The Significance of Igm Antibodies to Hepatitis B Core Antigen in Hepatitis B Carriers and Hepatitis B–Associated Chronic Liver Disease

Abstract

IgM antibody to hepatitis B core antigen (IgM anti‐HBc) was determined in 60 patients whose serum was positive for hepatitis B surface antigen (HBsAg) and 18 patients whose serum was negative for HBsAg, but positive for antibody to hepatitis B core antigen (anti‐HBc). Two radioimmunoassays were done utilizing either anti‐u antibody to capture IgM or Staphylococcus A protein to separate IgG and IgM. Both methods failed to detect IgM anti‐HBc in 30 healthy carriers, 5 HBsAg‐positive cirrhotics, 2 patients with HBsAg‐positive hepatocellular carcinoma, and 18 HBsAg‐negative anti‐HBc‐positive patients. IgM anti‐HBc was present in all 4 patients with acute hepatitis B and in 4 of 8 patients with HBsAg‐positive chronic active hepatitis. In patients with chronic active hepatitis, IgM anti‐HBc was positive in those with the most intense infiltrate of mononuclear cells on liver biopsy. There was no correlation with the presence of hepatitis B e antigen or anti‐HBe. Three of 11 patients with HBsAg‐positive chronic persistent hepatitis were intermittently positive by the Staphylococcus A method but all were negative by the u‐capture method when a low sensitivity cutoff was employed. The sensitivity of the test can be adjusted at will by the manufacturers and, therefore, introduction of interchangeable controls and standards will enable clinical application of this testing system with meaningful results. Testing for IgM anti‐HBc may help the clinician in differentiating healthy HBsAg carriers from patients with HBsAg‐positive acute and chronic hepatitis. It is also of value in differentiating patients with acute hepatitis B from HBsAg carriers who develop acute hepatitis of different etiology. Accumulation of more data and correlations with the intensity and nature of the mononuclear infiltrates in chronic hepatitis will increase understanding of the mechanism of switchover from IgM to IgG anti‐HBc response and factors favoring chronicity in hepatitis B.

Diagnostic value of anti‐HBc IgM in high hbv prevalence areas

“…Very few similar cases have been reported up to now [Kryger et al, 19811, although the potential clinical value of the anti-HBc IgM assay in differentiating acute hepatitis B patients from HBsAg carriers. who develop acute hepatitis caused by different agents, has been implied by several investigators [Feinman et al, 1982;Gitnick, 1983;Shimizu et al, 19831. Such false positive diagnoses of acute type B hepatitis may have exaggerated the risk of an adult becoming an HBsAg carrier following primary acute HBV infection IDcinhardt and Gust, 19821.…”

“…Contrasting results have been reported regarding the diagnostic value of various anti-HBc IgM assays used to differentiate acute from chronic HBV infection. Thus the estimated prevalence of anti-HBc IgM in asymptomatic HBsAg carriers has ranged from 34.9 to 100% in some studies [Gerlich et al, 1980: Hawkes et al, 1980Schalm et al, 1980;Kryger et al, 1981;Lemon et al, 1981;Roggendorf at al, 19811, while other investigators have found no anti-HBc IgM activity [Cohen, 1978;Tedder and Wilson-Croome 1980;Feinman et al, 1982;Shimizu et al, 19831. Discrepancies have also been reported in the ability of assays to distinguish between recent and past HBV infection in HBsAg-negative patients [Cohen, 1978;Gerlich et al, 1980;Hawkes et al, 1980;Tedder and Wilson-Croome, 1980;Kryger et al, 1981;Lemon et 1981; Roggendorf et al, 1981;Feinman et al, 1982;Shimizu et al, 19831.…”

“…This would be extremely useful for the rapid and accurate diagnosis of acute hepatitis B, especially in fulminant hepatitis [Shimizu et al, 19831. However, the use of various assays yielded contrasting results regarding its persistence after recovery from acute as well as its presence in asymptomatic HBsAg carriers [Cohen, 1978;Gerlich et al, 1980;Hawkes et al, 1980;Tedder and Wilson-Croome, 1980;Kryger et al, 1981;Lemon et al, 1981 ;Roggendorf et al, 1981;Feinman et al, 1982;Shimizu et al, 19831. In the present investigation we used a sensitive and specific enzyme immunoassay for anti-HBc IgM in a large number of prospectively followed, carefully documented cases of acute viral hepatitis as well as in groups of patients with chronic hepatitis B liver disease, asymptomatic HBsAg carriers, and healthy individuals immune to HBV. According to our results, this assay may identify and distinguish between acute and chronic (HBsAg-positive) as well as between recent and old (HBsAg-negative) HBV infection.…”

“…This would be extremely useful for the rapid and accurate diagnosis of acute hepatitis B, especially in fulminant hepatitis [Shimizu et al, 19831. However, the use of various assays yielded contrasting results regarding its persistence after recovery from acute as well as its presence in asymptomatic HBsAg carriers [Cohen, 1978;Gerlich et al, 1980;Hawkes et al, 1980;Tedder and Wilson-Croome, 1980;Kryger et al, 1981;Lemon et al, 1981 ;Roggendorf et al, 1981;Feinman et al, 1982;Shimizu et al, 19831.…”

Diagnostic significance of anti‐HBc IgM (RIA) in healthy HBsAg carriers and in chronic hepatitis B

“…Others found no detectable IgM anti-HBc in such patients [Feinman et al, 1982;Shimizu et al, 1983;Papavangelou et al, 19841.…”