Non A/non B hepatitis.

The concept that human viral hepatitis was caused by no more than two etiologic agents stemmed from early volunteer studies in which two epidemiologically distinct types of hepatitis were transmitted to humans (1). These experimentally transmitted diseases closely resembled two forms of naturally occurring viral hepatitis that could be distinguished on epidemiologic grounds. One form was highly infectious, spread by the fecal oral route, with a relatively short incubation period of 2 to 6 weeks ("in­ fectious hepatitis" or hepatitis type A); the other usually occurred following parenteral inoculations and was characterized by a long incubation period (ap­ proximately 6 weeks to 6 months), little, if any, person-to-person spread, and lack of association with epidemics except where multiple inoculations with the same contaminated syringe had occurred ("serum hepatitis" o r hepatitis type B). Early epidemiologic studies failed to provide evidence for more than two viral hep­ atitis agents (1). However, the possibility of other human hepatitis viruses was sug­ gested by the finding of hepatitis cases with an incubation period intermediate between that of hepatitis A and B viruses (2). More recently, multiple cases of hepa­ titis occurring among illicit drug users suggested that three o r more etiologic agents might exist (2). With the discovery of hepatitis B surface antigen (HB sAg) and its association specifically with type B hepatitis (3, 4), a method to reevaluate accepted beliefs about type B hepatitis became available. Some surprises emerged. Among these was the finding that a significant proportion of "sporadic" hepatitis not acquired by demon­ strable percutaneous exposure was, in reality, associated with HBsAg. Furthermore, epidemiologic surveys for HBsAg and antibody to HB sAg (anti-HBs) provided serologic evidence of exposure to hepatitis B virus (HBV) among a proportion of affected individuals whose mode of infection was incompatible with the concept of strictly percutaneous spread of the virus (5). Even more interesting was the finding that a significant proportion of transfusion-associated hepatitis could not be related serologically t o hepatitis B virus infection (6, 7). I t was thought that such "non-B" hepatitis was undiagnosed type B infection or , more likely, percutaneously transmit­ ted type A hepatitis. However, epidemiologic studies a s far back as 1962 strongly suggested tha t t he latter was not the case: The incubation period of transfusionassociated hepatitis defined a unimodal curve with its peak 45 to 49 days after ex­ posure, strongly suggesting that short incubation period type A hepatitis was not an important cause of illness in blood recipients (8). Similar conclusions were reached in a recent study of transfusion-associated hepatitis (9).