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Ma X, Huang T, Song Y, Pan H, Du A, Zhou X, Zeng Y, Yuan K. Bioinformatics and system biology approach to discover the common pathogenetic processes between COVID-19 and chronic hepatitis B. PLoS One 2025; 20:e0323708. [PMID: 40408617 PMCID: PMC12101853 DOI: 10.1371/journal.pone.0323708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 04/12/2025] [Indexed: 05/25/2025] Open
Abstract
INTRODUCTION The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents a significant global public health threat. Concurrently, hepatitis B virus (HBV) remains a significant public health challenge. While previous studies have indicated an association between COVID-19 and chronic hepatitis B, the common underlying pathogenesis of these diseases remains incompletely understood. METHODS To investigate the shared molecular mechanisms between chronic HBV infection and COVID-19, a comprehensive investigation was conducted using bioinformatics and systems biology. Specifically, we utilized RNA-seq datasets (GSE196822 and GSE83148) to identify differentially expressed genes (DEGs) associated with both SARS-CoV-2 and HBV infection. Subsequently, these common DEGs were utilized to identify shared pathways, hub genes, transcriptional regulatory networks, and potential drugs. The differential expression of hub genes in both COVID-19 and HBV was verified using the GSE171110 and GSE94660 datasets, respectively. RESULTS From the 106 shared DEGs identified, immune-related pathways were found to play a role in the development and progression of chronic hepatitis B and COVID-19. Protein-protein interaction (PPI) network analysis revealed 8 hub genes: CDK1, E2F7, E2F8, TYMS, KIF20A, CENPE, TPX2, HMMR, CD8A, GZMA. In the validation set, the expression of hub genes was statistically significant in both the COVID-19 group and the HBV group compared with the healthy control group. Transcriptional regulatory network analysis identified 155 microRNAs (miRNAs) and 43 transcription factors (TFs) as potential regulatory signals. Notably, we identified potential therapeutic drugs for HBV chronic infection and COVID-19, including progesterone, estradiol, dasatinib, aspirin, etoposide, irinotecan hydrochloride, phorbol 12-myristate 13-acetate, lucanthone, calcitriol. CONCLUSION This research elucidates potential molecular targets, signaling pathways, and promising small molecule compounds that could aid in the treatment of chronic HBV infection and COVID-19.
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Affiliation(s)
- Xiao Ma
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Tengda Huang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yujia Song
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Hongyuan Pan
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Ao Du
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xinyi Zhou
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Zeng
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Kefei Yuan
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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Salfi AB, Hussain M, Majeed MI, Nawaz H, Rashid N, Albekairi NA, Alshammari A, Yousaf A, Ullah MH, Fatima E, Mehmood S, Hakeem M, Amin I, Javed M. Surface-enhanced Raman spectroscopy for the characterization of filtrate portions of hepatitis B blood serum samples using 100 kDa ultra filtration devices. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 333:125883. [PMID: 39978181 DOI: 10.1016/j.saa.2025.125883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 12/30/2024] [Accepted: 02/08/2025] [Indexed: 02/22/2025]
Abstract
The blood serum of patients infected by the Hepatitis B virus contains high molecular weight fractions and low molecular weight fractions (LMWF) of biomarker proteins of the disease. The LMWF including the associated peptidome and metabolome, is recognized as a critical molecular population with high potential for research on disease-associated biomarkers. This fraction of biomarkers can be suppressed by HMWF, proteins such as albumin, and immunoglobulins hence difficult to be detected. The purpose of this study is to separate HMWF) and LMWF using 100 kDa centrifugal filtration devices resulting in two parts including residue (HMWF) and filtrate parts (LMWF) of blood serum followed by the analysis of the later part employing surface-enhanced Raman spectroscopy (SERS). This strategy can enhance this optical technique's capability to characterize the biochemical changes caused by the infection of HBV and the diagnosis of the disease. The silver nanoparticles (Ag-NPs) were employed as a SERS substrate to distinguish between filtrate parts of the blood serum of HBV patients and healthy individuals based on their specific SERS peaks. The SERS spectral features associated with the filtrate parts of HBV patients' blood serum are well differentiated from the healthy volunteers. Principle component analysis (PCA) was applied on the SERS spectral data sets of HBV patients and healthy individuals and found extremely beneficial for the classification of their SERS spectral groups. Moreover, partial least square regression analysis (PLSR) has shown excellent performance in the quantitative analysis of the viral load values of the HBV patients using their SERS spectral data sets.
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Affiliation(s)
- Abu Bakar Salfi
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000 Pakistan
| | - Munawar Hussain
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000 Pakistan
| | - Muhammad Irfan Majeed
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000 Pakistan.
| | - Haq Nawaz
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000 Pakistan.
| | - Nosheen Rashid
- Department of Chemistry, University of Education, Faisalabad Campus, Faisalabad 38000 Pakistan
| | - Norah A Albekairi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451 Saudi Arabia
| | - Abdulrahman Alshammari
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451 Saudi Arabia
| | - Arslan Yousaf
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000 Pakistan
| | - Muhammad Hafeez Ullah
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000 Pakistan
| | - Eman Fatima
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000 Pakistan
| | - Sana Mehmood
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000 Pakistan
| | - Munazza Hakeem
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000 Pakistan
| | - Imran Amin
- PCR Laboratory, PINUM Hospital, Faisalabad 38000 Pakistan
| | - Mahrosh Javed
- Nacionalinis Fizinių ir technologijos mokslų centras (NFTMC), Department of Environmental Research, Lithuania
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Qu Y, Gao N, Zhang S, Gao L, He B, Wang C, Gong C, Shi Q, Li Z, Yang S, Xiao Y. Role of N6-methyladenosine RNA modification in cancer. MedComm (Beijing) 2024; 5:e715. [PMID: 39252821 PMCID: PMC11381670 DOI: 10.1002/mco2.715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 08/13/2024] [Accepted: 08/13/2024] [Indexed: 09/11/2024] Open
Abstract
N6-methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells. Previous studies have shown that m6A is pivotal in diverse diseases especially cancer. m6A corelates with the initiation, progression, resistance, invasion, and metastasis of cancer. However, despite these insights, a comprehensive understanding of its specific roles and mechanisms within the complex landscape of cancer is still elusive. This review begins by outlining the key regulatory proteins of m6A modification and their posttranslational modifications (PTMs), as well as the role in chromatin accessibility and transcriptional activity within cancer cells. Additionally, it highlights that m6A modifications impact cancer progression by modulating programmed cell death mechanisms and affecting the tumor microenvironment through various cancer-associated immune cells. Furthermore, the review discusses how microorganisms can induce enduring epigenetic changes and oncogenic effect in microorganism-associated cancers by altering m6A modifications. Last, it delves into the role of m6A modification in cancer immunotherapy, encompassing RNA therapy, immune checkpoint blockade, cytokine therapy, adoptive cell transfer therapy, and direct targeting of m6A regulators. Overall, this review clarifies the multifaceted role of m6A modification in cancer and explores targeted therapies aimed at manipulating m6A modification, aiming to advance cancer research and improve patient outcomes.
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Affiliation(s)
- Yi Qu
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
| | - Nannan Gao
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
| | - Shengwei Zhang
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
| | - Limin Gao
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
| | - Bing He
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
| | - Chao Wang
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
| | - Chunli Gong
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
| | - Qiuyue Shi
- Department of Gastroenterology the First Affiliated Hospital of Guangxi Medical University Nanning Guangxi China
| | - Zhibin Li
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
| | - Shiming Yang
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
| | - Yufeng Xiao
- Department of Gastroenterology Xinqiao Hospital Army Medical University Chongqing China
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Du K, Wang X, Bai Y, Zhang X, Xue J, Li S, Xie Y, Sang Z, Tang Y, Wang X. Development of benzimidazole-based compounds as novel capsid assembly modulators for the treatment of HBV infection. Eur J Med Chem 2024; 271:116402. [PMID: 38636128 DOI: 10.1016/j.ejmech.2024.116402] [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: 03/03/2024] [Revised: 04/06/2024] [Accepted: 04/07/2024] [Indexed: 04/20/2024]
Abstract
Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV infection. In this study, the hit compound CDI (IC50 = 2.46 ± 0.33 μM) was identified by screening of an in-house compound library. And then novel potent benzimidazole derivatives were designed and synthesized as core assembly modulators, and their antiviral effects were evaluated in vitro and in vivo biological experiments. The results indicated that compound 26f displayed the most optimized modulator of HBV capsid assembly (IC50 = 0.51 ± 0.20 μM, EC50 = 2.24 ± 0.43 μM, CC50 = 84.29 μM) and high selectivity index. Moreover, treatment with compound 26f for 14 days significantly decreased serum levels of HBV DNA levels in the Hydrodynamic-Injection (HDI) mouse model. Therefore, compound 26f could be considered as a promising candidate drug for further development of novel HBV CAMs with the desired potency and safety.
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Affiliation(s)
- Kaixin Du
- Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China
| | - Xianyang Wang
- Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China
| | - Yuxin Bai
- Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China
| | - Xue Zhang
- Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China
| | - Jie Xue
- Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China
| | - Shanshan Li
- Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China
| | - Youhua Xie
- Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infectious Diseases and Biosecurity, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
| | - Zhipei Sang
- Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China.
| | - Yu Tang
- Key Laboratory of Marine Drugs, Chinese Ministry of Education, Ocean University of China, Qingdao, 266003, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, 266237, China; Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China.
| | - Xin Wang
- Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China.
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Liu S, Hu M, Liu X, Liu X, Chen T, Zhu Y, Liang T, Xiao S, Li P, Ma X. Nanoparticles and Antiviral Vaccines. Vaccines (Basel) 2023; 12:30. [PMID: 38250843 PMCID: PMC10819235 DOI: 10.3390/vaccines12010030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/19/2023] [Accepted: 12/22/2023] [Indexed: 01/23/2024] Open
Abstract
Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to induce strong protective immunity while generating few adverse effects. With advancements in biochemistry and biophysics, different kinds of vaccines in versatile forms have been utilized to prevent virus infections, although the safety and effectiveness of these vaccines are diverse from each other. In this review, we first listed and described major pathogenic viruses and their pandemics that emerged in the past two centuries. Furthermore, we summarized the distinctive characteristics of different antiviral vaccines and adjuvants. Subsequently, in the main body, we reviewed recent advances of nanoparticles in the development of next-generation vaccines against influenza viruses, coronaviruses, HIV, hepatitis viruses, and many others. Specifically, we described applications of self-assembling protein polymers, virus-like particles, nano-carriers, and nano-adjuvants in antiviral vaccines. We also discussed the therapeutic potential of nanoparticles in developing safe and effective mucosal vaccines. Nanoparticle techniques could be promising platforms for developing broad-spectrum, preventive, or therapeutic antiviral vaccines.
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Affiliation(s)
- Sen Liu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China
| | - Meilin Hu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511400, China
| | - Xiaoqing Liu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China
| | - Xingyu Liu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
| | - Tao Chen
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511400, China
| | - Yiqiang Zhu
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
| | - Taizhen Liang
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511400, China
| | - Shiqi Xiao
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
| | - Peiwen Li
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
| | - Xiancai Ma
- Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China; (S.L.); (M.H.); (X.L.); (X.L.); (T.C.); (Y.Z.); (T.L.); (S.X.); (P.L.)
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511400, China
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China
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Chen SJ, Rai CI, Wang SC, Chen YC. Point-of-Care Testing for Infectious Diseases Based on Class 2 CRISPR/Cas Technology. Diagnostics (Basel) 2023; 13:2255. [PMID: 37443646 PMCID: PMC10340307 DOI: 10.3390/diagnostics13132255] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 06/25/2023] [Accepted: 06/28/2023] [Indexed: 07/15/2023] Open
Abstract
The early detection of infectious diseases and microorganisms is critical for effective disease treatment, control, and prevention. Currently, nucleic acid testing and antigen-antibody serum reaction are the two methods most commonly used for the detection of infectious diseases. The former is highly accurate, specific, and sensitive, but it is time-consuming, expensive, and has special technician and instrument requirements. The latter is rapid and economical, but it may not be accurate and sensitive enough. Therefore, it is necessary to develop a quick and on-site diagnostic test for point-of-care testing (POCT) to enable the clinical detection of infectious diseases that is accurate, sensitive, convenient, cheap, and portable. Here, CRISPR/Cas-based detection methods are detailed and discussed in depth. The powerful capacity of these methods will facilitate the development of diagnostic tools for POCT, though they still have some limitations. This review explores and highlights POCT based on the class 2 CRISPR/Cas assay, such as Cas12 and Cas13 proteins, for the detection of infectious diseases. We also provide an outlook on perspectives, multi-application scenarios, clinical applications, and limitations for POCT based on class 2 CRISPR/Cas technology.
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Affiliation(s)
- Shiu-Jau Chen
- Department of Neurosurgery, Mackay Memorial Hospital, Taipei 10449, Taiwan;
- Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan
| | - Chung-I Rai
- Health Care Business Group, Foxconn Technology Co., Ltd., New Taipei City 23680, Taiwan;
- Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei City 106335, Taiwan
| | - Shao-Cheng Wang
- Department of Psychiatric, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan
- Department of Nurse-Midwifery and Women Health, National Taipei University of Nursing and Health Sciences, Taipei 112303, Taiwan
| | - Yuan-Chuan Chen
- Department of Nursing, Jenteh Junior College of Medicine, Nursing and Management, Miaoli County 35664, Taiwan
- Department of Medical Technology, Jenteh Junior College of Medicine, Nursing and Management, Miaoli County 35664, Taiwan
- Program in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA
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Gao C, Ni J, Gao Y, Xie D, Yang L, Yang B, Lu X, Guo Q. Association of current hepatitis B virus infection with mortality in adults with sepsis. Epidemiol Infect 2023; 151:e94. [PMID: 37203184 PMCID: PMC10311682 DOI: 10.1017/s0950268823000729] [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: 03/19/2023] [Accepted: 05/04/2023] [Indexed: 05/20/2023] Open
Abstract
This study aimed to determine the impact of current hepatitis B virus (HBV) infection on patients hospitalised with sepsis. This was a retrospective cohort study. Patients from three medical centres in Suzhou from 10 January 2016 to 23 July 2022 participated in this study. Demographic characteristics and clinical characteristics were collected. A total of 945 adult patients with sepsis were included. The median age was 66.0 years, 68.6% were male, 13.1% presented with current HBV infection, and 34.9% of all patients died. In the multivariable-adjusted Cox model, patients with current HBV infection had significantly higher mortality than those without (hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.11-2.02). A subgroup analysis showed that being infected with HBV significantly increased in-hospital mortality in patients younger than 65 years old (HR 1.74, 95% CI 1.16-2.63), whereas no significant impact was observed in patients ≥65 years. The propensity score-matched case-control analysis showed that the rate of septic shock (91.4% vs. 62.1%, P < 0.001) and in-hospital mortality (48.3% vs. 35.3%, P = 0.045) were much higher in the propensity score-matched HBV infection group compared with the control group. In conclusion, current HBV infection was associated with mortality in adults with sepsis.
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Affiliation(s)
- Chang Gao
- Department of Emergency and Critical Care Medicine, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China
- Medical Center of Soochow University, Suzhou, China
- Institute of Critical Care Medicine, Soochow University, Suzhou, China
| | - Jingjing Ni
- Department of Critical Care Medicine, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China
| | - Ye Gao
- Department of Critical Care Medicine, Taicang Hospital Affiliated to Soochow University, Suzhou, China
| | - Dan Xie
- Department of Emergency and Critical Care Medicine, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, China
| | - Lijuan Yang
- Suzhou Medical College, Soochow University, Suzhou, China
| | - Bining Yang
- Department of Emergency and Critical Care Medicine, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China
- Medical Center of Soochow University, Suzhou, China
- Institute of Critical Care Medicine, Soochow University, Suzhou, China
| | - Xiaoting Lu
- Department of Emergency and Critical Care Medicine, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China
- Medical Center of Soochow University, Suzhou, China
- Institute of Critical Care Medicine, Soochow University, Suzhou, China
| | - Qiang Guo
- Department of Emergency and Critical Care Medicine, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China
- Medical Center of Soochow University, Suzhou, China
- Institute of Critical Care Medicine, Soochow University, Suzhou, China
- Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China
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Sarowar A, Hirode G, Janssen HLA, Feld JJ. Controversies in Treating Chronic Hepatitis B Virus Infection: Discordant Serologic Results. Clin Liver Dis 2021; 25:805-816. [PMID: 34593154 DOI: 10.1016/j.cld.2021.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Despite effective vaccines and approved therapeutic agents, hepatitis B virus (HBV) remains a prevalent global health problem. Current guidelines rely on a combination of serologic, virological, and biochemical markers to identify the phase in the natural history of chronic HBV infection. Discordant serologic results can occur, which may lead to misclassification. Commonly encountered results that differ from the typical profiles seen in chronic HBV infection are described. For each scenario, the frequency of occurrence, possible explanations, and recommendations for clinical management are discussed. Recognition of discordant serologic findings is crucial for optimal clinical decision.
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Affiliation(s)
- Arif Sarowar
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | - Grishma Hirode
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
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Abstract
Hepatitis B was discovered by researchers who were investigating jaundice associated with blood transfusions as well as parenterally administered medications. Through trial and error, the HBV was identified. There are specific tests that detect HBV infection, whether it is a previous exposure or active infection. The various HBV serologies are reviewed in this work as well. Hepatitis B surface antigen has emerged as a tool in defining treatment endpoint and its significance is reviewed. HBV genotypes are distributed uniquely throughout the world, in particular, genotype C is associated with higher rates of hepatocellular carcinoma. Various HBV genotypes and their impact on the clinical course are discussed. The relationship of HBV serologies and HBV DNA to disease progression is outlined. There are specific recommendations on monitoring those infected with HBV and this is reviewed here. HBV mutations have an impact on the disease course and those of significance are also discussed.
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Abd Muain MF, Cheo KH, Omar MN, Amir Hamzah AS, Lim HN, Salleh AB, Tan WS, Ahmad Tajudin A. Gold nanoparticle-decorated reduced-graphene oxide targeting anti hepatitis B virus core antigen. Bioelectrochemistry 2018; 122:199-205. [PMID: 29660648 DOI: 10.1016/j.bioelechem.2018.04.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Revised: 04/03/2018] [Accepted: 04/06/2018] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus core antigen (HBcAg) is the major structural protein of hepatitis B virus (HBV). The presence of anti-HBcAg antibody in a blood serum indicates that a person has been exposed to HBV. This study demonstrated that the immobilization of HBcAg onto the gold nanoparticles-decorated reduced graphene oxide (rGO-en-AuNPs) nanocomposite could be used as an antigen-functionalized surface to sense the presence of anti-HBcAg. The modified rGO-en-AuNPs/HBcAg was then allowed to undergo impedimetric detection of anti-HBcAg with anti-estradiol antibody and bovine serum albumin as the interferences. Upon successful detection of anti-HBcAg in spiked buffer samples, impedimetric detection of the antibody was then further carried out in spiked human serum samples. The electrochemical response showed a linear relationship between electron transfer resistance and the concentration of anti-HBcAg ranging from 3.91ngmL-1 to 125.00ngmL-1 with lowest limit of detection (LOD) of 3.80ngmL-1 at 3σm-1. This established method exhibits potential as a fast and convenient way to detect anti-HBcAg.
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Affiliation(s)
- Mohamad Farid Abd Muain
- Enzyme and Microbial Technology Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia; Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Kooi Hoong Cheo
- Enzyme and Microbial Technology Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia; Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Muhamad Nadzmi Omar
- Enzyme and Microbial Technology Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia; Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Amir Syahir Amir Hamzah
- Enzyme and Microbial Technology Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia; Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Hong Ngee Lim
- Functional Device Laboratory, Institute of Advanced Technology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Abu Bakar Salleh
- Enzyme and Microbial Technology Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia; Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Wen Siang Tan
- Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia; Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Asilah Ahmad Tajudin
- Enzyme and Microbial Technology Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia; Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia.
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Silva Souza ACD, Souza Marasca GD, Kretzmann-Filho NA, Dall-Bello A, Alexandre Kliemann D, Valle Tovo C, Gorini da Veiga AB. Identification of hepatitis B virus A1762T/G1764A double mutant strain in patients in Southern Brazil. Braz J Infect Dis 2017; 21:525-529. [PMID: 28606415 PMCID: PMC9425463 DOI: 10.1016/j.bjid.2017.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 04/12/2017] [Accepted: 05/11/2017] [Indexed: 01/09/2023] Open
Abstract
Infection by hepatitis B virus (HBV) is a worldwide public health problem. Chronic HBV infection with high viral replication may lead to cirrhosis and/or hepatocellular carcinoma. Mutant HBV strains, such as the HBV A1762T/G1764A double mutant, have been associated with poor prognosis and higher risk of the patient for developing cirrhosis and/or hepatocellular carcinoma. This study analyzed the presence of the HBV A1762T/G1764A double mutant in patients with chronic HBV and its association with clinical parameters such as viral load, aminotransferases, and HBV antigens. A total of 49 patients with chronic hepatitis B were included in the study, and the HBV A1762T/G1764A double mutant strain was detected in four samples (8.16%) by polymerase chain reaction followed by restriction fragment length analysis (PCR-RFLP). The viral load was not significantly different between patients with or without the double mutant strain (p=0.43). On the other hand, carriers of the HBV A1762T/G1764A double mutant had higher levels of ALT (p=0.0028), while AST levels did not differ between groups (p=0.051). In this study, 75% of the samples with the HBV A1762T/G1764A double mutation were HBeAg negative and anti-HBe positive, reflecting seroconversion even though they still displayed high viral loads. Our study has shown that the HBV A1762T/G1764A double mutant strain circulates in Brazilian patients, and is associated with elevated levels of ALT and HBeAg seroconversion.
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Affiliation(s)
- Adaliany Cecília da Silva Souza
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pos-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brazil
| | - Giórgia de Souza Marasca
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pos-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brazil
| | - Nélson Alexandre Kretzmann-Filho
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pos-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brazil
| | - Aline Dall-Bello
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pos-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brazil
| | - Dimas Alexandre Kliemann
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pos-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brazil; Hospital Nossa Senhora da Conceição (HNSC), Porto Alegre, RS, Brazil
| | - Cristiane Valle Tovo
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pos-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brazil; Hospital Nossa Senhora da Conceição (HNSC), Porto Alegre, RS, Brazil
| | - Ana Beatriz Gorini da Veiga
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pos-Graduação em Medicina: Hepatologia, Porto Alegre, RS, Brazil.
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12
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Mulrooney-Cousins P, Michalak T. Molecular Testing in Hepatitis Virus Related Disease. DIAGNOSTIC MOLECULAR PATHOLOGY 2017:63-73. [DOI: 10.1016/b978-0-12-800886-7.00006-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Piroth L, Pol S, Miailhes P, Lacombe K, Lopes A, Fillion A, Loustaud-Ratti V, Borsa-Lebas F, Salmon D, Rosenthal E, Carrat F, Cacoub P. Therapeutic management and evolution of chronic hepatitis B: does HIV still have an impact? The EPIB 2012 study. Liver Int 2015; 35:1950-1958. [PMID: 25559645 DOI: 10.1111/liv.12777] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Accepted: 12/22/2014] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS To compare the management of chronic hepatitis B (CHB) and its evolution over time in currently followed HIV-positive and HIV-negative patients. METHODS A total of 709 consecutive patients with past or present positive HBs antigenemia seen in October 2012 in 19 French participating centres were included. The data were retrospectively collected from the first visit onwards through standardized questionnaires. RESULTS Chronic hepatitis B was less often assessed in the 299 HIV-positive patients, who were older, more likely to be male, excessive alcohol drinkers and HBe antigen-, HCV- and HDV-positive. They were also followed up for a longer time (11.3 +/-8.8 vs. 8.6 +/-6.9 years, P < 10(-3) ) and were more frequently treated for HBV (95.3% vs. 56.8%, P < 10(-3) ). HBV was undetectable at the last visit in 80.8% of HIV-positive vs. 55.1% of HIV-negative patients (P < 10(-3) ). In multivariate analyses, undetectable HBV was significantly associated with older age, lower baseline HBV DNA, longer HBV therapy and no previous lamivudine monotherapy, but not with HIV. Cirrhosis was associated with age, male gender, Asian origin, alcoholism, HCV, HDV, but not with HIV infection. Hepatocellular carcinoma, less frequently observed in HIV-positive patients (0.7% vs. 4.7%, P = 0.002), was positively associated with age, male gender, cirrhosis and negatively associated with HIV infection (OR 0.15, 95%CI 0.03-0.67, P = 0.01). CONCLUSIONS Although the assessment of CHB still has to be improved in HIV-positive patients, the negative impact of HIV on the virological, histological and clinical evolution of CHB seems to be disappearing, probably because of the immunovirological impact of HAART and the more frequent and longer use of HBV therapy.
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Affiliation(s)
- Lionel Piroth
- Infectious Diseases Department, CHU and UMR 1347, University of Burgundy, Dijon, France
| | - Stanislas Pol
- Institut Pasteur, INSERM UMS 20, Service d'Hépatologie, Université Paris Descartes and APHP, Paris, France
| | - Patrick Miailhes
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales and INSERM U1052, Lyon, France
| | - Karine Lacombe
- Infectious Diseases Department, CHU and UMR-S707, University Pierre and Marie Curie, Paris, France
| | - Amanda Lopes
- Université Paris Diderot and AP-HP Service de Medecine Interne A, Paris, France
| | - Aurélie Fillion
- Infectious Diseases Department, CHU and UMR 1347, University of Burgundy, Dijon, France
| | - Véronique Loustaud-Ratti
- Federation of Hepatology CHU Limoges and Inserm UMR 1092, University of Limoges, Limoges, France
| | | | - Dominique Salmon
- Cochin Hospital, Infectious Pathology unit, Paris Descartes University, Infectious Pathology unit, Paris, France
| | - Eric Rosenthal
- Department of internal medicine, CHU De Nice and University of Nice Sophia Antipolis, Nice, France
| | - Fabrice Carrat
- UPMC Université Paris 06, UMR-S707, INSERM U-707, AP-HP, Public Health Department, Paris, France
| | - Patrice Cacoub
- Departement Hospitalo Universitaire I2B, UPMC Université Paris 06, Paris, France
- UMR 7211, INSERM, UMR_S 959, Paris, France
- CNRS, UMR 7211, Paris, France
- Department of Internal Medicine, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
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14
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Liu W, Hu Y, Yang Y, Hu T, Wang X. Comparison of two immunoassays for quantification of hepatitis B surface antigen in Chinese patients with concomitant hepatitis B surface antigen and hepatitis B surface antibodies. Arch Virol 2014; 160:191-8. [PMID: 25323529 DOI: 10.1007/s00705-014-2253-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Accepted: 09/30/2014] [Indexed: 01/15/2023]
Abstract
Two commercial quantitative immunoassay platforms are currently available for the detection of hepatitis B surface antigen (HBsAg) within a wide range of concentrations: the Architect HBsAg assay and the Elecsys HBsAg II. However, there are limited data concerning their performance in patients who are positive for both HBsAg and anti-HBs antibodies. In the present study, 127 serum samples from Chinese patients with hepatitis B carrying both HBsAg and anti-HBs antibodies were analyzed. HBsAg levels measured in parallel using the Elecsys HBsAg II and Architect HBsAg assay were compared. There was a significant correlation between HBsAg levels measured by Elecsys HBsAg II and Architect HBsAg assay (correlation coefficient, r = 0.992, P < 0.05). Bland-Altman analysis indicated only minor discordance between the methods (mean difference between Elecsys HBsAg II and Architect HBsAg assay, -0.02 log10 IU/ml; 95 % confidence interval, -0.40-0.37 log10 IU/ml). In conclusion, the results of the quantitative Elecsys HBsAg II were highly correlated with those of the Architect HBsAg assay in patients carrying both HBsAg and anti-HBs antibodies, but differences were observed between the platforms in samples with low HBsAg levels.
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Affiliation(s)
- Weiwei Liu
- Department of Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China,
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15
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Tan WS, Ho KL. Phage display creates innovative applications to combat hepatitis B virus. World J Gastroenterol 2014; 20:11650-11670. [PMID: 25206271 PMCID: PMC4155357 DOI: 10.3748/wjg.v20.i33.11650] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Accepted: 05/05/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) has killed countless lives in human history. The invention of HBV vaccines in the 20th century has reduced significantly the rate of the viral infection. However, currently there is no effective treatment for chronic HBV carriers. Newly emerging vaccine escape mutants and drug resistant strains have complicated the viral eradication program. The entire world is now facing a new threat of HBV and human immunodeficiency virus co-infection. Could phage display provide solutions to these life-threatening problems? This article reviews critically and comprehensively the innovative and potential applications of phage display in the development of vaccines, therapeutic agents, diagnostic reagents, as well as gene and drug delivery systems to combat HBV. The application of phage display in epitope mapping of HBV antigens is also discussed in detail. Although this review mainly focuses on HBV, the innovative applications of phage display could also be extended to other infectious diseases.
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Monjezi R, Tan SW, Tey BT, Sieo CC, Tan WS. Detection of hepatitis B virus core antigen by phage display mediated TaqMan real-time immuno-PCR. J Virol Methods 2012; 187:121-6. [PMID: 23022731 DOI: 10.1016/j.jviromet.2012.09.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2011] [Revised: 05/03/2012] [Accepted: 09/19/2012] [Indexed: 12/12/2022]
Abstract
The core antigen (HBcAg) of hepatitis B virus (HBV) is one of the markers for the identification of the viral infection. The main purpose of this study was to develop a TaqMan real-time detection assay based on the concept of phage display mediated immuno-PCR (PD-IPCR) for the detection of HBcAg. PD-IPCR combines the advantages of immuno-PCR (IPCR) and phage display technology. IPCR integrates the versatility of enzyme-linked immunosorbent assay (ELISA) with the sensitivity and signal generation power of PCR. Whereas, phage display technology exploits the physical association between the displayed peptide and the encoding DNA within the same phage particle. In this study, a constrained peptide displayed on the surface of an M13 recombinant bacteriophage that interacts tightly with HBcAg was applied as a diagnostic reagent in IPCR. The phage displayed peptide and its encoding DNA can be used to replace monoclonal antibody (mAb) and chemically bound DNA, respectively. This method is able to detect as low as 10ng of HBcAg with 10(8)pfu/ml of the recombinant phage which is about 10,000 times more sensitive than the phage-ELISA. The PD-IPCR provides an alternative means for the detection of HBcAg in human serum samples.
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Affiliation(s)
- Razieh Monjezi
- Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
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17
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Piroth L, Pol S, Lacombe K, Miailhes P, Rami A, Rey D, Loustau-Ratti V, Morlat P, Goderel I, Sene D, Rosenthal E, Carrat F, Cacoub P. Management and treatment of chronic hepatitis B virus infection in HIV positive and negative patients: the EPIB 2008 study. J Hepatol 2010; 53:1006-12. [PMID: 20800920 DOI: 10.1016/j.jhep.2010.04.041] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2010] [Revised: 03/23/2010] [Accepted: 04/06/2010] [Indexed: 12/04/2022]
Abstract
BACKGROUND & AIMS To compare the management and the virological and serological efficacy of treatments for chronic hepatitis B (CHB) in HIV positive and negative patients. METHODS Two hundred and forty-six HIV positive and 205 HIV negative consecutive patients with past or present CHB, seen in October 2008 in participating departments, were included in a multicenter study. All the data were retrospectively collected from the first visit to October 2008 through a standardized questionnaire. RESULTS Compared to HIV negative patients, HIV positive patients more often presented positive HBeAg (46.4% vs. 32.8%, p=0.01), HBV genotype A (54.8% vs. 17.1%, p<0.0001), co-infection with HCV (12.4% vs. 5.9%, p=0.0002) or HDV (12.6% vs. 2.9%, p=0.04). HIV positive patients were more often on HBV therapy (92.7% vs. 57.1%, p<0.0001), leading to undetectable serum HBV DNA levels (71.0% vs. 44.1%, p<0.0001). In HIV positive patients, multivariate analysis showed that older age, lower initial HBV DNA levels, and longer time on HBV therapy significantly correlated with undetectable HBV DNA. No difference in efficacy was observed between tenofovir used alone or in combination. HBsAg (but not HBe) loss was more often observed in HIV positive patients, sometimes followed by HBsAg re-appearance after withdrawal of HBV treatment. Excluding the 37 HBV-HCV-co-infected patients, the last clinical presentation and liver fibrosis scores were similar in HIV positive and negative patients. CONCLUSIONS The assessment of CHB and the efficacy of HBV therapy have improved in HIV positive patients. HIV infection did not have a negative impact on the likelihood of HBV therapeutic success.
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Affiliation(s)
- Lionel Piroth
- Service de Maladies Infectieuses et Tropicales, CHU Dijon and Université de Bourgogne, France.
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Mahboobi N, Agha-Hosseini F, Mahboobi N, Safari S, Lavanchy D, Alavian SM. Hepatitis B virus infection in dentistry: a forgotten topic. J Viral Hepat 2010; 17:307-16. [PMID: 20196802 DOI: 10.1111/j.1365-2893.2010.01284.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
More than two billion people have been infected with hepatitis B virus (HBV). Globally, 350-400 million suffer from chronic HBV infection. It is postulated that dentists and dental staff are infected and transmit the virus to their patients more than any other occupation. The aim of this article is to review the HBV incidence in dental society, the points of view of dentists and their patients regarding transmission of the virus during dental procedures, the occurrence of HBV outbreaks in dental clinics and the importance of methods of preventing HBV infection in dentistry.
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Affiliation(s)
- N Mahboobi
- Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
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19
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Ferraro D, Pizzillo P, Di Marco V, Vultaggio A, Iannitto E, Venezia G, Craxì A, Di Stefano R. Evaluating the risk of hepatitis B reactivation in patients with haematological malignancies: is the serum hepatitis B virus profile reliable? Liver Int 2009; 29:1171-7. [PMID: 19602139 DOI: 10.1111/j.1478-3231.2009.02071.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND/AIM Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases. METHODS We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients requiring chemotherapy. RESULTS Thirty-three patients (44%) were HBV seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV seropositive (anti-HBc and/or anti-HBs positive). Baseline serum HBV DNA was positive in nine out of 33 HBV-seronegative patients and in nine out of 42 HBV-seropositive patients (27.3 vs. 21.4%; P=NS). HBsAg seroconversion was observed in five out of 33 seronegative vs. six out of 42 seropositive patients (15 vs. 14%, P=0.9), and in five out of 18 HBV DNA-positive vs. six out of 57 HBV DNA-negative patients (27.7 vs. 10.6%P=0.11). Hepatitis C virus infection was found in 18 patients (24.3%), although with no correlation to HBV serological status, presence of serum HBV DNA or frequency of HBsAg seroconversion. CONCLUSIONS In oncohaematological patients undergoing chemotherapy, highly sensitive serum HBV DNA testing at baseline has a 28% predictive ability to forecast HBsAg seroconversion in HBV DNA-positive patients, and a 90% ability to forecast persistent HBsAg negativity in HBV DNA-negative patients, a better performance than serological tests.
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Affiliation(s)
- Donatella Ferraro
- Cattedra di Virologia, Dipartimento di Scienze per la Promozione della Salute 'G. D'Alessandro', University of Palermo, Sicily, Italy.
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20
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Cha BH, Lee SM, Park JC, Hwang KS, Kim SK, Lee YS, Ju BK, Kim TS. Detection of Hepatitis B Virus (HBV) DNA at femtomolar concentrations using a silica nanoparticle-enhanced microcantilever sensor. Biosens Bioelectron 2009; 25:130-5. [PMID: 19616931 DOI: 10.1016/j.bios.2009.06.015] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2009] [Revised: 06/05/2009] [Accepted: 06/08/2009] [Indexed: 02/08/2023]
Abstract
We report Hepatitis B Virus (HBV) DNA detection using a silica nanoparticle-enhanced dynamic microcantilever biosensor. A 243-mer nucleotide of HBV DNA precore/core region was used as the target DNA. For this assay, the capture probe on the microcantilever surface and the detection probe conjugated with silica nanoparticles were designed specifically for the target DNA. For efficient detection of the HBV target DNA using silica nanoparticle-enhanced DNA assay, the size of silica nanoparticles and the dimension of microcantilever were optimized by directly binding the silica nanoparticles through DNA hybridization. In addition, the correlation between the applied nanoparticle concentrations and the resonant frequency shifts of the microcantilever was discussed clearly to validate the quantitative relationship between mass loading and resonant frequency shift. HBV target DNAs of 23.1 fM to 2.31 nM which were obtained from the PCR product were detected using a silica nanoparticle-enhanced microcantilever. The HBV target DNA of 243-mer was detected up to the picomolar (pM) level without nanoparticle enhancement and up to the femtomolar (fM) level using a nanoparticle-based signal amplification process. In the above two cases, the resonant frequency shifts were found to be linearly correlated with the concentrations of HBV target DNAs. We believe that this linearity originated mainly from an increase in mass that resulted from binding between the probe DNA and HBV PCR product, and between HBV PCR product and silica nanoparticles for the signal enhancement, even though there is another potential factor such as the spring constant change that may have influenced on the resonant frequency of the microcantilever.
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Affiliation(s)
- Byung Hak Cha
- Nano Bio Research Center, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea
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Pan AP, Huang GY, Chen J, He YL. Relationship between hepatitis B virus covalently closed circular DNA and HBx protein expression in hepatocellular carcinoma and its significance. Shijie Huaren Xiaohua Zazhi 2009; 17:712-715. [DOI: 10.11569/wcjd.v17.i7.712] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore relationship of hepatitis B virus covalently closed circular DNA (HBV cccDNA) expression to the expression of HBx protein within hepatocellular carcinoma and to investigate their significance.
METHODS: The tumor tissues and their adjacent-tumor tissues of 42 HCC cases were selected. The expression of the HBx protein was detected by SABC immunohistochemistry and the expression levels of hepatitis B virus covalently closed circular DNA were measured by real time polymerase chain reaction (RT-PCR).
RESULTS: The expression of the HBx protein was negative in normal liver tissues while there were 31 positive cases (73.8%) in tumor tissues and 35 positive cases (83.3%) in adjacent-tumor tissues without significant difference. The levels of HBV cccDNA in the adjacent-tumor tissues were higher than those in HCC tissues but no significant difference was detected between them. The levels of HBV cccDNA in tumor tissues whose HBx proteins expression were positive were higher than those whose HBx proteins expression were negative (P < 0.05), and similar result existed in the adjacent-tumor tissues (P < 0.05). There was a positive correlation between HBx protein expression and the expression levels of HBV cccDNA (r = 0.778, P < 0.01).
CONCLUSION: There is a positive correlation between the expression of the HBx protein and the level of HBV cccDNA, and their interaction might have a very important effect on emergence and development of HCC.
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Kleinberg M. Viruses. MANAGING INFECTIONS IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES 2009. [PMCID: PMC7114983 DOI: 10.1007/978-1-59745-415-5_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Viral infections are an important and often unrecognized component of disease in immunocompromised patients. The diagnosis and management of viral infections have expanded largely because of new quantitative molecular diagnostic assays. Well-recognized pathogens such as herpes simplex virus (HSV), cytomegalovirus (CMV), and respiratory viruses have been joined by newly recognized pathogens such as BK virus, human herpesvirus-6 (HHV-6), and human metapneumovirus in this highly susceptible patient population. The role of Epstein-Barr virus (EBV) and Human herpesvirus-8 (HHV-8) in lymphoproliferative diseases also continue to be clarified. As a result, the management of viral infections in patients with hematologic malignancies continues to be a growing challenge for the clinician.
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Affiliation(s)
- Michael Kleinberg
- School of Medicine, University of Maryland, S. Greene St. 22, Baltimore, 21201 U.S.A
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Omland LH, Weis N, Skinhøj P, Laursen A, Christensen PB, Nielsen HI, Møller A, Engsig F, Sørensen HT, Obel N. Impact of hepatitis B virus co-infection on response to highly active antiretroviral treatment and outcome in HIV-infected individuals: a nationwide cohort study. HIV Med 2008; 9:300-6. [PMID: 18400077 DOI: 10.1111/j.1468-1293.2008.00564.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND The impact of chronic hepatitis B virus (HBV) infection on viral suppression, immune recovery and mortality in HIV-1 infected patients on highly active antiretroviral treatment (HAART) is a matter of debate. The impact of HBeAg status is unknown. METHODS This prospective cohort study included all adult Danish HIV-1 infected patients who started HAART between 1 January 1995 and 1 December 2006 (3180 patients). Patients were classified as chronic HBV-infected (6%), HBV-negative (87%) or HBV-unknown (7%). HBV-positive patients were divided into HBeAg-positive or -negative (3.0 vs. 2.6%). Study endpoints were viral load, CD4 cell count and mortality. RESULTS HBV co-infection had no impact on response to HAART regarding viral suppression or immune recovery. HBV co-infection was associated with several outcomes: overall mortality [mortality rate ratio (MRR) 1.5; 95% confidence interval (CI) 1.1-2.1], liver-related mortality (MRR 4.0; 95% CI 1.6-9.9) and AIDS-related deaths (MRR 1.7; 95% CI 1.0-3.0). The presence of HBeAg did not influence patients' response to HAART. CONCLUSIONS In HIV patients, chronic HBV infection has no impact on response to HAART concerning viral load and increase in CD4 cell count. However, co-infected patients have an increased mortality compared to HIV-monoinfected patients.
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Affiliation(s)
- L H Omland
- Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
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Ozaras R, Tabak F, Tahan V, Ozturk R, Akin H, Mert A, Senturk H. Correlation of quantitative assay of HBsAg and HBV DNA levels during chronic HBV treatment. Dig Dis Sci 2008; 53:2995-2998. [PMID: 18409002 DOI: 10.1007/s10620-008-0263-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2007] [Accepted: 03/26/2008] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIM Viral load is used for the diagnosis and monitoring the treatment of chronic hepatitis B (CHB). These methods are molecular-based and are expensive. Previous studies suggest that quantitative hepatitis B surface antigen (HBsAg) studied by automated chemiluminescent microparticle immunoassay can be a surrogate marker. In this study, we aimed to investigate whether quantitative HBsAg correlates hepatitis B virus (HBV) DNA levels during CHB treatment. METHODS The study included 18 patients (13 male, 5 female, mean age: 33 +/- 9 years) with CHB. They were given pegylated interferon +/- lamivudine for 52 months and serum samples were obtained in weeks 0, 4, 8, 24, 48, 52, and 76. HBV DNA was measured by TaqMan polymerase chain reaction (PCR; Erasmus MC, University Medical Center, Rotterdam, The Netherlands). Quantitative HBsAg was studied by automated chemiluminescent microparticle immunoassay (Architect HBsAg, Abbott, IL). Results HBV DNA levels were measured as follows: 9.66, 7.69, 7.06, 5.93, 5.89, 5.88, and 7.27 logarithmic genome equivalent/ml, respectively. The corresponding HBsAg quantitation results were 42,888, 31,176, 37,882, 27,277, 28,279, 29,471, and 31,535 IU/ml, respectively. They showed a significant correlation (canonical correlation = 0.85). CONCLUSIONS HBsAg studied by automated chemiluminescent microparticle immunoassay correlates with HBV DNA and can be a surrogate marker during the monitoring of the efficacy of HBV treatment.
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Affiliation(s)
- Resat Ozaras
- Department of Infectious Diseases, Cerrahpasa Medical Faculty, Istanbul University, 34098, Cerrahpasa, Istanbul, Turkey.
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Fonseca JCFD. [Natural history of chronic hepatitis B]. Rev Soc Bras Med Trop 2008; 40:672-7. [PMID: 18200423 DOI: 10.1590/s0037-86822007000600015] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2007] [Accepted: 12/03/2007] [Indexed: 01/24/2023] Open
Abstract
An estimated 350 million people worldwide are chronically infected with hepatitis B virus (HBV). Three phases of chronic hepatitis B virus infection is are recognized: the immune tolerant phase (HBeAg-positive, high levels of serum HBV-DNA, normal ALT, and no evidence of active liver diseases), the immune clearance phase or chronic hepatitis phase (HBeAg-positive, high levels of serum HBV-DNA, elevated ALT, and active liver disease ), and the inactive carrier state or asymptomatic phase (HBsAg-positive in serum without HBeAg, HBV-DNA levels than < 10(5) copies/mL, and normal ALT levels). Chronic hepatitis B is classified into 2 major forms: HBeAg-positive disease (wild-type HBV) and HBeAg negative disease (pre-core/core promoter HBV variant). Both forms can lead to liver cirrhosis, hepatic decompensation and liver cancer. The purpose of this article is to review the principal aspects of natural history of chronic hepatitis B.
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Galli C, Orlandini E, Penzo L, Badiale R, Caltran G, Valverde S, Gessoni G. What is the role of serology for the study of chronic hepatitis B virus infection in the age of molecular biology? J Med Virol 2008; 80:974-9. [PMID: 18428144 DOI: 10.1002/jmv.21179] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
To assess quantitative serology in chronic hepatitis B virus (HBV) infection, testing by novel immunoassays has been carried out on 202 specimens from untreated patients and in 83 samples from 10 patients with chronic hepatitis B treated with lamivudine. Serum samples were assayed for quantitative HBsAg, in comparison with quantitative HBV-DNA, and for anti-HBc IgM and the avidity index (AI) of total anti-HBc antibodies. The AI was high (mean: 0.93 +/- 0.19) in all groups, confirming the consistency of this procedure in chronic HBV infections. A low-level positivity (2-28 Paul-Ehrlich units/ml) for IgM anti-HBc was detectable both in HBeAg-positive and in HBeAg-negative untreated chronic hepatitis cases (mean S/CO values by the Abbott Architect assay: 0.51 +/- 0.12 and 0.48 +/- 0.10, respectively; correlation between assays: r = 0.685), while treated patients (mean: 0.20 +/- 0.15) and inactive carriers (mean: 0.17 +/- 0.21), were generally negative for IgM. The levels of HBsAg (IU/ml) showed a weak correlation with HBV-DNA (IU/ml). A difference in HBsAg levels was found between inactive carriers (1,935 +/- 2,887 IU/ml) and chronic hepatitis B cases, either treated (5,199 +/- 9,259 IU/ml) or untreated (14,596 +/- 15,227 IU/ml). Pre-treatment levels of HBsAg in patients undergoing lamivudine treatment were correlated with a sustained response to therapy over 13-33 months (mean: 27.3) of follow-up: mean HBsAg values were 1,576 + 1,487 IU/ml in five responders and 6,063 + 5,142 in five nonresponders or breakthrough responders (P < 0.05). The availability of standardized quantitative immunoassays for HBsAg and anti-HBc IgM may be considered in addition to quantitative HBV-DNA in the staging and monitoring of chronic HBV infection.
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Abstract
The hepatitis B virus (HBV) belongs to the hepadnavirus family. The genome of the virus, formed by a small DNA molecule with 3,200 base pairs, has 4 strongly overlapping protein coding regions: ORF preS/S, corresponding to the envelope proteins that constitute the HBV surface antigen (HBsAg); ORF preC/C, which encodes the viral capsid component (core antigen or HBcAg) and a non-structural protein that, after postranslation modification, is secreted and constitutes the "e" antigen (HBeAg); ORF P, which encodes the viral polymerase (polyprotein with DNA polymerase activity, reverse transcriptase and RNAase), and ORF X, which encodes a protein that acts as a multifunctional regulator for both the viral and cell cycles. HBV has a mutation rate of 1.4-3.2 x 105 substitutions/nucleotide/year. As a result of this variability, the virus circulates as a complex mixture of genetic variants, constituting a semi-species, that evolves throughout the infection depending on the evolutionary pressure of factors such as the immune response and antiviral treatments. Based on this variability, HBV has been classified into 8 genotypes (A-H) defined by a difference of more than 8% in the sequences of the complete viral genome. This variability is also responsible for HBV resistance to antiviral treatments with nucleotide and nucleoside analogs. Diagnosis of HBV infection includes determination of virological markers: viral antigens (HBsAg, HBeAg), specific antibodies (anti-HBc, anti-HBe, anti-HBs) and study of HBV-DNA for its detection and quantification and determination of genotypes and viral variants.
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García Bermejo I. Anomalías y patrones serológicos infrecuentes de los marcadores diagnósticos del virus de la hepatitis B. Enferm Infecc Microbiol Clin 2007. [DOI: 10.1157/13111834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Le Pendeven C, Cuzon G, Fontaine H, Zatla F, Schneider V, Amiel C, Khayat R, Nicolas JC, Soussan P. Hepatitis B escape mutant reactivation in a renal transplant patient. J Clin Virol 2007; 40:74-6. [PMID: 17652016 DOI: 10.1016/j.jcv.2007.06.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2007] [Revised: 06/11/2007] [Accepted: 06/14/2007] [Indexed: 01/25/2023]
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Cao B, Yang H, Ding H, Qi S, Gao L, Cui H, Dai Y, Xu C. Association analysis of hepatitis virus B infection with haplotypes of the TBX21 gene promoter region in the Chinese population. Clin Chem Lab Med 2007; 45:333-8. [PMID: 17378728 DOI: 10.1515/cclm.2007.062] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND The T-box21 (TBX21) gene encodes the transcription factor T-bet (T-box expressed in T-cells), which influences naive T-lymphocyte development and has been implicated in the pathogenesis of many diseases. METHODS We selected 208 hepatitis B patients and 213 healthy volunteers to examine whether polymorphisms or haplotypes of the TBX21 gene promoter were associated with hepatitis B virus (HBV) infection in the Chinese population. Two polymorphisms at -1499 and -1514 located in the TBX21 promoter region were identified by the PCR-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS Single nucleotide polymorphism (SNP) at -1499 was significantly different between HBV patients and healthy controls [p=0.003; odds ratio (OR) 3.65, 95% confidence interval (CI) 1.58-8.45]. Similarly, our results showed a significantly higher level of haplotype D (--/AC) in HBV patients compared to control subjects (p=0.005; OR 4.82, 95% CI 1.59-14.61). CONCLUSIONS Based on our findings, it seems that genetic variations of allele -1499 and haplotype D (--/AC) within the TBX21 promoter region contribute to susceptibility to HBV infection in the Chinese population.
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Affiliation(s)
- Bangwei Cao
- Department of Anti-infection and Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China
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Piroth L, Sène D, Pol S, Goderel I, Lacombe K, Martha B, Rey D, Loustau-Ratti V, Bergmann JF, Pialoux G, Gervais A, Lascoux-Combe C, Carrat F, Cacoub P. Epidemiology, diagnosis and treatment of chronic hepatitis B in HIV-infected patients (EPIB 2005 STUDY). AIDS 2007; 21:1323-31. [PMID: 17545709 DOI: 10.1097/qad.0b013e32810c8bcf] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To describe the characteristics of hepatitis B (HBV) infection in HIV-infected patients and the impact of anti-HBV treatments. PATIENTS AND METHODS All the patients with past or present chronic HBV infection seen in October 2005 in 17 French hospitals were included. Data were retrospectively collected from their first visit in a time-dependent manner, through a detailed standardized questionnaire. RESULTS Among 477 HBV-infected patients, 261 (55%) were co-infected with HIV. The HBV-HIV co-infected patients underwent fewer serological, virological and histological evaluations. Initial positive HBe antigenemia (HBe Ag) was more frequent in these patients (57.9 versus 28.6%; P < 10), as was cirrhosis on the initial liver biopsy (17.9 versus 7.6%; P = 0.05). Throughout the mean 5-year follow-up, HBe Ag loss was less frequent (P = 0.04), as was HBe seroconversion (incidence rate 2.6 versus 10/100 patient-years; P < 10). HBe Ag loss was associated with fibrosis improvement (METAVIR score -0.5 +/- 0.4 versus +0.2 +/- 0.6 if persistent positive HBe Ag, P = 0.01). In co-infected patients on tenofovir, adefovir or interferon, HBe seroconversions were seen in patients on combined HBV treatment, the use of which is increasing (58% in 2005). Nevertheless, no significant difference in virological, immunological or biochemical evolution was observed between these different treatments. CONCLUSIONS In HBV-HIV co-infected patients, the assessment of HBV infection still needs to be improved, the HBV wild-type remains predominant, and HBe Ag loss is rare and associated with a better histological evolution. There is insufficient evidence of the superiority of combined HBV treatment, and this still needs be demonstrated in long term studies.
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Affiliation(s)
- Lionel Piroth
- Service de Maladies Infectieuses et Tropicales, CHU Dijon, 10 boulevard du Maréchal de Lattre de Tassigny, 21079 Dijon cedex, France.
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Xu C, Qi S, Gao L, Cui H, Liu M, Yang H, Li K, Cao B. Genetic polymorphisms of LMP/TAP gene and hepatitis B virus infection risk in the Chinese population. J Clin Immunol 2007; 27:534-41. [PMID: 17525827 DOI: 10.1007/s10875-007-9095-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2007] [Accepted: 03/22/2007] [Indexed: 01/28/2023]
Abstract
Despite the availability of effective vaccines, hepatitis B virus (HBV) infection is still commonly seen worldwide. Several reports show that the human major histocompatibility complex (MHC) systems were involved in the elimination of HBV via the restrictive antigen-processing pathway. We investigate whether LMP/TAP gene polymorphisms coded by MHC-II region were associated with HBV infection. A total of seven polymorphisms of LMP/TAP gene were identified by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assays. Three hundred fifty-six patients and 326 unrelated healthy volunteers were included in the case-control study. Of the seven polymorphisms, three of which (LMP7 codons 145, TAP1 codons 637, and TAP2 codons 651) were observed to have statistically significant association with HBV infection (P < 0.05). We analyzed the three-locus haplotype constructed with three such polymorphisms and found that the frequency of haplotypes D and E increased significantly in patients, in comparison with that in controls (OR = 3.57, 95% CI: 2.09-6.12, P < 0.001; OR = 2.74, 95% CI: 1.35-5.56, P = 0.005, respectively). The results imply that LMP7-145, TAP1-637, and TAP2-651 sites were associated with the risk of HBV infection. Haplotypes D and E might be involved in the development of HBV infection. These data suggest a potential role of LMP/TAP gene as a candidate gene for susceptibility to HBV infection.
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Affiliation(s)
- Changqing Xu
- Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, China
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Velappan N, Martinez JS, Valero R, Chasteen L, Ponce L, Bondu-Hawkins V, Kelly C, Pavlik P, Hjelle B, Bradbury ARM. Selection and characterization of scFv antibodies against the Sin Nombre hantavirus nucleocapsid protein. J Immunol Methods 2007; 321:60-9. [PMID: 17336997 DOI: 10.1016/j.jim.2007.01.011] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2006] [Revised: 12/02/2006] [Accepted: 01/07/2007] [Indexed: 11/16/2022]
Abstract
Rodent-borne hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in the old world and hantavirus cardio-pulmonary syndrome (HCPS) in the new. Most cases of HCPS in North America are caused by Sin Nombre Virus (SNV). Current viral detection technologies depend upon the identification of anti-viral antibodies in patient serum. Detection of viral antigen may facilitate earlier detection of the pathogen. We describe here the characterization of two single-chain Fv antibodies (scFvs), selected from a large naïve phage antibody library, which are capable of identifying the Sin Nombre Virus nucleocapsid protein (SNV-N), with no cross reactivity with the nucleocapsid protein from other hantaviruses. The utility of such selected scFvs was increased by the creation of an scFv-alkaline phosphatase fusion protein which was able to directly detect virally produced material without the need for additional reagents.
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Affiliation(s)
- Nileena Velappan
- Los Alamos National Laboratory, TA-43, HRL-1, MS M888, Los Alamos NM 87545, USA
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Tan GH, Yusoff K, Seow HF, Tan WS. A phage-displayed single chain variable fragment that interacts with hepatitis B core antigen: library construction, selection and diagnosis. J Clin Virol 2006; 38:49-56. [PMID: 17074533 DOI: 10.1016/j.jcv.2006.09.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2006] [Revised: 08/11/2006] [Accepted: 09/19/2006] [Indexed: 01/04/2023]
Abstract
BACKGROUND Phage display is an alternative method for constructing and selecting antibodies with desired specificity towards an antigen. OBJECTIVES To construct a library of single chain variable fragment (ScFv) towards hepatitis B core antigen (HBcAg). To isolate a ScFv phage clone that interacts with HBcAg and to develop a phage-ELISA for detecting the antigen. STUDY DESIGN Mice were inoculated with HBcAg and RNA was extracted from their spleen cells. The genes encoding heavy (V(H)) and light (V(L)) chains were amplified, linked via PCR and cloned into a phagemid vector. Phage particles displaying ScFv were panned against HBcAg and a selected clone was characterized and employed as a diagnostic reagent for detecting HBcAg in serum samples. RESULTS A phage clone that interacts with HBcAg was selected from the antibody library. The binding of the phage to HBcAg was inhibited by a cyclic peptide bearing the WSFFSNI sequence. A phage-ELISA was established using the recombinant phage and as low as 10ng of HBcAg can be detected by the assay. CONCLUSION The ScFv displayed on the surface of filamentous phage is an alternative choice for diagnosis of HBcAg in serum samples.
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Affiliation(s)
- Geok Hun Tan
- Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
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Rodríguez-Frías F, Jardí R. Marcadores virológicos en la infección por VHB. GASTROENTEROLOGÍA Y HEPATOLOGÍA 2006; 29:11-19. [DOI: 10.1157/13097570] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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N/A, 秦 波. N/A. Shijie Huaren Xiaohua Zazhi 2006; 14:1999-2002. [DOI: 10.11569/wcjd.v14.i20.1999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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