An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.

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We measured antibody (anti-HCV) to hepatitis C virus, which causes non-A, non-B hepatitis, by radioimmunoassay in prospectively followed transfusion recipients and their donors. Of 15 patients with chronic non-A, non-B hepatitis documented by liver biopsy, all seroconverted for the antibody; of 5 with acute resolving non-A, non-B hepatitis, 3 (60 percent) seroconverted. The development of anti-HCV was delayed (mean delay, 21.9 weeks after transfusion, or 15 weeks after the onset of clinical hepatitis) and took approximately one year in one patient. Antibody has persisted in 14 of the 15 patients with chronic disease (mean follow-up, greater than or equal to 6.9 years; maximum, greater than or equal to 12), but has disappeared in the 3 with acute resolving disease after a mean of 4.1 years. Anti-HCV was detected in samples of donor serum given to 14 (88 percent) of the 16 anti-HCV-positive patients for whom all donor samples were available. Only 33 percent of the anti-HCV-positive donors tested had an elevated serum concentration of alanine aminotransferase; 54 percent were positive for antibody to the hepatitis B core antigen (anti-HBc). We conclude that hepatitis C virus is the predominant agent of transfusion-associated non-A, non-B hepatitis and that screening of donors for anti-HCV could prevent the majority of cases of the disease. "Surrogate" assays for anti-HBc and alanine aminotransferase would have detected approximately half the anti-HCV-positive donors involved in the transmission of hepatitis that we identified.

The hepatitis B virus-associated , antigen was found in the serum of experimentally infected chimpanzees as an internal component of a discrete subpopulation of hepatitis B surface antigen (HBsAg) particles. The 35-to 37-nm particles banded in CsCl at 1.24-1.25 g/cm3 and sedimented with a mobility intermediate between that of the hepatitis B virion and that of the 22-nm form of HBsAg. The particles contained only indistinct internal structure by electron microscopy and were not unique to 5 agent infection, similar particles without 5-antigen activity being observed in the preinfection serum of HBsAg carrier chimpanzees. A small RNA (Mr, 5 X 105) was temporally associated with 5 antigen in the serum of infected chimpanzees and copurified with the -antigen-associated particles. This RNA is smaller than the genomes of known RNA viruses but larger than the viroids of higher plants. The 3 antigen (6-Ag), a relatively new specificity, first was detected by immunofluorescence in the liver of human subjects with chronic hepatitis B surface antigen (HBsAg) hepatitis (1). Ultrastructural studies have failed to demonstrate components of hepatitis B virus (HBV) in b-Ag-positive nuclei (2) and the b-Ag-anti-b-Ag system is distinct from the known antigenantibody systems of HBV (3). Prevalence studies of b-Ag-anti-3-Ag in human populations (4,5) and transmission experiments in chimpanzees (6) indicate that b-Ag is associated with a transmissible pathogenic agent, 3 agent, that is either a HBV mutant with characteristics of a defective interfering particle or a new agent which requires helper functions of HBV for its expression.After extraction from hepatocyte nuclei with guanidine hydrochloride, b-Ag was characterized as a protein with a molecular weight of approximately 68,000 (2). Although b-Ag has not been detected in the sera of patients with intrahepatic b-Ag, such individuals develop high titers of anti-3-Ag which might interfere with the available solid-phase radioimmunoassay for b-Ag. The analysis of serial specimens from chimpanzees to which 3-agent was transmitted revealed 6-Ag in the sera during the acute phase of infection and prior to the development of anti-3-Ag (6). We report here the association of 3-Ag in serum with a discrete subpopulation of HBsAg and a low molecular weight RNA. MATERIALS AND METHODSSource of 5Ag. Two chronic HBsAg-carrier chimpanzees (nos. 29 and 800) were infected with 3 agent by inoculation with serum from a patient with chronic type B hepatitis and intrahepatic b-Ag. Serum samples and percutaneous liver biopsies were taken from each animal before inoculation and weekly thereafter and analyzed for markers of b-Ag and HBV. TheseThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 6124 chimpanzees were part of a transmission study of the 3 agent and experimental details are reported elsewhere (6). Serum samples containing b-Ag...

During the early phase of primary HCV infection, there is a period of several months of sero-negativity during which HCV RNA is the only diagnostic marker of infection. The disappearance of HCV RNA from serum appears to correlate with the resolution of non-A, non-B hepatitis, whereas viremia persists in patients whose disease progresses to chronic hepatitis. In contrast, antibody levels do not necessarily remain elevated in patients with chronic disease.

Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).

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The prevalence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is considerably lower in the U.S. than in Japan. To elucidate this difference, we determined the time origin of the HCV epidemic in each country by using molecularly clocked long-term serial samples obtained from HCV carriers of genotypes 1a and 1b. The molecular clock estimated that HCV genotype 1 first appeared in Japan in around 1882, whereas emergence in the U.S. was delayed until around 1910. In addition, by statistical analysis using coalescent theory, the major spread time for HCV infection in Japan occurred in the 1930s, whereas widespread dissemination of HCV in the U.S. occurred in the 1960s. These estimates of viral spread time are consistent with epidemiologic observations and predict that the burden of HCC in the U.S. will increase in the next two to three decades, possibly to equal that currently experienced in Japan.