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Liu H, Hong J, Yan Z, Li M, Zhai X, Pan B, Ling C. Hepatitis B Virus Knowledge and HBV-Related Surveillance Status Among HBsAg-Positive Patients in Qidong City: A Rural-Based Cross-Sectional Survey. Healthcare (Basel) 2024; 13:17. [PMID: 39791624 PMCID: PMC11719656 DOI: 10.3390/healthcare13010017] [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: 11/14/2024] [Revised: 12/15/2024] [Accepted: 12/18/2024] [Indexed: 01/12/2025] Open
Abstract
OBJECTIVE This study aimed to investigate hepatitis B knowledge and hepatitis B virus (HBV)-related surveillance status among HBsAg-positive patients, as well as to further explore the relevant influencing factors. METHODS A cross-sectional study was conducted on the HBsAg-positive patients from 8 October 2023 to 10 November 2023 in Qidong City. A self-report questionnaire was developed based on a literature review of similar studies. Univariate analysis of variance, multivariate logistic regression, and t-test analysis were conducted to analyze the collected data. RESULTS Of the 982 respondents who completed the on-site questionnaire, all participants were HBsAg-positive patients. Moreover, 51.32% had "good" knowledge of HBV. Multivariate logistic regression analysis showed that participants with a doctor in the family, those with an average monthly income above CNY 3000, and those with an average monthly income of CNY 1500-3000 were more likely to obtain a "good" cognitive evaluation (p < 0.001). The scores of the populations using HBV-related surveillance methods were low (2.02 ± 0.87); 64.87% (637/982) of the populations monitored had a score of no more than 2. CONCLUSIONS This study suggests that the awareness of HBV prevention and treatment among participants, especially those of low-income classes and individuals lacking physician clinical management, should be promoted to increase the dissemination of HBV knowledge.
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Affiliation(s)
- Hailiang Liu
- School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Department of Integrative Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
- School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China
| | - Jing Hong
- Department of Integrative Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
- School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China
- Department of Integration of Chinese and Western Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhaoxian Yan
- Department of Integrative Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
- School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China
| | - Mei Li
- The Fourth People’s Hospital of Jinan, Jinan 250102, China
| | - Xiaofeng Zhai
- Department of Integrative Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
- School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China
| | - Bo Pan
- Department of Integrative Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
- School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China
| | - Changquan Ling
- School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Department of Integrative Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
- School of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China
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Ahmad A, Imran M, Ahsan H. Biomarkers as Biomedical Bioindicators: Approaches and Techniques for the Detection, Analysis, and Validation of Novel Biomarkers of Diseases. Pharmaceutics 2023; 15:1630. [PMID: 37376078 DOI: 10.3390/pharmaceutics15061630] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/24/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
A biomarker is any measurable biological moiety that can be assessed and measured as a potential index of either normal or abnormal pathophysiology or pharmacological responses to some treatment regimen. Every tissue in the body has a distinct biomolecular make-up, which is known as its biomarkers, which possess particular features, viz., the levels or activities (the ability of a gene or protein to carry out a particular body function) of a gene, protein, or other biomolecules. A biomarker refers to some feature that can be objectively quantified by various biochemical samples and evaluates the exposure of an organism to normal or pathological procedures or their response to some drug interventions. An in-depth and comprehensive realization of the significance of these biomarkers becomes quite important for the efficient diagnosis of diseases and for providing the appropriate directions in case of multiple drug choices being presently available, which can benefit any patient. Presently, advancements in omics technologies have opened up new possibilities to obtain novel biomarkers of different types, employing genomic strategies, epigenetics, metabolomics, transcriptomics, lipid-based analysis, protein studies, etc. Particular biomarkers for specific diseases, their prognostic capabilities, and responses to therapeutic paradigms have been applied for screening of various normal healthy, as well as diseased, tissue or serum samples, and act as appreciable tools in pharmacology and therapeutics, etc. In this review, we have summarized various biomarker types, their classification, and monitoring and detection methods and strategies. Various analytical techniques and approaches of biomarkers have also been described along with various clinically applicable biomarker sensing techniques which have been developed in the recent past. A section has also been dedicated to the latest trends in the formulation and designing of nanotechnology-based biomarker sensing and detection developments in this field.
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Affiliation(s)
- Anas Ahmad
- Julia McFarlane Diabetes Research Centre (JMDRC), Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Hotchkiss Brain Institute, Cumming School of Medicine, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 4N1, Canada
| | - Mohammad Imran
- Therapeutics Research Group, Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane 4102, Australia
| | - Haseeb Ahsan
- Department of Biochemistry, Faculty of Dentistry, Jamia Millia Islamia, New Delhi 110025, India
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Zhang X, You Y, Liu Q, Sun X, Chen W, Duan L. Reduced Circulating Soluble Receptor for Advanced Glycation End-products in Chronic Hepatitis B Are Associated with Hepatic Necroinflammation. Inflammation 2022; 45:2559-2569. [PMID: 35790658 DOI: 10.1007/s10753-022-01712-2] [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: 04/04/2022] [Revised: 06/06/2022] [Accepted: 06/29/2022] [Indexed: 11/05/2022]
Abstract
The diagnosis and disease management of chronic hepatitis B (CHB) remain challenging due to the elusive assessment of disease severity. Recently, soluble receptor for advanced glycation end-products (sRAGE) has been implicated in the inflammatory-immune response initiated by liver injury. Nonetheless, its natural behavior and clinical importance in CHB remain elusive. One hundred and twenty CHB patients and forty healthy controls (HCs) were enrolled, and the serum sRAGE as well as RAGE expression in biopsy specimens from these subjects was analyzed, and correlation of sRAGE with clinical features as well as its potential predictive value for monitoring the CHB was also evaluated. Reduced serum sRAGE levels and decreased tissular RAGE expression were observed in CHB patients. sRAGE and RAGE were inversely correlated with gradually increased grades of hepatic necroinflammation as well as the routine indicator ALT. Furthermore, receiver operating characteristic (ROC) analysis showed that combination of ALT and sRAGE exerted better predictive power (area under the ROC curve (AUC) of 0.86) for hepatic necroinflammation than that of ALT (AUC of 0.82), sRAGE (AUC of 0.81), or sRAGE-to-ALT ratio (sRAGE/ALT) (AUC of 0.85) alone. More importantly, circulating sRAGE alone exerted valuable predictive power for hepatic moderate-to-severe necroinflammation in CHB patients but with normal ALT (AUC of 0.81) or minimally elevated ALT (AUC of 0.85). In conclusion, reduced serum sRAGE levels may imply an increased severity for necroinflammation, and it may serve as a potential alternative biomarker for monitoring hepatic necroinflammation in CHB.
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Affiliation(s)
- Xiuyu Zhang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjiang Road, Yu Zhong District, Chongqing, 400010, China
| | - Yan You
- Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Qiao Liu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Xiaoyu Sun
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjiang Road, Yu Zhong District, Chongqing, 400010, China
| | - Weixian Chen
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjiang Road, Yu Zhong District, Chongqing, 400010, China
| | - Liang Duan
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjiang Road, Yu Zhong District, Chongqing, 400010, China.
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Transaminase Elevations during Treatment of Chronic Hepatitis B Infection: Safety Considerations and Role in Achieving Functional Cure. Viruses 2021; 13:v13050745. [PMID: 33922828 PMCID: PMC8146791 DOI: 10.3390/v13050745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/20/2021] [Accepted: 04/22/2021] [Indexed: 11/17/2022] Open
Abstract
While current therapies for chronic HBV infection work well to control viremia and stop the progression of liver disease, the preferred outcome of therapy is the restoration of immune control of HBV infection, allowing therapy to be removed while maintaining effective suppression of infection and reversal of liver damage. This “functional cure” of chronic HBV infection is characterized by the absence of detectable viremia (HBV DNA) and antigenemia (HBsAg) and normal liver function and is the goal of new therapies in development. Functional cure requires removal of the ability of infected cells in the liver to produce the hepatitis B surface antigen. The increased observation of transaminase elevations with new therapies makes understanding the safety and therapeutic impact of these flares an increasingly important issue. This review examines the factors driving the appearance of transaminase elevations during therapy of chronic HBV infection and the interplay of these factors in assessing the safety and beneficial nature of these flares.
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A Noninvasive Prediction Model for Hepatitis B Virus Disease in Patients with HIV: Based on the Population of Jiangsu, China. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6696041. [PMID: 33860053 PMCID: PMC8024075 DOI: 10.1155/2021/6696041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 03/17/2021] [Indexed: 02/07/2023]
Abstract
Objective To establish a machine learning model for identifying patients coinfected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) through two sexual transmission routes in Jiangsu, China. Methods A total of 14197 HIV cases transmitted by homosexual and heterosexual routes were recruited. After data processing, 12469 cases (HIV and HBV, 1033; HIV, 11436) were left for further analysis, including 7849 cases with homosexual transmission and 4620 cases with heterosexual transmission. Univariate logistic regression was used to select variables with significant P value and odds ratio for multivariable analysis. In homosexual transmission and heterosexual transmission groups, 10 and 6 variables were selected, respectively. For identifying HIV individuals coinfected with HBV, a machine learning model was constructed with four algorithms, including Decision Tree, Random Forest, AdaBoost with decision tree (AdaBoost), and extreme gradient boosting decision tree (XGBoost). The detective value of each variable was calculated using the optimal machine learning algorithm. Results AdaBoost algorithm showed the highest efficiency in both transmission groups (homosexual transmission group: accuracy = 0.928, precision = 0.915, recall = 0.944, F − 1 = 0.930, and AUC = 0.96; heterosexual transmission group: accuracy = 0.892, precision = 0.881, recall = 0.905, F − 1 = 0.893, and AUC = 0.98). Calculated by AdaBoost algorithm, the detective value of PLA was the highest in homosexual transmission group, followed by CR, AST, HB, ALT, TBIL, leucocyte, age, marital status, and treatment condition; in the heterosexual transmission group, the detective value of PLA was the highest (consistent with the condition in the homosexual group), followed by ALT, AST, TBIL, leucocyte, and symptom severity. Conclusions The univariate logistics regression combined with the AdaBoost algorithm could accurately screen the risk factors of HBV in HIV coinfection without invasive testing. Further studies are needed to evaluate the utility and feasibility of this model in various settings.
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Ahmed FA, Bajaifar MS, Ahmed MA, Alalwan A, Sanai FA, Albeladi K, Aljumah AA, Sanai FM. Quantitative HBsAg levels do not identify hepatic fibrosis in HBeAg-negative chronic hepatitis B patients. Saudi J Gastroenterol 2019; 25:286-292. [PMID: 31044750 PMCID: PMC6784435 DOI: 10.4103/sjg.sjg_80_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND/AIMS Quantitative serum hepatitis B surface antigen (qHBsAg) has been evaluated in limited patient groups as a marker of histological fibrosis. The accurate identification of inactive chronic hepatitis B virus (HBV) carriers from those with active carriers is difficult because of wide and frequent HBV DNA fluctuations. We aimed to assess the utility of qHBsAg in distinguishing histologically significant fibrosis in untreated HBeAg-negative chronic HBV patients. PATIENTS AND METHODS qHBsAg levels were measured at baseline as single-point quantification and correlated with virologic and biochemical profiles of consecutive carriers (median, 29; range, 12-110 months). HBeAg-negative patients (n = 75) with HBV DNA <2000 (n = 5), 2000-20,000 (n = 16) and >20,000 IU/mL (n = 54) were included and all had liver biopsy. A qHBsAg cutoff point of 1000 IU/mL was assessed to demonstrate whether it better delineated patients with non-significant histology (F0-1, inflammatory grade A0-1). RESULTS Mean age of the patients was 39.4 ± 11.4 years and 58 (77.3%) were male. Patients with qHBsAg levels >1000 IU/mL were more likely to be males (84.5%, P = 0.006) or with elevated AST (68.4%, P = 0.0002) and ALT levels (72.4%, P < 0.0001), higher HBV DNA (log10 6.4 ± 1.4, P < 0.0001) and those with F2-4 fibrosis (48.3%, P = 0.028). Serum log10 qHBsAg were significantly lower in patients with HBV DNA <2000 (2.80 ± 1.47) and HBV DNA 2000-20,000 (2.71 ± 0.83) vs. >20,000 IU/mL (3.89 ± 0.61, P < 0.0001). Overall, qHBsAg were not different in patients with F0-1 (3.44 ± 0.91) and F2-4 fibrosis (3.74 ± 0.85, P = 0.161). Serum qHBsAg were higher in patients with significant (A2-3) inflammation (3.85 ± 0.72) compared to A0-1 (3.38 ± 0.95; P = 0.018). Serum qHBsAg demonstrated poor accuracy (AUROC, 0.61, P = 0.111) in identification of F2-4 fibrosis. CONCLUSION Serum qHBsAg levels do not help differentiate between those with HBV DNA <2000 or 2000 - 20,000 IU/mL or distinguish patients with significant fibrosis. Moreover, more than half of the patients with non-significant fibrosis have a qHBsAg level greater than 1000 IU/mL.
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Affiliation(s)
- Fatima A. Ahmed
- College of Medicine, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia
| | | | - Mohammed A. Ahmed
- College of Medicine, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia
| | - Abduljaleel Alalwan
- Hepatology Division, Department of Hepatobiliary Sciences and Organ Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia,King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Faraaz A. Sanai
- Emergency Department, King Fahd Hospital, Jeddah, Saudi Arabia
| | - Khalid Albeladi
- Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Abdulrahman A. Aljumah
- Hepatology Division, Department of Hepatobiliary Sciences and Organ Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia,King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Faisal M. Sanai
- Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia,Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia,Address for correspondence: Dr. Faisal M. Sanai, Gastroenterology Unit, Dept. of Medicine, King Abdulaziz Medical City, PO Box: 9515, Jeddah 21423, Saudi Arabia. E-mail:
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Demosthenes JP, Sachithanandham J, Fletcher GJ, Zachariah UG, Varghese GM, John Daniel HD, Jeyaseelan L, Abraham P, Kannangai R. Characteristics of treatment-naïve HBV-infected individuals with HIV-1 coinfection: A cross-sectional study from South India. Indian J Med Microbiol 2019; 37:219-224. [PMID: 31745022 DOI: 10.4103/ijmm.ijmm_19_16] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Purpose Human immunodeficiency virus-1 (HIV-1) and hepatitis B virus (HBV) coinfection has become a major health problem across the globe. The increased life expectancy of HIV-1 patients due to antiretroviral therapy has led to the emergence of liver disease as a major mortality factor among them. The purpose of the study was to examine the baseline characteristics of HBV in treatment-naïve HBV/HIV coinfection from southern India compared to monoinfected individuals. Materials and Methods The study was cross sectional in design, and samples were examined from 80 HIV-1, 70 HBV and 35 HBV/HIV-coinfected individuals using chemiluminescent microparticle immunoassay, real-time polymerase chain reaction and flow cytometry assays. Results There was a significant increase in HBV DNA (P = 0.0001), higher hepatitis B e antigen percentage difference (P = 0.027) and lower CD4 counts (P = 0.01) among the HBV/HIV-coinfected individuals, but no difference in the HIV-1 viral load compared to HIV-1-monoinfected individuals. Also, the aspartate aminotransferase levels, prothrombin time and the international normalised ratio were significantly high among coinfected individuals. Conclusion These findings conclude that HIV-1 coinfection can have serious implications on the outcome of HBV-related liver disease. To the contrary, HBV infection had no consequence on the progression of HIV-1 disease but distinctly lowered CD4+ T-cells.
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Affiliation(s)
- John Paul Demosthenes
- Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India
| | | | | | | | - George Mathew Varghese
- Department of Infectious Diseases, Christian Medical College, Vellore, Tamil Nadu, India
| | | | | | - Priya Abraham
- Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Rajesh Kannangai
- Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India
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Hong YS, Ryu S, Chang Y, Caínzos-Achirica M, Kwon MJ, Zhao D, Shafi T, Lazo M, Pastor-Barriuso R, Shin H, Cho J, Guallar E. Hepatitis B virus infection and development of chronic kidney disease: a cohort study. BMC Nephrol 2018; 19:353. [PMID: 30537940 PMCID: PMC6288894 DOI: 10.1186/s12882-018-1154-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 11/23/2018] [Indexed: 02/07/2023] Open
Abstract
Background The effect of chronic hepatitis B virus (HBV) infection on the risk of chronic kidney disease (CKD) is controversial. We examined the prospective association between hepatitis B surface antigen (HBsAg) serology status and incident CKD in a large cohort of men and women. Methods Cohort study of 299,913 adults free of CKD at baseline who underwent health screening exams between January 2002 and December 2016 in South Korea. Incident CKD was defined as the development of an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 and/or proteinuria. Results Over 1,673,701 person-years of follow-up, we observed 13,924 incident cases of CKD (3225 cases of eGFR < 60 ml/min/1.73m2 and 11,072 cases of proteinuria). In fully adjusted models comparing positive to negative HBsAg participants, the hazard ratio (HR, 95% confidence interval) for incident CKD was 1.11 (1.03–1.21; P = 0.01). The corresponding HR for incident proteinuria and for eGFR < 60 ml/min/1.73m2 were 1.23 (1.12–1.35; P < 0.001) and 0.89 (0.73–1.07; P = 0.21), respectively. The associations were similar across categories of liver enzyme levels at baseline. Conclusion In this large cohort, HBsAg positive serology was associated with higher risk of incident CKD, and we provide novel evidence that this association was due to a higher incidence of proteinuria in HBsAg positive participants. Our study adds to the growing body of evidence suggesting that chronic HBV infection may be a contributor to the increasing incidence of CKD. Electronic supplementary material The online version of this article (10.1186/s12882-018-1154-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yun Soo Hong
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health, Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health, Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Miguel Caínzos-Achirica
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.,Ciccarone Center for the Prevention of Heart Disease, Department of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.,Bellvitge University Hospital, Barcelona, Spain.,RTI Health Solutions, Pharmacoepidemiology and Risk Management, Barcelona, Spain
| | - Min-Jung Kwon
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Di Zhao
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Tariq Shafi
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.,Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mariana Lazo
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Roberto Pastor-Barriuso
- National Center for Epidemiology, Carlos III Institute of Health and Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Hocheol Shin
- Department of Family Medicine, Kangbuk Samsung Hospital and Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Juhee Cho
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. .,Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. .,Department of Health Sciences and Technology, Samsung Advanced Institute for Health, Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
| | - Eliseo Guallar
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
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Kang Y, Li F, Guo H, Yang S, Zhang Y, Zhu H, Wang J, Mao R, Qin Y, Xu J, Chen X, Wu C, Zhang J. Amino acid substitutions Q129N and T131N/M133T in hepatitis B surface antigen (HBsAg) interfere with the immunogenicity of the corresponding HBsAg or viral replication ability. Virus Res 2018; 257:33-39. [PMID: 30179704 DOI: 10.1016/j.virusres.2018.08.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 08/27/2018] [Accepted: 08/28/2018] [Indexed: 12/21/2022]
Abstract
Variants of hepatitis B surface antigen (HBsAg) influenced its antigenicity and immunogenicity. In our study, we aim to investigate biological significance of amino acid (aa) substitutions in HBsAg, Q129 N and T131 N/M133 T, for glycosylation, antigenicity and immunogenicity of variant HBsAg (vtHBsAg) and viral replication. Expression plasmids of vtHBsAg with aa substitutions Q129 L, T123 N, Q129 N and T131 N/M133 T were constructed. Immunofluorescence (IF) staining and Western blot were simultaneously utilized to examine expression of vtHBsAg proteins in Huh7 cells transfected with vtHBsAg constructs. vtHBsAg of Q129 N and T131 N/M133 T created new N-glycosylation and displayed perinuclear distribution by IF staining with the anti-HA. Antigenicity of vtHBsAg of Q129 N and T131 N/M133 T was reduced compared with wild type (wt) HBsAg. In addition, we discovered impaired ability to induce anti-HBs responses against wtHBsAg in mice immunized with plasmids pHBsAg- Q129 N and T131 N/M133 T. Even so, efficient protective response toward wild type HBV can be primed by the two vtHBsAgs in mice. Further, we discovered that vtHBsAg with Q129 N distinctly impaired HBV replication capacity, but vtHBsAg with T131 N/M133 T had no impact on viral replication. Thus, we conclude that vtHBsAg with Q129 N or T131 N/M133 T creates new N-glycosylation and interferes with both the antigenicity and immunogenicity of vtHBsAg. And vtHBsAg with Q129 N impaired HBV replication ability.
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Affiliation(s)
- Yaoyue Kang
- Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; Department of Infectious Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fahong Li
- Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
| | - Hongying Guo
- Department of Hepatitis Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Sisi Yang
- Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
| | - Yongmei Zhang
- Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
| | - Haoxiang Zhu
- Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
| | - Jinyu Wang
- Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
| | - Richeng Mao
- Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
| | - Yanli Qin
- Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
| | - Jie Xu
- Department of Infectious Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinwen Chen
- Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Chunchen Wu
- Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China.
| | - Jiming Zhang
- Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; Key laboratory of Medical Molecular Virology of the Ministries of Education and Health (MOH&MOE), Fudan University, Shanghai, China.
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Liu W, Xie Y, Gao T, Huang F, Wang L, Ding L, Wang W, Liu S, Dai J, Wang B. Reflection and observation: cell-based screening failing to detect HBV in HUMSCs derived from HBV-infected mothers underscores the importance of more stringent donor eligibility to reduce risk of transmission of infectious diseases for stem cell-based medical products. Stem Cell Res Ther 2018; 9:177. [PMID: 29973264 PMCID: PMC6030788 DOI: 10.1186/s13287-018-0920-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Revised: 05/31/2018] [Accepted: 06/06/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND In cell-based therapy, the transmission of communicable diseases imposes a substantial threat to recipients. In this study, we investigated whether cell-based screening could detect hepatitis B virus (HBV) in human umbilical cord-derived mesenchymal stem cells (HUMSCs) isolated from HBV-infected donors to understand the susceptibility of HUMSCs to HBV infection. METHODS HBV assay was performed in HUMSCs derived from healthy and HBV-infected donors with enzyme-linked immunosorbent assay (ELISA), fluorescence quantitative PCR (FQ-PCR) assay, and droplet digital PCR (ddPCR) assay. Further, HBV DNA was assayed in HUMSCs derived from healthy donors after incubation with human sera containing a high titer of HBV using FQ-PCR. RESULTS HBV antigen/antibody and DNA failed to be detected using ELISA, FQ-PCR, and ddPCR. After incubation with HBV infection sera, HBV DNA could be detected, but below the valid titer of the assay kit. The HBV DNA levels in HBV-incubated HUMSCs gradually decreased with medium change every 2 days and then significantly decreased, not even detected after passage. CONCLUSIONS The current cell-based screening methods could not detect HBV in HUMSCs derived from HBV-infected donors, indicating the importance of more stringent donor eligibility to reduce the risk of transmission of communicable diseases in cell-based therapy. To solve the problem of an occult HBV window period in donor eligibility determination, we recommend that the donors undergo another HBV serological test 3 months after the first serological communicable disease screening.
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Affiliation(s)
- Wei Liu
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008 China
| | - Yuanyuan Xie
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008 China
| | - Tianyun Gao
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008 China
| | - Feifei Huang
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008 China
| | - Liudi Wang
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008 China
| | - Lijun Ding
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008 China
| | - Wenqing Wang
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008 China
| | - Shuo Liu
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008 China
| | - Jianwu Dai
- Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing, 100190 China
| | - Bin Wang
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008 China
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Liang RL, Yang YS, Zhou JW, Liu TC, Xu XP, Liang QN, Chen ZH, Dong ZN, Wu YS. Dual-Labeled Time-Resolved Immunofluorometric Assay for the Simultaneous Quantitative Detection of Hepatitis B Virus Antigens in Human Serum. J Fluoresc 2016; 27:309-316. [PMID: 27878521 DOI: 10.1007/s10895-016-1959-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 10/19/2016] [Indexed: 12/27/2022]
Abstract
In this paper, a novel time-resolved fluorescence immunoassay (TRFIA) is described that allows the simultaneous quantitative detection of hepatitis B virus surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in human serum to aid the diagnosis and monitoring of hepatitis B virus infection. The proposed method was developed based on a two-step sandwich immunoassay protocol in which monoclonal antibodies against HBsAg and HBeAg were co-coated in 96 microtitration wells, then tracer polyclonal antibodies against HBsAg labeled with samarium and tracer monoclonal antibodies against HBeAg labeled with europium chelates were used for detection. The detection range was 0.1-150 IU/mL for HBsAg and 0.5-160 PEIU/mL for HBeAg, and the detection limits were 0.03 IU/L and 0.09 PEIU/ml, respectively. The intra- and inter-assay coefficients of variation were below 8 % for both virus antigens. The dilution linearity and accuracy of the assay were satisfactory. No statistically significant differences were observed in sensitivity or specificity for the serum samples between the dual-label TRFIA and a commercial single-label TRFIA. These results demonstrate that an effective, reliable and convenient HBsAg/HBeAg dual-label TRFIA was successfully developed that may be clinically applicable for blood screening to monitor the course of hepatitis B virus infection and predict treatment responses.
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Affiliation(s)
- Rong-Liang Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Yun-Sen Yang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Jian-Wei Zhou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Tian-Cai Liu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Xu-Ping Xu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Qian-Ni Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Zhen-Hua Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Zhi-Ning Dong
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Ying-Song Wu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
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Mori S, Fujiyama S. Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and prophylaxis recommendations. World J Gastroenterol 2015; 21:10274-10289. [PMID: 26420955 PMCID: PMC4579875 DOI: 10.3748/wjg.v21.i36.10274] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Revised: 06/20/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
Accompanying the increased use of biological and non-biological antirheumatic drugs, a greater number of cases of hepatitis B virus (HBV) reactivation have been reported in inactive hepatitis B surface antigen (HBsAg) carriers and also in HBsAg-negative patients who have resolved HBV infection. The prevalence of resolved infection varies in rheumatic disease patients, ranging from 7.3% to 66%. Through an electronic search of the PubMed database, we found that among 712 patients with resolved infection in 17 observational cohort studies, 12 experienced HBV reactivation (1.7%) during biological antirheumatic therapy. Reactivation rates were 2.4% for etanercept therapy, 0.6% for adalimumab, 0% for infliximab, 8.6% for tocilizumab, and 3.3% for rituximab. Regarding non-biological antirheumatic drugs, HBV reactivation was observed in 10 out of 327 patients with resolved infection from five cohort studies (3.2%). Most of these patients received steroids concomitantly. Outcomes were favorable in rheumatic disease patients. A number of recommendations have been established, but most of the supporting evidence was derived from the oncology and transplantation fields. Compared with patients in these fields, rheumatic disease patients continue treatment with multiple immunosuppressants for longer periods. Optimal frequency and duration of HBV-DNA monitoring and reliable markers for discontinuation of nucleoside analogues should be clarified for rheumatic disease patients with resolved HBV infection.
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13
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Zeng DW, Liu YR, Dong J, Zhu YY, Li YB, Chen J, Zheng Q, Jiang JJ. Serum HBsAg and HBeAg levels are associated with liver pathological stages in the immune clearance phase of hepatitis B virus chronic infection. Mol Med Rep 2015; 11:3465-3472. [PMID: 25592612 DOI: 10.3892/mmr.2015.3207] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Accepted: 05/28/2014] [Indexed: 01/04/2023] Open
Abstract
The association between hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg) levels and liver inflammation and fibrosis in patients with chronic hepatitis B (CHB) in the immune clearance (IC) remains elusive. The aim of the present study was to investigate whether HBsAg and HBeAg levels were associated with liver inflammation and fibrosis in CHB patients during the IC phase. Kendall's rank correlation analysis and receiver operating characteristic curves were used to determine the correlation between HBsAg, HBeAg and liver pathological stages. Multivariate analysis by forward logistic regression was used to analyze significant predictors of cirrhosis. A liver pathology‑predicting model (IC model), which used routinely assessed markers in combination with HBsAg and HBeAg levels, was constructed. There were significantly positive correlations between the HBsAg and HBeAg levels (γ=0.317, P<0.001), and between the HBsAg and HBV‑DNA levels (γ=0.489, P<0.001). However, there was no correlation between the HBsAg and alanine aminotransferase levels. HBsAg and HBeAg levels differed significantly at various liver pathological stages and declined progressively in advanced liver pathological stages. Multivariate logistic regression analysis showed that age, HBsAg and HBeAg levels as well as the international normalized ratio (INR) were independent predictors of liver fibrosis during the IC phase. The IC model had a specificity and sensitivity of 88.64 and 78.24%, respectively, a positive predictive value of 48.15% and negative predictive value of 96.79%. In conclusion, HBsAg and HBeAg levels were negatively and indirectly correlated with liver inflammation and fibrosis in CHB patients in the IC phase. The IC model reliably predicted the probability of liver cirrhosis.
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Affiliation(s)
- Da-Wu Zeng
- Liver Center, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Yu-Rui Liu
- Liver Center, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Jing Dong
- Liver Center, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Yue-Yong Zhu
- Liver Center, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - You-Bing Li
- Liver Center, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Jing Chen
- Liver Center, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Qi Zheng
- Liver Center, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
| | - Jia-Ji Jiang
- Liver Center, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
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Liang LB, Zhu X, Yan LB, Du LY, Liu C, Chen LY, Liao J, Tang H. Serum hepatitis B surface antigen titer and transient elastography in screening for insignificant fibrosis in HBeAg-positive chronic hepatitis B patients. Ther Clin Risk Manag 2015; 11:229-35. [PMID: 25709465 PMCID: PMC4335620 DOI: 10.2147/tcrm.s73827] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Objective To explore the predictive value of serum hepatitis B surface antigen (HBsAg) titer and transient elastography in screening for insignificant fibrosis in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients. Methods We conducted a cross-sectional study of eligible patients treated from March 2012 to May 2013 at the West China Hospital of Sichuan University. Eligible patients underwent liver transient elastography and liver biopsy. We assessed the serum HBsAg level, serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, HBV genotypes, liver stiffness measurement (LSM) values by transient elastography, and histological fibrosis staging by METAVIR classification. Results A total of 129 consecutive patients were recruited. The LSM value (P<0.001, odds ratio 14.67, 95% CI 0.158–0.551) and log10HBsAg (P=0.045, odds ratio 4.03, 95% CI 0.136–0.976) correlated with a liver fibrosis score <F2, independently. Inverse correlations were found between log10HBsAg and the LSM value (r=−576, P<0.001) and fibrosis staging (r=−374, P<0.001). Patients with a fibrosis score <F2 had a significantly higher log10HBsAg than patients with a fibrosis score ≥F2 among those with an LSM value under 9.4 kPa (4.6±0.7 vs 4.3±0.5, P=0.006). The HBsAg titer achieved an area under the receiver operating characteristic curve of 0.758 (P<0.001, 95% CI 0.631–0.884) in predicting a fibrosis score <F2, with a cut-off value of 10,400 IU/mL, a positive predictive value of 73%, and a negative predictive value of 79%. Conclusion In HBeAg-positive patients with an alanine aminotransferase level <2× the upper limit of normal, high serum HBsAg levels can predict a fibrosis score <F2, and a lower HBsAg titer could be supportive of early fibrosis in patients with an LSM value under 9.4 kPa.
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Affiliation(s)
- Ling-Bo Liang
- Center of Infectious Disease, West China Hospital, West China School of Medicine, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People's Republic of China
| | - Xia Zhu
- Center of Infectious Disease, West China Hospital, West China School of Medicine, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People's Republic of China
| | - Li-Bo Yan
- Center of Infectious Disease, West China Hospital, West China School of Medicine, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People's Republic of China
| | - Ling-Yao Du
- Center of Infectious Disease, West China Hospital, West China School of Medicine, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People's Republic of China
| | - Cong Liu
- Center of Infectious Disease, West China Hospital, West China School of Medicine, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People's Republic of China
| | - Li-Yu Chen
- Center of Infectious Disease, West China Hospital, West China School of Medicine, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People's Republic of China
| | - Juan Liao
- Center of Infectious Disease, West China Hospital, West China School of Medicine, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People's Republic of China
| | - Hong Tang
- Center of Infectious Disease, West China Hospital, West China School of Medicine, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People's Republic of China
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15
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Xu Z, Pan X, Wei K, Ding H, Wei M, Yang H, Liu Q. Serum Golgi protein 73 levels and liver pathological grading in cases of chronic hepatitis B. Mol Med Rep 2014; 11:2644-52. [PMID: 25524053 PMCID: PMC4337480 DOI: 10.3892/mmr.2014.3114] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 11/25/2014] [Indexed: 12/20/2022] Open
Abstract
The present study was designed to assess the correlation between serum Golgi protein 73 (GP73) and liver pathological grading and staging in patients with chronic hepatitis B (CHB). Two hundred and fifty‑three patients with chronic hepatitis B virus (HBV) infections were enrolled in the present study. All patients received a serum GP73 test, and 91 CHB patients underwent liver biopsy. GP73 expression in liver tissue was assessed by immunohistochemical analysis. The results indicated that serum GP73 levels were positively correlated with disease progression in patients with chronic HBV infection (r=0.677). There was no significant difference in serum GP73 levels between hepatitis B e antigen‑positive and ‑negative patients (P>0.05). There were also no significant differences in serum GP73 levels among specimens with varying HBV DNA contents (P>0.05). Serum GP73 levels were positively correlated with increased liver pathological grading (r=0.737) and staging (r=0.692), and immunohistochemical analysis indicated that GP73 protein expression increased concurrently with liver pathological grading and staging. In conclusion, serum GP73 was found to be correlated with liver pathological grading and staging in patients with CHB, and may be an effective indicator for the evaluation of disease progression. However, serum GP73 levels were not associated with HBV replication.
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Affiliation(s)
- Zhengju Xu
- Clinical Liver Center, The 180th Hospital of the People's Liberation Army, Quanzhou, Fujian 362000, P.R. China
| | - Xingnan Pan
- Clinical Liver Center, The 180th Hospital of the People's Liberation Army, Quanzhou, Fujian 362000, P.R. China
| | - Kaipeng Wei
- Central Laboratory of Clinical Hepatology, The 180th Hospital of the People's Liberation Army, Quanzhou, Fujian 362000, P.R. China
| | - Hongbing Ding
- Liver Center Clinical Pathology, The 180th Hospital of the People's Liberation Army, Quanzhou, Fujian 362000, P.R. China
| | - Meijuan Wei
- Central Laboratory of Clinical Hepatology, The 180th Hospital of the People's Liberation Army, Quanzhou, Fujian 362000, P.R. China
| | - Huanwen Yang
- Clinical Liver Center, The 180th Hospital of the People's Liberation Army, Quanzhou, Fujian 362000, P.R. China
| | - Qian Liu
- Clinical Liver Center, The 180th Hospital of the People's Liberation Army, Quanzhou, Fujian 362000, P.R. China
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Zeng DW, Zhang JM, Liu YR, Dong J, Wu YL, Lin S, Jiang JJ, Zhu YY. A new model for predicting liver cirrhosis in chronic hepatitis B virus carriers with low serum alanine transaminase activity. Clin Res Hepatol Gastroenterol 2014; 38:727-734. [PMID: 25048838 DOI: 10.1016/j.clinre.2014.06.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Accepted: 06/06/2014] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To develop a cirrhosis-predicted model in chronic hepatitis B virus carriers with alanine transarninase (ALT) less than two times the upper limit of normal (ULN). METHODS Treatment-naive patients (n=278), who had undergone liver biopsies, were randomly divided into two groups - a training group and a validation group. Thirteen bio-clinical parameters were analyzed. A liver cirrhosis-predicting model (PPT model) was constructed using multivariate analysis. The diagnostic value of the model was analyzed by the receiving operating characteristics (ROC) method and compared with other available models. RESULTS A PPT model to predict liver cirrhosis was derived from three independent predictors of liver fibrosis [platelet count (PLT), prothrombin time (PT) and total bile acid (TBA)]. PPT model predicted cirrhosis with an area under the ROC (AUROC) curve of 0.83, a positive predictive value of 86.7% and a negative predictive value of 95.2%. Compared with APRI, FIB-4, age-AST model, AP index and APGA model, PPT model had the highest correlation coefficient (r=0.49) and greater predictive performance (AUROC of 0.83). CONCLUSIONS The PPT model was accurate in predicting cirrhosis and may reduce the need for liver biopsy in chronic hepatitis B virus carriers with ALT less than two times ULN.
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Affiliation(s)
- Da-Wu Zeng
- Liver center, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, 350005 Taijiang District, Fuzhou, Fujian Province, China
| | - Jie-Min Zhang
- Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, 350005 Taijiang District, Fuzhou, Fujian, China
| | - Yu-Rui Liu
- Liver center, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, 350005 Taijiang District, Fuzhou, Fujian Province, China
| | - Jing Dong
- Liver center, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, 350005 Taijiang District, Fuzhou, Fujian Province, China
| | - Yin-Lian Wu
- Liver center, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, 350005 Taijiang District, Fuzhou, Fujian Province, China
| | - Su Lin
- Liver center, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, 350005 Taijiang District, Fuzhou, Fujian Province, China
| | - Jia-Ji Jiang
- Liver center, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, 350005 Taijiang District, Fuzhou, Fujian Province, China
| | - Yue-Yong Zhu
- Liver center, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, 350005 Taijiang District, Fuzhou, Fujian Province, China.
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Kim JH, Moon HW, Ko SY, Choe WH, Kwon SY. Hepatitis B surface antigen levels at 6 months after treatment can predict the efficacy of lamivudine-adefovir combination therapy in patients with lamivudine-resistant chronic hepatitis B. Clin Mol Hepatol 2014; 20:274-282. [PMID: 25320731 PMCID: PMC4197176 DOI: 10.3350/cmh.2014.20.3.274] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 08/28/2014] [Accepted: 09/11/2014] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/AIMS Quantitation of hepatitis B surface antigen (HBsAg) is an increasingly popular method to determine the treatment response in chronic hepatitis B (CHB) patients. The clinical value of HBsAg level measurement during rescue therapy for lamivudine (LMV)-resistant CHB patients have not been evaluated to date. Therefore, this study investigated the correlation between HBsAg level and treatment response in LMV-resistant CHB patients treated with adefovir (ADV) add-on therapy. METHODS LMV-resistant CHB patients treated with LMV-ADV combination therapy for over 2 years were included. HBsAg levels were measured at 6 month intervals until 1 year, and annually thereafter. Treatment response was assessed by determining the virological response (VR, undetectable HBV DNA levels) during treatment. RESULTS Fifty patients were included, of which 40 showed a VR. HBsAg levels were not different significantly at baseline (4.0 vs. 3.6 Log10 IU/mL, P=0.072). However, the HBsAg level decreased after 6 months of treatment in patients with a VR and became different significantly between the groups thereafter (3.9 vs. 3.3 at 6 months, P=0.002; 3.8 vs. 3.2 at 1 year, P=0.004; 3.9 vs. 3.2 at 2 years, P=0.008; 3.7 vs. 3.1 at 3 years, P =0.020). CONCLUSIONS The HBsAg level at 6 months after treatment can help predict treatment response.
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Affiliation(s)
- Jeong Han Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Hee Won Moon
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Soon Young Ko
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Won Hyeok Choe
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - So Young Kwon
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Kim JH, Choi YJ, Moon HW, Ko SY, Choe WH, Kwon SY. HBsAg level and clinical course in patients with chronic hepatitis B treated with nucleoside analogue: five years of follow-up data. Clin Mol Hepatol 2013; 19:409-416. [PMID: 24459646 PMCID: PMC3894441 DOI: 10.3350/cmh.2013.19.4.409] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 11/14/2013] [Accepted: 11/20/2013] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND/AIMS Quantification of the hepatitis B surface antigen (HBsAg) is increasingly used to determine the treatment response in patients with chronic hepatitis B (CHB). However, there are limited data about the clinical implications of Quantification of HBsAg long-term nucleoside analogue treatment for CHB. We investigated the clinical correlation between HBsAg level and clinical course in patients with CHB who are treated long-term with nucleoside analogues. METHODS Patients with CHB who started lamivudine or entecavir monotherapy before June 2007 were enrolled. HBsAg was quantified at baseline, at 6 months, and at 1, 2, 3, 4, and 5 years of treatment. We compared data between the groups according to the presence or absence of a virological response (VR) and resistance. RESULTS Forty-eight patients were analyzed. There was no definite reduction in HBsAg level during the early period of treatment; differences in HBsAg levels between baseline and each time point were significant only at 5 years (P=0.028). In a subgroup analysis, this difference was significant only in non-resistant patients at 5 years (P=0.041). CONCLUSIONS There was no definite decrease in the HBsAg level during the early period of nucleoside analogue treatment, with long-term treatment being required to observe a significant reduction.
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Affiliation(s)
- Jeong Han Kim
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Yun Jung Choi
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Hee Won Moon
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Soon Young Ko
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Won Hyeok Choe
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - So Young Kwon
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Hu Q, Zhu SY, Kang LK, Wang XY, Lun HM, Xu CM. Non-invasive assessment of liver fibrosis using real-time tissue elastography in patients with chronic hepatitis B. Clin Radiol 2013; 69:194-9. [PMID: 24290780 DOI: 10.1016/j.crad.2013.10.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Revised: 09/20/2013] [Accepted: 10/03/2013] [Indexed: 01/06/2023]
Abstract
AIM To evaluate the utility of the elastic ratio calculated using real-time tissue elastography for assessing liver fibrosis in patients with chronic hepatitis B (CHB). MATERIALS AND METHODS Ninety-six patients with CHB were enrolled between September 2012 and August 2013. The elastic ratio of the liver for the intrahepatic venous small vessel was calculated to measure liver stiffness. Diagnostic performance of the elastic ratio and aminotransferase-to-platelet ratio index (APRI) were compared with histological fibrosis stage at liver biopsy. In addition, 45 healthy adult volunteers were participated in intra- and interobserver reliability studies. RESULTS There was no significant influence of hepatitis B e antigen (HBeAg) status or hepatitis B virus DNA levels on the elastic ratio measurements in CHB patients. The elastic ratio was significantly correlated with histological fibrosis stage (r = 0.873, p < 0.001). Cut-off values were 2.62 for stage 2 and over (S ≥ 2), 3.20 for state 3 and over, and 3.86 for stage 4, respectively. The areas under the receiver operating characteristic (ROC) curves for elastic ratio and APRI diagnosis of significant fibrosis (S ≥ 2) was 0.91 (95% CI: 0.84-0.98) and 0.71 (95% CI: 0.57-0.86), and 0.94 (95% CI: 0.89-0.99) and 0.81 (95% CI: 0.71-0.91) for cirrhosis (S = 4), respectively. The elastic ratio measurements had good reproducibility: 0.838 for intra-observer reliability and 0.805 for inter-observer reliability, respectively (p < 0.001). CONCLUSION Elastic ratio determined using real-time tissue elastography was an accurate and reproducible method for evaluating liver fibrosis in patients with CHB.
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Affiliation(s)
- Q Hu
- Department of Diagnostic Ultrasound, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi, China
| | - S Y Zhu
- Department of Diagnostic Ultrasound, First Affiliated Hospital of Guangxi Medical University, Guangxi, China.
| | - L K Kang
- Department of Diagnostic Ultrasound, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi, China
| | - X Y Wang
- Department of Diagnostic Ultrasound, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi, China
| | - H M Lun
- Department of Diagnostic Ultrasound, First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - C M Xu
- Department of Diagnostic Ultrasound, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi, China
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Chen EQ, Wang TT, Bai L, Tao CM, Liang T, Liu C, Liao J, Tang H. Quantitative hepatitis B surface antigen titres in Chinese chronic hepatitis B patients over 4 years of entecavir treatment. Antivir Ther 2013; 18:955-965. [PMID: 23639885 DOI: 10.3851/imp2579] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/18/2013] [Indexed: 02/05/2023]
Abstract
BACKGROUND The clinical value of quantitative hepatitis B surface antigen (qHBsAg) titre in patients taking nucleotide/nucleoside analogues (NAs) is still controversial. This study aims to investigate the dynamic changes of qHBsAg titres and their significance for predicting virological response (VR) and serological response (SR) to long-term entecavir (ETV) treatment. METHODS A total of 48 ETV-naive patients were enrolled and followed prospectively for 4 years, 32 of whom were hepatitis B e antigen (HBeAg)-positive at baseline. Serum alanine aminotransferase (ALT), qualitative HBV serological markers and HBV DNA were detected; qHBsAg titres were measured using Elecsys(®) HBsAg II Quant Assay (Roche Diagnostics, Penzberg, Germany). RESULTS The mean baseline HBV DNA and qHBsAg were 7.51 log10 copies/ml and 3.78 log10 IU/ml, respectively. After 48 months of ETV treatment, the rates of VR (<291 copies/ml), ALT normalization and SR (HBeAg/antibody to HBeAg [anti-HBe]) were 89.6% (43/48), 89.6% (43/48) and 34.4% (11/32), respectively. There was a decrease in qHBsAg titres from baseline to month 48, ranging from 3.78 to 3.10 log10 IU/ml. The greatest decrease of qHBsAg was observed in the first 3 months of treatment (0.47 log10 IU/ml), which was significantly correlated with corresponding HBV DNA decreases (3.89 log10 copies/ml; P=0.032). By using receiver operating characteristic (ROC) curve analysis, qHBsAg titres at baseline (area under the curve [AUROC]=0.647) and 3 months after treatment (AUROC=0.586) had poor power in predicting 48-month VR; qHBsAg titres at baseline (AUROC=0.779) and 3 months after ETV treatment (AUROC=0.658) had poor power in predicting 48-month SR in patients who were HBeAg-positive at baseline. Additionally, the decrease of qHBsAg in the first 3 months of treatment also had poor power in predicting either 48 month VR or SR. CONCLUSIONS ETV is efficacious in NA-naive patients, and qHBsAg titres decreased significantly in the first 3 months of ETV treatment. However, qHBsAg titre was not a good predictor of 4-year VR and HBeAg/anti-HBe SR in this cohort.
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Affiliation(s)
- En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, PR China
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21
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Wang Y, Xu MY, Zheng RD, Xian JC, Xu HT, Shi JP, Li SB, Qu Y, Dong YW, Lu LG. Prediction of significant fibrosis and cirrhosis in hepatitis B e-antigen negative patients with chronic hepatitis B using routine parameters. Hepatol Res 2013; 43:441-51. [PMID: 23006433 DOI: 10.1111/j.1872-034x.2012.01094.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2012] [Revised: 08/02/2012] [Accepted: 08/22/2012] [Indexed: 12/24/2022]
Abstract
AIM As liver biopsy has considerable limitations in the assessment of liver fibrosis, non-invasive models have achieved great progress in the past. However, many tests consist of variables that are not readily available, and there are few data about patients with hepatitis B e-antigen (HBeAg) negative chronic hepatitis B (CHB). The aim of this study was to develop a model using routine data to predict liver fibrosis in HBeAg negative CHB patients. METHODS We randomly divided 349 patients who underwent liver biopsy into training (n = 200) and validation (n = 149) sets. Multivariable logistic regression and receiver-operator curve (ROC) analyses were used to develop a model for predicting both significant fibrosis (stages 2-4) and cirrhosis (stage 4) in the training set. The model was validated in 149 patients in comparison to FIB-4, Forn's, S and aspartate aminotransferase-to-platelet ratio index indices using ROC. RESULTS Multivariable logistic regression analysis showed that the parameters of the model for predicting both significant fibrosis and cirrhosis included sex, age, prothrombin time, platelet count, cholesterol and γ-glutamyltransferase. In the training set, the areas under the ROC (AUC) for predicting significant fibrosis and cirrhosis were 0.856 and 0.956, respectively. In the validation group, the AUC for predicting significant fibrosis and cirrhosis were 0.889 and 0.937, respectively. Using the best cut-off values, significant fibrosis and cirrhosis can be accurately predicted in 40.9% and 91.3% of patients, respectively. CONCLUSION Our model can accurately predict both significant fibrosis and cirrhosis and may decrease the need of liver biopsy in a considerable proportion of patients with HBeAg negative CHB.
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Affiliation(s)
- Yan Wang
- Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai
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22
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Hepatitis B virus and hepatitis C virus infections in Belgium: similarities and differences in epidemics and initial management. Eur J Gastroenterol Hepatol 2013; 25:613-9. [PMID: 23325285 DOI: 10.1097/meg.0b013e32835d83a2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Nationwide studies comparing patients with hepatitis B and C virus (HBV and HCV) infections are mandatory for assessing changes in epidemiology. AIM The aim of this study was to compare epidemiological data and initial management of newly diagnosed patients with persistent HBV (HBsAg positive) or HCV (detectable HCV RNA) infection in Belgium. PATIENTS AND METHODS Data were extracted from two Belgian observational databases. RESULTS A total of 655 patients (387 HBV and 268 HCV) were included. Compared with HCV patients, HBV patients were younger, more frequently men, more often of Asian or African origin (43 vs. 10%, P<0.0001), and less frequently contaminated by transfusion or intravenous drug use (9 and 6% vs. 34 and 44%, P<0.0001). Viral replication was assessed in 89% of HBV patients. Compared with HCV patients, HBV patients more frequently had normal alanine aminotransferase (ALT) levels (65 vs. 29%, P<0.0001), less frequently underwent liver biopsy (29 vs. 67%, P<0.0001), and were less often considered for antiviral therapy (25 vs. 54%, P<0.0001). When taking only HBV patients with detectable viral replication into consideration, results remained unchanged. During the multivariate analysis, ALT was a major factor for performing liver biopsy or considering antiviral therapy in both groups. CONCLUSION HBV and HCV screening policies should be targeted toward immigrants and intravenous drug users, respectively. Guidelines recommending systematic search for viral replication should be reinforced in HBV patients. HBV patients less frequently underwent liver biopsy and were less often considered for antiviral therapy compared with HCV patients. Despite the lack of sensitivity and specificity, ALT remains a pivotal decision-making tool for liver biopsy and antiviral therapy in both infections.
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Erdogan S, Dogan HO, Sezer S, Uysal S, Ozhamam E, Kayacetin S, Koca Y. The diagnostic value of non-invasive tests for the evaluation of liver fibrosis in chronic hepatitis B patients. Scandinavian Journal of Clinical and Laboratory Investigation 2013; 73:300-8. [PMID: 23514016 DOI: 10.3109/00365513.2013.773592] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Liver biopsy, which is considered the gold standard for the evaluation of hepatic fibrosis in patients with chronic hepatitis B (CHB), has certain limitations. The aim of this study was to investigate the diagnostic performance of non-invasive markers of hepatic fibrosis as potential alternatives to liver biopsy. METHODS The medical records of 221 patients with a diagnosis of CHB who underwent a liver biopsy were reviewed. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas [Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), cirrhosis discriminant score (CDS), AST-platelet ratio index (APRI), Forns index, FIB-4, Pohl score, AAR-platelet score (AARP), fibro-quotient (FibroQ), AST/platelet/Gammaglutamyl transpeptidase (GGT)/Alphafetoprotein (AFP) (APGA) index, Platelet/Age/Phosphatase (ALP)/AFP/AST (PAPAS) index, Lok's model, Goteborg University Cirrhosis Index (GUCI)]. Diagnostic adequacy of these indices was evaluated by receiver operating characteristic curve analysis. RESULTS Area under the receiver operating characteristic curves for the FIB-4, Forns, GUCI, APRI, PAPAS, APGA and FibroQ indices were 0.701, 0.680, 0.670, 0.670, 0.639, 0.638 and 0.588, respectively. The AAR, API, CDS and AARP indices, Pohl score and Lok's model were all deemed diagnostically inadequate. FIB-4 had the best diagnostic adequacy whereas AAR had the worst. CONCLUSIONS Our results suggest that out of the 13 indices evaluated, only FIB-4 index may be useful in estimating the extent of fibrosis in patients with CHB. There is a need for more comprehensive prospective studies to help determine the diagnostic value of non-invasive tests for liver fibrosis.
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Affiliation(s)
- Serpil Erdogan
- a Department of Clinical Biochemistry, Ankara Numune Training and Research Hospital , Ankara, Turkey
| | - Halef Okan Dogan
- a Department of Clinical Biochemistry, Ankara Numune Training and Research Hospital , Ankara, Turkey
| | - Sevilay Sezer
- a Department of Clinical Biochemistry, Ankara Numune Training and Research Hospital , Ankara, Turkey
| | - Sema Uysal
- a Department of Clinical Biochemistry, Ankara Numune Training and Research Hospital , Ankara, Turkey
| | - Esra Ozhamam
- b Department of Clinical Pathology, Ankara Numune Training and Research Hospital , Ankara, Turkey
| | - Serra Kayacetin
- b Department of Clinical Pathology, Ankara Numune Training and Research Hospital , Ankara, Turkey
| | - Yuksel Koca
- a Department of Clinical Biochemistry, Ankara Numune Training and Research Hospital , Ankara, Turkey
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Wan S, Hann HW, Myers RE, Fu X, Hann RS, Kim SH, Tang H, Xing J, Yang H. Telomere length in circulating serum DNA as a novel non-invasive biomarker for cirrhosis: a nested case-control analysis. Liver Int 2012; 32:1233-1241. [PMID: 22471856 DOI: 10.1111/j.1478-3231.2012.02801.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2011] [Accepted: 03/06/2012] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Previous studies have indicated that telomere length is associated with altered risk of various tumours including hepatitis B virus (HBV)-related hepatocellular carcinoma. However, the association between telomere length and the risk of cirrhosis has not been reported. METHODS In this nested case-control study, we used real-time quantitative PCR to determine the relative telomere length (RTL) in serum DNA samples from 100 HBV-related cirrhosis cases and 100 frequency-matched HBV controls, and evaluated the associations between RTL and cirrhosis risk by logistic regression analyses. RESULTS We found that cirrhotic cases had a significantly longer RTL (median, 0.36; range, 0.08-1.87) than non-cirrhotic controls (median, 0.20; range, 0.05-1.11) (P < 0.0001). Compared with subjects with short RTL, those with long RTL had a significantly increased cirrhosis risk [odds ratio, 2.76, 95% confidence interval, 1.50-5.10; P = 0.001]. Quartile analysis further indicated a dose-response effect for this association. Compared with patients with the lowest quartile of RTL, the cirrhosis risk for those with the second, third and highest quartile of RTL was 2.68 (0.91-7.87, P = 0.073), 3.37 (1.32-10.54, P = 0.013) and 6.64 (2.41-18.32, P < 0.0001) respectively (P(trend) <0.0001). Moreover, the area under the receiver operating characteristic curve increased from 0.60 (epidemiological variables) to 0.72 (epidemiological variables plus RTL), with statistically significant difference assessed by bootstrap analysis. CONCLUSIONS Our study presents the first epidemiological evidence that RTL in serum DNA could potentially be used as a simple, inexpensive and non-invasive marker of cirrhosis risk, a finding that warrants further investigations in independent retrospective and prospective populations.
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Affiliation(s)
- Shaogui Wan
- Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, PA 19107, USA
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Buti M, García-Samaniego J, Prieto M, Rodríguez M, Sánchez-Tapias JM, Suárez E, Esteban R. Documento de consenso de la AEEH sobre el tratamiento de la infección por el virus de la hepatitis B (2012). GASTROENTEROLOGIA Y HEPATOLOGIA 2012; 35:512-28. [PMID: 22749508 DOI: 10.1016/j.gastrohep.2012.04.006] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2012] [Accepted: 04/23/2012] [Indexed: 12/13/2022]
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Oketani M, Ido A, Uto H, Tsubouchi H. Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy. Hepatol Res 2012; 42:627-36. [PMID: 22686858 DOI: 10.1111/j.1872-034x.2012.00998.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
With the increasing use of potent immunosuppressive therapy, reactivation of hepatitis B virus (HBV) in endemic regions is becoming a clinical problem requiring special attention. A recent annual nationwide survey clarified that HBV reactivation related to immunosuppressive therapy has been increasing in patients with malignant lymphoma, other hematological malignancies, oncological or rheumatological disease. In the survey, rituximab plus steroid-containing chemotherapy was identified as a risk factor for HBV reactivation in hepatitis B surface antigen (HBsAg) negative patients with malignant lymphoma. In this setting, HBV reactivation resulted in fatal fulminant hepatitis regardless of the treatment of nucleoside analog. The Intractable Hepatobiliary Disease Study Group and the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis jointly developed guidelines for preventing HBV reactivation. The essential features of the guideline are as follows. All patients should be screened for HBsAg by a sensitive method before the start of immunosuppressive therapy. Second, hepatitis B core antigen (HBcAb) and hepatitis B surface antibody (HBsAb) testing should be performed in HBsAg negative patients, especially those receiving intensive immunosuppressive therapy. Prophylaxis with nucleoside analogs is essential for preventing HBV reactivation in HBsAg positive patients. In contrast, HBsAg negative with HBcAb and/or HBsAb positive patients should be monitored monthly for an increase in serum HBV DNA during and 12 months after completion of chemotherapy. Nucleoside analogs should be administrated immediately when HBV DNA becomes positive during this period. This strategy facilitates commencement of nucleoside analogs at an early stage of HBV reactivation and results in prevention of severe hepatitis.
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Affiliation(s)
- Makoto Oketani
- Department of Digestive and Lifestyle-related Diseases, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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Buti M, Rodríguez Frías F, Esteban R. [Quantification of hepatitis B virus HBsAg: clinical implications]. Med Clin (Barc) 2012; 138:483-488. [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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Viganò M, Lampertico P. Clinical implications of HBsAg quantification in patients with chronic hepatitis B. Saudi J Gastroenterol 2012; 18:81-6. [PMID: 22421711 PMCID: PMC3326981 DOI: 10.4103/1319-3767.93805] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Accepted: 01/16/2012] [Indexed: 02/06/2023] Open
Abstract
Quantification of serum hepatitis B surface antigen (HBsAg) helps the management of patients with chronic hepatitis B virus (HBV) infection. Median HBsAg levels differ significantly during the natural history of HBV infection, progressively declining from immune tolerance to inactive phase. The combination of an HBsAg <1000 IU/mL and HBV DNA <2000 IU/mL at a single time point accurately identifies true inactive carriers. During antiviral treatment, HBsAg levels decline more rapidly in patients under peg-interferon (Peg-IFN) than in those under nucleos(t)ide analogues (NUC), and in responders to peg-IFN compared to non responders suggesting that a response-guided therapy in both HBeAg-positive and -negative patients treated with Peg-IFN could improve to cost-effectiveness of this therapeutic approach. Given the low rates of HBsAg clearance on NUC therapy, new studies to test whether Peg-IFN and NUC combination fosters HBsAg decline in long-term responders to NUC, are being explored.
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Affiliation(s)
- Mauro Viganò
- Hepatology Unit, Ospedale San Giuseppe, Università degli Studi di Milano, Milano, Italy
| | - Pietro Lampertico
- 1 Division of Gastroenterology, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy
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Schiff ER, Lee SS, Chao YC, Kew Yoon S, Bessone F, Wu SS, Kryczka W, Lurie Y, Gadano A, Kitis G, Beebe S, Xu D, Tang H, Iloeje U. Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B. Clin Gastroenterol Hepatol 2011; 9:274-276. [PMID: 21145419 DOI: 10.1016/j.cgh.2010.11.040] [Citation(s) in RCA: 135] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2010] [Revised: 11/22/2010] [Accepted: 11/24/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Long-term treatment with entecavir resulted in durable virologic suppression and continued histologic improvement in nucleoside-naive chronic hepatitis B patients. Patients with advanced fibrosis or cirrhosis, who received long-term entecavir treatment, were evaluated for improvement in liver histology. METHODS The study included a subset of patients from phase III and long-term rollover studies, who received entecavir for at least 3 years, had advanced fibrosis or cirrhosis, and evaluable biopsies at baseline and after long-term treatment. RESULTS Ten patients had advanced fibrosis or cirrhosis at baseline (Ishak fibrosis score, ≥ 4). After approximately 6 years of cumulative entecavir therapy (range, 267-297 wk), all 10 patients showed improvement in liver histology and Ishak fibrosis score. The mean change from baseline in Ishak fibrosis and Knodell necroinflammatory scores were -2.2 and -7.6, respectively. A reduction in Ishak fibrosis score to 4 or less was observed for all 4 patients who had cirrhosis at baseline. CONCLUSIONS Chronic hepatitis B patients with advanced fibrosis or cirrhosis demonstrated histologic improvement and reversal of fibrosis and cirrhosis after long-term treatment with entecavir.
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Affiliation(s)
- Eugene R Schiff
- University of Miami Hospital and Clinics, Miami, Florida, USA.
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Moucari R, Marcellin P. Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B. Liver Int 2011; 31 Suppl 1:122-8. [PMID: 21205149 DOI: 10.1111/j.1478-3231.2010.02390.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
HBsAg is a very important clinical test that might not only indicate active hepatitis B virus (HBV) infection but might also be used to predict clinical and treatment outcome. Clearance of HBsAg in patients with chronic HBV infection is associated with a much better clinical outcome, although surveillance for early detection of hepatocellular carcinoma (HCC) should continue. HBV DNA quantification is currently used for selecting candidates for therapy, monitoring response to therapy and detecting the emergence of drug resistance. Assays for HBsAg quantification are less expensive than HBV DNA and fully automated with a high throughput capacity. HBsAg titering may be a useful tool to manage patients with chronic HBV, to more clearly define which patients may, and more importantly, may not, benefit from treatment. Baseline and on-treatment HBsAg quantification may help to refine future treatment algorithms for both immune-modulator therapy and nucleos(t)ide analogues. Both HBV markers provide complementary information on the status of HBV infection. However, the relevance of serum HBsAg levels and its use as a reliable replacement for both covalently closed circular DNA and HBV DNA remain unclear.
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Affiliation(s)
- Rami Moucari
- Hepatology Department and INSERM U773, Beaujon Hospital, Clichy, France.
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32
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Brunetto MR. A new role for an old marker, HBsAg. J Hepatol 2010; 52:475-7. [PMID: 20185190 DOI: 10.1016/j.jhep.2009.12.020] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2009] [Revised: 12/18/2009] [Accepted: 12/24/2009] [Indexed: 01/04/2023]
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Bonino F, Piratvisuth T, Brunetto MR, Liaw YF. Diagnostic markers of chronic hepatitis B infection and disease. Antivir Ther 2010; 15 Suppl 3:35-44. [PMID: 21041902 DOI: 10.3851/imp1622] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Tan HH, Martin P. Current treatment of chronic HBV infection: A North American perspective. CURRENT HEPATITIS REPORTS 2009; 8:148-153. [DOI: 10.1007/s11901-009-0021-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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