Midzonal lesions in yellow fever: a specific pattern of liver injury caused by direct virus action and in situ inflammatory response. Med Hypotheses. 2006;67(3):618-21. Epub 2006 May 2.

Yellow fever is an acute infectious, non-contagious disease characterized by intense vasculopathy and lesions in different organs. In the liver, one of the main targets of the virus, the infection induces a characteristic midzonal injury characterized by hepatocyte necrosis, apoptosis and steatosis. This characteristics pattern of liver injury in yellow fever is also observed in conditions of low-flow hypoxia and other infections such as dengue and Rift Valley fever. There are no reports in the literature explaining the genesis of this peculiar histopathological pattern in yellow fever. Some hypotheses have been proposed to explain the mechanism of this midzonal distribution pattern observed in the liver such as low-flow hypoxia and tropism of the virus toward hepatocytes in this area. These hypotheses are discussed in view of more recent findings regarding the pathogenesis of yellow fever and regarding hepatic physiopathology, and a new hypothesis is proposed: the midzonal necrosis is consequence of action of combined factors mainly the direct cytopathic effect of YFV associated with a potent immune response in which CD4+ and CD8+ lymphocytes and the cytokines, especially TGF-beta, but also TNF-alpha and IFN-gamma play an important role.

Histopathology of the human liver in yellow fever with special emphasis on the diagnostic role of the Councilman body.Histopathology. 1983 Mar;7(2):195-208.

Liver specimens from 10 cases of yellow fever (YF) were studied by light and four by electron microscopy to review morphological aspects of the disease relevant to its diagnosis, with special emphasis on acidophilic bodies (AB) and on the possible presence of the virus within infected cells. The AB were compared with those found in 22 out of 69 liver specimens with other pathological processes. In YF the typical alteration was an acidophilic hepatocellular necrosis with a preferential midzonal distribution. Ceroid pigment was abundant, its amount was proportional to the degree of liver cell damage and it was found in altered hepatocytes and Kupffer cells in the most damaged areas. The inflammatory infiltrate was scanty, not only in portal tracts but also within the lobules. Electron microscopically, no viral particles were found in liver cells or AB. The latter appeared as round or elliptical cytoplasmic masses, surrounded by a conspicuous cellular membrane and densely packed with organelles, fat vacuoles and residual bodies. They differed from AB in other liver diseases by the presence of fat vacuoles and ceroid pigment. Some peculiarities of AB in other liver diseases such as presence of bile pigment and iron, would depend upon the presence of these pigments in the hepatocytes which originated them.