Hepatitis-associated antigen hepatitis. An electron microscopic study of virus-like particles in liver cells.

Light and electron microscopic examinations were carried out on liver tissues from 6 renal transplant recipients who developed Australia antigen-associated hepatitis, referred to in this paper as hepatitis-associated antigen (HAA) hepatitis. While under immunosuppressive therapy, the patients showed rapid progression of acute hepatitis to chronic active hepatitis and posthepatitic cirrhosis resulting in liver failure. By electron microscopy, in 5 of 6 patients, characteristic virus-like particles of 230 A size were observed in massive numbers in the nucleus and occasionally in the cytoplasm of liver cells. No similar particles were found in liver biopsies from other patients. These particles had an appearance of nucleocapsid without an outer coat, and were believed to be the viruses in their natural infective states. The predominantly intranuclear location of the particles and the associated nuclear changes suggested that the nucleus is the primary site of virus replication. The finding of the virus-like particles is believed to be diagnostic for HAA hepatitis. While HAA is implicated in serum hepatitis, the identification of HAA with the virus-like particles of this study is still to be established. In the phagosomes, there were some particles showing an outer membrane and a tail-like structure. Both the coated and the noncoated particles were believed to be the same virus. The phagosomes also contained what appeared to be "degradated" viral material. The lysosomal activity in the infected hepatitic cells seemed to be increased. This study showed nonspecific changes of the liver cell nuclei and organelles, probably related to viral infection. The precise mechanism of cell injury remains to be elucidated. However, the result of this study has provided a reasonable basis for future investigations of HAA hepatitis.