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Hayashi Y, Tajiri K, Ozawa T, Angata K, Sato T, Togayachi A, Nagashima I, Shimizu H, Murayama A, Muraishi N, Narimatsu H, Yasuda I. Impact of preS1 Evaluation in the Management of Chronic Hepatitis B Virus Infection. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1334. [PMID: 39202615 PMCID: PMC11356368 DOI: 10.3390/medicina60081334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/11/2024] [Accepted: 08/15/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: The measurement of hepatitis B surface antigen (HBsAg) is essential for managing chronic hepatitis B virus infection (CHB). HBsAg consists of three different surface envelope proteins: large, middle, and small HB surface proteins. However, in clinical practice, it is not common to evaluate each of these HB surface proteins separately. Materials and Methods: In this study, we investigated preS1 expression using seven monoclonal antibodies (mAbs) in 68 CHB patients, as well as examining their antigenicity. Results: Although the seven mAbs had been derived from genotype (Gt) C, they could recognize preS1 with Gts A to D. The epitopes were concentrated within the aa33-47 region of preS1, and their antigenicity was significantly reduced by an aa45F substitution. We found that preS1 expression remained consistent regardless of HBsAg levels and different Gts in CHB patients, in contrast to what was observed in SHBs. Conclusions: These results suggest that the antigenic epitope is preserved among different Gts and that the expression pattern of preS1 is altered during CHB, highlighting its vital role in the HBV infection cycle. Our present results suggest preS1 is a promising therapeutic target in CHB.
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Affiliation(s)
- Yuka Hayashi
- Third Department of Internal Medicine, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.H.)
| | - Kazuto Tajiri
- Third Department of Internal Medicine, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.H.)
| | - Tatsuhiko Ozawa
- Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
- Center for Advanced Antibody Drug Development, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Kiyohiko Angata
- Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8560, Japan; (K.A.); (T.S.); (A.T.); (I.N.); (H.S.)
| | - Takashi Sato
- Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8560, Japan; (K.A.); (T.S.); (A.T.); (I.N.); (H.S.)
| | - Akira Togayachi
- Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8560, Japan; (K.A.); (T.S.); (A.T.); (I.N.); (H.S.)
| | - Izuru Nagashima
- Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8560, Japan; (K.A.); (T.S.); (A.T.); (I.N.); (H.S.)
| | - Hiroki Shimizu
- Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8560, Japan; (K.A.); (T.S.); (A.T.); (I.N.); (H.S.)
| | - Aiko Murayama
- Third Department of Internal Medicine, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.H.)
| | - Nozomu Muraishi
- Third Department of Internal Medicine, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.H.)
| | - Hisashi Narimatsu
- Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8560, Japan; (K.A.); (T.S.); (A.T.); (I.N.); (H.S.)
| | - Ichiro Yasuda
- Third Department of Internal Medicine, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; (Y.H.)
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Liu Y, Wu D, Zhang K, Ren R, Liu Y, Zhang S, Zhang X, Cheng J, Chen L, Huang J. Detection technology and clinical applications of serum viral products of hepatitis B virus infection. Front Cell Infect Microbiol 2024; 14:1402001. [PMID: 39035352 PMCID: PMC11257880 DOI: 10.3389/fcimb.2024.1402001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 06/12/2024] [Indexed: 07/23/2024] Open
Abstract
Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field.
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Affiliation(s)
- Ying Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Di Wu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Kui Zhang
- State Key Laboratory of Resource Insects, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing, China
| | - Rongrong Ren
- Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang, China
| | - Yuxuan Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Shuya Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Xuanyu Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Jilin Cheng
- Department of Gastroenterology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Liping Chen
- Department of Gastroenterology, Shanghai Geriatric Medical Center, Shanghai, China
| | - Jun Huang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
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Salama II, Sami SM, Salama SI, Abdel-Latif GA, Shaaban FA, Fouad WA, Abdelmohsen AM, Raslan HM. Current and novel modalities for management of chronic hepatitis B infection. World J Hepatol 2023; 15:585-608. [PMID: 37305370 PMCID: PMC10251278 DOI: 10.4254/wjh.v15.i5.585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 03/13/2023] [Accepted: 04/12/2023] [Indexed: 05/24/2023] Open
Abstract
Over 296 million people are estimated to have chronic hepatitis B viral infection (CHB), and it poses unique challenges for elimination. CHB is the result of hepatitis B virus (HBV)-specific immune tolerance and the presence of covalently closed circular DNA as mini chromosome inside the nucleus and the integrated HBV. Serum hepatitis B core-related antigen is the best surrogate marker for intrahepatic covalently closed circular DNA. Functional HBV “cure” is the durable loss of hepatitis B surface antigen (HBsAg), with or without HBsAg seroconversion and undetectable serum HBV DNA after completing a course of treatment. The currently approved therapies are nucleos(t)ide analogues, interferon-alpha, and pegylated-interferon. With these therapies, functional cure can be achieved in < 10% of CHB patients. Any variation to HBV or the host immune system that disrupts the interaction between them can lead to reactivation of HBV. Novel therapies may allow efficient control of CHB. They include direct acting antivirals and immunomodulators. Reduction of the viral antigen load is a crucial factor for success of immune-based therapies. Immunomodulatory therapy may lead to modulation of the host immune system. It may enhance/restore innate immunity against HBV (as toll-like-receptors and cytosolic retinoic acid inducible gene I agonist). Others may induce adaptive immunity as checkpoint inhibitors, therapeutic HBV vaccines including protein (HBsAg/preS and hepatitis B core antigen), monoclonal or bispecific antibodies and genetically engineered T cells to generate chimeric antigen receptor-T or T-cell receptor-T cells and HBV-specific T cells to restore T cell function to efficiently clear HBV. Combined therapy may successfully overcome immune tolerance and lead to HBV control and cure. Immunotherapeutic approaches carry the risk of overshooting immune responses causing uncontrolled liver damage. The safety of any new curative therapies should be measured in relation to the excellent safety of currently approved nucleos(t)ide analogues. Development of novel antiviral and immune modulatory therapies should be associated with new diagnostic assays used to evaluate the effectiveness or to predict response.
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Affiliation(s)
- Iman Ibrahim Salama
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Samia M Sami
- Department of Child Health, National Research Centre, Giza 12411, Dokki, Egypt
| | - Somaia I Salama
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Ghada A Abdel-Latif
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Fatma A Shaaban
- Department of Child Health, National Research Centre, Giza 12411, Dokki, Egypt
| | - Walaa A Fouad
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Aida M Abdelmohsen
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Hala M Raslan
- Department of Internal Medicine, National Research Centre, Giza 12411, Dokki, Egypt
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Lee J, Lee SY, Cho YG, Kim DS, Park J. Accuracy Validation of the Elecsys HBsAg II Quant Assay and Its Utility in Resolving Equivocal Qualitative HBsAg Results. Medicina (B Aires) 2023; 59:medicina59030443. [PMID: 36984443 PMCID: PMC10056079 DOI: 10.3390/medicina59030443] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 02/18/2023] [Accepted: 02/20/2023] [Indexed: 02/25/2023] Open
Abstract
Background and Objectives: There are reports of false qualitative HBsAg results, because of various causes, such as samples with low HBsAg concentrations that may produce false positives. The main aims of this study were to validate the analytical accuracy and to assess the utility of the Elecsys assay compared to that of the qualitative HbsAg assay as a screening test in resolving equivocal qualitative HbsAg results. Materials and Methods: The limit of blank (LoB), the limit of detection (LoD), the limit of quantification (LoQ), and linearity were estimated to validate the analytical accuracy of the Elecsys HBsAg II Quant assay. A total of 449 serum samples showing initial equivocal results (1–50 index) were evaluated by Elecsys HBsAg II Quant and ADVIA Centaur HBsAg II assays. Results: The LoQ of the assay was determined to be 0.050 IU/mL, as provided by the manufacturer. The Kappa agreement between the two assays was almost perfect, at 0.9669, despite seven discordant results. With a specificity of 100% at new cut-off index value ≥5.42, about 78 samples (17%, 78/449) with index value ≥5.42 were interpreted as positives without further duplicate tests, however the remaining 371 samples with index value <5.42 need to be confirmed with additional HBV marker assays. Conclusions: We confirm that the Elecsys HBsAg II Quant assay is accurate and sensitive for HBV infection and recommend it as an alternative confirmatory HBsAg assay for resolving equivocal qualitative HBsAg results.
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Affiliation(s)
- Jaehyeon Lee
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
- Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
| | - Seung Yeob Lee
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
- Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
| | - Yong Gon Cho
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
- Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
| | - Dal Sik Kim
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
- Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
| | - Joonhong Park
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
- Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
- Correspondence: ; Tel.: +82-63-250-1218
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Validation of Baveno VII criteria for recompensation in entecavir-treated patients with hepatitis B-related decompensated cirrhosis. J Hepatol 2022; 77:1564-1572. [PMID: 36038017 DOI: 10.1016/j.jhep.2022.07.037] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 06/03/2022] [Accepted: 07/18/2022] [Indexed: 12/04/2022]
Abstract
BACKGROUND & AIMS Antiviral therapy improves the clinical outcomes of patients with chronic hepatitis B (CHB), including those with cirrhosis. In the present study, we validated the Baveno VII definition of recompensation and explored the criteria for stable improvement of liver function tests in entecavir-treated patients with CHB-related decompensated cirrhosis. METHODS In this multicentre prospective study, patients with decompensated (ascites) CHB-related cirrhosis were enrolled and treated with entecavir for 120 weeks. Patients were followed up for clinical events, viral and biochemical tests, and ultrasonography every 6 months. The recompensation rate per Baveno VII criteria was calculated. Multivariate regression models were used to identify the predictors of recompensation. Finally, the criteria for stable improvement of liver function tests were explored. RESULTS Of the 320 recruited patients, 283 completed the 120-week study, with 261/283 (92.2%) achieving HBV DNA levels <20 IU/ml and 171/283 (60.4%) achieving resolution of ascites, encephalopathy, and absence of recurrent variceal bleeding for at least 12 months. We identified model for end-stage liver disease <10 and/or liver function tests within Child-Pugh Class A (albumin >35 g/L, international normalised ratio <1.50 and total bilirubin <34 μmol/L) as the criteria for stable improvement of liver function tests. Accordingly, 56.2% (159/283) of patients fulfilled the Baveno VII definition of recompensation with a stable improvement of liver function tests defined by the current study. CONCLUSIONS Our study defined the criteria for a stable improvement of liver function tests required by the Baveno VII definition of recompensation in patients with CHB-related decompensated cirrhosis on antiviral therapy. The criteria derived from this multicentre prospective study warrant further validation in patients with cirrhosis of other aetiologies. LAY SUMMARY Decompensation of cirrhosis marks the point at which the liver is no longer able to function normally (and symptoms become apparent). Recently the idea of recompensation was proposed for individuals who may experience an improvement in liver function if the underlying cause of their liver disease is addressed (e.g. antivirals for viral cirrhosis). Herein, we show that over 50% of patients with hepatitis B-related decompensated cirrhosis treated with antivirals could recompensate and we propose laboratory criteria which could be used to define recompensation.
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Chen M, Tian Y, Zhang D, Ren W, Wang W. An improved method for rapid identification of hook effect samples in HBsAg quantitative assay. J Virol Methods 2022; 309:114606. [PMID: 35963582 DOI: 10.1016/j.jviromet.2022.114606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 08/05/2022] [Accepted: 08/09/2022] [Indexed: 12/24/2022]
Abstract
Quantitative hepatitis B surface antigen assay is widely used for diagnosis of hepatitis B virus infection; however, specimens with high levels of the antigen can cause false-negative results (Hook effect), which needs to be resolved. The hook effect samples and non-hook effect samples were detected on the LiCA® 500 instrument using three methods, viz., 1, 2, and 3. Method 1, the currently used procedure, was performed in two steps with a total reaction time of 25 min in a final volume of 250 µL: first incubation was with two reagents for 15 min and then with one other reagent for 10 min. In Method 2, all three reagents were added in one step with a final volume of 250 µL, and the total reaction time was still 25 min. In Method 3, the improved method, all three reagents were added in one step while the final volume was only 130 µL and the total reaction time was only 1 min. Signal values of the non-hook effect samples obtained using Method 2 were significantly lower than those with Method 1, showing competitive inhibition. The hook effect samples tested with Method 2 approximated those obtained using Method 1. Method 3 took 1 min and differentiated hook effect samples successfully, similar to the results with Method 2 which took 25 min. Changing the timing of one reagent addition and incubation time in Method 3 provided a rapid and effective method for the identification of hook effect. The results were more clearly distinguishable due to the phenomenon of competitive inhibition. Method 3 can be considered an improvement on the chemiluminescence platform.
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Affiliation(s)
- Mingxin Chen
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
| | - Yu Tian
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
| | - Dai Zhang
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
| | - Weihong Ren
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China.
| | - Wei Wang
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China.
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Research Progress on the Mechanism of Persistent Low-Level HBsAg Expression in the Serum of Patients with Chronic HBV Infection. J Immunol Res 2022; 2022:1372705. [PMID: 35465353 PMCID: PMC9020929 DOI: 10.1155/2022/1372705] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 03/28/2022] [Indexed: 12/17/2022] Open
Abstract
Among HBV-infected persons, there is a group of people with hepatitis B surface antigen (HBsAg) showing persistently low levels of expression. The production of low-level HBsAg does not mean a good outcome of chronic HBV infection. Patients still have virus replication and sustained liver damage, and they have the potential to transmit the infection. This risk poses a challenge to clinical diagnosis and blood transfusion safety and is a major concern of experts. However, the mechanism behind persistent low-level HBsAg expression in serum is not completely clear, and complete virus clearance by the host is vital. In this review, we summarize the research progress on the mechanism behind low-level expression of HBsAg in patients with chronic HBV infection in recent years.
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A Systematic Review of T Cell Epitopes Defined from the Proteome of Hepatitis B Virus. Vaccines (Basel) 2022; 10:vaccines10020257. [PMID: 35214714 PMCID: PMC8878595 DOI: 10.3390/vaccines10020257] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/04/2022] [Accepted: 02/05/2022] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) infection remains a worldwide health problem and no eradicative therapy is currently available. Host T cell immune responses have crucial influences on the outcome of HBV infection, however the development of therapeutic vaccines, T cell therapies and the clinical evaluation of HBV-specific T cell responses are hampered markedly by the lack of validated T cell epitopes. This review presented a map of T cell epitopes functionally validated from HBV antigens during the past 33 years; the human leukocyte antigen (HLA) supertypes to present these epitopes, and the methods to screen and identify T cell epitopes. To the best of our knowledge, a total of 205 CD8+ T cell epitopes and 79 CD4+ T cell epitopes have been defined from HBV antigens by cellular functional experiments thus far, but most are restricted to several common HLA supertypes, such as HLA-A0201, A2402, B0702, DR04, and DR12 molecules. Therefore, the currently defined T cell epitope repertoire cannot cover the major populations with HLA diversity in an indicated geographic region. More researches are needed to dissect a more comprehensive map of T cell epitopes, which covers overall HBV proteome and global patients.
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Park J, Bae T, Cho Y, Kim D, Lee J. Analytical Performance of the Sysmex HISCL HBsAg Assay and Comparison with the Roche Elecsys HBsAg II Quant Assay in the Quantification of Hepatitis B Surface Antigen. Medicina (B Aires) 2021; 57:medicina57121307. [PMID: 34946252 PMCID: PMC8705794 DOI: 10.3390/medicina57121307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/16/2021] [Accepted: 11/25/2021] [Indexed: 12/03/2022] Open
Abstract
Background and Objectives: This study aims to estimate the analytical performance of the Sysmex HISCL HBsAg assay and to assess the analytical correlation with the Roche Elecsys HBsAg II quant assay with clinical samples and the WHO International Standard (IS). Materials and Methods: The intra-assay precision, linearity, assay limitation, accuracy, and comparative evaluation of the HISCL HBsAg assay were estimated. Results: Extrapolating from the plot of the average total allowable error versus the reference value, an accuracy goal of 20% would be achieved around a limit of quantification (LoQ) of 0.014867 IU/mL. The percentage of biases for each level of the WHO IS measured by the two assays were less than 15%, except for the WHO 3rd IS, for which the HISCL HBsAg assay achieved a percentage of bias of 33%. In the comparative evaluation, Passing–Bablok regression analysis did not reveal any significant deviation from linearity between the two assays (y = −48.6998 + 1.9206x; p = 0.79 by the CUSUM test for linearity). The mean difference of the quantitative HBsAg level between the two assays was 1762.5 IU/mL in the Bland–Altman plot. Conclusions: The HISCL HBsAg assay, with a highly sensitive LoQ of 0.03 IU/mL, showed similar analytical performance in HBsAg quantification to the Elecsys HBsAg II quant assay and may be helpful in obtaining better diagnoses and therapeutic strategies for treating HBV infections.
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Affiliation(s)
- Joonhong Park
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (J.P.); (T.B.); (Y.C.); (D.K.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea
| | - Taewon Bae
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (J.P.); (T.B.); (Y.C.); (D.K.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea
| | - Yonggon Cho
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (J.P.); (T.B.); (Y.C.); (D.K.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea
| | - Dalsik Kim
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (J.P.); (T.B.); (Y.C.); (D.K.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea
| | - Jaehyeon Lee
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (J.P.); (T.B.); (Y.C.); (D.K.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea
- Correspondence: ; Tel.: +82-63-250-2693
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Yang R, Cui L, Liu Y, Cong X, Fei R, Wu S, Wei L. A hook-effect-free homogeneous light-initiated chemiluminescence assay: is it reliable for screening and the quantification of the hepatitis B surface antigen? ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:606. [PMID: 32566632 PMCID: PMC7290535 DOI: 10.21037/atm.2020.02.59] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background Hepatitis B virus (HBV) infection remains a threat to global public health. As a hallmark of HBV infection, hepatitis B surface antigen (HBsAg) has been used to screen for HBV infection for decades, and quantitative assays are also being clinically rejuvenated to predict the disease outcome and monitor the antiviral response. Herein, we developed and evaluated a hook-effect-free homogeneous quantitative HBsAg assay based on the light-initiated chemiluminescence immunoassay (LICA). Methods A hook-effect-free LICA algorithm was established by measuring the relative light units (RLUs) of two time points during the immunoreaction. The precision was assessed using low- and high-level controls. Consecutive clinical serum samples were tested using the LICA and Abbott Architect assay; samples producing inconsistent results were retested using supplementary assays including the HBsAg neutralization, HBV DNA, and Roche Elecsys HBsAg assays for further confirmation. The consistency, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. For the quantitative results, the correlation was analyzed. The coverage of different genotypes and mutations by the LICA was evaluated. Moreover, serial on-treatment and follow-up samples from chronic hepatitis B patients were also measured using the two assays. Results The LICA had better within-run and within-laboratory precisions than the Architect assay. In total, 5,176 clinical samples were tested. The two assays showed a consistency of 99.63%. The LICA showed greater specificity (99.95% vs. 99.77%) and PPV (99.75% vs. 98.77%) than the Architect assay, whereas the Architect assay showed greater sensitivity (100.00% vs. 99.01%) and NPV (100.00% vs. 99.82%). The two assays displayed an excellent correlation independent of genotypes and mutations. The LICA hook-free algorithm recognized 100% of the underestimated results. Furthermore, similar HBsAg dynamics were demonstrated using the LICA and Architect HBsAg assay. Conclusions The hook-free LICA provides a reliable tool for screening for HBV infection and quantifying HBsAg.
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Affiliation(s)
- Ruifeng Yang
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China
| | - Liyan Cui
- Department of Clinical Laboratory, Peking University Third Hospital, Beijing 100191, China
| | - Yan Liu
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China
| | - Xu Cong
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China
| | - Ran Fei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China
| | - Shuping Wu
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China
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11
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A Global View to HBV Chronic Infection: Evolving Strategies for Diagnosis, Treatment and Prevention in Immunocompetent Individuals. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16183307. [PMID: 31505743 PMCID: PMC6766235 DOI: 10.3390/ijerph16183307] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 08/22/2019] [Accepted: 08/23/2019] [Indexed: 02/07/2023]
Abstract
Hepatitis B Virus (HBV) is a significant public health challenge. Around 250 million people live with chronic HBV infection. With a global approach to this issue, we focus on new perspective in diagnosis, management and prevention of HBV chronic infection. Precise diagnosis of HBV status is crucial to guide patient management. Although available drugs reduce the risk of liver disease progression, they are not able to definitely eradicate HBV, and new therapeutic options are urgently needed. Thus, prevention of HBV infection is still the most effective strategy to achieve the control of the disease. Key aspects of prevention programs include surveillance of viral hepatitis, screening programs and immunization strategies. In spite of the high success rate of licensed HBV vaccines, a need for improved vaccine persists, especially in order to provide coverage of current non-responders.
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12
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Afolabi AY, Bakarey AS, Adewumi MO. Evaluation of performance testing of different rapid diagnostic kits in comparison with EIAs to validate detection of hepatitis B virus among high risk group in Nigeria. J Immunoassay Immunochem 2018; 39:218-227. [PMID: 29764292 DOI: 10.1080/15321819.2018.1458238] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) causes chronic liver-associated diseases and its early detection is of high public health importance. Its diagnosis is mainly based on immunological assays among which Enzyme-Linked Immunosorbent Assay (ELISA) and rapid tests are the most common and widespread methods. However, a major challenge is the discordance of results of any two laboratory assays which cannot be easily resolved. Therefore, this study was designed to evaluate the validity and reliability of commercially available five rapid test kits in comparison with two Enzyme Immunoassays (EIAs) in Nigeria using hepatitis B surface antigen as a reference marker. METHODS A total of 100 sera of previously diagnosed consenting HBV-positive patients from private diagnostic laboratories in Ibadan between March and August, 2011 were tested using two EIA and five rapid commercially available HBV test kits in Nigeria. Data were analyzed by SPSS version 15, while bivariate and multivariate analyses were carried out to identify associations at P < 0.05 considered significant. RESULTS Overall, the sensitivity rates of the two EIA kits were 100% and 99.9% (95% confidence interval [CI] = 98.9-99.7) with specificity of 100% and 99.9% (95% CI = 98.9-99.7), respectively. The sensitivity of the five rapid test kits ranged from 97.5% (95% CI = 96.4-97.6) to 98.9% (95% CI = 97.9-99.9) with specificity of 80% (95% CI = 79.3-80.9) to 90% (95% CI = 89.2-91.0). Also, the positive predictive value ranged from 88% (95% CI = 88.2-89.9) to 89% (95% CI = 88.2-89.9), while the negative predictive value ranged from 80% (95% CI = 79.3-80.9) to 90% (95% CI = 89.2-91.0) for the five rapid kits. However, that of the two EIAs ranged from 99.9% (98.9-99.7) to 100%. Further analysis showed significant (P = 0.033) variations in the sensitivity and specificity of the EIAs and rapid test kits. CONCLUSIONS The results from this study have clearly revealed the challenges of diagnosis of HBV infections in Nigeria. This study has also demonstrated that the sensitivity of most of the rapid test kits may not be adequate when compared with EIA for early detection of HBV infections. The implications of possible misdiagnosis on the various intervention strategies that rely predominantly on correct HBV status of an individual are enormous. Therefore, there is the need to further compliment the use of rapid test kits with EIAs for HBV control in Nigeria.
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Affiliation(s)
- Abosede Yetunde Afolabi
- a Department of Obstetrics and Gynaecology, College of Medicine , University of Ibadan , Ibadan , Nigeria
| | - Adeleye Solomon Bakarey
- b Institute for Advanced Medical Research and Training, College of Medicine , University of Ibadan , Ibadan , Nigeria
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Hassemer M, Finkernagel M, Peiffer KH, Glebe D, Akhras S, Reuter A, Scheiblauer H, Sommer L, Chudy M, Nübling CM, Hildt E. Comparative characterization of hepatitis B virus surface antigen derived from different hepatitis B virus genotypes. Virology 2017; 502:1-12. [PMID: 27951436 DOI: 10.1016/j.virol.2016.12.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 11/28/2016] [Accepted: 12/02/2016] [Indexed: 02/07/2023]
Abstract
For human hepatitis B virus eight distinct and two candidate genotypes are described. These genotypes differ with respect to geographic distribution, molecular virology and virus-associated pathogenesis. Comparative analysis of HBV genotypes revealed, with exception of HBV/G that shows impaired HBsAg release, that no fundamental disparities between genotypes exist regarding glycosylation, subcellular distribution, release of HBsAg and formation of subviral particles. However, there are distinctions regarding the proportion of L to M to S HBs proteins detected intra- and extracellularly for different genotypes. 2D electrophoresis revealed different posttranslational modification patterns for LHBs. In light of the relevance of HBsAg as diagnostic marker, detectability of purified recombinant HBsAg of various genotypes by HBsAg-specific detection systems licensed in Europe was investigated, showing similar sensitivities for genotypes included in this analysis. These data indicate that recombinant HBsAg reproducibly purified following a defined protocol might be used as an alternative to reference materials currently established.
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Affiliation(s)
| | | | - Kai-Henrik Peiffer
- University Hospital Frankfurt, Frankfurt/Main, Germany; Goethe University Frankfurt, Frankfurt/Main, Germany
| | - Dieter Glebe
- Justus Liebig University, Institute of Medical Virology, Gießen, Germany; German Center for Infection Research (DZIF), Gießen-Marburg-Langen, Germany
| | - Sami Akhras
- Paul-Ehrlich-Institut, Department of Virology, Langen, Germany
| | - Andreas Reuter
- Paul-Ehrlich-Institut, Department of Allergology, Langen, Germany
| | | | - Lisa Sommer
- University Hospital Frankfurt, Frankfurt/Main, Germany; Goethe University Frankfurt, Frankfurt/Main, Germany
| | - Michael Chudy
- Paul-Ehrlich-Institut, Department of Virology, Langen, Germany
| | - C Micha Nübling
- Paul-Ehrlich-Institut, Department of Virology, Langen, Germany
| | - Eberhard Hildt
- Paul-Ehrlich-Institut, Department of Virology, Langen, Germany; German Center for Infection Research (DZIF), Gießen-Marburg-Langen, Germany.
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14
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Chung KH, Kim W, Kim BG, Lee HY, Jin E, Cho Y, Seo JY, Kim HY, Jung YJ, Kim JW, Jeong JB, Lee KL. Hepatitis B Surface Antigen Quantification across Different Phases of Chronic Hepatitis B Virus Infection Using an Immunoradiometric Assay. Gut Liver 2016; 9:657-64. [PMID: 25717049 PMCID: PMC4562784 DOI: 10.5009/gnl14188] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIMS Quantification of hepatitis B surface antigen (HBsAg) is an emerging serologic test and may be useful for identifying treatment strategies for chronic hepatitis B (CHB). This study aimed to evaluate HBsAg titers during the natural course of CHB and identify correlations between HBsAg titers and hepatitis B virus (HBV) DNA concentrations across different CHB phases measured using an immunoradiometric assay (IRMA). METHODS CHB phases were defined on the basis of HBV DNA concentrations, the presence of hepatitis B e antigen/antibody (HBeAg/Ab) and serum alanine aminotransferase levels. Serum HBsAg titers and paired HBV DNA concentrations in the different phases of CHB were compared using 627 serum samples. RESULTS Mean HBsAg titers were significantly higher in the immunotolerant (IT) phase and immunoreactive (IR) HBeAg-positive phase than in the low-replicative (LR) and HBeAg-negative CHB (ENH) states. The correlation between HBsAg titers and HBV DNA concentrations was modest in the IT (n=36, r=0.804, p<0.001) and IR (n=48, r=0.773, p<0.001) phases, and it was poor in the LR state (n=116, r=0.289, p=0.002); however, no significant correlation was observed in the ENH state (n=67, r=0.146, p=0.237) or in the oral nucleos(t)ide analogue-treated group (n=267). CONCLUSIONS HBsAg quantification using IRMA might be useful for discriminating different CHB phases and different stages of chronic liver disease.
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Affiliation(s)
- Kwang Hyun Chung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Byeong Gwan Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Ho-Young Lee
- Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Eunhyo Jin
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Yeon Seo
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hwi Young Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Yong Jin Jung
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Ji Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Ji Bong Jeong
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Kook Lae Lee
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
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16
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Wang L, Zou ZQ, Wang K, Yu JG, Liu XZ. Role of serum hepatitis B virus marker quantitation to differentiate natural history phases of HBV infection. Hepatol Int 2016; 10:133-138. [PMID: 26427997 DOI: 10.1007/s12072-015-9657-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Accepted: 07/27/2015] [Indexed: 02/06/2023]
Abstract
PURPOSE The purpose of this study was to characterize roles of serum hepatitis B virus marker quantitation in differentiation of natural phases of HBV infection. METHODS A total of 184 chronic hepatitis B (CHB) patients were analyzed retrospectively. Patients were classified into four categories: immune tolerant phase (IT, n = 36), immune clearance phase (IC, n = 81), low-replicative phase (LR, n = 31), and HBeAg-negative hepatitis phase (ENH, n = 36), based on clinical, biochemical, serological, HBV DNA level and histological data. RESULTS Hepatitis B surface antigen (HBsAg) quantitation in four phases were 4.7 ± 0.2, 3.8 ± 0.5, 2.5 ± 1.2 and 3.4 ± 0.4 log10 IU/mL, respectively. There were significant differences between IT and IC (p < 0.001) and between LR and ENH phases (p < 0.001). Quantitation of hepatitis B e antigen (HBeAg) in IT and IC phases are 1317.9 ± 332.9 and 673.4 ± 562.1 S/CO, respectively (p < 0.001). Hepatitis B core antibody (HBcAb) quantitation in the four groups were 9.48 ± 3.3, 11.7 ± 2.8, 11.2 ± 2.6 and 13.2 ± 2.9 S/CO, respectively. Area under receiver operating characteristic curve (AUCs) of HBsAg and HBeAg at cutoff values of 4.41 log10 IU/mL and 1118.96 S/CO for differentiation of IT and IC phases are 0.984 and 0.828, with sensitivity 94.4 and 85.2 %, specificity 98.7 and 75 %, respectively. AUCs of HBsAg and HBcAb at cutoff values of 3.4 log10 IU/mL and 10.5 S/CO for differentiation of LR and ENT phases are 0.796 and 0.705, with sensitivity 58.1 and 85.7 %, and specificity 94.4 and 46.2 %, respectively. CONCLUSIONS HBsAg quantitation has high predictive value and HBeAg quantitation has moderate predictive value for discriminating IT and IC phase. HBsAg and HBcAb quantitations have moderate predictive values for differentiation of LR and ENH phase.
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Affiliation(s)
- Li Wang
- Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai, 264001, Shandong, China.
| | - Zhi-Qiang Zou
- Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai, 264001, Shandong, China
| | - Kai Wang
- Hepatology Department, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Ji-Guang Yu
- Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai, 264001, Shandong, China
| | - Xiang-Zhong Liu
- Infectious Disease Hospital of Yantai, 62 Huanshan Road, Zhifu District, Yantai, 264001, Shandong, China
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Hernández S, Jiménez G, Alarcón V, Prieto C, Muñoz F, Riquelme C, Venegas M, Brahm J, Loyola A, Villanueva RA. Replication of a chronic hepatitis B virus genotype F1b construct. Arch Virol 2015; 161:583-94. [PMID: 26620585 DOI: 10.1007/s00705-015-2702-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 11/23/2015] [Indexed: 12/18/2022]
Abstract
Genotype F is one of the less-studied genotypes of human hepatitis B virus, although it is widely distributed in regions of Central and South American. Our previous studies have shown that HBV genotype F is prevalent in Chile, and phylogenetic analysis of its full-length sequence amplified from the sera of chronically infected patients identified it as HBV subgenotype F1b. We have previously reported the full-length sequence of a HBV molecular clone obtained from a patient chronically infected with genotype F1b. In this report, we established a system to study HBV replication based on hepatoma cell lines transfected with full-length monomers of the HBV genome. Culture supernatants were analyzed after transfection and found to contain both HBsAg and HBeAg viral antigens. Consistently, fractionated cell extracts revealed the presence of viral replication, with both cytoplasmic and nuclear DNA intermediates. Analysis of HBV-transfected cells by indirect immunofluorescence or immunoelectron microscopy revealed the expression of viral antigens and cytoplasmic viral particles, respectively. To test the functionality of the ongoing viral replication further at the level of chromatinized cccDNA, transfected cells were treated with a histone deacetylase inhibitor, and this resulted in increased viral replication. This correlated with changes posttranslational modifications of histones at viral promoters. Thus, the development of this viral replication system for HBV genotype F will facilitate studies on the regulation of viral replication and the identification of new antiviral drugs.
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Affiliation(s)
- Sergio Hernández
- Laboratorio de Virus Hepatitis, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Avda República 217, 2do piso, 8370146, Santiago, Chile
| | - Gustavo Jiménez
- Laboratorio de Virus Hepatitis, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Avda República 217, 2do piso, 8370146, Santiago, Chile
| | - Valentina Alarcón
- Laboratorio de Epigenética y Cromatina, Fundación Ciencia and Vida, 7780272, Santiago, Chile
| | - Cristian Prieto
- Laboratorio de Virus Hepatitis, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Avda República 217, 2do piso, 8370146, Santiago, Chile
| | - Francisca Muñoz
- Laboratorio de Epigenética y Cromatina, Fundación Ciencia and Vida, 7780272, Santiago, Chile
| | - Constanza Riquelme
- Laboratorio de Virus Hepatitis, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Avda República 217, 2do piso, 8370146, Santiago, Chile
| | - Mauricio Venegas
- Sección de Gastroenterología, Hospital Clínico Universidad de Chile, 8380456, Santiago, Chile
| | - Javier Brahm
- Sección de Gastroenterología, Hospital Clínico Universidad de Chile, 8380456, Santiago, Chile
| | - Alejandra Loyola
- Laboratorio de Epigenética y Cromatina, Fundación Ciencia and Vida, 7780272, Santiago, Chile.,Universidad San Sebastián, 7510157, Santiago, Chile
| | - Rodrigo A Villanueva
- Laboratorio de Virus Hepatitis, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Avda República 217, 2do piso, 8370146, Santiago, Chile.
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18
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Liu YP, Yao CY. Rapid and quantitative detection of hepatitis B virus. World J Gastroenterol 2015; 21:11954-11963. [PMID: 26576084 PMCID: PMC4641117 DOI: 10.3748/wjg.v21.i42.11954] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 07/29/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Despite availability of a universal vaccine, hepatitis B virus (HBV) infection has a huge impact on public health worldwide. Accurate and timely diagnosis of HBV infection is needed. Rapid developments have been made in the diagnostic and monitoring methods for HBV infection, including serological and molecular assays. In clinical practice, qualitative hepatitis B surface antigen (HBsAg) testing has long served as a diagnostic marker for individuals infected with HBV. More recently, HBsAg level has been used to predict treatment outcome when determined early during treatment or at baseline. However, identification of HBV DNA positive cases that do not have detectable HBsAg has encouraged the application of molecular tests. Hence, combination of quantitative detection of HBV DNA and HBsAg can be used to discriminate patients during the course of HBV infection and to monitor therapy. This article reviews the most commonly used quantitative methods for HBsAg and HBV DNA.
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Wang Q, Luan W, Warren L, Fiel MI, Blank S, Kadri H, Tuvin D, Hiotis SP. Serum hepatitis B surface antigen correlates with tissue covalently closed circular DNA in patients with hepatitis B-associated hepatocellular carcinoma. J Med Virol 2015; 88:244-51. [DOI: 10.1002/jmv.24326] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/04/2015] [Indexed: 12/17/2022]
Affiliation(s)
- Qin Wang
- Department of Surgery; The Icahn School of Medicine at Mount Sinai; New York City New York
| | - Wei Luan
- Department of Surgery; The Icahn School of Medicine at Mount Sinai; New York City New York
| | - Leslie Warren
- Department of Surgery; The Icahn School of Medicine at Mount Sinai; New York City New York
| | - M. Isabel Fiel
- Department of Pathology; The Icahn School of Medicine at Mount Sinai; New York City New York
| | - Sima Blank
- Department of Surgery; The Icahn School of Medicine at Mount Sinai; New York City New York
| | - Hena Kadri
- Department of Surgery; The Icahn School of Medicine at Mount Sinai; New York City New York
| | - Daniel Tuvin
- Department of Surgery; The Icahn School of Medicine at Mount Sinai; New York City New York
| | - Spiros P. Hiotis
- Department of Surgery; The Icahn School of Medicine at Mount Sinai; New York City New York
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Abdelnabi Z, Saleh N, Baraghithi S, Glebe D, Azzeh M. Subgenotypes and mutations in the s and polymerase genes of hepatitis B virus carriers in the West Bank, palestine. PLoS One 2014; 9:e113821. [PMID: 25503289 PMCID: PMC4264744 DOI: 10.1371/journal.pone.0113821] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Accepted: 10/31/2014] [Indexed: 12/17/2022] Open
Abstract
The mutation rate and genetic variability of hepatitis B virus (HBV) are crucial factors for efficient treatment and successful vaccination against HBV. Until today, genetic properties of this virus among the Palestinian population remain unknown. Therefore, we performed genetic analysis of the overlapping S and polymerase genes of HBV, isolated from 40 Palestinian patients' sera. All patients were HBsAg positive and presented with a viral load above 105 HBV genome copies/ml. The genotyping results of the S gene demonstrated that HBV D1 was detected in 90% of the samples representing the most prominent subgenotype among Palestinians carrying HBV. Various mutations existed within the S gene; in five patients four known escape mutations including the common G145R and D144E were found. Furthermore, a ratio of 4.25 of non-synonymous to synonymous mutations in the S gene indicated a strong selection pressure on the HBs antigen loops of HBV strains circulating in those Palestinian patients. Although all patients were treatment-naïve, with the exception of one, several mutations were found in the HBV polymerase gene, but none pointed to drug resistance. The study presented here is the first report to address subgenotypes and mutation analyses of HBV S and polymerase genes in Palestine.
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Affiliation(s)
- Zakeih Abdelnabi
- Virology Research Laboratory, Medical Research Center, Al-Quds University, Abu Dies-East Jerusalem, Palestine
| | - Niveen Saleh
- Virology Research Laboratory, Medical Research Center, Al-Quds University, Abu Dies-East Jerusalem, Palestine
| | - Sabri Baraghithi
- Al-Makassed Islamic Charitable Hospital (MICH) Central Laboratory, East Jerusalem, Palestine
| | - Dieter Glebe
- Institute of Medical Virology, Justus-Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research (DZIF), Biomedical Research Center, Giessen, Germany
| | - Maysa Azzeh
- Virology Research Laboratory, Medical Research Center, Al-Quds University, Abu Dies-East Jerusalem, Palestine
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Zeng LY, Lian JS, Chen JY, Jia HY, Zhang YM, Xiang DR, Yu L, Hu JH, Lu YF, Zheng L, Li LJ, Yang YD. Hepatitis B surface antigen levels during natural history of chronic hepatitis B: A Chinese perspective study. World J Gastroenterol 2014; 20:9178-9184. [PMID: 25083092 PMCID: PMC4112899 DOI: 10.3748/wjg.v20.i27.9178] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2013] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China.
METHODS: Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immune-tolerant (IT, n = 108), immune-clearance (IC, n = 161), hepatitis B e antigen negative hepatitis (ENH, n = 149), low-replicative (LR, n = 135), and liver cirrhosis (LC, n = 70). HBsAg was quantified (Abbott ARCHITECT assay) and correlated with hepatitis B virus (HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) in each phase of CHB was also determined.
RESULTS: Median HBsAg titers were different in each phase of CHB (P < 0.001): IT (4.85 log10 IU/mL), IC (4.36 log10 IU/mL), ENH (2.95 log10 IU/mL), LR (3.18 log10 IU/mL) and LC (2.69 log10 IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase (r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed.
CONCLUSION: The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immune-modulator or oral nucleos(t)ide analogue therapy.
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Kang W, Park JY. When to stop nucleos(t)ide analogues treatment for chronic hepatitis B? Durability of antiviral response. World J Gastroenterol 2014; 20:7207-7212. [PMID: 24966590 PMCID: PMC4064065 DOI: 10.3748/wjg.v20.i23.7207] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 12/13/2013] [Accepted: 01/15/2014] [Indexed: 02/06/2023] Open
Abstract
Introduction of nucleos(t)ide analogues (NAs) for oral antiviral therapy has dramatically improved the clinical outcome in patients with chronic hepatitis B (CHB). Although current international guidelines for the management of CHB provide information regarding when to begin the antiviral therapy with NAs, there is no clear consensus on when to stop the treatment, especially for those who respond to the therapy. Hepatitis B surface antigen loss has been regarded as an ideal endpoint of oral antiviral therapy with NAs, however since this is rarely achieved, practical endpoints have been suggested by the international guidelines. Despite the stopping rules recommended by the international guidelines, whether oral antiviral therapy with NAs can be safely discontinued is of major concern. While attention has been drawn to whether antiviral treatment with NAs can be a finite therapy, there is lack of sufficient data on off-treatment durability of highly potent NAs. Based on the available evidences, current guidelines for stopping NA therapy seems to be inadequate in terms of off-treatment durability, with relapse rates of more than 40% for both hepatitis Be antigen (HBeAg)-positive and HBeAg-negative patients. Therefore, further studies are required to accumulate data on off-treatment durability of highly potent NAs, and future studies are warranted to identify adequate predictive markers that could provide supplementary information to guide the timing of stopping NA therapy.
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Manyazewal T, Sisay Z, Biadgilign S, Abegaz WE. Hepatitis B and hepatitis C virus infections among antiretroviral-naive and -experienced HIV co-infected adults. J Med Microbiol 2014; 63:742-747. [PMID: 24757219 DOI: 10.1099/jmm.0.063321-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Most HIV positive people have not been tested for viral hepatitis and their treatments have not been optimized for possible co-infections. The aim of this study was to investigate the serological pattern of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among antiretroviral (ARV)-naive and -experienced HIV co-infected adults in Addis Ababa, Ethiopia. A total of 500 frozen HIV positive serum and plasma samples collected from ARV-naive (n = 250) and -experienced (n = 250) adults were randomly selected and screened for HBsAg, anti-HBs, HBeAg and anti-HCV using rapid two-site sandwich immunochromatographic assay. The test was performed at Aklilu Lemma Institute of Pathobiology, Addis Ababa University. Positive specimens for HBsAg and anti-HCV markers were further confirmed using third generation ELISA. Of the 500 specimens tested, 15 (3 %), 58 (11.6 %), 3 (0.6 %), 18 (3.6 %), 3 (0.6 %) and 1 (0.2 %) were positive for HBsAg, anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. No specimen tested positive for both HBeAg and anti-HBs, and 442 (88.4 %) individuals were non-immune to HBV. Of the 250 ARV-naive individuals, 8 (3.2 %), 33 (13.2 %), 2 (0.8 %), 10 (4 %), 2 (0.8 %), and 1 (0.4 %) were positive for HBsAg, anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. Of the 250 ARV-experienced individuals, 7 (2.8 %), 25 (10 %), 1 (0.4 %), 8 (3.2 %), 1 (0.4 %), and 0 (0 %) were positive for HBsAg, Anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. In summary, seroprevalence of HIV/HBV and HIV/HCV co-infections was lower in Addis Ababa, Ethiopia, than in Sub-Saharan Africa and globally. HBV and HCV infections were not significantly different between HIV positive subjects who were or who were not on ARV. This suggests that the two groups have equal chance of being infected with these two viruses; despite this, disease progression could be different.
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Affiliation(s)
- Tsegahun Manyazewal
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Zufan Sisay
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Sibhatu Biadgilign
- Department of Epidemiology and Biostatistics, College of Public Health and Medical Science, Jimma University, Jimma, Ethiopia
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Kim BK, Choi SH, Ahn SH, Chung AR, Park YK, Han KH, Kim S, Kim HS, Park JH, Kim KS, Lee HS, Cho YS, Kim KH, Ahn SH. Pre-S mutations of hepatitis B virus affect genome replication and expression of surface antigens. J Gastroenterol Hepatol 2014; 29:843-50. [PMID: 24783251 DOI: 10.1111/jgh.12415] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUNDS AND AIMS In chronic hepatitis B virus (HBV) infection, quantitative HBV surface antigen (qHBsAg) is useful for monitoring viral replication and treatment responses. We aimed to determine whether pre-S mutations have any effect on circulating qHBsAg. METHODS Plasmids expressing 1–8 amino acid deletion in pre-S1 ("pre-S1Δ1-8") and 3-25 amino acid deletion in pre-S2 ("pre-S2Δ3-25") were constructed. At 72 h posttransfection into Huh7 cells, qHBsAg were measured using electrochemiluminescence immunoassay analyzer. To mimic milieus of quasispecies, we co-transfected either pre-S1Δ1-8 or pre-S2Δ3-25 with wild type (WT). RESULTS Pre-S mutations affected transcription and replication ability of HBV because of altered overlapping polymerase. Compared with WT, extracellular qHBsAg in pre-S1Δ1-8 and pre-S2Δ3-25 were on average 3.87-fold higher and 0.92-fold lower, respectively, whereas intracellular qHBsAg in pre-S1Δ1-8 and pre-S2Δ3-25 were 0.57-fold lower and 1.60-fold higher, respectively. Immunofluorescence staining of cellular HBsAg showed that pre-S1Δ1-8 had less staining and that pre-S2Δ3-25 had denser staining. As ratios of either pre-S1Δ1-8 or pre-S2Δ3-25:WT increased from 0:10 to 10:0 gradually, relative extracellular qHBsAg increased from 1.0 to 3.85 in pre-S1Δ1-8 co-transfection, whereas those decreased from 1.0 to 0.88 in pre-S2Δ3-25 co-transfection. CONCLUSION Pre-S mutations exhibit different phenotypes of genome replication and HBsAg expression according to their locations. Thus, qHBsAg level for diagnosis and prognostification in chronic HBV infection should be used more cautiously, considering emergences of pre-S deletion mutants.
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Li X, Wang Y, Han D, Zhang W, Zhang Z, Ye X, Tian L, Dong Y, Zhu Q, Chen Y. Correlation of hepatitis B surface antigen level with response to telbivudine in naive patients with chronic hepatitis B. Hepatol Res 2014; 44:187-93. [PMID: 23607803 DOI: 10.1111/hepr.12105] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2012] [Revised: 01/31/2013] [Accepted: 02/24/2013] [Indexed: 02/08/2023]
Abstract
AIM Hepatitis B surface antigen (HBsAg) has become a marker to judge immunological response to hepatitis B therapy. Quantified serum HBsAg levels can predict the response to pegylated interferon and entecavir. In this study, we aimed to explore the correlation of serum HBsAg levels with response to telbivudine (LdT) treatment in patients with chronic hepatitis B (CHB). METHODS Seventy-three treatment-naive CHB patients were recruited and received LdT monotherapy for 52 weeks and serial HBsAg levels were measured at five protocol time points. According to therapeutic efficacy at week 52, three subgroups of patients were identified, including complete responders (CR), partial responders (PR) and non-responders (NR). RESULTS After 52 weeks of treatment, CR, PR and NR represented 19 (26%), 33 (45%) and 21 (29%) patients in the sample of 73, respectively. The median values of baseline HBsAg (log10 IU/mL) were 4.05, 4.50 and 5.03 for CR, PR and NR, respectively. There was a distinct decline of HBsAg at week 52; median log10 HBsAg levels (IU/mL) were 3.61 (CR), 3.86 (PR) and 4.31 (NR). Positive correlation between HBsAg levels and HBV DNA loads was observed in the group of NR and early antiviral treatment of PR, but not in CR. CONCLUSION Initial HBsAg level was closely correlated with the efficacy of LdT. Patients with low HBsAg levels presented satisfactory responses. Therefore, initial level and correlation with HBV DNA of the serum HBsAg levels could predict responsiveness in CHB patients receiving LdT.
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Affiliation(s)
- Xuefen Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Hadziyannis E, Hadziyannis SJ. Hepatitis B surface antigen quantification in chronic hepatitis B and its clinical utility. Expert Rev Gastroenterol Hepatol 2014; 8:185-95. [PMID: 24417264 DOI: 10.1586/17474124.2014.876362] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Serum HBsAg levels have been quantified extensively in recent years with simple completely automated assays in the various phases of the natural course of chronic HBV infection, have been compared with cccDNA in the liver, with various markers of HBV replication and have been correlated with several viral, host and environmental variables. Low HBsAg levels in inactive carriers predict a spontaneous HbsAg loss. Quantification of HBsAg in serum at baseline and its decline under interferon-alfa based regimens, both in HBeAg-positive and HBeAg-negative CHB, provides important information on the prediction of sustained post-treatment outcomes and on subsequent HBsAg clearance. The value of HBsAg quantification in the monitoring of long term nucleos(t)ide analogue treatment of CHB and in the prediction of sustained response remains unclear. In this review, the most recent data regarding the overall clinical utility of HBsAg measurement in HBeAg-positive and -negative CHB and in their treatment, is critically presented.
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Affiliation(s)
- Emilia Hadziyannis
- Academic Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, 114 Vas. Sophias Ave, Athens 11529, Greece
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Shouval D. Focus: quantitative HBsAg measurement as a new surrogate marker for assessment of hepatic fibrosis in HBeAg+ chronic hepatitis B. J Hepatol 2013; 58:1063-4. [PMID: 23499728 DOI: 10.1016/j.jhep.2013.03.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Accepted: 03/08/2013] [Indexed: 12/12/2022]
Affiliation(s)
- Daniel Shouval
- Liver Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
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Cabezas-Fernandez MT, Cabeza-Barrera MI. Introduction of an automated system for the diagnosis and quantification of hepatitis B and hepatitis C viruses. Open Virol J 2012; 6:122-34. [PMID: 23284598 PMCID: PMC3531716 DOI: 10.2174/1874357901206010122] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Revised: 09/18/2012] [Accepted: 09/20/2012] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections pose major public health problems because of their prevalence worldwide. Consequently, screening for these infections is an important part of routine laboratory activity. Serological and molecular markers are key elements in diagnosis, prognosis and treatment monitoring for HBV and HCV infections. Today, automated chemiluminescence immunoassay (CLIA) analyzers are widely used for virological diagnosis, particularly in high-volume clinical laboratories. Molecular biology techniques are routinely used to detect and quantify viral genomes as well as to analyze their sequence; in order to determine their genotype and detect resistance to antiviral drugs. Real-time PCR, which provides high sensitivity and a broad dynamic range, has gradually replaced other signal and target amplification technologies for the quantification and detection of nucleic acid. The next-generation DNA sequencing techniques are still restricted to research laboratories.The serological and molecular marker methods available for HBV and HCV are discussed in this article, along with their utility and limitations for use in Chronic Hepatitis B (CHB) diagnosis and monitoring.
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Analysis of mutations in the S gene of hepatitis B virus strains in patients with chronic infection by online bioinformatics tools. J Clin Microbiol 2012; 51:163-8. [PMID: 23115258 DOI: 10.1128/jcm.01630-12] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) genomes show a high rate of mutations. This can lead to a variety of amino acid changes in the surface and polymerase genes, causing changes in viral protein conformation that can result in diminished antibody binding or decreased secretion of surface antigen (HBsAg). HBV monitoring increasingly relies on HBsAg detection and quantification, and therefore epidemiological data on HBsAg mutations are needed. We therefore analyzed the frequency of HBsAg mutations possibly influencing the quantification of HBsAg (MUPIQHs) in an unselected patient collective. To this end, we determined the HBV surface and polymerase gene sequences of an unselected patient collective of 237 individuals chronically infected with HBV and analyzed the MUPIQHs in these sequences using three different online HBV sequence analysis tools. We found that 17 or 34% of the patients, depending on the online interpretation algorithm used, harbored MUPIQHs and that MUPIQHs were not significantly associated with the duration of disease, treatment, or HBV genotype. Thus, this study shows that a substantial amount of HBV sequences derived from unselected patients chronically infected with HBV carry MUPIQHs, and therefore the reliability of routine quantitative and qualitative HBsAg tests needs to be reevaluated.
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Abstract
UNLABELLED The guideline on the management of chronic hepatitis B (CHB) was first developed in 2004 and revised in 2007 by the Korean Association for the Study of the Liver (KASL). Since then there have been many developments, including the introduction of new antiviral agents and the publications of many novel research results from both Korea and other countries. In particular, a large amount of knowledge on antiviral resistance--which is a serious issue in Korea--has accumulated, which has led to new strategies being suggested. This prompted the new guideline discussed herein to be developed based on recent evidence and expert opinion. TARGET POPULATION The main targets of this guideline comprise patients who are newly diagnosed with CHB and those who are followed or treated for known CHB. This guideline is also intended to provide guidance for the management of patients under the following special circumstances: malignancy, transplantation, dialysis, coinfection with other viruses, pregnancy, and children.
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MESH Headings
- Acute Disease
- Adolescent
- Adult
- Aged
- Alanine Transaminase/blood
- Antiviral Agents/therapeutic use
- Asian People
- Aspartate Aminotransferases/blood
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/etiology
- Child
- Child, Preschool
- Coinfection/drug therapy
- DNA, Viral/blood
- Drug Resistance, Viral
- Drug Therapy, Combination
- Female
- Hepatitis B Surface Antigens/blood
- Hepatitis B e Antigens/blood
- Hepatitis B virus/genetics
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Humans
- Immunosuppression Therapy
- Infectious Disease Transmission, Vertical/prevention & control
- Liver/pathology
- Liver/physiology
- Liver Cirrhosis/physiopathology
- Liver Neoplasms/diagnosis
- Liver Neoplasms/etiology
- Liver Transplantation
- Male
- Middle Aged
- Pregnancy
- Renal Dialysis
- Republic of Korea
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Buti M, Rodríguez Frías F, Esteban R. [Quantification of hepatitis B virus HBsAg: clinical implications]. Med Clin (Barc) 2012; 138:483-8. [PMID: 21719049 DOI: 10.1016/j.medcli.2011.04.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2011] [Revised: 04/18/2011] [Accepted: 04/28/2011] [Indexed: 02/07/2023]
Abstract
The surface antigen of hepatitis B virus (HBsAg) is the main serological marker of HBV infection since its discovery almost 50 years ago. Currently the quantification of HBsAg has acquired special relevance as there are commercial tests to measure its levels. Several studies have shown that in patients treated with pegylated interferon alfa the fall of HBsAg levels predicts the loss of HBsAg and persistent virologic response. The role of the quantification of HBsAg in the treatment with nucleoside analogues is still not well understood and requires further studies.
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Affiliation(s)
- Maria Buti
- Servicio de Hepatología, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
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Lee JM, Ahn SH, Kim HS, Park H, Chang HY, Kim DY, Hwang SG, Rim KS, Chon CY, Han KH, Park JY. Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir. Hepatology 2011; 53:1486-93. [PMID: 21520167 DOI: 10.1002/hep.24221] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
UNLABELLED Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen-positive [HBeAg(+)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/mL), and 1.71 Paul Ehrlich (PE) IU/mL (-0.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(+) patients, baseline alanine aminotransferase (P = 0.013), HBV DNA (P = 0.040), and qHBsAg levels (P = 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(+) group versus the SR(-) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(+) patients. CONCLUSION Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(+) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated.
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Affiliation(s)
- Jung Min Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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