Liver enzyme levels, viral RNA, and the immune response against both structural and nonstructural hepatitis C virus (HCV) proteins have been studied in experimentally infected chimpanzees in order to further understand the natural history of HCV infection. An ELISA for measuring both IgG and IgM responses to core (c22), 33c (NS3), and c100 (NS4) was employed. The IgG response rates were 5/8 for core, and 8/8 for both 33c and c100. Utilizing this antigen combination, at least one antibody response is measureable at, or within 3 weeks of, the major ALT peak. Although no individual antibody response is universally associated with initial detection of seroconversion, the combination of all three recombinant proteins measures seroconversion an average of 54 days earlier than with c100 alone, in 6/8 of the animals. IgM responses were measureable in 5/8 of the chimpanzees, were of shorter duration, and usually arose concomitantly with IgG responses. IgM appears to be a good indicator of primary infection since neither boosting nor recrudescence of disease during the chronic phase of disease elicited a secondary IgM response. Viral RNA can be measured 4-7 days (average = 9 days) postinfection with the period preceding the ALT peak being characterized by several PCR positive segments interrupted by periods in which no viral RNA can be measured. Following the ALT peak, chronically infected animals with recurring ALT elevations are generally PCR positive with intercedent PCR negative periods. Those animals that appear to have biochemically resolved disease generally have PCR negative profiles, although they still may periodically exhibit PCR positive sera. This indicates that with the recent advent of new screening techniques, a more stringent definition of HCV resolution will be required.

We report the development of three rapid, fully automated immunoassays allowing the differential diagnosis of acute viral hepatitis. These assays detect HBsAg, IgM antibody to hepatitis B core antigen (IgM anti-HBc) and IgM antibody to hepatitis A virus (IgM anti-HAV) using the IMx instrument system. All IMx assays were run in less than 45 minutes and all steps were fully automated including specimen dilution steps. Specimens from blood donors, diagnostic and hospital patients, and individuals with a variety of infectious and immune diseases were tested for IgM anti-HAV (n = 1473) or for IgM anti-HBc (n = 1606) or for HBsAg (n = 9700) by the IMx and commercially available EIA and RIA. Each IMx assay showed 99.8% agreement with current EIA. Reproducibility in all hepatitis IMx assays was significantly better than that observed with manual or semiautomated assays; within-run and between-run % CV ranged from 2.2 to 4.8 and 3.5 to 10.3 respectively. In 29 acute hepatitis B patients studied, HBsAg and IgM anti-HBc were detected in the first available patient bleed collected from 0 to 4 week from the onset of symptoms. IgM anti-HBc persisted at reactive levels in the IMx assay for 1 to 24 weeks (mean 12.1 +/- 5.3 weeks) after the patient presented with symptoms. In individuals exposed to hepatitis A, IgM anti-HAV was detectable by IMx by 40 days post exposure (average 33.5 days) and IgM had declined to unreactive levels in IMx for all patients by from 3 to 6 months post exposure. These data demonstrate the use of these rapid IMx assays for differentiation of acute hepatitis A and B.

No abstract

could be attributed to hepatitis C infection. 5 Rarely, acute Patients presenting with clinical and laboratory feahepatitis E has been identified among U.S. or European patures consistent with a diagnosis of acute non-A, non-B tients with a history of recent travel to underdeveloped counhepatitis were evaluated for evidence of hepatitis C or tries. 6 Indeed, because first generation anti-HCV tests were hepatitis E infection and for evidence of severe or profrequently negative early in the course of hepatitis C infection longed disease. Antibody to hepatitis C virus (anti-HCV) and anti-HEV testing was not widely available, it seemed was detected in 75 of 108 (69%) patients, antibody to heppossible that nearly all cases of acute hepatitis in the U.S. atitis E virus (anti-HEV) in three patients (3%), and neicould be attributed to one of the known hepatitis viruses.7 ther antibody in 31 (29%) patients. One patient had both However, analysis of fulminant or subfulminant acute nonanti-HCV and anti-HEV. HCV RNA was not detected in A, non-B hepatitis at numerous institutions in the U.S. and sera from any of 20 patients with seronegative (nonEurope has suggested that the majority of such cases cannot ABCDE) hepatitis, but in all 10 patients with anti-HCV be attributed to hepatitis A, B, C, D, or E virus infections who were tested by polymerase chain reaction (PCR).(non-ABCDE). [8][9][10][11][12][13] In addition, acute non-A, non-B hepatitis Compared with patients with acute hepatitis C, those complicated by development of aplastic anemia is not associwith non-ABCDE hepatitis had a lower incidence of parated with evidence of hepatitis C infection. 14 More recently, enteral risk factors (6% vs. 70%; P õ .001), higher peak an additional flavivirus associated with human hepatitis has serum bilirubin levels (45% vs. 5% with peak levels ú15 been identified, 15-17 but this agent has been detected in only mg/dL; P õ .001), more prolonged jaundice (25% vs. 0% a small fraction of cases of acute non-A, non-B hepatitis. 17with peak bilirubin ú5 weeks after onset; P õ .01), more Previous reports of non-ABCDE hepatitis in the U.S. have severe prothrombin time abnormalities (26% vs. 0% with focused on populations of patients with unique or severe com-ú3 second prolongation; P õ .001), more severe hypoalplications of acute non-A, non-B hepatitis seen in tertiary buminemia (39% vs. 9% with albumin õ3 g/dL; P õ .01), care referral centers. 4,8,11,13,14 Because adult liver transand more frequent major clinical complications (13% vs.plantation is not performed in any of the hospitals within 0% with encephalopathy; P õ .01; 10% vs. 0% with death our university medical center, the vast majority of patients or transplant; P Å .024). Patients with acute non-ABCDE with acute hepatitis that are seen are either self-referred or hepatitis were less likely to develop chronic hepatitis referred from primary care physicians within our own instituthan those with acute hepatitis C (23% vs. 68%; P õ .05).tion and few have developed acute liver failure or...

As part of a project involving the labeling of the ribosomal proteins of the extreme halophile Halobacterium cutirubrum with 14C-lysine, the chemically defined medium of Gochnauer and Kushner (2) was modified to allow maximal incorporation of 14C-lysine. The utilization of the other amino acids present in this medium was also measured. Of special interest was the rapid and complete disappearance of arginine from the medium before the beginning of log-phase growth.