In 1942 the U.S. Army experienced an unprecedented outbreak of post- vaccinal hepatitis that offered an unusual opportunity to study the relation between the hepatitis B virus (HBV) and primary hepatocellular carcinoma (HCC). The record systems of the Army and the Department of Veterans Affairs, and the taxpayer address list maintained by the Internal Revenue Service made it possible to locate and bleed representative samples of men who were ill with hepatitis in 1942, men who were exposed to contaminated vaccine without becoming ill, and men with no exposure to contaminated vaccine. Serologic studies demonstrated that the epidemic had been caused by HBV. Large cohorts of these three groups were followed for mortality in order to explore the relation between subclinical infection with HBV and subsequent liver disease, especially cirrhosis and HCC. The investigation has now been completed, with two papers published and a third in press. The final report shows that the relation between HBV infection and HCC probably depends on age at infection, since there was no more than a borderline increase in HCC among the healthy young males vaccinated in 1942, and no increase in cirrhosis. The suggestion is that age at infection has a strong influence on the carrier rate and perhaps also on the transition probability from carrier state to HCC.
