Histologic Studies of Severe Delta Agent Infection in Venezuelan Indians

Abstract

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.Six years ago in Italy, Rizzetto and coworkers (1) described the delta agent as a pathogenic factor complicating infection with hepatitis B virus (HBV). It is now thought to contain a small RNA genome surrounded by delta antigen and a coat of HBV surface antigen and to elicit a specific immune response which permits clinical diagnosis of delta infection. The delta agent requires coinfection with HBV for its replication which is associated with inhibition of synthesis of HBV markers. Delta antigen can be demonstrated immunohistochemically in hepatocellular nuclei (2, 3). Delta agent frequently occurs as a superinfection in HBV carriers with preexisting, sometimes minimal, degrees of histologic injury. In these persons, superinfection produces severe deterioration of the clinical and histologic picture often with fatal progression (4,5). Histologically, exacerbation

Treatment of hepatitis D

“…In four of these five patients, HBV infection converted to the typical productive pattern within a few weeks, and concurrently the histology changed to the classic necroinflammatory picture of viral hepatitis. These cytopathic changes which may accompany nonviral acute hepatitis syndromes such as fatty liver of pregnancy [53], Reye syndrome [54], and tetracycline and valproic acid toxicity [55], appear also to be a feature of human HDV infection, causing fulminant hepatitis in tropical areas [56]. In transplant recipients, this unusual histological pattern was associated with incomplete HBV synthesis, which presumably resulted from some inhibitory interaction of the HDV on the HBV replicative cycle.…”

Hepatitis B virus and hepatitis delta virus genotypes in outbreaks of fulminant hepatitis (Labrea black fever) in the western Brazilian Amazon region

“…Cases of fulminant hepatitis with similar features have been described in other countries in northern South America (Colombia, Venezuela, Peru and Ecuador) and in the Central African Republic. This severe form of liver disease has been identified as HBV and HDV super-or coinfection (Bensabath et al, 1987; Buitrago et al, 1986;Casey, 1996;Casey et al, 1996; Hadler et al, 1984;Lesbordes et al, 1987;Ljunggren et al, 1985;Manock et al, 2000;Popper et al, 1983;Sjogren & Colichon, 1991;Torres & Mondolfi, 1991).The disease associated with HDV infection is typically more severe than that due to HBV infection alone, but its clinical spectrum ranges from asymptomatic carriage of the virus to very severe disease. A factor that may influence the course of disease is the genetical heterogeneity of HDV prevalent in different geographical areas (Casey, 1996;Rizzetto & Durazzo, 1991;Smedile et al, 1982).…”

“…Cases of fulminant hepatitis with similar features have been described in other countries in northern South America (Colombia, Venezuela, Peru and Ecuador) and in the Central African Republic. This severe form of liver disease has been identified as HBV and HDV super-or coinfection (Bensabath et al, 1987;Buitrago et al, 1986;Casey, 1996;Casey et al, 1996;Hadler et al, 1984;Lesbordes et al, 1987;Ljunggren et al, 1985;Manock et al, 2000;Popper et al, 1983;Sjogren & Colichon, 1991;Torres & Mondolfi, 1991).…”

Liver and Bile Duct Infections

“…Liver specimens from an outbreak among Venezuelan Indians showed a range of histologic severity from diffuse small-droplet steatosis with focal necrosis in the earliest stages to confluent necrosis and, in the late stage, postnecrotic cirrhosis with massive collapse. 76 Immunohistochemistry in cases of hepatitis D demonstrates delta antigen in nuclei of hepatocytes, reduced or absent expression of HBcAg, but continued expression of HBsAg. [75][76][77]…”