Until the mid-1900s, hepatitis was frequently equated with jaundice, although jaundice is only a sign of a failure to clear normal breakdown products from the blood. Under this terminology, hepatitis and other liver diseases played a very important role in early medical writings, but it is difficult to determine which references relate to hepatitis as we now know it, and which refer to the various other causes of jaundice. It is even more difficult to distinguish one type of hepatitis from another in the early references. Hippocrates identified at least four kinds of jaundice, one of which he considered epidemic and thus, by implication, infectious. Another was "autumnal hepatitis"; this condition, which appeared after an interval appropriate to the incubation period following the dry Mediterranean summer when water supplies would have shrunk, could have been hepatitis A. An emphasis on the liver has persisted into modern times in French popular medicine, where the liver is commonly blamed for ill-defined ailments.

Postclassical writers continued to have difficulty in distinguishing infectious forms from noninfectious forms of jaundice because of the long and variable incubation periods of the infectious diseases. Clear recognition of the infectivity of hepatitis is usually ascribed to Pope Zacarias (St. Zachary), who in the eighth century advocated a quarantine of cases. This had little effect on general thinking, however, because of the variety of circumstances that were associated with different outbreaks. Many cases seemed to be sporadic, but epidemics of what must have been hepatitis A, or enterically transmitted non-A, non-B, were known from the early seventeenth century to be common in troops under campaign conditions. An epidemic of hepatitis B, associated with one lot of smallpox vaccine of human origin, was well described by A. Lurman in 1885. In spite of this, as late as 1908, the dominant medical opinion held that all hepatitis was due to obstruction of the bile duct. The picture did not really begin to clear until the middle of the twentieth century.

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