The epidemiological patterns of hepatitis non-A, non-B

The etiological structure of viral hepatitides in three cities of the Volga region was studied. The proportion of hepatitis non A, non B was established: it varied from 3.6% to 18.1% at different territories and depended on the total morbidity level, on the season, as well as on the age of patients. A suggestion was made concerning the role of the parenteral mechanism of the transfer of hepatitis non A, non B at the territory under study.     

A cDNA clone closely associated with non-A, non-B hepatitis.

A lambda gt11 cDNA library was constructed from RNA purified from hepatitis B viral surface antigen-negative human plasma with high alanine aminotransferase activity. A cDNA clone, designated as C8-2, was isolated by immunoscreening with mixed sera from non-A, non-B hepatitis (NANBH) carrier and convalescent chimpanzees. The recombinant protein produced by C8-2 reacted specifically with sera of patients in the chronic phase of NANBH. The sequence of C8-2, 269 bp, did not hybridized with any human or chimpanzee genomic DNA, and had no homology with those of primates and viruses. The existence of this sequence in RNA of possibly infectious plasma was shown by RNA blot hybridization and by Southern blot analysis of products amplified by the polymerase chain reaction. These results strongly suggest that C8-2 is derived from the agent of this viral hepatitis.     

Lack of susceptibility of congenitally athymic nude mice to human non-A, non-B hepatitis

Nude mice were inoculated intravenously with chimpanzee serum containing a human non-A, non-b hepatitis agent. Control groups of nude mice were inoculated with normal saline or normal chimpanzee serum. During 77 days of observation, evidence of non-A, non-B hepatitis was not detected. Serum alanine aminotransferase levels remained within normal limits, and normal liver histology was seen in serially killed mice.     

Hepatitis non-A,non-B.

Evidence for the existence of hepatitis non-A, non-B includes epidemiologic data and results of transmission studies indicating the presence of hepatitis that could not be explained by known causative agents. The diagnosis is suggested in patients who have multiple episodes of acute hepatitis or who contract hepatitis after transfusion, hemodialysis or drug abuse. Sporadic cases are common. Three such cases are described to illustrate that the disease is clinically indistinguishable from hepatitis A or B. The diagnosis is based on the absence of serologic markers of hepatitis A and B and of infection by Epstein-Barr virus and cytomegalovirus, or on serologic evidence of previous infection with hepatitis A and B.     

Transmission of non-A, non-B hepatitis agent to chimpanzees from patients of epidemic hepatitis

Two chimpanzees were inoculated intravenously with acute-phase sera obtained from two patients with epidemic hepatitis. They developed histopathologically confirmed hepatitis. Electron microscopic examination of the liver showed peculiar cytoplasmic tubular structures in the hepatocytes. These ultrastructural findings were similar to those described for the livers of chimpanzees inoculated with the F strain of non-A, non-B hepatitis agent derived from a posttransfusion hepatitis case. The chimpanzee that had recovered from hepatitis caused by the F strain of non-A, non-B hepatitis agent was re-challenged with the serum from one of the patients. The chimpanzee developed neither clinical signs nor histological changes of hepatitis. These results suggested that non-A, non-B hepatitis agent was involved not only in post-transfusion hepatitis but also in epidemic hepatitis.     

Isolation of the novel agent from human stool samples that is associated with sporadic non-A, non-B hepatitis.

The agent(s) responsible for sporadic non-A, non-B hepatitis in humans was serially transmitted in rhesus monkeys by intravenous inoculation of the stool extract from a patient. A novel agent called HFV (hepatitis French [origin] virus) was present as 27- to 37-nm particles in the infectious stool extract. Hepatopathic lesions were noticed in infected monkeys during the acute phase of illness. The purified viral 27- to 37-nm particles consist of a double-stranded DNA of approximately 20 kb and are detected in infected monkey liver. Analysis of cell culture detects the approximately 20-kb-long viral DNA in stool samples from infected monkeys and sporadic enteric non-A, non-B hepatitis patients. Furthermore, the 27- to 37-nm viral particles were able to protect monkeys challenged with infectious stool extract. Our results indicate that 27- to 37-nm virus like particles are responsible for sporadic non-A, non-B hepatitis in rhesus monkeys.     

Ultrastructural alterations in serial liver biopsy specimens from chimpanzees experimentally infected with a human non-A, non-B hepatitis agent

Four chimpanzees experimentally infected with an agent of human non-A, non-B hepatitis were studied to determine the sequence of ultrastructural alterations in hepatocytes during infection. Three of the four types of cytoplasmic alterations previously described in association with non-A, non-B hepatitis were observed in the hepatocytes. Sponge-like cytoplasmic inclusions (designated C-I) were detected at or near the time of peak serum aminotransferase elevations in two of the four chimpanzees. Undulating membranes (designated C-II) were observed in all four chimpanzees, at the time of the first elevation of serum aminotransferase levels. Cytoplasmic tubules (designated C-III) were first observed four, eight, and twelve weeks, respectively, after inoculation in three of the chimpanzees. Four weeks after the peak of serum aminotransferase elevations, cytoplasmic alterations could no longer be detected in hepatocytes of the four chimpanzees. Intranuclear inclusions consisting of 20-27 nm granules and vermicular particles were observed in hepatocytes from preinoculation liver biopsy specimens, as well as biopsies obtained during non-A, non-B hepatitis. The number of these particles was greatest near the time of peak elevation of serum aminotransferase levels, however. Tubulo-crystalline inclusions were noted as well in the endothelial cells from both preinoculated and infected chimpanzees. Cytoplasmic alterations in hepatocytes of chimpanzees experimentally infected with an agent of non-A, non-B hepatitis appear characteristic of infection with this agent. In contrast, intranuclear particles were not specifically related to the non-A, non-B hepatitis infection.     

Epidemic focus of non-A, non-B viral hepatitis in a plasmapheresis unit]

Non-A, non-B hepatitis has been diagnosed in 12 blood donors in a plasmapheresis unit. The course of the disease has been symptomatic, accompanied by jaundice, fatigue, and nausea in 8 cases, and subclinical in the remaining 4 patients. Nine patients were followed-up to 2 years and only 2 patients liver biochemical tests were normalized permanently. The biopsies performed, a year after the acute phase of hepatitis period revealed chronic active disease in patients, chronic persistent hepatitis in 2 patients, acute hepatitis in one, and normal liver in one patient. Repeated liver biopsies, performed one year later, have basically shown similar lesions except one patient in whom chronic active hepatitis progressed to incipient liver cirrhosis. No symptoms of the disease have been usually noted in patients with chronic form of the disease, and liver function tests have occasionally been normal.     

The epidemiological problems of viral non-A, non-B hepatitis with a fecal-oral mechanism of infection transmission

The results of the study of the epidemiological regularities of viral hepatitis non-A, non-B with the fecal-oral mechanism of the transfer of infection in one of the regions of the Turkmenian SSR are presented. These results have been confirmed by serological and virological laboratory methods. The territories, groups of the population (age groups) and the time of the maximum epidemic risk of infection have been determined. The main (primary) role of the water route (polluted ground water) in the spread of this infection has been proved.     

Prevalence of hepatitis C virus antibody among healthy blood donors and non-A, non-B hepatitis patients in Thailand

With the antigen expressed in yeast from a cDNA clone encoding a non-structural region of newly discovered hepatitic C virus (HCV) genome, the prevalence of HCV antibody in people in Thailand was investigated. Antibody was detected in 2.6% of healthy blood donors and in 2.8% of healthy pregnant women. These prevalence rates were higher than those reported previously from Japan, USA and European countries. Among community-acquired, sporadic cases of acute and chronic non-A, non-B hepatitis, however, only 5.7% and 15.4% were shown to possess the antibody, respectively. Among hepatocellular carcinoma patients who were negative for hepatitis B surface antigen in the sera, 11.1% had antibody to HCV. These seroepidemiological data suggest that HCV plays an important role as an etiological agent in Thailand; however, other agents must also be involved in etiologic agents of viral hepatitis and chronic liver disease.