INTRODUCTION Identification of a surrogate serological marker of his- tological severity is an important goal in the practical management of patients with chronic hepatitis B. Serum aminotransferases provide little information about the activity of liver disease, and hepatitis B virus (HBV) DNA serum levels have been shown to be inversely related to the degree of histological portal infiltrate and periportal necrosis [1]. The IgM antibody to hepatitis B core antigen (IgM HBcAb) is considered an indirect marker of the immune reaction against HBV and it is the standard test for the diagnosis of acute and chronic HBV-induced liver disease [2,3]. Some authors have reported a corre- lation between serum levels of IgM HBcAb and the his- tological activity of chronic hepatitis [2,4,5] but these results have not been confirmed by others [6,7]. Therefore the question as to whether IgM HBcAb is a Journal of Viral Hepatitis, 1999, 6, 429–434 © 1999 Blackwell Science Ltd REVIEW ARTICLE Semiquantitative assessment of IgM antibody to hepatitis B core antigen and prediction of the severity of chronic hepatitis B G. Colloredo, 1 G. Bellati, 2 A. Sonzogni, 3 C. Zavaglia, 2 O. Fracassetti, 4 G. Leandro, 5 R. Ghislandi, 3 E. Minola 2 and G. Ideo 2 1 Department of Internal Medicine of Seriate Hospital (Bergamo), 2 ‘Crespi’ Liver Unit of Niguarda Hospital, Milano, 3 Pathology Department of Maggiore Hospital, Bergamo, 4 Infectious Disease Department of Maggiore Hospital, Bergamo and 5 Biostatistics, Castellana Grotte (Bari), Italy Received 1 December 1998; accepted for publication 26 January 1999 SUMMARY. Controversial results have been reported concerning the correlation between serum levels of IgM antibodies to hepatitis B core antigen (IgM HBcAb) and the histological activity of chronic hepati- tis B. In this study, paired serum samples and liver biopsies were collected from 200 consecutive chronic hepatitis B patients (mean age 39.2 ± 0.8 years; M:F 154:46; 41 hepatitis B e antigen (HBeAg) positive) and tested for IgM HBcAb using a semiquantitative highly sensitive assay (IMx CORE-M®). The severity of liver disease was assessed by the Ishak score, grading the necroinflammatory activity (by using the histology activity index, HAI) and staging the fibrosis. The index values of IgM HBcAb were significantly different among patients with mild (HAI ≤ 6), moderate (HAI 7–12) and severe (HAI ≥ 13) necroinflammatory activity but the stage of fibrosis was unrelated to the IgM HBcAb. According to the index value of IgM HBcAb, we selected three groups of patients: Group A included 36 patients with an index value below 0.200; Group B, 99 patients with an index value between 0.200 and 0.500; and Group C, 65 patients with an index value over 0.500. The mean HAI grading in Group A was 5.3 ± 0.4, in Group B it was 7.4 ± 0.3 and in Group C it was 8.9 ± 0.4 (f = 16.5, P < 0.0001). A mild HAI grading was observed in 77.8% of Group A, in 47.5% of Group B and in 23.1% of Group C patients; conversely, severe grading was detected in 0% of Group A, in 11.1% of Group B and in 18.5% of Group C patients (P < 0.0001). An index value of IgM HBcAb below 0.200 was 75% predictive of a mild necroinflammatory activity (29% sensitivity and 91.6% specificity) and ruled out a severe activity. Therefore, the quantitative assessment of IgM HBcAb appears to be a useful clinical tool in the prediction of the necroinflammatory activity of chronic hepatitis B. A serum index value of IgM HBcAb consistently below 0.200 could be considered a surrogate marker of remission of hepatitis B virus-induced liver disease. Keywords: chronic hepatitis B, histological activity index, IgM HBcAb. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; IgM HBcAb, IgM antibody to hepatitis B core antigen. Correspondence: Giorgio Bellati MD, ‘Crespi’ Liver Unit, Niguarda Hospital, Piazza Ospedale Maggiore 3, 20162 Milano, Italy.