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Over a 3-year period, 149 Yucpa Indians in Venezuela developed hepatitis; 34 persons died and at least 22 developed chronic hepatitis. Children and young adults were primarily affected, especially males. Serologic testing showed that hepatitis B virus infection was highly endemic in this population, but also that 65% of patients had hepatitis B virus surface antigen (HBsAg) during or after illness. Most patients had evidence of delta-agent superinfection; 86% of HBsAg-positive patients had delta antibody, and delta antigen was found in specimens taken during autopsies on 7 of 9 patients. Serologic data suggested that most infections were due to delta superinfection of hepatitis B carriers, and that more than 60% of these infections progressed to chronic disease. Delta agent infection, and particularly delta superinfection of hepatitis B carriers, appears to be an ominous occurrence that may develop in populations among whom hepatitis B virus infection is endemic, and who have no other risk factor for delta infection.

Stimulated by observations in an outbreak of hepatitis delta-virus infection among Yucpa Indians in Venezuela, in which unusual histologic features were found, we studied 100 cases of fatal hepatitis from Colombia, South America, which had been obtained by autopsy or viscerotomy. These cases were considered to be "Santa Marta hepatitis," or "hepatitis of the Sierra Nevada de Santa Marta," which has been observed in this region for more than 40 years. Of the 100 cases, 19 had a variety of histologic lesions or were normal, and hepatitis delta-virus antigen was not demonstrated immunocytochemically in any of them. By contrast, 81 cases had a characteristic histologic picture with intense microvesicular steatosis associated with conspicuous eosinophilic necrosis of the hepatocytes, which apparently were sluggishly removed by cytolysis. Hepatitis delta-virus antigen was detected in 70% of the 81 cases, and the absence of detection of this antigen was often associated with poor tissue preservation and more extensive hepatocyte necrosis. A smaller percentage of patients had hepatitis B virus antigens detectable in liver tissue. The characteristic lesion in these 81 cases could be distinguished from other causes of microvesicular steatosis by the extensive eosinophilic necrosis. Other variable accompanying features included intraacinar, mainly macrophagic, scavenger cell inflammation, intense portal inflammation, a parenchymal regeneration, and ductular and arteriolar proliferation. Santa Marta hepatitis as a severe form of hepatitis delta-virus infection differs markedly from fulminant delta-hepatitis in Europe and the United States in which the microsteatosis with marked eosinophilic degeneration is not found. The causes for these differences are unknown but may relate to nutritional factors or environmental toxins.(ABSTRACT TRUNCATED AT 250 WORDS)

To supplement a detailed epidemiologic study of an outbreak of viral hepatitis in Venezuelan Indians in isolated valleys, apparently resulting from delta agent infection, 10 autopsy specimens were studied histologically and immunocytochemically, and five biopsy specimens were examined. The patients were children and young adults and predominantly males. A sequence of hepatitis from focal necrosis with conspicuous small-droplet steatosis, through massive necrosis, prolonged postnecrotic collapse to early cirrhosis with massive collapse was postulated. The histologic changes tentatively suggest a cytopathic effect of the delta agent without significant indication of lymphocytotoxicity, at least in the parenchyma. Delta agent was demonstrated in hepatocyte nuclei in moderate amounts in the focal-necrotic stage and in isolated cells in the massive-necrotic stage, but in large amounts during the transition to cirrhosis. Whether these patients, in whom neither HBcAg nor HBsAg were demonstrable in the liver, suffered exclusively from superinfection of hepatitis B virus carriers and/or coinfection of hepatitis B virus with the delta agent remains to be resolved. Delta infection may occur in isolated settings with no relation to Italian origin, drug addiction, or polytransfusion. The infection is far more widely spread than previously assumed.