Hepatitis delta virus infection and Labrea hepatitis. Prevalence and role in fulminant hepatitis in the Amazon Basin.

To define more exactly the epidemiology of delta virus infection and confirm its role in causing fulminant Labrea hepatitis in the Amazon Basin, we studied the prevalence of delta virus infection among persons with acute and chronic hepatitis B virus infection in the Boca do Acre district of the southern Amazon Basin. Delta virus infection was found in 24% of asymptomatic hepatitis B virus carriers, 29% of acute nonfulminant hepatitis B cases, 74% of fulminant hepatitis B cases, and 100% of chronic hepatitis B cases. Chronic delta virus infection occurred primarily in older children and adults, while acute and fulminant delta virus infection occurred in young children as well. In fulminant hepatitis cases, delta virus superinfection of hepatitis B virus carriers was the most common serological pattern; histopathologic examination showed features identical to those described in fulminant hepatitis cases of similar etiology in Colombia and Venezuela. Delta virus infection is highly endemic in the southern Amazon Basin and is the principal cause of Labrea hepatitis.

Specific histologic features of Santa Marta hepatitis: a severe form of hepatitis delta-virus infection in northern South America.

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)

Epidemiologic aspects of Santa Marta hepatitis over a 40-year period.

"Santa Marta" hepatitis has been recognized as an unusual type of severe hepatitis occurring in northern Colombia since 1930. Liver specimens from a historic viscerotomy series, used by Gast-Galvis to identify cases and describe epidemiologic features of this disease, were available for review and histopathologic staining for delta-virus. Of 86 liver specimens examined from cases of fulminant Santa Marta hepatitis, 81 showed a distinct histopathologic picture, in various stages of progression, with features of eosinophilic necrosis, microvesicular fat infiltration of the liver parenchyma and morula cells; 69% were positive for delta-antigen by immunoperoxidase staining. This disease occurred predominantly in several small towns within 50 km of Santa Marta, with mortality reaching 1.25 per 1,000 inhabitants per year during the 1940's. Children under age 15 were most commonly affected and males affected twice as frequently as females. Liver specimens obtained from children, or within 15 hr of death, or which showed early histologic stages of disease were most likely to be positive for delta-antigen. This and the accompanying study confirm the existence of a distinct type of fulminant hepatitis in Colombia for over 50 years. The epidemiologic and histopathologic features are comparable to severe hepatitis in Venezuela Indians and in the Amazon basin of Brazil, suggesting that all are caused by delta-superinfection of hepatitis B virus carriers.

Histologic studies of severe delta agent infection in Venezuelan Indians.

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.