Evaluation of the specificity of an immunoprecipitin test for non-A, non-B hepatitis.

The specificity of a new antigen-antibody system (devised at the International Center for Medical Research and Training [ICMRT], San José, Costa Rica) for non-A, non-B (NANB) hepatitis was evaluated. ICMRT antigen was found in eight (21%) of 38 patients with acute NANB hepatitis; 22 patients (58%) seroconverted, including three who were positive for ICMRT antigen. Five patients with chronic NANB hepatitis were persistently positive for ICMRT antigen and negative for ICMRT antibody during several years of observation. Neither ICMRT antigen nor seroconversion was found among 11 patients with hepatitis A and 19 with hepatitis B occurring concomitantly with NANB hepatitis; only two of 56 patients with other liver diseases had ICMRT antigen, both presumably with chronic antigenemia. Seven of 128 household contacts of patients with NANB hepatitis had ICMRT antigen; 27 had antibody initially, and 35 (37% of susceptible contacts) seroconverted during the observation period. Less than 4% of household contacts of patients with hepatitis A or B seroconverted.

Hepatitis A virus infection in households.

The behavior of hepatitis A virus (HAV) infection among 980 members of 230 families in two rural districts of Costa Rica was studied prospectively from the recognition of the index case. The initial prevalence of detectable antibody (anti-HAV) ranged from 26.2% in children to 71.4% in adults. The ratio of index to household-associated infections was significantly higher among children than among adolescents and adults, indicating that children were most often responsible for the HAV introduction. The rates of household-associated cases among susceptible contacts were 70-83%; the final prevalences of anti-HAV were 90-95%. Neither index showed significant differences related to age. The ratio of clinical to silent infections in household-associated cases was uniformly 1.8:1 among children and adolescents; among adults, almost all associated infections were silent. Beginning with the 5-9-year age group, however, an immunoglobulin M response was absent in a progressively larger proportion of inapparent infections, strongly suggesting restimulation of specific immunoglobulin G antibodies by reinfection.

Immunoglobulin M level in the diagnosis of type A hepatitis.

The serum immunoglobulin M level has often but not always been found to be higher in type A than in type B hepatitis. Studies of this question, however antedated the recognition of non-A, non-B disease, and the etiologic characterization may have been mistaken in many instances. It was appropriate, therefore, to reopen the question by an investigation of 62 serologically defined cases. IgM values above 300 U/ml occurred in 28 of 33 type A episodes, three of 24 type B, and none of ten non-A, non-B cases. Although nonspecific, the IgM assay is a generally available procedure that may provide useful evidence concerning the etiologic form of acute viral hepatitis.

Identity of antibody to hepatitis B e/1 antigen as an atypical rheumatoid factor.

Chronic carriers of hepatitis B surface antigen (HBsAg) who were positive for antibody to hepatitis B e antigen were tested for precipitating specificities of the antibody and for rheumatoid factor (RF) over a two-year period. Twenty-one of 69 carriers were RF-positive by the latex-RF test with human IgG, but all were negative by the hemagglutination-RF test with rabbit IgG. Antibody to e/1 antigen was identified as an IgM antibody reactive in the latex-RF test, whereas antibody to e/2 antigen belonged to the IgG class and showed no RF reactivity. Antibody production seems to follow a sequential evolution: antibody to e/1 antigen appears early and that to e/2 antigen follows shortly thereafter. Antibody to e/2 antigen remains as the permanent antibody, whereas that to e/1 antigen sometimes disappears. The fact that antibody to e/1antigen is present only in certain chronic carriers of HBsAg would account for discrepancies in reported results of RF test in viral hepatitis.

The threat of hepatitis B from dental school patients. A one-year study.

A study was conducted at the Louisiana State University School of Dentistry using the radioimmunoassay technique of serum analysis for presence of hepatitis B surface antigen (HBsAg) in all new patients accepted for treatment over a period of one year. The prevalence was 0.61 percent (22 seropositive patients from a total of 3,626 patients screened). Chronic HBsAg carriers, presence of e antigen, and high titers of antibody to hepatitis B core antigen (anti-HBc) were documented. Eighteen of the 22 seropositive patients had no past history of hepatitis, indicating the inadequacy of a history for revealing carriers of HBsAg.

Anti-DNA, anti-HBc correlations with RIA-detected HBeAg and anti-HBe in chronic HBsAg carriers.

The interrelations of 1) antibody to hepatitis B core antigen (HBcAg)--anti-HBc; 2) single-stranded DNA-binding antibodies (anti-DNA); and 3) the e-antigen/antibody system--hepatitis B e antigen (HBeAg) and antibody (anti-HBe), were studied in 150 hepatitis B surface antigen (HBsAg) carriers, in 43 of whom diagnostic liver biopsies had been performed. There was a good correlation between titers of anti-HBc and anti-DNA, regarded as indicators of viral and pathological activity, respectively, as well as between levels of these two antibodies and the presence of HBeAg or anti-HBE as detected by radio-immune assay (RIA). In general, HBeAg-positive carriers showed high anti-HBc and high anti-DNA titers, while the carriers positive for anti-HBe had low titers of both. These findings were in accord with the histopathological results. The three serologic parameters, anti-HBc, anti-DNA, and e-antigen/antibody, should together prove useful for the evaluation of the clinical status of chronic HBsAg carriers.

Antibodies to single stranded DNA: a diagnostic aid in chronic hepatitis B virus infections.

Serial determinations of titers of binding antibodies to single stranded DNA were performed over a period of three years in 43 type B hepatitis patients with persisting HBsAg who had either developed chronic hepatitis or were asymptomatic carriers. Patients with histopathological diagnosis of chronic active or chronic persistent hepatitis, with or without clinical symptoms, showed high titers of anti-DNA throughout the course of the disease, whereas in most of these patients the serum alanine transaminase and bilirubin levels fluctuated widely and were often normal; in such cases the elevation of anti-DNA was frequently the only positive sign present. On the other hand anti-DNA titers were within the normal range in chronic asymptomatic HBsAg carriers who showed no histopathological or biochemical changes. Anti-DNA determinations are proposed as a reliable diagnostic aid to supplement current procedures for assessment of the disease status during the course of chronic hepatitis B virus infections.

Dane particles and associated DNA-polymerase activity in saliva of chronic hepatitis B carriers.

To investigate furhter the problem of salivary transmission of type B hepatitis, salivas free of blood contamination from three HBsAg-positive carriers with chronic active hepatitis were examined by CsCl equilibrium density gradients and electron microscopy (EM). In the CsCl gradient HBsAg of whole salivas distributed in a band centered at 1.19gm/cm3 with a clearly defined shoulder at 1.24 gm/cm3; the HBsAg was found mainly in the mucous component. On EM examination, fractions from the 1.19 gm/cm3 peak contained spherical HBsAg particles of 22 +/- 3 nm diameter, whereas in the 1.24 gm/cm3 shoulder Dane particles 43 nm in diameter with 28 nm cores were found. Specific hepatitis B virus associated DNA-polymerase activity also was found in the 1.24 gm/cm3 shoulder where the Dane particles occurred and was absent from the saliva of healthy controls. When salivas were incubated for three hours at 37 degrees C the total amount of HBsAg diminished and the 1.24 gm/cm3 shoulder disappeared, probably as a result of endogenous degradation of the Dane particles and the free HBsAg. These findings clearly indicate that the hepatitis B viral particle is present in the saliva of chronic HBsAg carriers with active disease and further confirm that saliva is an important vehicle of infection.

Evidence that e-antigen is not transmitted with hepatitis B infection.

The correlation between transmission of e-antigen (e-Ag) and hepatitis B antigen (HBsAg) was investigated in primary and secondary cases of type B hepatitis occurring in 15 families. The e-Ag was not consistently transmitted in the familial environment, as were the d and y subtypes of HBsAg, but occurred in erratic fashion among genetically and epidemiologically related cases. It is concluded that e-Ag is probably the non-transmissible product of a specific individual response to hepatitis B infection.

Tests in rufiventer and other marmosets of susceptibility to human hepatitis A virus.

The rufiventer marmoset proved equally satisfactory to S. mystax for studies of human hepatitis A virus. C. jacchus, C. argentata, S. weddelli, and S. oedipomidas oedipus were not satisfactory. Livers of rufiventer marmosets produced satisfactory CR326 strain hepatitis A antigen for immune adherence tests both in amount and specificity. Rufiventer marmosets infected with human hepatitis A virus showed enzyme elevations and high titers of viral antigen in their livers as early as seven days after viral inoculation, indicating that a primary viral infection can cause hepatitis without need for a secondary autoimmune response to liver tissue.

Antibodies to single-stranded DNA: an aid in diagnosis of viral hepatitis.

In clinical and subclinical viral hepatitis a significant increase of antibodies to single-stranded DNA revealed by the prepatent stage of the disease before any elevation of serum transaminases. In type A hepatitis, a rise in anti-DNA titers was detectable one to two weeks before onset of clinical and biochemical signs; in type B hepatitis, the rise of anti-DNA coincided with or preceded the appearance of HBSAg, several weeks before the onset of clinical illness. In both hepatitis types anti-DNA titers reached a peak (640--2,560) at onset and dropped shortly after serum transaminases returned to normal at the end of acute illness. The anti-DNA response in non-A/non-B hepatitis was of similar magnitude. Anti-DNA elevation was the only positive sign found in most silent infections of either type that later showed specific seroconversion. Anti-DNA levels in noninfected contacts were in the same range as those found in a group of health individuals. The anti-DNA test is useful for early diagnosis of viral hepatitis and should be a valuable addition to current epidemiological and clinical procedures.