Toga virus-like particles in acute liver failure attributed to sporadic non-A, non-B hepatitis and recurrence after liver transplantation.

Toga virus-like particles (typically 60-70 nm: enveloped with small surface spikes) were detected in the native hepatectomy specimens in 7 of 18 patients grafted for acute liver failure attributed to sporadic non-A, non-B hepatitis and in 2 patients grafted for fulminant hepatitis attributed to anti-epileptic drug hepatotoxicity. These particles were not detected in the hepatectomies from 12 other patients grafted for other causes of acute liver failure, 12 for various chronic liver diseases, and 2 histologically normal livers. Acute hepatic failure, characterized histologically by severe haemorrhagic necrosis, developed 7 days after grafting in 5 patients, all in the non-A, non-B group with toga virus-like particles in native liver. Similar virus-like particles were detected in all grafts and were in greater abundance than in the native livers. The agent may be novel because pre- and post-grafting sera were negative for antibodies against representative panels of arboviruses and in first and second generation antibody tests for hepatitis C virus.

Toga-like virus as a cause of fulminant hepatitis attributed to sporadic non-A, non-B.

Virus-like particles (60-70 nm) with spiked surfaces budding into cell vacuoles and rod-shaped inclusions were detected in nuclei of hepatocytes from a British patient transplanted for sporadic non-A, non-B fulminant hepatitis (NANB-FHF), probably contracted in Kenya. Identical particles were seen in two successive grafts (days 2 and 10) at regrafting for recurrent FHF. Ultrastructural features resembled those of the RNA-containing arbovirus, Rift Valley fever virus, but serological markers against a representative panel for arboviruses (Togaviruses) and transmission in mice proved negative. The particles shared features with the different arboviruses seen in the hepatectomy specimen of a second patient with NANB-FHF, and in both patients an insect vector was implicated in the clinical history. The particles were identical in size to those of a third patient with NANB-FHF, who had remained in the United Kingdom. These findings, together with the recent report of isolation of an RNA-containing virus resembling the Togaviridae, in parenteral NANB, suggest that several exotic virus-like agents resembling the arboviruses may be involved in the aetiology of NANB, including in the sporadic forms of FHF in the United Kingdom.

Viruslike particles in liver in sporadic non-A, non-B fulminant hepatitis.

In a patient who followed the typical clinical course of fulminant hepatitis attributable to "sporadic" non-A,non-B (NANB) hepatitis and who finally received treatment by orthotopic liver grafting, three, apparently separate, virus-like agents (26, 45, and 80 nm) and cytoplasmic, reticular tubular structures (CTS) were identified in collapsed and regenerating areas of liver using electron microscopy. The 80-nm particles present within vacuoles, together with the finding of intranuclear rods in association with the smaller particles (26 nm), are similar to those found in the nuclei of cells infected with several different arboviruses. The third type of particle, existing as 45-nm spheres and rods, is similar in morphology only to some form of polyoma virus, which, hitherto, has not been reported as affecting the liver. Unlike typical polyoma virus, replication of the virus "cores" (25-26 nm) was extranuclear and appeared to be occurring in vacuoles. Although analysis for serological markers against a representative panel for arboviruses, flaviviruses, phleboviruses, arenavirus, and nairovirus was negative, an insect vector was implicated in the clinical history.

Microbial structures in a patient with sporadic non-A, non-B fulminant hepatitis treated by liver transplantation.

Double-shelled virus-like particles (60 nm) and long cytoplasmic tubular structures were found in the cytoplasm of hepatocytes from areas of collapsed and regenerating areas of hepatectomised liver in a 13-year-old boy who received a liver graft for fulminant hepatitis attributed to sporadic non-A, non-B hepatitis. The patient died on the ninth postoperative day from acute graft failure. Although virus-like particles were not found, instead, gram-negative rods were identified in the necrotic graft and the most likely cause of death was a gram-negative septicaemia with a Shwartzman-like reaction localized to the liver.