|
1
|
Li Y, Yang HS, Klasse PJ, Zhao Z. The significance of antigen-antibody-binding avidity in clinical diagnosis. Crit Rev Clin Lab Sci 2025; 62:9-23. [PMID: 39041650 DOI: 10.1080/10408363.2024.2379286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 06/07/2024] [Accepted: 07/09/2024] [Indexed: 07/24/2024]
Abstract
Immunoglobulin G (IgG) and immunoglobulin M (IgM) testing are commonly used to determine infection status. Typically, the detection of IgM indicates an acute or recent infection, while the presence of IgG alone suggests a chronic or past infection. However, relying solely on IgG and IgM antibody positivity may not be sufficient to differentiate acute from chronic infections. This limitation arises from several factors. The prolonged presence of IgM can complicate diagnostic interpretations, and false positive IgM results often arise from antibody cross-reactivity with various antigens. Additionally, IgM may remain undetectable in prematurely collected samples or in individuals who are immunocompromised, further complicating accurate diagnosis. As a result, additional diagnostic tools are required to confirm infection status. Avidity is a measure of the strength of the binding between an antigen and antibody. Avidity-based assays have been developed for various infectious agents, including toxoplasma, cytomegalovirus (CMV), SARS-CoV-2, and avian influenza, and are promising tools in clinical diagnostics. By measuring the strength of antibody binding, they offer critical insights into the maturity of the immune response. These assays are instrumental in distinguishing between acute and chronic or past infections, monitoring disease progression, and guiding treatment decisions. The development of automated platforms has optimized the testing process by enhancing efficiency and minimizing the risk of manual errors. Additionally, the recent advent of real-time biosensor immunoassays, including the label-free immunoassays (LFIA), has further amplified the capabilities of these assays. These advances have expanded the clinical applications of avidity-based assays, making them useful tools for the diagnosis and management of various infectious diseases. This review is structured around several key aspects of IgG avidity in clinical diagnosis, including: (i) a detailed exposition of the IgG affinity maturation process; (ii) a thorough discussion of the IgG avidity assays, including the recently emerged biosensor-based approaches; and (iii) an examination of the applications of IgG avidity in clinical diagnosis. This review is intended to contribute toward the development of enhanced diagnostic tools through critical assessment of the present landscape of avidity-based testing, which allows us to identify the existing knowledge gaps and highlight areas for future investigation.
Collapse
Affiliation(s)
- Yaxin Li
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - He S Yang
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - P J Klasse
- Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA
| | - Zhen Zhao
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| |
Collapse
|
|
2
|
Owusu DO, Phillips R, Owusu M, Sarfo FS, Frempong M. Increased levels of circulating IL-10 in persons recovered from hepatitis C virus (HCV) infection compared with persons with active HCV infection. BMC Res Notes 2020; 13:472. [PMID: 33028385 PMCID: PMC7542684 DOI: 10.1186/s13104-020-05313-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 09/28/2020] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE Approximately 70% of all hepatitis C (HCV) infections develop chronic disease. Active or exacerbated chronic hepatitis C infection subsequently progress to liver disease. The role of T-cells secretions in achieving viral clearance is still not well understood. Thus, the current study was set to determine the relationship between the T cell cytokine profiles, biochemical parameters and persistent HCV infection or spontaneous recovery. RESULTS Twenty-five percent (41/163) of the anti-HCV positive participants had recovered from HCV and had significantly higher concentration of IL-10 compared to those with active HCV infection (P < 0.012). Other circulating cytokines measured; IL-2, IFN gamma, TNF alpha, IL-5 and IL-17 were similar in both groups. Participants with active HCV infection had significantly higher aspartate transaminase (AST) (35 units) and alanine transaminase (46 units) compared to those in the recovered state (P < 0.001). Thus, serum levels of IL10 could be explored in larger prospective cohort study as a predictive marker of recovering from an active HCV infection.
Collapse
Affiliation(s)
- Dorcas Ohui Owusu
- Department of Medical Laboratory Technology, Garden City University College (GCUC), P.O. Box 12775, Kumasi, Ghana.
| | - Richard Phillips
- Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kwame Nkrumah University of Science and Technology (KNUST), PMB, KNUST, Kumasi, Ghana
| | - Michael Owusu
- Department of Medical Diagnostics, Kwame Nkrumah University of Science and Technology (KNUST), University Post Office, Kumasi, Ghana
| | - Fred Stephen Sarfo
- Department of Medicine, Komfo Anokye Teaching Hospital, Kwame Nkrumah University of Science and Technology, University Post Office, Kumasi, Ghana
| | - Margaret Frempong
- Department of Molecular Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| |
Collapse
|
|
3
|
Shepherd SJ, McDonald SA, Palmateer NE, Gunson RN, Aitken C, Dore GJ, Goldberg DJ, Applegate TL, Lloyd AR, Hajarizadeh B, Grebely J, Hutchinson SJ. HCV avidity as a tool for detection of recent HCV infection: Sensitivity depends on HCV genotype. J Med Virol 2017; 90:120-130. [PMID: 28843002 DOI: 10.1002/jmv.24919] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 08/15/2017] [Indexed: 12/26/2022]
Abstract
Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as ≥250 IU/mL). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR = 0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (≥52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognized.
Collapse
Affiliation(s)
- Samantha J Shepherd
- West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, Glasgow, Scotland, UK
| | - Scott A McDonald
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, Scotland, UK.,Health Protection Scotland, Glasgow, Scotland, UK
| | | | - Rory N Gunson
- West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, Glasgow, Scotland, UK
| | - Celia Aitken
- West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, Glasgow, Scotland, UK
| | - Gregory J Dore
- Kirby Institute, University of New South Wales, Sydney, Australia
| | - David J Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, Scotland, UK.,Health Protection Scotland, Glasgow, Scotland, UK
| | | | - Andrew R Lloyd
- Kirby Institute, University of New South Wales, Sydney, Australia
| | | | - Jason Grebely
- Kirby Institute, University of New South Wales, Sydney, Australia
| | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, Scotland, UK.,Health Protection Scotland, Glasgow, Scotland, UK
| |
Collapse
|
|
4
|
Pondé RADA. The serological markers of acute infection with hepatitis A, B, C, D, E and G viruses revisited. Arch Virol 2017; 162:3587-3602. [PMID: 28884240 DOI: 10.1007/s00705-017-3538-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Accepted: 12/20/2016] [Indexed: 12/19/2022]
Abstract
Viral hepatitis is a liver infection caused by one of the six hepatitis viruses: hepatitis A, B, C, D, E, and G virus (HAV to HEV and HGV). These agents differ in their biological, immunological, pathological and epidemiological characteristics. They cause infections that, when symptomatic, lead to clinical manifestations and laboratory findings that are not specific to a particular virus, often making differential diagnosis difficult, especially when no knowledge is available regarding the patient's medical history or the epidemiological background. A number of acute-phase serological markers, such as anti-HAV, anti-HBc, anti-HDV and anti-HEV IgM antibodies, are able to provide a clear indication of an infection caused by HAV, HBV, HDV or HEV. Anti-HCV antibodies and HGV/RNA are used for the diagnosis of HCV and HGV infections. The importance of each of these markers will be reviewed, and different factors that can interfere with the diagnosis of acute infections caused by these viruses will be described.
Collapse
Affiliation(s)
- Robério Amorim de Almeida Pondé
- Laboratory of Human Virology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goiânia, Goiás, Brazil. .,Secretaria Estadual de Saúde -SES/Superintendência de Vigilância em Saúde-SUVISA/GO, Gerência de Vigilância em Saúde-GVE/Coordenação de Análises e Pesquisas-CAP, Goiânia, Goiás, Brazil. .,Faculdade União de Goyazes-FUG (College Union of Goyazes), Department of Hematology and Clinical Microbiology, Trindade, Goiás, Brazil. .,, Rua 136 Qd F44 Lt 22/24 Ed. César Sebba - Setor Sul, Goiânia, Goiás, 74-093-250, Brazil.
| |
Collapse
|
|
5
|
Salminen T, Juntunen E, Khanna N, Pettersson K, Talha SM. Anti-HCV immunoassays based on a multiepitope antigen and fluorescent lanthanide chelate reporters. J Virol Methods 2015; 228:67-73. [PMID: 26615808 DOI: 10.1016/j.jviromet.2015.11.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 11/05/2015] [Accepted: 11/06/2015] [Indexed: 02/06/2023]
Abstract
There is a need for simple to produce immunoassays for hepatitis C virus (HCV) antibody capable of detecting all genotypes worldwide. Current commonly used third generation immunoassays use three to six separate recombinant proteins or synthetic peptides. We have developed and expressed in Escherichia coli a single recombinant antigen incorporating epitopes from different HCV proteins. This multiepitope protein (MEP) was used to develop two types of HCV antibody immunoassays: a traditional antibody immunoassay using a labeled secondary antibody (indirect assay) and a double-antigen assay with the same MEP used as capture binder and labeled binder. The secondary antibody assay was evaluated with 171 serum/plasma samples and double-antigen assay with 148 samples. These samples included an in-house patient sample panel, two panels of samples with different HCV genotypes and a seroconversion panel. The secondary antibody immunoassay showed 95.6% sensitivity and 100% specificity while the double-antigen assay showed 91.4% sensitivity and 100% specificity. Both assays detected samples from all six HCV genotypes. The results showed that combining a low-cost recombinant MEP binder antigen with a high sensitivity fluorescent lanthanide reporter can provide a sensitive and specific immunoassay for HCV serology. The results also showed that the sensitivity of HCV double-antigen assays may suffer from the low avidity immune response of acute infections.
Collapse
Affiliation(s)
- Teppo Salminen
- Department of Biotechnology, University of Turku, Turku, Finland.
| | - Etvi Juntunen
- Department of Biotechnology, University of Turku, Turku, Finland
| | - Navin Khanna
- Recombinant Gene Products Group, International Centre for Genetic Engineering & Biotechnology, Aruna Asaf Ali Marg, New Delhi, India; Translational Health Science & Technology Institute, NCR Biotech Science Cluster, Faridabad, India; Department of Paediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Kim Pettersson
- Department of Biotechnology, University of Turku, Turku, Finland
| | - Sheikh M Talha
- Department of Biotechnology, University of Turku, Turku, Finland
| |
Collapse
|
|
6
|
Villar LM, Cruz HM, Barbosa JR, Bezerra CS, Portilho MM, Scalioni LDP. Update on hepatitis B and C virus diagnosis. World J Virol 2015; 4:323-42. [PMID: 26568915 PMCID: PMC4641225 DOI: 10.5501/wjv.v4.i4.323] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 09/25/2015] [Accepted: 10/23/2015] [Indexed: 02/05/2023] Open
Abstract
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.
Collapse
|
|
7
|
Coppola N, Pisaturo M, Sagnelli C, Onorato L, Sagnelli E. Role of genetic polymorphisms in hepatitis C virus chronic infection. World J Clin Cases 2015; 3:807-822. [PMID: 26380828 PMCID: PMC4568530 DOI: 10.12998/wjcc.v3.i9.807] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Revised: 12/09/2014] [Accepted: 06/08/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC).
METHODS: We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.
RESULTS: Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation.
CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.
Collapse
|
|
8
|
Li HC, Lo SY. Hepatitis C virus: Virology, diagnosis and treatment. World J Hepatol 2015; 7:1377-1389. [PMID: 26052383 PMCID: PMC4450201 DOI: 10.4254/wjh.v7.i10.1377] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/22/2014] [Accepted: 04/02/2015] [Indexed: 02/06/2023] Open
Abstract
More than twenty years of study has provided a better understanding of hepatitis C virus (HCV) life cycle, including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviral treatments. At present, serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the likelihood of response. In the early 2000s, pegylated interferon plus ribavirin became the standard anti-HCV treatment. However, this therapy is not ideal. To 2014, boceprevir, telaprevir, simeprevir, sofosbuvir and Harvoni are approved by Food and Drug Administration for the treat of HCV infections. It is likely that the new all-oral, interferon-free, pan-genotyping anti-HCV therapy will be available within the next few years. Majority of HCV infections will be cured by these anti-viral treatments. However, not all patients are expected to be cured due to viral resistance and the high cost of antiviral treatments. Thus, an efficient prophylactic vaccine will be the next challenge in the fight against HCV infection.
Collapse
|
|
9
|
Abstract
Liver-related biomarkers have been developed and validated mainly in patients with chronic hepatitis C for the prediction of liver fibrosis or cirrhosis, which is a final pathway of chronic liver injury. They are noninvasive, traceable, and easy-to-use. Biomarkers provide implications related to screening, diagnosis, treatment, and prognosis of chronic hepatitis. For the improvement of performance and coverage, biomarker panels, imaging biomarkers, and even genetic biomarkers have been developed. With the advancement of genomics and proteomics, earlier and more precise prediction is expected in the near future. In this review, multiple biomarker panels for the estimation of the degree of fibrosis in chronic hepatitis C, biomarkers for the screening and diagnosis of hepatitis C, biomarkers for the treatment of hepatitis C, biomarkers for the prediction of complications related to the chronic hepatitis C, and future perspectives will be summarized.
Collapse
Affiliation(s)
- Seung Ha Park
- Department of Internal Medicine, Inje University College of Medicine, Busan, South Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea.
| |
Collapse
|
|
10
|
Establishment of an antibody avidity test to differentiate vaccinated cattle from those naturally infected with Mycoplasma bovis. Vet J 2014; 203:79-84. [PMID: 25467991 DOI: 10.1016/j.tvjl.2014.10.032] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 10/08/2014] [Accepted: 10/11/2014] [Indexed: 01/13/2023]
Abstract
Mycoplasma bovis is a major pathogen of bovine respiratory disease (BRD) in China and a live attenuated vaccine has recently been developed. This study aimed to establish an IgG avidity test to differentiate between naturally infected and vaccinated animals. An indirect ELISA (iELISA) was first established in the laboratory to detect antibodies specific to M. bovis using whole cell proteins as coating antigens and serum samples from experimentally infected cattle. The specificity and sensitivity of the iELISA was confirmed using a commercial ELISA kit as a reference standard. Both tests showed substantial agreement as indicated by a κ value of 0.78 (95% confidence interval, CI, 0.62, 0.93), and an overall 92.0% (80/87) agreement between the two tests. Based on the laboratory iELISA, a sodium thiocyanate (NaSCN) competitive iELISA was then developed for the detection of IgG avidity, expressed as relative avidity index (AI). Two-hundred and one experimentally immunised and naturally infected animals were used. These comprised 36 immunised calves, 38 negative control calves, 37 naturally infected calves, 87 calves of unknown status, and an additional three immunised calves that were used for a time trial. By testing true positive and negative antisera from either naturally infected or immunised calves, the AI cut-off value was defined as 70.4%. The diagnostic accuracy of the in-house NaSCN competitive iELISA was determined using serum samples collected from the experimental animals. The IgG avidity test demonstrated 96.0% sensitivity (95% CI 80.5%, 99.3%) and 95.8% specificity (95% CI 79.8%, 99.3%), and was successfully established as a valuable first test for differentiating vaccinated animals from those infected with M. bovis. This test may be a useful tool for clarifying the magnitude of M. bovis infection and in assessing the efficacy of vaccination in exposed animal populations.
Collapse
|
|
11
|
Gentile I, Buonomo AR, Zappulo E, Coppola N, Borgia G. GS-9669: a novel non-nucleoside inhibitor of viral polymerase for the treatment of hepatitis C virus infection. Expert Rev Anti Infect Ther 2014; 12:1179-86. [PMID: 25096404 DOI: 10.1586/14787210.2014.945432] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) is an RNA virus that chronically infects 2-3% of the world's population. About 25% of these chronic carriers evolve towards liver cirrhosis, a disease that is significantly associated with reduced survival and quality of life. Antiviral therapy can eradicate the infection - a process that is associated with a reduced disease progression rate. Several oral direct agents have been developed and tested for the treatment of HCV infection. This review focuses on the mechanism of action, pharmacokinetics, efficacy, safety and resistance of GS-9669, a non-nucleoside inhibitor of viral polymerase, active against HCV genotype 1. In combination with other oral antivirals, GS-9669 results: in very high rates of viral eradication (90-100%) in patients with HCV genotype 1 infection, with a good tolerability and safety profile. In conclusion, GS-9669 is a good candidate to be used in interferon-free combinations for the treatment of chronic HCV infection.
Collapse
Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples 'Federico II', via S. Pansini 5,I-80131 Naples, Italy
| | | | | | | | | |
Collapse
|
|
12
|
Sagnelli E, Santantonio T, Coppola N, Fasano M, Pisaturo M, Sagnelli C. Acute hepatitis C: clinical and laboratory diagnosis, course of the disease, treatment. Infection 2014; 42:601-610. [PMID: 24619833 DOI: 10.1007/s15010-014-0608-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 02/24/2014] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Acute hepatitis C (AHC) is asymptomatic in about 70-80 % of cases and, therefore, is usually undiagnosed. Although the clinical course is typically mild, AHC has a high rate of transition to chronicity. MATERIAL AND METHODS We evaluated the literature data concerning risk factors for HCV transmission, diagnosis, natural history, and antiviral treatment of AHC. RESULTS Although new methods have been developed, anti-HCV seroconversion remains the gold standard for the diagnosis of AHC. This phenomenon, however, is identifiable in less than half of cases in the everyday clinical practice, since most AHC patients do not know their previous anti-HCV/HCV-RNA status. An early short-term interferon treatment in AHC patients prevents progression to chronicity in most of treated patients. CONCLUSION The literature data give evidence of the clinical relevance of an early diagnosis of AHC for an early short-term interferon treatment. There is also the suggestion to use newly developed laboratory methods to distinguish AHC from an acute exacerbation of a chronic HCV infection.
Collapse
Affiliation(s)
- E Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, via L. Armanni, No. 3, 80135, Naples, Italy,
| | | | | | | | | | | |
Collapse
|
|
13
|
Gentile I, Buonomo AR, Borgia G. Ombitasvir: a potent pan-genotypic inhibitor of NS5A for the treatment of hepatitis C virus infection. Expert Rev Anti Infect Ther 2014; 12:1033-43. [PMID: 25074011 DOI: 10.1586/14787210.2014.940898] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) chronically infects about 150,000,000 people worldwide and is a relevant cause of liver cirrhosis, hepatocellular carcinoma and death. Antiviral treatment is rapidly moving from interferon (IFN)-based therapy to IFN-free approaches. This review focuses on the mechanism of action, pharmacokinetics, efficacy, tolerability, safety and resistance of ombitasvir, which is an inhibitor of the HCV nonstructural protein 5A. The pharmacokinetics of ombitasvir enables its once daily administration. In vivo, in combinations with other oral direct acting antivirals, ombitasvir achieves very high rates of sustained virological response (about 95%) in patients with HCV genotype 1 infection with a good tolerability. Resistance profiling revealed a low barrier to resistance when given as monotherapy. However, coadministration of ombitasvir and other antivirals enhances its barrier to resistance. In conclusion, ombitasvir is a good drug to be used in IFN-free combinations for the treatment of chronic hepatitis C.
Collapse
Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", via S. Pansini 5, I-80131 Naples, Italy
| | | | | |
Collapse
|
|
14
|
Gentile I, Buonomo AR, Zappulo E, Minei G, Morisco F, Borrelli F, Coppola N, Borgia G. Asunaprevir, a protease inhibitor for the treatment of hepatitis C infection. Ther Clin Risk Manag 2014; 10:493-504. [PMID: 25061308 PMCID: PMC4079632 DOI: 10.2147/tcrm.s66731] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
According to the World Health Organization, approximately 150 million people worldwide are chronic carriers of hepatitis C virus (HCV). HCV infection can evolve into cirrhosis of the liver and its complications, which are ultimately responsible for more than 350,000 deaths every year. Antiviral therapy, when successful, is able to decrease the rate of progression and increase survival. Two types of therapies are currently available, ie, interferon-based therapies and interferon-free ones. The latter have several advantages in terms of safety and tolerability, and could be used even in the most advanced stages of the disease. However, their use is restricted to some viral genotypes (genotype 2 and 3) and they are expensive. Several molecules are in an advanced phase of development. This review deals with the pharmacokinetics, pharmacodynamics, tolerability, and safety of asunaprevir, an inhibitor of HCV nonstructural 3 protease. Asunaprevir exerts optimal in vitro activity particularly against HCV genotypes 1 and 4, and its pharmacokinetic profile enables twice daily administration. The drawback of asunaprevir, and of all protease inhibitors, is its low barrier to resistance. Consequently, it is used in association with other drugs to prevent resistance. Specifically, when combined with daclatasvir, an NS5A inhibitor, asunaprevir results in a very high rate of viral eradication in both treatment-naïve and treatment-experienced patients, with a sustained virological response rate of 80%-90%. Tolerability is fair; in fact, asunaprevir is associated with a transient increase in aminotransferase levels, which is mild in most cases. In conclusion, asunaprevir is a good candidate component of interferon-free combinations and may revolutionize the treatment of chronic HCV infection in the near future.
Collapse
Affiliation(s)
- Ivan Gentile
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Antonio Riccardo Buonomo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Emanuela Zappulo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Giuseppina Minei
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Filomena Morisco
- Section of Gastroenterology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Francesco Borrelli
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Nicola Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy
| | - Guglielmo Borgia
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| |
Collapse
|
|
15
|
Sagnelli E, Sagnelli C, Pisaturo M, Coppola N. Hepatic flares in chronic hepatitis C: spontaneous exacerbation vs hepatotropic viruses superinfection. World J Gastroenterol 2014; 20:6707-6715. [PMID: 24944463 PMCID: PMC4051912 DOI: 10.3748/wjg.v20.i22.6707] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 01/13/2014] [Accepted: 04/01/2014] [Indexed: 02/06/2023] Open
Abstract
The hepatitis C virus (HCV) causes an acute infection that is frequently asymptomatic, but a spontaneous eradication of HCV infection occurs only in one-third of patients. The remaining two-thirds develop a chronic infection that, in most cases, shows an indolent course and a slow progression to the more advanced stages of the illness. Nearly a quarter of cases with chronic hepatitis C (CHC) develop liver cirrhosis with or without hepatocellular carcinoma. The indolent course of the illness may be troubled by the occurrence of a hepatic flare, i.e., a spontaneous acute exacerbation of CHC due to changes in the immune response, immunosuppression and subsequent restoration, and is characterized by an increase in serum aminotransferase values, a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment. A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses, namely hepatitis B virus (HBV), HBV plus hepatitis D virus, hepatitis E virus, cytomegalovirus, particularly in geographical areas with high endemicity levels. The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.
Collapse
|
|
16
|
Gentile I, Coppola N, Buonomo AR, Zappulo E, Borgia G. Investigational nucleoside and nucleotide polymerase inhibitors and their use in treating hepatitis C virus. Expert Opin Investig Drugs 2014; 23:1211-23. [PMID: 24848437 DOI: 10.1517/13543784.2014.921680] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION About 150 million people worldwide are estimated to be chronically infected with the hepatitis C virus (HCV). Successful antiviral treatment can stop the progression of the disease toward liver cirrhosis, hepatocellular carcinoma and death. IFN has been the drug of choice and the backbone of all combinations in the past two decades. However, an IFN-free combination (sofosbuvir and ribavirin) has been recently approved for genotypes 2 and 3 patients with many other drugs in preclinical and clinical development. AREAS COVERED This review focuses on investigational nucleoside or nucleotide inhibitors of viral polymerase that are potential treatments of HCV. The article reviews drugs that are currently under investigational status. EXPERT OPINION Currently, mericitabine has the most robust data but its efficacy appears to be less than optimal. Other drugs such as ALS-2200 (and its diastereomer VX-135) and BMS-986094 are promising but the data in humans are too scanty to draw conclusions about their future role at this current point in time. Other promising molecules are LG-7501, ACH-3422 and EP-NI266, although no clinical studies have been performed thus far, so this must be rectified. Another drug of promise GS-6620 has displayed a high degree of pharmacokinetic and pharmacodynamic variability, which makes further development unlikely.
Collapse
Affiliation(s)
- Ivan Gentile
- University of Naples "Federico II", Department of Clinical Medicine and Surgery , via S. Pansini 5, I-80131 Naples , Italy +39 0 81 7463083 ; +39 0 81 7463190 ;
| | | | | | | | | |
Collapse
|
|
17
|
Gentile I, Zappulo E, Buonomo AR, Borgia G. Prevention of mother-to-child transmission of hepatitis B virus and hepatitis C virus. Expert Rev Anti Infect Ther 2014; 12:775-82. [PMID: 24840817 DOI: 10.1586/14787210.2014.920254] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
About 240 million people worldwide are chronically infected with hepatitis B virus (HBV). Vertical transmission is the most important mechanism of infection persistence in endemic areas. About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). Mother-to-child transmission of HCV, which occurs in 3-10% of cases, is the leading route of infection in childhood. This review focuses on strategies to reduce the vertical transmission of HBV and HCV. The at-birth prophylaxis of newborns of HBV-infected mothers with specific immunoglobulin and vaccine plus administration of antivirals (tenofovir or telbivudine) in the third trimester of pregnancy (in case of high maternal viral load) greatly reduces the risk of transmission. In contrast, currently there is no drug able to reduce the vertical transmission of HCV infection. We discuss the possibility of reducing mother-to-child HCV transmission using newly available antivirals or antivirals in the pipeline for the treatment of hepatitis C.
Collapse
Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", via S. Pansini 5, Naples, Italy
| | | | | | | |
Collapse
|
|
18
|
Gentile I, Buonomo AR, Borgia F, Zappulo E, Castaldo G, Borgia G. MK-5172 : a second-generation protease inhibitor for the treatment of hepatitis C virus infection. Expert Opin Investig Drugs 2014; 23:719-28. [PMID: 24666106 DOI: 10.1517/13543784.2014.902049] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Approximately 170 million people worldwide are chronic carriers of the hepatitis C virus (HCV). Twenty-five percent of them develop liver cirrhosis and hepatocellular carcinoma during their life. Successful antiviral treatment dramatically reduces the risk of disease progression. HCV infection is treated with pegylated interferon and ribavirin; the addition of a protease inhibitor (boceprevir or telaprevir) can also be considered for patients with genotype 1. AREAS COVERED This review summarizes the data about the pharmacokinetics, pharmacodynamics, efficacy and safety of MK-5172 , a second-generation inhibitor of HCV NS3/4A protease. EXPERT OPINION The pharmacokinetic profile allows for once-a-day administration. Combined with pegylated interferon and ribavirin, MK-5172 results in a high rate of HCV eradication (in about 90% of cases) and a better outcome than boceprevir-based triple therapy. Also in interferon-free combinations, MK-5172-associated eradication rates are very high (89 - 100%). MK-5172 has a higher barrier to resistance than first-generation protease inhibitors and is active against most variants associated with resistance to first-generation protease inhibitors. Tolerability and safety profile are good. Although data are limited, MK-5172 appears to overcome most of the drawbacks of the first-generation protease inhibitors and is thus a very promising agent to be used in combination with other antivirals to eradicate HCV infection.
Collapse
Affiliation(s)
- Ivan Gentile
- University of Naples "Federico II", Department of Clinical Medicine and Surgery (Ed. 18) , via S. Pansini 5, I-80131 Naples , Italy +39 0 81 7463178 ; +39 0 81 7463190 ;
| | | | | | | | | | | |
Collapse
|
|
19
|
Gentile I, Buonomo AR, Borgia F, Castaldo G, Borgia G. Ledipasvir: a novel synthetic antiviral for the treatment of HCV infection. Expert Opin Investig Drugs 2014; 23:561-71. [DOI: 10.1517/13543784.2014.892581] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
|
|
20
|
Ciotti M, D’Agostini C, Marrone A. Advances in the Diagnosis and Monitoring of Hepatitis C Virus Infection. Gastroenterology Res 2013; 6:161-170. [PMID: 27785248 PMCID: PMC5051090 DOI: 10.4021/gr576e] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/03/2013] [Indexed: 12/18/2022] Open
Abstract
Hepatitis C virus (HCV) infection represents a major health problem worldwide. Approximately 350,000 people die every year from hepatitis C related diseases. Antiviral therapy is given to prevent such complications. Advances in serological and molecular assays greatly improved the diagnosis of hepatitis C virus infection and the management of chronically infected patients. Sensitive real-time PCR methods are currently used to monitor the response to antiviral therapy, to guide treatment decisions, and to assess the sustained virological response 24 weeks after the end of therapy. HCV genotyping is part of the pretreatment evaluation. Determination of HCV genotype is important both for tailoring antiviral treatment and for determining treatment duration. It predicts also response to therapy. With the recent introduction of the serine protease inhibitors telaprevir and boceprevir, approved for the treatment of genotype 1 chronic hepatitis C in combination with INF-a and ribavirin, subtyping has become clinically relevant. Indeed, subtypes 1a and 1b may respond differently to current telaprevir-based or boceprevir-based triple therapy. This review summarizes the most recent advances in the diagnosis and monitoring of HCV chronic infection.
Collapse
Affiliation(s)
- Marco Ciotti
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81-00133, Rome, Italy
| | - Cartesio D’Agostini
- Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy
- Laboratory of Clinical Microbiology and Virology, Polyclinic “Tor Vergata” Foundation, Viale Oxford 81, 00133, Rome, Italy
| | - Aldo Marrone
- Internal Medicine and Hepatology, School of Medicine of Naples, Second University of Naples, Via Pansini 5, Edificio 10, 80131, Napoli, Italy
| |
Collapse
|
|
21
|
Sagnelli E, Pisaturo M, Stanzione M, Messina V, Alessio L, Sagnelli C, Starace M, Pasquale G, Coppola N. Clinical presentation, outcome, and response to therapy among patients with acute exacerbation of chronic hepatitis C. Clin Gastroenterol Hepatol 2013; 11:1174-1180.e11. [PMID: 23591280 DOI: 10.1016/j.cgh.2013.03.025] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Revised: 03/12/2013] [Accepted: 03/28/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The slow asymptomatic progression of chronic hepatitis C (CHC) can be interrupted by an acute exacerbation, characterized by increased serum levels of alanine aminotransferase (ALT) and bilirubin and other symptoms of acute hepatitis. We aimed to provide more information about the clinical presentation of acute exacerbation of CHC. METHODS We identified 82 consecutive patients, from 2 locations in Italy, who had an acute exacerbation of CHC from January 2005 through June 2010; we followed them up for a median period of 36 months. These cases were hepatitis C virus (HCV) RNA positive, hepatitis B surface antigen-negative, and had not received anti-HCV therapy. They were matched with 82 subjects with hepatitis C without reactivation for age, sex, and HCV genotype (controls). Sixty-nine cases and 73 controls were followed up for at least 2 years. Liver biopsy specimens had been taken from 23 cases and 31 controls-once before enrollment in the study and once during the follow-up period. RESULTS HCV genotype 2 was detected in 46.4% of cases, and HCV genotype 1 was detected in 43.9%. Among cases, the mean ALT level was 1063 ± 1038 IU/dL, and the mean total bilirubin level was 15.87 ± 7.15 mg/dL. A higher percentage of cases carried the interleukin-28B CC genotype than controls (40.2% vs 24.4%; P < .05). Among cases, 43.5% had a steady increase in ALT level (>2-fold baseline value); for 56.5% of these patients, ALT levels returned to baseline values before the acute exacerbation of chronic hepatitis. Based on comparisons of biopsy specimens, 18 cases (78.3%) and 11 controls (35.5%) had increasing fibrosis, with Ishak scores increasing by more than 2 (P < .005); 14 cases (60.9%) and 3 controls (9.6%) had increases in necroinflammation of more than 2 points (P < .005). Thirty-two cases (46.4%) and 38 controls (52%) received treatment with pegylated interferon and ribavirin; a sustained virologic response was achieved in 26 cases (81.2%) and 23 controls (60.5%). CONCLUSIONS Although an acute exacerbation of chronic hepatitis is a serious medical condition, most patients achieve a sustained virologic response after treatment with pegylated interferon and ribavirin.
Collapse
Affiliation(s)
- Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
22
|
Shepherd SJ, Kean J, Hutchinson SJ, Cameron SO, Goldberg DJ, Carman WF, Gunson RN, Aitken C. A hepatitis C avidity test for determining recent and past infections in both plasma and dried blood spots. J Clin Virol 2013; 57:29-35. [PMID: 23369886 DOI: 10.1016/j.jcv.2013.01.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Revised: 11/26/2012] [Accepted: 01/03/2013] [Indexed: 12/17/2022]
Abstract
BACKGROUND DBS testing has been used successfully to detect HCV antibody positive individuals. Determining how long someone has been infected is important for surveillance initiatives. Antibody avidity is a method that can be used to calculate recency of infection. OBJECTIVES A HCV avidity assay was evaluated for both plasma and DBS. STUDY DESIGN To measure antibody avidity a commercial HCV ELISA was modified using 7 M urea. The plasma samples were split into: group 1 (recently infected N = 19), group 2 (chronic carrier N = 300) and group 3 (resolved infection N = 82). Mock DBS made from group 1 (N = 12), group 2 (N = 50), group 3 (N = 25) and two seroconverter panels were evaluated. 133 DBS taken from patients known to have a resolved infection or be a chronic carrier were also tested. RESULTS The avidity assay cut-off was set at AI≤30 for a recent infection. Using sequential samples the assay could detect a recent infection in the first 4-5 months from the point of infection. Most of the false positive results (AI < 30 among cases known not to have had recent infection) were detected among known resolved infections, in both the plasma and DBS; as a result, a testing algorithm has been designed incorporating both PCR and two dilution factors. The sensitivity and specificity of the assay on plasma was 100% and 99.3%, respectively, while DBS had 100% sensitivity and 98.3% specificity. CONCLUSION The HCV avidity assay can be used to distinguish between chronic and recent infection using either plasma or DBS as the sample type.
Collapse
Affiliation(s)
- Samantha J Shepherd
- West of Scotland Specialist Virology Centre, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, United Kingdom.
| | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Sagnelli E, Tonziello G, Pisaturo M, Sagnelli C, Coppola N. Clinical applications of antibody avidity and immunoglobulin M testing in acute HCV infection. Antivir Ther 2012; 17:1453-1458. [PMID: 23322703 DOI: 10.3851/imp2471] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2012] [Indexed: 12/13/2022]
Abstract
Acute hepatitis C is often asymptomatic, frequently remains undiagnosed and frequently evolves to chronic hepatitis. Early, short-term interferon treatment is efficacious in acute hepatitis C, and so underscores the importance of an early diagnosis and the need to distinguish acute infection from acute exacerbation of chronic HCV infection. The gold standard for the diagnosis of acute hepatitis C is demonstration of conversion to anti-HCV positivity, HCV RNA positivity or both, events that frequently occur before the patient comes to medical attention. Several laboratory approaches to assist with early diagnosis of acute hepatitis C have been developed. Our studies, reviewed here, show that testing for antibody avidity and anti-HCV immunoglobulin M allow diagnosis in up to 90% of cases of acute hepatitis C.
Collapse
Affiliation(s)
- Evangelista Sagnelli
- Department of Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy.
| | | | | | | | | |
Collapse
|
|
24
|
Hajarizadeh B, Grebely J, Dore GJ. Case definitions for acute hepatitis C virus infection: a systematic review. J Hepatol 2012; 57:1349-60. [PMID: 22796896 DOI: 10.1016/j.jhep.2012.07.007] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2012] [Revised: 07/03/2012] [Accepted: 07/05/2012] [Indexed: 01/18/2023]
Abstract
BACKGROUND & AIMS Case definitions for recent hepatitis C virus (HCV) infection vary considerably between studies. The aim of this systematic review was to characterize case definitions for recent HCV and explore the heterogeneity in studies performed to date. METHODS A systematic literature search of MEDLINE, SCOPUS, and ISI Web of Knowledge was performed covering all studies of recent HCV infection cited between January 2000 and June 2011. The criteria used by each study to define cases of recent HCV infection were extracted, structured, and analyzed. RESULTS Overall, 195 articles were included, with 87% (n=169) providing a clear case definition for recent HCV infection. The most frequently used individual criteria for defining a case included HCV antibody seroconversion (77%), alanine aminotransferase (ALT) elevation (68%), and HCV RNA detection (63%). In studies using HCV antibody seroconversion, the window period between the last negative and the first positive antibody test varied widely across studies (4 weeks to 4 years). Considerable diversity was also observed with respect to the ALT threshold used to characterize ALT elevations, ranging from 2 to 20 times the upper limit of normal. HCV antibody seroconversion was used as a single criterion in 41% of the studies, while all other studies used at least two criteria (range: 2-9). Epidemiology/surveillance studies mostly used a more sensitive case definition, whereas treatment studies, natural history studies, and diagnosis studies used more specific case definitions. CONCLUSIONS Marked heterogeneity in case definitions for recent HCV infection was observed. Although a single case definition for recent HCV is not warranted, a degree of standardization within specific study categories would enable improved cross-study comparison and more uniform evaluation of HCV prevention and management strategies.
Collapse
Affiliation(s)
- Behzad Hajarizadeh
- Viral Hepatitis Clinical Research Program, The Kirby Institute, The University of New South Wales (UNSW), Sydney, NSW, Australia.
| | | | | |
Collapse
|
|
25
|
Acute hepatitis C in HIV-infected individuals: recommendations from the European AIDS Treatment Network (NEAT) consensus conference. AIDS 2011; 25:399-409. [PMID: 21139491 DOI: 10.1097/qad.0b013e328343443b] [Citation(s) in RCA: 116] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
|
|
26
|
Abstract
Approximately 200 million people are chronically infected with hepatitis C virus (HCV). Infection with HCV is curable by therapy, with the current standard treatment based on the combination of pegylated interferon-α and ribavirin. Viral eradication is achieved in approximately half of treated patients. In 2011 a new antiviral treatment based on a triple combination with a protease inhibitor will become available. Virological tools are essential to diagnose HCV infection but they have found their principal application in guiding treatment decisions and assessing the virological responses to therapy. These include the anti-HCV antibody assay, measurements of HCV core antigen and HCV viral load and HCV genotyping. The HCV RNA can be ideally assayed by a real-time assay with a limit of detection of 10-15 IU/mL. Monitoring of viral kinetics during the early phases of antiviral treatment is crucial in making treatment decisions such as early stopping rules and also in optimizing the treatment duration. The HCV genotype should be assessed before the start of treatment because it determines the treatment length and ribavirin dose and also offers prognostic information on treatment outcomes as certain genotypes respond more favourably to treatment.
Collapse
Affiliation(s)
- S Chevaliez
- French National Reference Centre for Viral Hepatitis B, C and delta, Department of Virology & INSERM U955, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
| |
Collapse
|
|
27
|
Use of an anti-hepatitis C virus (HCV) IgG avidity assay to identify recent HCV infection. J Clin Microbiol 2010; 48:3281-7. [PMID: 20610669 DOI: 10.1128/jcm.00303-10] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
There is no reliable and simple diagnostic marker available to diagnose recent hepatitis C virus (HCV) infection. It has been shown that the avidity of specific IgG antibody is low in primary viral infection and increases with time. We report the development of an anti-HCV avidity assay derived from a commercially available test. A panel of 117 sera was first examined for IgG avidity. It was composed of samples from patients with recent (group 1, n = 14), chronic (group 2, n = 70), and resolved (group 3, n = 33) HCV infections. Avidity index (AI) values observed in recently infected patients were significantly lower (12.0% +/- 9.2% [mean +/- standard deviation]) than those found in chronic carriers (83.1% +/- 15.2%). Using a threshold of 43.0%, this assay distinguished between groups 1 and 2 with very high sensitivity (98%) and specificity (100%). For group 3, a broader distribution of the AI values was observed (54.8% +/- 27.3%), suggesting that this index would not be useful in HCV RNA-negative patients. Blind validation of the test was carried out with a panel of 36 serum samples from 17 HCV seroconverters. The assay described here is a useful tool to distinguish recent from chronic infection in HCV-viremic patients.
Collapse
|
|
28
|
Abstract
Hepatitis C virus infection is a global health problem that has important epidemiological and clinical consequences. It has been well established that exposure to infected blood is the main risk factor for HCV transmission. However, in 20% of cases the agent transmission occurs by unknown route or in the presence of an unidentified source of infection. Understanding of the epidemiology of HCV is needed to help us define future control and preventive strategies. Herein, we discuss about diagnosis of HCV infection and hepatitis C surveillance in the context of its transmission.
Collapse
|
|
29
|
Coppola N, Pisapia R, Tonziello G, Masiello A, Martini S, Pisaturo M, Messina V, Sagnelli C, Macera M, Signoriello G, Sagnelli E. Improvement in the aetiological diagnosis of acute hepatitis C: a diagnostic protocol based on the anti-HCV-IgM titre and IgG Avidity Index. J Clin Virol 2009; 46:222-229. [PMID: 19758839 DOI: 10.1016/j.jcv.2009.08.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2009] [Revised: 08/12/2009] [Accepted: 08/13/2009] [Indexed: 01/21/2023]
Abstract
BACKGROUND The gold standard for the diagnosis of acute hepatitis C (AHC) is seroconversion to anti-HCV/HCV-RNA positivity, an occurrence frequently missed in clinical practice. OBJECTIVES This study aims to diagnose AHC by the combined use of the HCV Avidity Index (HCV-AI) and HCV-IgM titre. STUDY DESIGN We enrolled 45 patients with AHC diagnosed by seroconversion to anti-HCV/HCV-RNA positivity and 36 with exacerbation of chronic hepatitis C (e-CHC) diagnosed at least 1 year earlier. HCV-IgM titres were determined by a commercial enzyme-linked immunosorbent assay (ELISA) and HCV-AI by an ELISA for detection of HCV IgG with a partial modification. For each test, specific cut-off values at four selected checking points were established during the observation (<10 days, 11-15 days, 16-20 days and >20 days from the onset of symptoms): for the HCV-IgM assay, the highest value in e-CHC +5% and for HCV-AI assay, the lowest value in e-CHC -5%. RESULTS Around 90% of patients with AHC or e-CHC were correctly diagnosed at all checking points by combining the results of both tests. This practice afforded an improvement in sensitivity for the diagnosis of AHC, with the highest values at first and third checking points (92.3% and 92.6%, respectively) and an improvement in negative predictive value (NPV), with the highest value at first checking point (92.6%). CONCLUSIONS The diagnosis of AHC, made by seroconversion to anti-HCV/HCV-RNA positivity, was confirmed in more than 90% of patients by combining the results of IgG Avidity Index (IgG-AI) and HCV-IgM obtained in a single serum sample.
Collapse
Affiliation(s)
- Nicola Coppola
- Department of Public Medicine, Section of Infectious Diseases, 2nd University of Naples, Italy
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Abstract
Chronic hepatitis C is a global health problem that may cause cirrhosis and progression to hepatocellular carcinoma. Currently available antiviral treatments are moderately effective. Several virological assays are available to help diagnose and manage patients infected with the hepatitis C virus (HCV). These include the anti-HCV antibody assays, measurement of HCV RNA viral load and HCV genotyping. HCV RNA can be assayed by two types of molecular biology-based techniques: target amplification as in polymerase chain reaction methods and signal amplification such as the branched DNA assay. Monitoring of viral kinetics during the early phases of antiviral treatment is crucial in making treatment decisions such as early stopping rules and also in optimizing the length of treatment. The HCV genotype can be determined by several methods. Whatever the method, pretreatment determination allows treatment length and ribavirin dose to be optimized and also offers prognostic information on treatment outcomes as certain genotypes respond more favourably to treatment. Thus, virological assays are indispensable in the diagnosis and management of individuals infected with the HCV.
Collapse
Affiliation(s)
- Stéphane Chevaliez
- Department of Virology & INSERM U841, French National Reference Center for Viral Hepatitis B, C and delta, Hôpital Henri Mondor, Université Paris 12, Créteil, France
| | | |
Collapse
|
|
31
|
Chevaliez S, Pawlotsky JM. Diagnosis and management of chronic viral hepatitis: antigens, antibodies and viral genomes. Best Pract Res Clin Gastroenterol 2008; 22:1031-48. [PMID: 19187865 DOI: 10.1016/j.bpg.2008.11.004] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Virological tools, including serological and molecular tools, are needed to diagnose chronic hepatitis B and C infections. They may also be useful to establish their prognosis, but they have found their principal application in guiding treatment decisions and assessing the virological responses to therapy. The goal of chronic hepatitis B therapy is to prevent progression of liver disease. This is achieved if HBV replication is durably abolished or significantly reduced. In HBeAg-positive patients, HBeAg clearance followed by the HBe seroconversion phase can be achieved. In HBeAg-negative patients, long-term antiviral suppression of viral replication is needed. The loss of HBsAg, eventually associated with an HBs seroconversion, is the most desirable endpoint of therapy but is rarely achieved. The efficacy endpoint of chronic hepatitis C treatment is the sustained virological response, defined by an undetectable HCV RNA in serum with a sensitive assay 24 weeks after the end of treatment. The HCV genotype and on-treatment viral kinetics can be used to tailor treatment dosages and duration.
Collapse
Affiliation(s)
- Stéphane Chevaliez
- Department of Virology & INSERM U955, French National Reference Centre for Viral Hepatitis B, C and delta, Hôpital Henri Mondor, Université Paris, Créteil, France
| | | |
Collapse
|
|
32
|
Abstract
As hepatitis B and C share modes of transmission, their combined occurrence is not uncommon, particularly in areas where both viruses are endemic and in individuals at high-risk of parenteral infection. Both viral hepatitis infections form an important global public health problem, responsible for over half a billion chronic infections worldwide. Their distinctive characteristics impact upon their epidemiology, transmission, and the success of the different prevention strategies. Since several decades a safe and effective vaccine has been available to prevent hepatitis B virus (HBV) infection. Universal vaccination is the cornerstone of global HBV control. Despite major success, vaccine uptake is hampered, and increasing efforts are required to eliminate acute and chronic hepatitis B. Unlike hepatitis C and HIV, HBV has not captured sufficient attention from policymakers, advocacy groups, or the general public: a major challenge for the future. Although progress has been made in the development of an hepatitis C vaccine, short-term successes are not expected. Even without a vaccine, successes can be reported in the field of hepatitis C due to e.g. implementation of universal precautionary measures in health-care settings, screening of blood and blood products, and identification and counselling of infected people. Despite important efforts, transmission in injecting drug users is increasing.
Collapse
Affiliation(s)
- Koen Van Herck
- Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
| | | | | |
Collapse
|
|
33
|
|