The cholestatic form of viral hepatitis: Experiences with viral hepatitis at Brooke Army Hospital during the years 1951 to 1953

Abstract During the period 1951 through 1953, 46 per cent of the cases of infectious hepatitis (studied by biopsy) occurring at Brooke Army Hospital, Texas, presented the histologic picture of cholestatic ("cholangiolitic") hepatitis. By contrast, during this same period, the patients at this hospital in whom serum hepatitis developed had a low incidence of cholestatic hepatitis, the majority showing the classic histologic picture of viral hepatitis. An epidemiologic analysis of the patients with serum hepatitis showed that they were soldiers who had received blood products for battle injuries in Korea and had been immediately transferred to Brooke Army Hospital, where they came down with serum hepatitis after the usual incubation period. Thus the high incidence of cholestatic hepatitis occurred only among persons residing in Texas in whom the infectious type of viral hepatitis developed. In the control cases of viral hepatitis (both infectious and serum hepatitis) from other military hospitals in the United States, Europe and the Far East that occurred during the same period (1951 to 1953), the patients showed a much lower incidence of the cholestatic variety, varying from 2 to 8 per cent. Microbiologic studies on fresh liver tissue failed to yield a specific pathogenic agent. Nevertheless, after analyzing all the data at hand, we are inclined to believe that the hepatitis occurring in the Texas residents represented a minor epidemic of infectious viral hepatitis, and that the unusually high incidence of the cholestatic histologic variety was probably the result of some variant in virus strain. This suggests that the "virus of infectious hepatitis" is probably not a single virus but is comprised of a family of related substrains of virus. This may account in part for differences in morbidity and mortality rates heretofore reported, as well as for differences in the histologic pictures evoked by the viruses. Our experience also indicates that we must broaden our histopathologic criteria for viral hepatitis to include not only the classic variety heretofore accepted but also the cholestatic type, and types intermediate between the two. A comparison of the two groups of patients at Brooke Army Hospital, the one showing the classic histologic picture and the other the cholestatic type of viral hepatitis, revealed no significant differences in (1) the clinical appearance, (2) the duration of illness, (3) the final outcome (all recovered) and (4) the initial values for total leukocyte count, the thymol turbidity test and the serum alkaline phosphatase. However, the mean value for serum bilirubin (both direct and total) was twice as high in the groups of patients showing intrahepatic bile stasis as in those in whom biopsy specimens were free of intrahepatic cholestasis. This indicated a correlation between the presence of intrahepatic cholestasis and the level of serum bilirubin. The intrahepatic bile ducts showed no lesions. For this and other reasons we favor the view that the predominant pathogenetic mechanism operating in cholestatic hepatitis is hepatocellular damage and not injury or obstruction to intrahepatic bile channels. It seems likely that hepatocellular damage, even without obvious necrosis, can lead to impairment of manufacture, secretion and propulsion of bile.