Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: application to diagnosis and blood screening for posttransfusion hepatitis.

Abstract

A cDNA clone has been derived from the plasma of a chimpanzee with chronic non-A, non-B viral hepatitis (NANBH). We have assayed for antibodies reacting with the encoded antigen in sera from posttrnnsfusion hepatitis patients (643 samples from 23 patients) and their corresponding donors collected during the past 10 years in Japan. The antibody was detected in 15 out of 17 (88.2%) posttransfusion NANBH (PT-NANBH) patients whose sera over time displayed multiple alanine aminotransferase (ALT) peaks. In general, the antibody was detected after several peaks of serum ALT elevations and, once detected, it persisted for years. In contrast to the patients of chronic hepatitis, the antibody was barely detected in patients with a single episode of ALT elevation (1 out of 6). Of the 15 well-dermed cases of PT-NANBH that showed multiple ALT peaks and hepatitis C virus seroconversions, 11(73.3%) were shown to be transfused with at least one unit of blood positive for the antibody. The retrospective analysis showed that all tested donor blood found to be positive for the antibody had been transfused to recipients who afterwards developed NANBH. These data strongly suggest that the cloned cDNA originated from an etiological agent of NANBH termed the hepatitis C virus. Furthermore, the present study demonstrates that had the screening been done with the anti-hepatitis C virus assay, 11 out of 17 (64.7%) cases of chronic PT-NANBH and 1 out of 6 (16.6%) acute PT-NANBH would have been prevented. The antibody assay thus can be used for diagnosis and blood screening for PT-NANBH.Even though donor blood is routinely screened for the hepatitis B virus (HBV) with sensitive assays, about 10% of blood transfusion recipients still develop viral hepatitis (refs. 1 and 2; T.K., unpublished data). Non-A, non-B hepatitis (NANBH) virus(es) is responsible for over 90%o of the posttransfusion hepatitis (PTH) cases and causes a serious health problem throughout the world. NANBH is much more likely to become chronic than HBV-induced hepatitis and often progresses to chronic liver disease, including liver cirrhosis (3, 4). A role for NANBH in the development of hepatocellular carcinoma has also been suggested (5, 6).The genome of a NANBH virus, termed hepatitis C virus (HCV), was cloned recently and shown to contain a positivestranded RNA molecule (7). An assay for circulating viral antibodies was developed by using an HCV antigen purified from recombinant yeast clones to capture reactive antibodies. Results obtained using this assay indicated that HCV is a major cause of transfusion-associated NANBH throughout the world as well as community-acquired NANBH in which no previous parenteral exposure to the virus could be identified (8).In this study, we assayed for HCV antibody in wellpedigreed transfusion-associated NANBH patients in Japan. The serum samples were from patients diagnosed on the basis of clinical presentation in the absence of markers indicating infection with HBV and hepatitis A virus (HAV).-The recipient sera were a series ...

High titers of antibodies inhibiting the binding of envelope to human cells correlate with natural resolution of chronic hepatitis C

“…Patients were from St. Marianna Hospital, Kawasaki, Kanagawa; Tokyo National Chest Hospital, Kiyose, Tokyo; and Shinshu University School of Medicine, Nagano. 12,13 Informed consent was obtained from all patients, and the study had the approval of the Ethical Committees of the hospitals. To study the natural history of acute non-A non-B hepatitis, serial sera samples had been collected over many years and maintained at Ϫ20°C.…”

“…11 This assay is used as a surrogate test to estimate the level of HCV-neutralizing (NOB) antibodies. Here we report on the serum antibody responses to HCV structural proteins in a rare group of patients who spontaneously resolved chronic hepatitis C. 12,13 We have found that the appearance and maintenance of high serum titers of NOB antibodies in the course of chronic hepatitis C is accompanied by virus clearance and clinical resolution of liver disease.…”

Comparison of Hepatitis C Virus Strains Obtained From Hemodialysis Patients

“…The cloning of the genome of this causal agent was recently accomplished and the virus was named as hepatitis C virus (HCV) (3). The subsequently established assay, detecting antibodies against core and nonstructural protein of HCV, has revealed that HCV is the major cause of posttransfusion-as well as sporadic community-acquired non-A, non-B hepatitis (4,5). A close relationship between HCV infection and the development of hepatocellular carcinoma (HCC) has also been suggested (6,7).…”

High Prevalence of Hepatitis C Virus Infection in Aborigines in Taiwan

“…In the meantime, the epidemiological status of hepatitis C virus (HCV) infection is similar to other areas of the world, with 0.8% prevalence among adult volunteer donors and high prevalences among intravenous drug users, hemodialysis patients, cases positive for antibodies to human immunodeficiency virus, patients with chronic liver disease, and female prostitutes, determined with anti-C100 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). However, all these data were obtained with the descendants of those having immigrated from the mainland China and been living in the developed plain region of western Taiwan since several hundred yeas ago, and no data concerning the aboriginal ethnic tribes residing in the underdeveloped mountain regions of this island have been obtained.…”