Seroprevalence of hepatitis C virus nucleocapsid antibodies in patients with cryptogenic chronic liver disease (original) (raw)
Related papers
Comparison of hepatitis C virus markers in patients with NANB hepatitis
Journal of Virological Methods, 1992
10 different HCV-specific assays and RT-PCR of the 5' untranslated region of HCV RNA were used to analyze sixty-four patients with chronic NANB liver disease. PO, CP-9 and C22 antigens are located in the putative core; C33c in the putative NS3; ClOO-3 in the putative NS3/4; KCL in the putative NS4/5 and C825 is located in the putative NS5. GOR protein is not part of the HCV genome, but antibodies to it appear to be present in response to a hepatitis C infection. Positive rates were 91% for PO, 89% for CP-9,94% for C22,97% for C33c, 88% for ClOO-3 (Ortho, EIA), 86% for ClOO-3 (Abbott, EIA), 84% for ClOO-3 (Ohtsuka, RIA), 88% for KCL, 59% for C825, 58% for GOR, and 83% for RT-PCR. There were 8 cases which were negative by all anti-Cl00 tests. 7 of these cases were positive by other anti-HCV markers and/or PCR suggesting the need for improved blood screening assays. There is a variation in the relative reactivity for different markers with different samples. Of the tests employed, anti C33c shows the highest positivity rate.
Update on hepatitis B and C virus diagnosis
World journal of virology, 2015
Viral hepatitis B and C virus (HBV and HCV) are responsible for the most of chronic liver disease worldwide and are transmitted by parenteral route, sexual and vertical transmission. One important measure to reduce the burden of these infections is the diagnosis of acute and chronic cases of HBV and HCV. In order to provide an effective diagnosis and monitoring of antiviral treatment, it is important to choose sensitive, rapid, inexpensive, and robust analytical methods. Primary diagnosis of HBV and HCV infection is made by using serological tests for detecting antigens and antibodies against these viruses. In order to confirm primary diagnosis, to quantify viral load, to determine genotypes and resistance mutants for antiviral treatment, qualitative and quantitative molecular tests are used. In this manuscript, we review the current serological and molecular methods for the diagnosis of hepatitis B and C.
Comparative evaluation of supplemental hepatitis C virus antibody test systems
…, 1992
Implementation of routine blood donor screening using anti-hepatitis C virus (HCV) enzyme immunoassay (EIA) has resulted in an ur ent need for well-characterized supplemental assays to confirm the presence of 8CV antibodies. A comparative study of four commercially available supplemental assays is reported here: first-and second-generation versions of a strip recombinant immunoblot assay (RIBA-1 and RIBA-2), an HCV neutralization EIA, and HCV neutralization plus synthetic peptide EIA. Three hundred sixty-seven blood donor specimens that were repeatedly reactive on HCV EIA were studied. Most specimens (93%) were also evaluated by radioimmunoassay (RIA) with a six-antigen panel, and 60 selected specimens were tested for HCV RNA by the polymerase chain reaction (PCR). RIBA-1 and RIBA-2 gave concordant results with 86 percent of specimens, while an additional 13 percent were correctly classified by RIBA-2 but not RIBA-1. Neutralization EIA alone correctly identified 94 percent of the study group, while the remaining 6 percent required the peptide EIA or the combined neutralization-peptide assay system for correct classification. The RIBA-2 and neutraiization-peptide assay systems yielded identical results for 86 percent of specimens, and these results were supported by RIA and selected PCR testing. Only 2 specimens (0.5%) were frankly discrepant, while 51 specimens were indeterminate on either (47) or both (4) assays. When either the RIBA-2 or neutralization-peptide.assay yielded an indeterminate interpretation, the other system correctly classified the specimen (based on concordance with RIA and PCR data) in a high proportion (92%) of cases. The overall high degree of concordance between RIBA-2 and neutralization-peptide assays, as well as the correlating RIA and PCR results, supports the validity and utility of these supplemental anti-HCV test systems. TRANSFUSION 1992;32:408-414.
Viral markers in the treatment of hepatitis B and C
Gut, 1993
Acute hepatitis B virus (HBV) infection is typically distinguished from chronic disease by a positive IgM anti-hepatitis B core antigen (anti-HBc) test. Patients with chronic hepatitis B remain hepatitis B surface antigen (HBsAg) positive, often with raised serum alanine aminotransferase (ALT) activities, for more than six months. The presence of hepatitis B e antigen (HBeAg) and HBV-DNA correlates with infectivity (although patients infected with the pre-core mutated virus may be HBeAg negative). Immunity after HBV infection is characterised by the presence of anti-HBs and anti-HBc antibodies. Patients who respond to interferon alfa treatment lose HBV-DNA and HBeAg from serum and their ALT values return to normal; some also lose HBsAg and acquire anti-HBs. Diagnosis of acute hepatitis C virus (HCV) infection remains largely dependent on history and exclusion, as anti-HCV antibodies may appear late or never at all, although HCV-RNA may be detectable on polymerase chain reaction (PCR) within days of infection. Second generation ELISAs detect a range of anti-HCV antibodies in chronic infections, and confirmatory RIBAs have reduced the incidence of false-positive results. Direct tests for HCV antigens in serum are not yet available, although PCR testing for HCV-RNA can be used to confirm viraemia. Patients who respond to interferon alfa treatment show continuous normalisation of serum ALT values, and some lose HCV-RNA. Relapse occurs in about half of all those who respond.
Non-A, Non-B Hepatitis and the Anti-HCV Assay
Vox Sanguinis, 1991
The successful cloning of a non-structural antigen from the genome of what is now designated as the 'hepatitis C virus' (HCV) has transformed an erstwhile diagnosis of exclusion for non-A, non-B hepatitis (NANBH). The assay has been validated against panels of known infectivity for NANBH and sera from haemophiliac patients treated either with virally inactivated or uninactivated factor VIII. The predictive value of the assay is being assessed clinically in prospective studies of post-transfusion hepatitis and by using laboratory techniques such as polymerase chain reaction. While the assay shows good predictability in high-risk subjects, an appreciable number of false-positive results are likely in blood donor populations. Furthermore, the extent of infectivity of seropositive blood donors is still the subject of active research. The prevalence of anti-HCV in blood donors varies from approximately 0.2 to 1.5% around the world, based on repeat reactivity in the Ortho antiglobulin ELISA assay. These rates may be appreciably reduced following supplementary testing with recombinant immunoblot assay (RIBA). Prevalence data in African sera are as yet unreliable, pending assessment by RIBA, presumably because of high levels of IgG interfering with the assay. Presence of anti-HBc or elevated alanine aminotransferase associates to a greater or lesser extent with seropositivity, especially when both surrogate markers are present, but conversely many (unconfirmed) seropositive subjects lack these surrogate markers. An understanding of the modes of transmission of HVC is of obvious importance to transfusion practice. Intravenous drug use is a striking risk factor, but the contribution made by sexual transmission is not so clear. Results with the highly innovative anti-HCV assay represent the first dramatic 'ranging shots' to hit the target of NANBH, albeit at the periphery. Some of the various limitations of this expensive assay and associated supplementary tests are likely to be resolved by the advent of improved tests based on other HCV antigens, including structural ones. Hopefully, they will produce results closer to the centre of the target.
The value of identifying hepatitis C virus in liver pathology specimens
Hepatology, 1996
THE VALUE OF IDENTIFYING HEPATITIS C positive after an ''open window phase'' variable in time from a few days to many months and are therefore, VIRUS IN LIVER PATHOLOGY SPECIMENS rarely helpful in the diagnosis of acute hepatitis C. Nouri-Aria KT, Sallie R, Mizokami M, Portmann BC, Third, despite their increasing sensitivity and specific-Williams R. Intrahepatic expression of hepatitis C viity, these tests are still hampered by false-negative and rus antigens in chronic liver disease. J Pathol false-positive results. Thus, the more sensitive method 1995;175:77-83. to assess viremia is based on the detection of amplified HCV-RNA sequences using the polymerase chain reac-ABSTRACT tion (PCR). PCR methods are extremely complex and must be performed under carefully controlled condi-Localization of hepatitis C virus (HCV) antigens was tions. Even in highly specialized research laboratories studied in fresh frozen and formalin-fixed, paraffin-emfalse-positive and false-negative results have been docbedded liver tissue by immunoperoxidase using monoclonal antibodies to nucleocapsid protein and polyclonal umented, and great caution is to be observed in dealing human immunoglobulin G purified from plasma conwith PCR tests. 1 Fourth, PCR-negative serum does not taining antibodies to structural and non-structural antiexclude infection, because HCV-RNA has been obgens of hepatitis C virus. The results observed using served in liver tissue of serum HCV-RNA-negative pamonoclonal antibody to HCV core were similar to those tients. 2 This is particularly crucial for the diagnosis of of polyclonal IgG against HCV antigens in the majority HCV infection and in the evaluation of viral clearance of cases and both correlated well with HCV status as after treatment. Fifth, the pathogenesis of liver injury defined by 'nested' polymerase chain reaction. HCV anti
Viral Immunology, 1993
The detection of antibody to the hepatitis C virus C100-3 antigen from the nonstructural region (NS3/NS4) of the viral genome was the first useful marker developed to detect past or potentially active infection with the hepatitis C virus. A systematic epitope survey of the nonstructural region has uncovered other immunogenic antigens. In order to assess the possible diagnostic utility of these antigens, their reactivity against a limited panel of sera from patients with chronic liver disease due to hepatitis C virus and other etiologies was tested. Antibody assays were performed using an immunoblot plaque assay and an enzyme-linked immunosorbent assay (ELISA). In a study of 16 C100-3-reactive individuals, all 16 patients were reactive using the plaque assay for the NS3 3' (409-1-1) and NS3 5' (C33u). In this same group of patients, antibodies by ELISA were reactive to NS3 3' in 12 of 16 patients (75%), NS3 5' in 15 of 16 patients (93%), and a capsid antigen (NC450) in 14 of 16 patients. In a group of five patients who were diagnosed with cryptogenic liver disease (C100-3 negative), 4 of 5 patients were reactive for antibody to all of the above epitopes. In a survey of 23 patients with other forms of chronic liver disease (nonviral liver disease, hepatitis B, alcoholic liver disease, cholestatic liver disease, and autoimmune hepatitis), only 1 of 23 patients was reactive for antibody to the C100-3 and 4 of 23 patients were reactive for antibodies to structural and nonstructural regions of the virus. The addition of other immunoreactive antigens to those already included in the available first generation test may result in further improvements in serological screening for present or past hepatitis C virus infection. Following the identification, cloning, and expression of proteins from the hepatitis C virus (HCV) in 1989 (5), an enzyme-linked immunosorbent assay (ELISA) that detected antibodies to the C100-3 antigen from HCV was developed and later licensed for clinical use (16). The C100-3 antigen is a protein that spans the third and fourth putative nonstructural regions (NS3 and NS4) of the HCV. This first generation antibody test has
Hepatitis C virus: Screening, diagnosis, and interpretation of laboratory assays
Asian Journal of Transfusion Science, 2014
An estimated 3% of the world population is infected with Hepatitis C virus (HCV), a hepatotropic RNA virus, transmitted primarily via the blood route. The major modes of transmission of the virus include injection drug use, unsafe injection practices, blood transfusion etc. HCV causes chronic hepatitis in about 80% of those infected by it. The mainstay in diagnosing infection with HCV is to initially screen high risk groups for antibodies to HCV (anti-HCV). The inclusion of serum to cutoff ratio (S/CO) in recent guidelines is helpful in deciding the supplemental assay to be used to confirm initially reactive screening results. Nucleic acid amplification tests (NAT) are used as confirmatory tools, and also to determine viral load prior to initiating treatment. Quantitative NAT has replaced qualitative assays. Genotyping is an important tool in clinical management to predict the likelihood of response and determine the optimal duration of therapy. The impact of this infection has begun to emerge in India. The problem of professional blood donation despite an existing law against it, and flourishing unsafe injection practices, are potential sources for the spread of hepatitis C in our country. All health care practitioners need to understand how to establish or exclude a diagnosis of HCV infection and to interpret the tests correctly. In the absence of a preventive or therapeutic vaccine, and also of post-exposure prophylaxis against the virus, it is imperative to diagnose infection by HCV so as to prevent hepatic insult and the ensuing complications that follow, including primary hepatocellular carcinoma (HCC). This review aims to help blood bank staff regarding options for diagnosis and management of donors positive for HCV.
Trends in Immunolabelled and Related Techniques, 2012
In the mid-1970s, a new disease entity termed 'non-A, non-B' (NANB) hepatitis was first described and, in the following years, led to discovery of the causative virus, posttransfusion, and to community-acquired NANB hepatitis increasingly becoming recognized as a potentially serious disease that results in liver cirrhosis and/or hepatocellular carcinoma. 16, 26 Hepatitis C virus (HCV) was first identified in 1989 using molecular methods at the Chiron Corporation, but to date, the virus has never been visualized or grown in cell culture. 37 Hepatitis C virus (HCV) is a single-stranded RNA virus with a genome of about 10 000 nucleotides containing a single large, continuous open reading frame and with organization most closely resembling the Flaviviridae. 11 HCV is a global healthcare problem and the World Health Organization (WHO) estimates that at least 170 million people (3 % of the world's population) are infected with HCV worldwide and most of the patients are concentrated in developing countries. 48 HCV Proteins. HCV proteins may be divided in two groups: Structural proteins and nonstructural proteins. Structural Proteins: The nucleocapsid proteins (core), two envelope glycoproteins (E1 and E2), and a small transmembrane protein p7. E2 likely mediates cell entry by binding to one ore more specific cellular receptors or coreceptors, and has also been suggested to interact with and inhibit interferon-inducible protein kinase R (PKR). 26 P7 may function as a viroporin. Non-structural proteins (NS): NS2, NS3, NS4 (A, B), NS 5 (A, B). NS2 may exist an E2p7NS2 processing intermediate due to inefficient signal peptidase cleavages at the E2-p7 and p7-NS2 junctions. NS2 has also been reported to coimmunoprecipitate. Other functions of NS2 are uncertain. NS3 has serine protease/helicase activity and a multifunctional protein. NS4A is associated with membranes. NS4B is important for RNA replication. It has a GTPase acitivity that is important RNA in replication. NS5B has RNA-depndent RNA polymerase activity resulting in initiating in-vitro RNA synthesis both primer dependent and independent. Anti-HCV reactives manufactured from these group of proteins. 4, 15, 35 Organization of the HCV genome and polyprotein processing presented in Figure 1. 26 www.intechopen.com 1. Indirect tests: (Anti-HCV and Strip immunoblot assays).