9 Preliminary Communication ANTIBODY TO HEPATITIS-B CORE ANTIGEN IN PATIENTS WITH PRIMARY HEPATIC CARCINOMA PHILIPPE MAUPAS BERNARD LAROUZÉ W. THOMAS LONDON BARBARA WERNER IRVING MILLMAN ANNA O’CONNELL BARUCH S. BLUMBERG Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania, U.S.A., and Department of Microbiology, University of Tours, Tours, France GERARD SAIMOT MAURICE PAYET Institut de Medicine et d’Épidémiologie Africaine, Hôpital Claude Bernard, Paris, France Summary Antibody to hepatitis-B core antigen (anti-HBc) was assayed in the serum of patients with primary hepatic carcinoma (P.H.C.) and controls from Hong Kong, West Africa, and the United States. In each region the prevalence of anti- HBc was higher in P.H.C. patients than in controls, ranging from 70 to 95 % in the patients and from 20 to 68% in the controls from Asia and Africa; 24% of P.H.C. patients and 4% of controls from the U.S. had anti-HBc. These data support the hypothesis that chronic infection with hepatitis-B virus is ætiologically related to P.H.C., especially in Asia and Africa, although other factors must also be involved. SONICATED LIVER HOMOGENATE Scheme for isolation and purification of HBcAg from liver of a human HBsAg carrier. (a) 1/2 HBcB2 centrifuged 106,000×g×2 hr. in Beckman concentrated x 10 in Amicon apparatus (SM-300 90 mm. filter). L2-65B. (c) Isopycnic centrifugation in CsClz (1’316 g./c.cm.) 108,000 (b) 1/2 HBcB2 dialysed against 0.1M P.B.S. pH 7’2x24 hr. ×g×72 hr. ppt. = precipitate. sup. = supernatant. C.E.P. = counter-electrophoresis. E.M.= electron microscopy. INTRODUCTION PRIMARY hepatic carcinoma (P.H.C.) is the most com- mon malignant neoplasm in several of the world’s major populations (Chinese, Africans, Filipinos). Therefore, it may be the most common cancer in man. On the basis of necropsy studies showing an associa- tion between chronic hepatitis and/or macronodular post-necrotic cirrhosis with P.H.C., Payet 1 and Steiner and Davies 2 suggested that viral hepatitis may be the major cause of P.H.C. in Africa. When tests for infec- tion with hepatitis-B virus (H.B.v.) became available it was possible to evaluate the association of H.B.V. with P.H.C. Several studies in Africa and Asia showed an increased prevalence (35-80%) of Australia antigen (hepatitis-B surface antigen, HBsAg) among patients with P.H.C. These high prevalences were generally detected only when sensitive methods (radioimmuno- assay, immune adherence hæmagglutination) for assaying HBgAg were used.3.4 This observation suggested that either HBsAg was present in decreased quantity in P.H.C. patients or there was some antigenic difference between the HBgAg in P.H.C. and that found in HBsAg carriers.4 No increase in the prevalence of antibody to hepatitis-B surface antigen (anti-HBs) has been reported in P.H.C. patients If patients with P.H.C. are infected with H.B.v. but are producing small quantities of HBgAg, there may be defects in viral assembly or viral replication in the malignant cells. Hoofnagle et al.6 have suggested that antibody to hepatitis-B core antigen (anti-HBc) is a better indicator of intracellular replication of H.B.V. than anti-HBs or HBsAg. In this paper we report