Integration of Hepatitis B Virus DNA into the Genome of Liver Cells in Chronic Liver Disease and Hepatocellular Carcinoma: Studies in Percutaneous Liver Biopsies and Post-Mortem Tissue Specimens

We used recombinant-DNA technology and gel electrophoresis to find hepatitis B virus DNA (HBV-DNA) in liver and tumor tissue from patients with hepatocellular carcinoma and chronic liver disease, and to study the integration of HBV-DNA into the genome of these tissues#x0027; cells. In 12 patients with hepatocellular carcinoma who had hepatitis B surface antigen (HBsAg) in their serum, integrated HBV-DNA was identified in the tumors; it was also found in tumors from three of eight patients who were seronegative for HBsAg but positive for antibody to HBsAg. In some cases, integrated HBV-DNA was also present in nontumorous liver tissue that had the same hybridization pattern or one different from that of the tumor. In five carriers of HBsAg who had evidence of the carrier state and chronic liver disease for less than two years, HBV-DNA was present but not integrated in liver tissue. In the two patients who had carried HBsAg for more than eight years, HBV-DNA was integrated into the host genome. These data suggest that integration of HBV-DNA into hepatocytes occurs during the course of persistent HBV infection and precedes development of gross neoplasm. (N Engl J Med. 1981; 305:1067–73.). EPIDEMIOLOGIC evidence suggests an etiologic relation between hepatitis B virus (HBV) infection and primary hepatocellular carcinoma.1 In the United States and Western Europe, the incidence of hepatocellular carcinoma is relatively low (about three cases per 100,000 deaths [corrected for age] per year) but has increased in recent decades.123 In certain parts of the world — e.g., the Mediterranean Basin, the Middle East, sub-Saharan Africa, South-east Asia, China, and Japan — HBV is endemic and the incidence of hepatocellular carcinoma is very high, ranging from 25 to 100 cases per 100,000 deaths per year.1 Worldwide, it is the leading cause of. . . © 1981, Massachusetts Medical Society. All rights reserved.