HBc) in the absence of other HBV markers (referred to as isolated anti-HBc). Participants were drawn from three groups: those positive only for anti-HBc (cases), those positive for hepatitis B surface antigen, a marker of acute/chronic HBV infection (control group 1), and those with no previous exposure to the HBV (control group 2). There were no significant differences between the groups in percentages of subjects with an elevated ALT level. The mean ALT level from active HBV infections was highest with HBV-negative controls having the lowest mean ALT concentration (p = 0.06), but no significant differences were found between ALT levels of those with isolated anti-HBc and either control group. This study may further aid in determining the presence of any liver damage when testing positive only for the antibodies to HBc.

Hepatitis C virus infection-related morbidity and mortality among patients with human immunodeficiency virus infection.

Hepatitis C virus (HCV) has emerged as a major pathogen among patients with human immunodeficiency virus (HIV). Morbidity and mortality were compared among 263 patients with HIV alone, 166 patients with HIV and HCV, and 60 patients with HCV alone (mean duration of follow-up, 2 years and 10 months). No differences in HIV loads and CD4 cells counts were observed between the HIV and HIV/HCV groups. Alanine aminotransferase levels were higher (52 U/L versus 35 U/L; P<.05) and albumin levels were lower (3.5 g/dL versus 3.8 g/dL; P <.02) among coinfected patients than they were among patients with HIV alone. Liver decompensation developed in 10% of patients with HIV/HCV coinfection. In contrast, no liver-related deaths or decompensation occurred in patients without coinfection (P<.05). Of the patients with HIV alone, 7% died, compared with 11% of the coinfected patients (P<.02); 47% of the deaths in the latter group were due to liver-related causes. In summary, HCV infection causes increased morbidity and mortality in patients with HIV infection.

Immunization of seronegative infants with hepatitis A vaccine (HAVRIX; SKB): a comparative study of two dosing schedules.

Hepatitis A virus (HAV) infection is of public health significance among infants and diapered children. Although two licensed HAV vaccines are available, they have not been assessed widely in children under the age of 2 years and are not currently licensed for this age group. The purpose of this study was to evaluate the immunogenicity and reactogenicity of HAV vaccine in seronegative infants. Fifty-three healthy infants were immunized with 360 ELISA Units (EL.U.) of an inactivated HAV vaccine at 2, 4, and 6 (Group 1) or 2, 4, and 15 months of age (Group 2). These injections were not received on the same day that participants received their routine childhood immunizations. HAV serum antibodies were detected using a modified radioimmunoassay procedure and concentrations were calculated using a World Health Organization serum anti-HAV reference standard. No serious-systemic or local reactions were noted among the immunized infants. Three months following the third immunization, seroconversion rates were 100% and 93% in groups 1 and 2, respectively. No significant differences were observed in the geometric mean anti-HAV concentrations between the two groups at comparable time points, i.e. 2 months after the second dose, 3 months after the third dose, and 19 months after the first dose. Three infants, not included in the data presented above, had preexisting maternal antibodies; one never responded to the vaccine and the other two did not respond until maternal antibody levels had become reduced. The results indicate that the inactivated HAV vaccine is highly immunogenic in seronegative infants and could be included in the routine harmonized infant immunization schedule.

Detection of antibodies to hepatitis C virus in seronegative patients using an immune complex dissociation assay.

Sera from a small percentage of hepatitis C virus (HCV)-infected blood donors do not react in the currently available assays for detection of antibody to HCV (anti-HCV) and, as a consequence, hepatitis C may develop in recipients of this blood. One possible explanation for this phenomenon is that antibody is present but cannot be detected because it is sequestered in circulating immune complexes. To test this hypothesis, an immune complex dissociation (ICD) assay was developed to disrupt any immune complexes that might be present in these anti-HCV-negative, HCV RNA-positive sera. A positive result in this test would indicate that antibody is present in these patients but is not detectable under routine anti-HCV testing conditions. Nine chronic and two acute HCV patients, all negative for antibody but positive for HCV RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) were tested, together with appropriate controls. Three of the nine study patients with chronic HCV had evidence of anti-HCV after immune complex dissociation compared with none of the two patients with acute HCV. Although the number of patients tested was small, the negative results in the patients with acute HCV presumably indicates that anti-HCV seroconversion had not yet occurred. Incorporation of an ICD step into existing anti-HCV assays may enable blood banks to detect those rare instances of patients with chronic HCV who are antibody negative; this would minimize potential cases of post-transfusion hepatitis in recipients.

A multicenter study of viral hepatitis in a United States hemophilic population.

Hemophilia A and B patients seen at nine US regional treatment centers were tested for serologic markers of hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) during 1987 and 1988. Because human immunodeficiency virus (HIV) infection, a potentially confounding variable, was present in 53% of the group, the population was divided by HIV status for analysis purposes. In the HIV-positive group (N = 382), less than 1% had not been infected with HBV, HCV, or HDV, whereas 75% had evidence of infection with HBV and 98% with HCV. HBsAg, a marker of active HBV infection, was present in 12% of subjects; 96% of these were HCV positive. Anti-HDV was detected in 35 subjects (9.1%); all were anti-HBc positive. Ten of the 35 (29%) also were positive for IgM anti-HDV, indicating current infection. All 10 were HBsAg positive and 7 of the 9 tested were HDV RNA positive. Severe/moderate hemophilia B patients were more likely to have experienced an HBV infection and to be anti-HDV positive than were similar hemophilia A patients (22% v 8%, P < .05). In the HIV-negative group (N = 345), the subjects were younger and had less severe hemophilia than the HIV-positive patients. No evidence of HBV, HCV, or HDV infection was found in 18%, whereas 33% had experienced HBV infection and 79% were anti-HCV positive. Within this group, 4% were HBsAg positive. All 13 subjects with anti-HDV (4% of the HIV-negative group) also possessed anti-HBc. One (7.7%) was IgM anti-HDV positive and the serum from another contained HDV RNA. Both of these individuals were HBsAg positive. As in the HIV-positive group, severe/moderate hemophilia B patients were more likely to be HBV and HDV positive than were hemophilia A patients (9% v 3%, P < .05). A prevalence study of viral hepatitis in a large US hemophilic population showed that active infection with HCV is common, occurring in 89% of all study patients regardless of HIV status. Evidence of active HBV infection was found in 8%; 19% of these were actively infected with HDV. HDV was more common in hemophilia B patients after controlling for disease severity.

Current tests for antibody to hepatitis b core antigen used to screen donors for non-A, non-B hepatitis are comparable to the original radioimmunoassay for hepatitis B core antigen.

Prospective studies have shown a relationship between the transfusion of donor blood which is positive for antibodies to hepatitis B core antigen (anti-HBc) and an increased incidence of non-A, non-B hepatitis. The anti-HBc test was selected on the assumption that epidemiologic circumstances predisposing donors to hepatitis B infection also might favor exposure to non-A, non-B hepatitis. Current radioimmunoassays (RIA) and enzyme-linked immunoassays (EIA) for anti-HBc utilize hepatitis B core antigen (HBcAg) prepared by recombinant DNA technology, whereas the original RIA anti-HBc assay used HBcAg derived from hepatitis B virions. In the current study, 1329 sera were evaluated of which 23.3 percent were anti-HBc positive. The results indicate that sensitivity, specificity, and positive and negative predictive values of the current EIA and RIA tests for anti-HBc (Abbott Diagnostic Laboratories) are virtually identical to the original RIA test kit. In addition, all donor samples (128 specimens) administered to 57 cases of non-A, non-B hepatitis that were prospectively followed at Baylor College of Medicine for the Transfusion-Transmitted Viruses (TTV) Study group were retested with the EIA-recombinant anti-HBc assay. All 21 samples which were reactive in the original RIA anti-HBc test also were positive by the current EIA procedure. One sample was EIA positive/RIA negative, and 106 other samples were negative by both assays. Thus, commercial anti-HBc kits based on HBcAg derived by recombinant DNA technology, should retain their predictive value for reducing the incidence of non-A, non-B hepatitis as described in the prospective studies.

Response to a hepatitis B polypeptide vaccine in micelle form in a young adult population.

Polypeptide micelles with relative molecular weights of 25,000 (p25) and 30,000 (gp30) daltons were prepared from native 22-nm hepatitis B surface antigen (HBsAg) particles. This p25/gp30 complex was alum-adsorbed, and three dosage levels (20 micrograms, 4 micrograms, and 0.8 micrograms) were administered at 0, 1, and 6 months to 51 human volunteers. Local and systemic reactions were clinically insignificant, and all vaccinees seroconverted, regardless of dose. As anticipated, antibody responses diminished as the dosage was reduced. Seroconversion rates and geometric mean antibody levels for the 20 micrograms dosage group were significantly better than those observed with a commercial vaccine and were comparable to those achieved after immunization with 40 micrograms of the intact 22-nm particles used to prepare the polypeptides. By 2 weeks, an anti-HBs response was elicited in 80% of the group receiving 20 micrograms of the polypeptide vaccine. This rapid response to immunization may be particularly beneficial for postexposure prophylaxis where the early development of immunity is advantageous.

Viral hepatitis risk in urban emergency medical services personnel.

Houston has large groups of people known to be at high risk for hepatitis B virus (HBV) infection. Emergency medical services (EMS) personnel are continuously exposed to blood from these high-risk individuals. We sought to determine the prevalence of HBV infection in the city's EMS personnel. Of the 350 Houston firefighters assigned to EMS, 344 were surveyed by questionnaire and a blood specimen was obtained. Each sample was assayed by radio-immunoassay or enzyme-linked immunoassay for hepatitis A antibody (anti-HAV), hepatitis B surface antigen (HBsAg), and antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc). A history of hepatitis was reported by 19 persons, 17 of whom had serologic evidence of infection with HAV (56%), HBV (26%), or both diseases (11%). The anti-HAV prevalence was 16% (12% in whites and 35% in nonwhites; P less than .001). No correlation was observed with years of occupational exposure. Of the 338 personnel evaluated for HBV seromarkers (six HBsAg-vaccinated subjects were excluded), 13% were positive; 0.6% had an active infection as determined by the presence of both HBsAg and anti-HBc; 6.8% were both anti-HBs and anti-HBc positive; 0.9% were positive for anti-HBc alone; and 4.7% of the sera contained only anti-HBs (all with geometric mean antibody levels of less than or equal to 13 mlU/mL). The 28 individuals (8.3%) whose sera contained anti-HBc were classified as cases of previous or concurrent HBV infection. A strong correlation (P less than .004) was observed between HBV infection and years of work exposure in EMS regardless of job description (paramedic versus emergency medical technician).(ABSTRACT TRUNCATED AT 250 WORDS)

Normal immune response to hepatitis B vaccine in patients with Down's syndrome. A basis for immunization guidelines.

Institutionalized patients with Down's syndrome (DS) are uniquely predisposed to develop chronic hepatitis B infection following exposure. Therefore vaccination is particularly warranted, but there have been concerns that these individuals may react suboptimally. We examined the immune responses of 62 institutionalized patients with DS to 20 and 40 micrograms of hepatitis B vaccine inactivated (Heptavax-B) over one year. The subjects were matched by weight, age, and sex. Seroconversion rates and levels of antibodies to hepatitis B surface antigen (anti-HBs) were comparable to those found in a normal population and were higher than those found in immunocompromised patients undergoing hemodialysis. The anti-HBs levels were consistently higher in the 40-micrograms vaccine group. In patients with DS who were over 30 years old, age was a significant factor in predicting anti-HBs responses. Conversely, in younger subjects, weight was negatively correlated with anti-HBs levels. These data clearly indicate that patients with DS respond normally to hepatitis B surface antigen vaccination and need not be considered a special group when guidelines for vaccination are recommended.

Detection of an IgM antiidiotype directed against anti-HBs in hepatitis B patients.

An IgM-specific anti-[anti-HBs] antibody was detected by radioimmunoassay using anti-IgM-coated beads and 125I-labeled anti-HBs. This antiidiotype was found only in the sera of hepatitis B virus-infected patients, both acute and chronic. However, not all HBsAg-positive patients exhibited this reaction, and activity was correlated with the presence of HBeAg. Approximately 93% of sera that contained antiidiotype activity also contained HBeAg. Conversely, 70% of the sera positive for HBeAg reacted in the IgM assay. No correlation was observed between the presence of antiidiotype and rheumatoid factor or elevated SGPT levels. Two approaches were used to determine whether the reactive moiety was an IgM anti-[anti-HBs] as postulated or an IgM anti-HBs/HBsAg complex. It was shown that chicken anti-HBs sera, which does not share the common idiotype of human and other mammalian anti-HBs, did not block a positive reaction in this radioimmunoassay even though it specifically bound HBsAg. It was also demonstrated that treatment with polyethylene glycol, which will precipitate IgM anti-HBs/HBsAg activity, did not precipitate the reactive moiety in 6 of 7 sera tested, lending further evidence to the existence of an IgM antiidiotype in these patients. It is suggested that this antiidiotype directed against anti-HBs may be involved in a defective feedback mechanism resulting in the suppression of production of anti-HBs and maintenance of the carrier state.

Comparison of enzyme-linked immunosorbent assay and hemagglutination inhibition in a seroepidemiological study of influenza type C infection.

An enzyme-linked immunosorbent assay was developed for the detection of antibodies to influenza type C. Based on replicate testing it was decided that an increase of more than three times the standard error of the mean from one serum specimen to the next represented a significant increase in antibody content. After removal of potentially chicken egg albumin antibodies, the test appeared to be more sensitive for the detection of rises in antibody levels than was hemagglutination inhibition. In some cases, heat treatment of the serum before use in the enzyme-linked immunosorbent assay increased the readings. The strains C/AA/1/59 and C/NJ/1/76 were used in a pilot epidemiological study of influenza C infection in Tecumseh, Mich. Sera tested were collected from autumn of 1976 to autumn of 1978. The overall incidence rate for influenza C infection in the 2-year period was 7.8%. Most cases occurred in children aged 5 to 9 years, and the rates decreased rapidly with increasing age. There appeared to be no relationship to influenza C infection with influenza A or B coinfection. All 17 influenza C infections observed occurred during the 1976 to 1977 respiratory disease season. This indicates that type C virus may not occur endemically, but may exhibit year-to-year variation in infection frequency, as is the case with types A and B.