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Arian A, Abdullah AD, Taher HJ, Suhail Alareer H, Fotouhi M. Diagnostic Values of the Liver Imaging Reporting and Data System in the Detection and Characterization of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Cureus 2023; 15:e36082. [PMID: 37065286 PMCID: PMC10097431 DOI: 10.7759/cureus.36082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 03/10/2023] [Indexed: 03/14/2023] Open
Abstract
This review was undertaken to assess the diagnostic value of the Liver Imaging Reporting and Data System (LI-RADS) in patients with a high risk of hepatocellular carcinoma (HCC). Google Scholar, PubMed, Web of Science, Embase, PROQUEST, and Cochrane Library, as the international databases, were searched with appropriate keywords. Using the binomial distribution formula, the variance of all studies was calculated, and using Stata version 16 (StataCorp LLC, College Station, TX, USA), the obtained data were analyzed. Using a random-effect meta-analysis approach, we determined the pooled sensitivity and specificity. Utilizing the funnel plot and Begg's and Egger's tests, we assessed publication bias. The results exhibited pooled sensitivity and pooled specificity of 0.80% and 0.89%, respectively, with a 95% confidence interval (CI) of 0.76-0.84 and 0.87-0.92, respectively. The 2018 version of LI-RADS showed the greatest sensitivity (0.83%; 95% CI 0.79-0.87; I 2 = 80.6%; P < 0.001 for heterogeneity; T 2 = 0.001). The maximum pooled specificity was detected in LI-RADS version 2014 (American College of Radiology, Reston, VA, USA; 93.0%; 95% CI 89.0-96.0; I 2 = 81.7%; P < 0.001 for heterogeneity; T 2 = 0.001). In this review, the results of estimated sensitivity and specificity were satisfactory. Therefore, this strategy can serve as an appropriate tool for identifying HCC.
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Zhang X, Jie Y, Wan Z, Lin S, Li Y, Lin M, Wu S, Wu X, Shi M, Xiao H, Cao M, Gong J, Chi X. Prognostic Value of Inflammatory Indicators in Chronic Hepatitis B Patients With Significant Liver Fibrosis: A Multicenter Study in China. Front Pharmacol 2021; 12:653751. [PMID: 34858162 PMCID: PMC8631540 DOI: 10.3389/fphar.2021.653751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 10/11/2021] [Indexed: 11/13/2022] Open
Abstract
Diagnosis of significant liver fibrosis is essential to facilitate the optimal treatment decisions and improve prognosis in patients with chronic hepatitis B (CHB). We aimed to evaluate the value of inflammatory indicators and construct a nomogram that effectively predicts significant liver fibrosis among CHB patients. 563 CHB patients from two centers in China from 2014 to 2019 were divided into three cohorts (development, internal validation, and independent validation cohorts), assigned into cases with significant fibrosis (liver fibrosis stages ≥2) and those without. Multiple biochemical and serological inflammatory indicators were investigated. Inflammatory indicators, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly associated with significant liver fibrosis in CHB patients but limited predictive performance, and then we combined them with prothrombin time activity percentage (PTA) and liver stiffness measurement (LSM) were identified by multivariate logistic regression analysis. Based on these factors, we constructed the nomogram with excellent performance. The area under the receiver operating characteristic curve (AUROC) for the nomogram in the development, internal validation, and independent validation cohorts were 0.860, 0.877, and 0.811, respectively. Our nomogram based on ALT and AST that had excellent performance in predicting significant fibrosis of CHB patients were constructed.
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Affiliation(s)
- Xiujuan Zhang
- Department of Hepatology Diseases, Guangdong Provincial Hospital of Chinese Medicine Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yusheng Jie
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zemin Wan
- Department of Laboratory Medicine, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shanshan Lin
- Department of Hepatology Diseases, Guangdong Provincial Hospital of Chinese Medicine Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yingxian Li
- Department of Medical Education, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ming Lin
- Department of Hepatology Diseases, Guangdong Provincial Hospital of Chinese Medicine Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shuduo Wu
- Department of Hepatology Diseases, Guangdong Provincial Hospital of Chinese Medicine Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaoju Wu
- Department of Hepatology Diseases, Guangdong Provincial Hospital of Chinese Medicine Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Meijie Shi
- Department of Hepatology Diseases, Guangdong Provincial Hospital of Chinese Medicine Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Huanming Xiao
- Department of Hepatology Diseases, Guangdong Provincial Hospital of Chinese Medicine Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Minling Cao
- Department of Hepatology Diseases, Guangdong Provincial Hospital of Chinese Medicine Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiao Gong
- Department of Laboratory Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaoling Chi
- Department of Hepatology Diseases, Guangdong Provincial Hospital of Chinese Medicine Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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SARIÇAM E, İNCE YUSUFOĞLU S. Comparison of hepatitis B-infected and healthy individuals in terms of DMFT scores, endodontic treatment and extraction numbers: a cross-sectional study. ACTA ODONTOLOGICA TURCICA 2021. [DOI: 10.17214/gaziaot.833326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Li K, Qin L, Jiang S, Li A, Zhang C, Liu G, Sun J, Sun H, Zhao Y, Li N, Zhang Y. The signature of HBV-related liver disease in peripheral blood mononuclear cell DNA methylation. Clin Epigenetics 2020; 12:81. [PMID: 32513305 PMCID: PMC7278209 DOI: 10.1186/s13148-020-00847-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 04/08/2020] [Indexed: 12/20/2022] Open
Abstract
Background Hepatitis B virus (HBV)-related liver disease induces liver damage by hepatic immune and inflammatory response. The association between aberrant peripheral blood mononuclear cell (PBMC) DNA methylation and progression of liver disease and fibrosis remains unclear. Results Here we applied Infinium 450 K BeadChip investigating PBMC genome-wide methylation profiling of 48 HBV-related liver disease patients including 24 chronic hepatitis B (CHB), 14 compensated liver cirrhosis (LC), and 10 decompensated liver cirrhosis (DLC). In total, there were 7888 differentially methylated CpG sites (36.06% hypermethylation, 63.94% hypomethylation) correlate with liver disease progression. LC was difficult to be diagnosed, intermediating between CHB and DLC. We used least absolute shrinkage and selection operator (LASSO)-logistic regression method to perform a LC predictive model. The predicted probability (P) of having LC was estimated by the combined model: P = 1/(1 − e−x), where X = 11.52 − 2.82 × (if AST within the normal range − 0.19 × (percent methylation of cg05650055) − 0.21 × (percent methylation of cg17149911 ). Pyrosequencing validation and confusion matrix analysis was used for internal testing, area under receiver operating characteristic curve (AUROC) of model was 0.917 (95% CI, 0.80–0.977). On the fibrosis progress, there were 1705 genes in LC compared with CHB, whose differentially methylated CpG sites loading within the “promoter” regions (including TSS1500, TSS200, 5′UTR, and the 1st exon of genes) subject into the enrichment analysis using Ingenuity Pathway Analysis (IPA). There were 113 enriched immune-related pathways indicated that HBV-related liver fibrosis progression caused epigenetic reprogramming of the immune and inflammatory response. Conclusions These data support idea that development of HBV-related chronic liver disease is linked with robust and broad alteration of methylation in peripheral immune system. CpG methylation sites serve as relevant biomarker candidates to monitor and diagnose LC, providing new insight into the immune mechanisms understanding the progression of HBV-related liver fibrosis and cirrhosis.
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Affiliation(s)
- Kang Li
- Biomedical Information Center, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Ling Qin
- Biomedical Information Center, Beijing You'An Hospital, Capital Medical University, Beijing, China.,Schools of Basic Medical Science, Capital Medical University, Beijing, China
| | | | - Ang Li
- Biomedical Information Center, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Chi Zhang
- Biomedical Information Center, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Guihai Liu
- Biomedical Information Center, Beijing You'An Hospital, Capital Medical University, Beijing, China.,University of Oxford, Oxford, UK
| | - Jianping Sun
- Biomedical Information Center, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Huanqing Sun
- Biomedical Information Center, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Yan Zhao
- Clinical Laboratory Center, Beijing You'An hospital, Capital Medical University, Beijing, China
| | - Ning Li
- Departments of Hepatobiliary Surgery, Beijing You'An Hospital, Capital Medical University, Beijing, China.
| | - Yonghong Zhang
- Biomedical Information Center, Beijing You'An Hospital, Capital Medical University, Beijing, China.
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Basen-Engquist K, Brown P, Coletta AM, Savage M, Maresso KC, Hawk E. Lifestyle and Cancer Prevention. ABELOFF'S CLINICAL ONCOLOGY 2020:337-374.e12. [DOI: 10.1016/b978-0-323-47674-4.00022-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abdurakhmanov DT, Rozina TP, Nikulkina EN, Burnevich EZ, Tanashuk EL, Severov MV, Filatova AL, Milovanova SY, Karpov VV, Moiseev SV. [Antiviral therapy of chronic hepatitis C: 30 years success story]. TERAPEVT ARKH 2019; 91:110-115. [PMID: 32598621 DOI: 10.26442/00403660.2019.11.000470] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 11/22/2022]
Abstract
Exactly 30 years ago, hepatitis C virus was identified. Over the years, tremendous success has been achieved in the treatment of hepatitis C, which is currently considered to be an almost completely curable disease. The review presents the main stages in the development of hepatitis C antiviral therapy, the efficacy of various treatment regimens. The greatest progress in treatment was noted over the past 5 years when drugs with direct antiviral action appeared and began to be widely used, including in Russia, which ensure the elimination of the virus in 90-95% of cases.
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Affiliation(s)
- D T Abdurakhmanov
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
| | - T P Rozina
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
| | - E N Nikulkina
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
| | - E Z Burnevich
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
| | - E L Tanashuk
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
| | - M V Severov
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
| | - A L Filatova
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
| | - S Y Milovanova
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
| | - V V Karpov
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
| | - S V Moiseev
- Tareev Clinic of Rheumatology Nephrology and Occupational Disease Sechenov First Moscow State Medical University
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Amidou SA, Dovonou CA, Houehanou C, Kpangon AA, Ahanhanzo-Glele R, Kpangon JH, Alassan KS, Angelo AC, Tchaou B, Salifou K, Adoukonou T, Zannou DM, Houinato DS. [Impact of HIV status on the overall prevalence of chronic hepatitis B infection in Parakou, Benin]. Pan Afr Med J 2018; 30:180. [PMID: 30455809 PMCID: PMC6235507 DOI: 10.11604/pamj.2018.30.180.16117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 06/05/2018] [Indexed: 11/11/2022] Open
Abstract
INTRODUCTION The prevalence of hepatitis B is very variable across geographic areas and seems to be influenced by HIV infection. This study aims to evaluate the impact of serologic HIV status on the overall prevalence of hepatitis B in a Hospital in Parakou, Benin. METHODS We conducted a cross-sectional study of adults aged 18 years old and over hospitalized in the Departmental University Hospital Center in Parakou between May 2011 and June 2012. The diagnosis of hepatitis B was made on the basis of rapid HBsAg tests while the diagnosis of HIV was made on the basis of rapid HIV tests using venous blood samples. Data were analyzed using EpiInfo software. Multivariate logistic regression model was implemented to investigate factors associated with hepatitis B. RESULTS Out of 1516 subjects included, 744 were HIV seropositive. The average age was 31.3 + 11.1 years and 65.1% were women. The prevalence rate of hepatitis B in the whole sample was 13.9% [CI95:12.2%-15.7%]. This prevalence was higher in HIV seropositive subjects (16.9% vs 10.9%; p < 0.0006), however there was not a more significant difference in multivariate analysis, except for the group of subjects from Borgou/Alibori (p < 0.02). A consistent association was observed between age group 24-44 years (p < 0.03), male sex (p < 0.01), primary school education (p < 0.02) and a high prevalence of hepatitis B. CONCLUSION The prevalence of hepatitis B was higher in HIV seropositive subjects. This was influenced by age, sex, education level and geographical origin.
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Affiliation(s)
- Salimanou Ariyoh Amidou
- Centre d'Information de Prospectives et de Conseils sur les IST/VIH/Sida, Parakou, Bénin
- Service de Médecine Interne, Centre Hospitalier Universitaire de Parakou, Bénin
- Laboratoire d'Epidémiologie des Maladies Chroniques et Neurologiques (LEMACEN), Faculté des Sciences de la Santé de Cotonou, Bénin
| | | | - Corine Houehanou
- Laboratoire d'Epidémiologie des Maladies Chroniques et Neurologiques (LEMACEN), Faculté des Sciences de la Santé de Cotonou, Bénin
| | | | - Rhonel Ahanhanzo-Glele
- Centre d'Information de Prospectives et de Conseils sur les IST/VIH/Sida, Parakou, Bénin
- Service de Médecine Interne, Centre Hospitalier Universitaire de Parakou, Bénin
| | | | | | | | - Blaise Tchaou
- Service des Urgences, Centre Hospitalier Universitaire de Parakou, Bénin
| | - Kabibou Salifou
- Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Parakou, Bénin
| | - Thierry Adoukonou
- Service de Médecine Interne, Centre Hospitalier Universitaire de Parakou, Bénin
- Laboratoire d'Epidémiologie des Maladies Chroniques et Neurologiques (LEMACEN), Faculté des Sciences de la Santé de Cotonou, Bénin
| | | | - Dismand Stephan Houinato
- Laboratoire d'Epidémiologie des Maladies Chroniques et Neurologiques (LEMACEN), Faculté des Sciences de la Santé de Cotonou, Bénin
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Nazzal M, Gadani S, Said A, Rice M, Okoye O, Taha A, Lentine KL. Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies. GLOBAL SURGERY (LONDON) 2018; 4. [PMID: 29782618 DOI: 10.15761/gos.1000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.
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Affiliation(s)
- Mustafa Nazzal
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Sameer Gadani
- Interventional Radiology, Department of Radiology, St. Louis University Hospital, USA
| | - Abdullah Said
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Mandy Rice
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Obi Okoye
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Ahmad Taha
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Krista L Lentine
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA.,Division of Nephrology, Department of Medicine, St Louis University Hospital, USA
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Di Poto C, He S, Varghese RS, Zhao Y, Ferrarini A, Su S, Karabala A, Redi M, Mamo H, Rangnekar AS, Fishbein TM, Kroemer AH, Tadesse MG, Roy R, Sherif ZA, Kumar D, Ressom HW. Identification of race-associated metabolite biomarkers for hepatocellular carcinoma in patients with liver cirrhosis and hepatitis C virus infection. PLoS One 2018; 13:e0192748. [PMID: 29538406 PMCID: PMC5851549 DOI: 10.1371/journal.pone.0192748] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 01/30/2018] [Indexed: 12/14/2022] Open
Abstract
Disparities in hepatocellular carcinoma (HCC) incidence and survival have been observed between ethnic groups including African-Americans (AA) and European-Americans (EA). The evaluation of the changes in the levels of metabolites in samples stratified by race could provide a snapshot of ethnically diverse disease related pathways and identify reliable biomarkers. In this study, we considered AA and EA to investigate metabolites that may be associated with HCC in a race-specific manner. The levels of 46 metabolites in plasma samples, collected from patients recruited at MedStar Georgetown University Hospital, were analyzed by Agilent GC-qMS in selected ion monitoring (SIM) mode. A least absolute shrinkage and selection operator (LASSO) regression model was applied to select metabolites with significant changes in HCC vs. cirrhosis in three groups: (1) AA and EA combined; (2) AA separately; and (3) EA separately. In addition, metabolites that distinguish HCC cases from cirrhosis in these three groups were selected by excluding those without HCV infection. The performances of the metabolites selected by LASSO in each group were evaluated through a leave-one-out cross-validation. We identified race-specific metabolites that differentiated HCC cases from cirrhotic controls, yielding better area under the receiver operating characteristics (ROC) curve (AUC) compared to alpha-fetoprotein (AFP), the serological marker widely used for the diagnosis of HCC. This study sheds light on metabolites that could potentially be used as biomarkers for HCC by monitoring their levels in high-risk population of cirrhotic patients in a race-specific manner.
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Affiliation(s)
- Cristina Di Poto
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, United States of America
| | - Shisi He
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, United States of America
| | - Rency S. Varghese
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, United States of America
| | - Yi Zhao
- Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America
| | - Alessia Ferrarini
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, United States of America
| | - Shan Su
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, United States of America
| | - Abdullah Karabala
- MedStar Georgetown University Hospital and Georgetown University Medical Center, Washington, DC, United States of America
| | - Mesfin Redi
- Department of Chemistry, Addis Ababa University, Addis Ababa, Ethiopia
| | - Hassen Mamo
- Department of Microbial, Cellular and Molecular Biology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Amol S. Rangnekar
- MedStar Georgetown University Hospital and Georgetown University Medical Center, Washington, DC, United States of America
| | - Thomas M. Fishbein
- MedStar Georgetown University Hospital and Georgetown University Medical Center, Washington, DC, United States of America
| | - Alexander H. Kroemer
- MedStar Georgetown University Hospital and Georgetown University Medical Center, Washington, DC, United States of America
| | - Mahlet G. Tadesse
- Department of Mathematics and Statistics, Georgetown University, Washington DC, United States of America
| | - Rabindra Roy
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, United States of America
| | - Zaki A. Sherif
- Department of Biochemistry & Molecular Biology, College of Medicine, Howard University, Washington DC, United States of America
| | - Deepak Kumar
- Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, North Carolina, United States of America
| | - Habtom W. Ressom
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, United States of America
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Jelski W, Strumnik A, Orywal K, Lapinski TW, Swiderska M, Szmitkowski M. Activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in sera of patients with hepatitis C. Arch Med Sci 2018; 14:281-287. [PMID: 29593800 PMCID: PMC5868663 DOI: 10.5114/aoms.2016.60406] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 09/30/2015] [Indexed: 01/15/2023] Open
Abstract
INTRODUCTION The changes of enzyme activity in the hepatocytes in the course of different liver diseases are reflected by increase of the corresponding enzyme activity in the plasma. For example, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) correlate with the severity of the condition during cirrhosis. In this study we measured the activity of ADH isoenzymes and ALDH in the sera of patients with hepatitis C. MATERIAL AND METHODS Serum samples were taken from 60 patients suffering from viral hepatitis C and from 66 control subjects. Total ADH activity and class III and IV isoenzymes were measured by the photometric method and ALDH activity, ADH I and II by the fluorometric method. RESULTS The ADH activity was significantly higher in patients with hepatitis C than in healthy (p < 0.001). The total activity of ADH was 1284 mU/l in patients, and 745 mU/l (controls). The activity of isoenzymes classes ADH I and ADH II in the hepatitis C group increased respectively 55% (4.24 vs. 1.88 mU/l; p < 0.001) and 47% (26.63 vs. 14.11 mU/l; p < 0.001) in the comparison to the control. There was significant increase in the activity of ADH I isoenzyme (4.96 vs. 3.81 mU/l; p < 0.001) and ADH total (1833 vs. 1105 mU/l; p < 0.001) in patients with high viral load in comparison to patients with low viral load. CONCLUSIONS The activity of class I and II ADH isoenzymes in the sera of patients with hepatitis C is increased, and it seems to be caused by the release of these isoenzymes from damaged liver cells.
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Affiliation(s)
- Wojciech Jelski
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | | | - Karolina Orywal
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | - Tadeusz W Lapinski
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
| | - Magdalena Swiderska
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
| | - Maciej Szmitkowski
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
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Nansseu JR, Mbogning DM, Monamele GC, Tamoh SF, Gonsu HK, Kouanfack C, Yanwou YN, Sando Z. Sero-epidemiology of human immunodeficiency virus, hepatitis B virus and hepatitis C virus: a cross-sectional survey in a rural setting of the West region of Cameroon. Pan Afr Med J 2017; 28:201. [PMID: 29610639 PMCID: PMC5878856 DOI: 10.11604/pamj.2017.28.201.12717] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 09/04/2017] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Human immunodeficiency Virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) are the three most common chronic viral infections worldwide, specifically in sub-Saharan Africa (SSA). This study aimed to determine the sero-epidemiology of HIV, HBV and HCV infections in a rural setting of the West region of Cameroon, a SSA country. METHODS We conducted a cross-sectional study from August 2 to 5, 2014 in the three health districts of the Menoua Division, West region of Cameroon. Sixteen villages were randomly selected. Participants were currently living in the Division at the time of the survey, and enrolled after they had provided a signed consent form. HIV screening used the "determine test" followed by Hexagon HIV for positive cases to the first assay. HBV and HCV were detected using DIASpot HBsAg and DIASpot HCV-Ab, respectively. RESULTS On the whole, 612 subjects consented to take part in this study, of whom 71.1% were females. Mean age of the study population was 45.3 ± 17.9 years. The seroprevalences of HIV, HBV and HCV infections were 1.0% (6/582), 4.5% (20/443) and 6.3% (23/365), respectively. The 41-50 years age group was the most represented among HIV-positive subjects. HBV prevalence was higher in the 21-30 years age group (13.4%), followed by the 51-60 years age group (7.8%), with a significant difference of prevalences among age groups (p = 0.002). All HCV-positive cases were above 40 years of age with a higher prevalence in the > 70 years age group (33.3%) followed by the 61-70 years age group (14.5%); there was a significant difference between the age groups (p = 0.001). CONCLUSION The seroprevalences of HIV, HBV and HCV infections in the Menoua Division of the West region of Cameroon were 1.0%, 4.5% and 6.3%, respectively. Preventive measures against these health threats need to be reinforced in this setting.
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Affiliation(s)
- Jobert Richie Nansseu
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
- Department of Disease, Epidemics and Pandemics Control, Ministry of Public Health, Yaoundé, Cameroon
| | | | | | | | - Hortense Kamga Gonsu
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
- Laboratory of Bacteriology, Yaoundé University Teaching Hospital, Yaoundé, Cameroon
| | | | - Yves Nathan Yanwou
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Zacharie Sando
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
- Department of Pathology, Yaoundé Gynaeco-Obstetrics and Pediatric Hospital, Yaoundé, Cameroon
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12
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Siravenha LG, Siravenha LQ, Madeira LDP, Oliveira-Filho AB, Machado LFA, Martins Feitosa RN, Vallinoto ACR, Ishak MDOG, Ishak R. Detection of HCV Persistent Infections in the Dental Pulp: A Novel Approach for the Detection of Past and Ancient Infections. PLoS One 2016; 11:e0165272. [PMID: 27783693 PMCID: PMC5082628 DOI: 10.1371/journal.pone.0165272] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Accepted: 10/10/2016] [Indexed: 01/12/2023] Open
Abstract
The dental pulp is a sterile highly vascularized tissue and has been commonly used as a biological material to detect the genome of infectious agents that reach the dental tissue. Indeed, the pulp is also used to reveal past and ancient infections in the field of paleomicrobiology. The present study aimed to detect the presence of Hepatitis C virus (HCV) in a small community (approximately 400 inhabitants) in the Amazon region of Brazil (Nossa Senhora do Perpetuo Socorro, Vizeu, Para, Brazil) and standardize a technique for the detection of the virus in the dental pulp. Serum samples were collected from 48 patients whose teeth were clinically recommended for surgical extraction. The group comprised an equal number of males and females, mostly agriculture workers and housewives, respectively. The majority (64.6%) received less than one minimum wage and were ill educated (less than four years of school years). An enzyme immune assay was used to detect antibodies to HCV and the 9 (18.8%) positive samples were submitted to nucleic acid extraction in the blood (using the EXTRAzol) and the pulp (QIAamp DNA Micro Kit e kit RNeasy Plus Micro). The pulp was removed using a modified protocol without the use of liquid nitrogen. Nucleic acid was found in 8 of the dental pulp, but in 7 of the blood samples. Sequencing of one of the samples showed the presence of genotype 1. CONCLUSIONS A novel simplified methodology for the extraction and amplification of HCV nucleic acid was successful to detect the presence of persistent infections of the virus within the dental pulp tissue. The protocol may be helpful to detect past and ancient infections and to better understand the natural history of HCV.
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Affiliation(s)
- Layla Gomes Siravenha
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Guamá, Belém, Pará, Brasil
| | - Leonardo Quintão Siravenha
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Guamá, Belém, Pará, Brasil
| | - Lucimar Di Paula Madeira
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Guamá, Belém, Pará, Brasil
| | | | - Luiz Fernando Almeida Machado
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Guamá, Belém, Pará, Brasil
| | - Rosimar Neris Martins Feitosa
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Guamá, Belém, Pará, Brasil
| | | | | | - Ricardo Ishak
- Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Guamá, Belém, Pará, Brasil
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13
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Sousa VCSD, Carmo RF, Vasconcelos LRS, Aroucha DCBL, Pereira LMMB, Moura P, Cavalcanti MSM. Association of Catalase and Glutathione Peroxidase 1 Polymorphisms with Chronic Hepatitis C Outcome. Ann Hum Genet 2016; 80:145-53. [PMID: 26990426 DOI: 10.1111/ahg.12152] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Accepted: 02/03/2016] [Indexed: 12/14/2022]
Abstract
The hepatic damage caused by hepatitis C virus (HCV) infection is associated with the host immune response and viral regulatory factors. Catalase (CAT) and glutathione peroxidase 1 (GPX1) are antioxidant enzymes located in the peroxisomes and mitochondria, respectively, and are responsible for the control of intracellular hydrogen peroxide levels. Polymorphisms in CAT (C-262T) and GPX1 (Pro198Leu) are correlated with serum levels and enzyme activity. This study aimed to investigate the association of genetic polymorphisms of CAT C-262T (rs1001179) and GPX1 Pro198Leu (rs1050450) with different stages of liver fibrosis and development of hepatocellular carcinoma (HCC). This study included 445 patients with chronic hepatitis C, of whom 139 patients had mild fibrosis (F0-F1), 200 had moderate/severe fibrosis (F2-F4), and 106 had HCC. Genotyping of SNPs was performed by real-time PCR using TaqMan probes. The Pro/Pro genotype of GPX1 was significantly associated with fibrosis severity, HCC, Child Pugh score, and BCLC staging. Additionally, patients carrying both CT+TT genotypes in the CAT gene and the Pro/Pro genotype in the GPX1 gene had higher risk for developing moderate/severe fibrosis or HCC (p = 0.009, OR 2.40 and p = 0.002, OR 3.56, respectively). CAT and GPX1 polymorphisms may be implicated in the severity of liver fibrosis and HCC caused by HCV.
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Affiliation(s)
- Vanessa C S D Sousa
- Instituto de Ciências Biológicas - ICB, Universidade de Pernambuco - UPE, Brazil
| | - Rodrigo F Carmo
- Colegiado de Farmácia, Universidade Federal do Vale do São Francisco - UNIVASF, Brazil.,Rede Nordeste de Biotecnologia - RENORBIO, Brazil
| | - Luydson R S Vasconcelos
- Instituto do Fígado e Transplantes de Pernambuco - IFP, Brazil.,Centro de Pesquisas Aggeu Magalhães (FIOCRUZ), Brazil
| | - Dayse C B L Aroucha
- Instituto do Fígado e Transplantes de Pernambuco - IFP, Brazil.,Faculdade de Ciências Médicas, UPE, Brazil
| | - Leila M M B Pereira
- Instituto do Fígado e Transplantes de Pernambuco - IFP, Brazil.,Faculdade de Ciências Médicas, UPE, Brazil
| | - Patrícia Moura
- Instituto de Ciências Biológicas - ICB, Universidade de Pernambuco - UPE, Brazil
| | - Maria S M Cavalcanti
- Instituto de Ciências Biológicas - ICB, Universidade de Pernambuco - UPE, Brazil
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14
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Lô G, Sow-Sall A, Diop-Ndiaye H, Mandiouba NCID, Thiam M, Diop F, Ndiaye O, Gueye SB, Seck SM, Dioura AAM, Mbow M, Gaye-Diallo A, Mboup S, Touré-Kâne C. Prevalence of hepatitis B markers in Senegalese HIV-1-infected patients. J Med Virol 2016; 88:461-465. [PMID: 26252424 DOI: 10.1002/jmv.24344] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/03/2015] [Indexed: 01/15/2023]
Abstract
The study aimed to estimate the prevalence of Hepatitis B virus (HBV) infection and to describe the HBV virological profiles among Senegalese HIV-1-infected patients. We conducted a retrospective study between 2006 and 2010 among Senegalese HIV-1-infected patients from the antiretroviral therapy cohort. Samples were screened using Determine(®) HBsAg or MONOLISA(®) POC test. The HBsAg positivity status was confirmed by Architect(®) HBsAg. Detection of HBeAg, anti-HBe Ab, and HBV DNA load were done for the HBsAg-positive samples. Then, Anti-HBcAb was tested for the HBsAg-negative samples. Microsoft Excel was used for data collection and statistical analyses were performed using Epi info 3.5.1. Overall, 466 HIV-infected patients were enrolled including 271 women (58.4%), and 193 men (41.6%) with a median age of 39 years (19-74 years). The global prevalence of HIV/HBV coinfection (HBsAg positive) was 8.8% (41/466). For HBsAg positives samples, the prevalence of HBeAg and the anti-HBeAb were, respectively, 24.4 and 69.2% and the median of HBV DNA viral load, for 27 HBsAg-positive samples, was 3.75 log10 copies/ml. The virological profiles were the following: 7, 15, and 5 patients infected, respectively, by a replicative virus, an inactive virus and a probably mutant virus. For HBsAg-negative samples, 83 out of 109 were positive for anti-HBcAb. This study showed a significant decrease of the prevalence of HBV/HIV coinfection between 2004 and 2014 (P = 0.003), which highlighted the performance of the Senegalese HBV vaccine program. However, implementing a systematic quantification of HBV DNA viral load could improve the monitoring of HBV-infected patient.
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Affiliation(s)
- Gora Lô
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | - Amina Sow-Sall
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | - Halimatou Diop-Ndiaye
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | | | - Moussa Thiam
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | - Fatou Diop
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | - Ousseynou Ndiaye
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | - Sokhna Bousso Gueye
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | | | | | - Moustapha Mbow
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | - Aïssatou Gaye-Diallo
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | - Souleymane Mboup
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
| | - Coumba Touré-Kâne
- Bacteriology and Virology Laboratory at Le Dantec Teaching Hospital of Dakar, Dakar, Senegal
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15
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Lee CM, Hu TH, Lu SN, Wang JH, Hung CH, Chen CH, Yen YH. Suppressor of cytokine signaling 1 expression in peripheral blood mononuclear cells of hepatitis C genotype 1 patients. J Formos Med Assoc 2016; 115:440-4. [PMID: 26786212 DOI: 10.1016/j.jfma.2015.12.004] [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: 09/09/2015] [Revised: 12/02/2015] [Accepted: 12/05/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND/PURPOSE While new direct-acting antiviral therapies for hepatitis C virus (HCV) are the standard of care, interferon-α (IFN-α) remains a standard therapy in Taiwan based on its low cost and high response rate to IFN-α-based therapy. IFN-α exerts antiviral activity by inducing the expression of hundreds of genes that establish an antiviral state via Jak kinase (JAK)/signal transducers and activators of transcription (STAT) signaling. We quantified the transcript levels of JAK/STAT signaling genes in peripheral blood mononuclear cells of HCV genotype 1 patients and estimated the correlation between transcript levels and patient responses to IFN-α-based therapy. METHODS A total of 100 HCV genotype 1 naïve patients were enrolled. All patients received response-guided therapy for 24-48 weeks with pegylated IFN-α and ribavirin. Peripheral blood mononuclear cells were collected before treatment. Twenty patients with sustained virological responses (SVR) and 20 patients without SVR were selected for a JAK/STAT signaling genes transcript analysis using multiplex reverse transcription-polymerase chain reaction. Transcripts that were upregulated or downregulated were further validated in 100 patients. RESULTS Suppressor of cytokine signaling 1 (SOCS1) expression was upregulated in SVR patients compared with non-SVR patients (relative quantification = 2.14) based on a multiplex reverse transcription-polymerase chain reaction analysis. We further analyzed SOCS1 expression in 100 patients. We found that SOCS1 expression did not differ significantly between SVR and non-SVR patients. CONCLUSION Peripheral blood SOCS1 expression before treatment was not associated with SVR in HCV genotype 1 patients treated with pegylated IFN-α and ribavirin.
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Affiliation(s)
- Chuan-Mo Lee
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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16
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Evaluation of Liver Fibrosis Using Texture Analysis on Combined-Contrast-Enhanced Magnetic Resonance Images at 3.0T. BIOMED RESEARCH INTERNATIONAL 2015; 2015:387653. [PMID: 26421287 PMCID: PMC4569760 DOI: 10.1155/2015/387653] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 10/15/2014] [Accepted: 10/18/2014] [Indexed: 01/02/2023]
Abstract
Purpose. To noninvasively assess liver fibrosis using combined-contrast-enhanced (CCE) magnetic resonance imaging (MRI) and texture analysis. Materials and Methods. In this IRB-approved, HIPAA-compliant prospective study, 46 adults with newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI following intravenous administration of superparamagnetic iron oxides (ferumoxides) and gadolinium DTPA (gadopentetate dimeglumine). The image texture of the liver was quantified in regions-of-interest by calculating 165 texture features. Liver biopsy specimens were stained with Masson trichrome and assessed qualitatively (METAVIR fibrosis score) and quantitatively (% collagen stained area). Using L1 regularization path algorithm, two texture-based multivariate linear models were constructed, one for quantitative and the other for quantitative histology prediction. The prediction performance of each model was assessed using receiver operating characteristics (ROC) and correlation analyses. Results. The texture-based predicted fibrosis score significantly correlated with qualitative (r = 0.698, P < 0.001) and quantitative (r = 0.757, P < 0.001) histology. The prediction model for qualitative histology had 0.814–0.976 areas under the curve (AUC), 0.659–1.000 sensitivity, 0.778–0.930 specificity, and 0.674–0.935 accuracy, depending on the binary classification threshold. The prediction model for quantitative histology had 0.742–0.950 AUC, 0.688–1.000 sensitivity, 0.679–0.857 specificity, and 0.696–0.848 accuracy, depending on the binary classification threshold. Conclusion. CCE MRI and texture analysis may permit noninvasive assessment of liver fibrosis.
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17
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Balk JM, Haenen GR, Koc ÖM, Peters R, Bast A, van der Vijgh WJ, Koek GH. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial. PHARMACOGENOMICS & PERSONALIZED MEDICINE 2015; 8:137-44. [PMID: 26445557 PMCID: PMC4593207 DOI: 10.2147/pgpm.s82782] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background The combination of ribavirin (RBV) and pegylated interferon (PEG-IFN) is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose) was significantly different between the two groups (P>0.05). Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0.05). No significant differences in the hematological profile were observed (P>0.05). Conclusion The standard twice-daily RBV regimen is interchangeable with the once-daily regimen. The once-daily regimen will improve compliance and opens the opportunity to combine RBV with other drugs dosed once a day, in a single pill.
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Affiliation(s)
- Jiska M Balk
- Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Guido Rmm Haenen
- Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Özgür M Koc
- Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | | | - Aalt Bast
- Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Wim Jf van der Vijgh
- Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Ger H Koek
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
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18
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Shaha M, Hoque SA, Ahmed MF, Rahman SR. Effects of Risk Factors on Anti-HBs Development in Hepatitis B Vaccinated and Nonvaccinated Populations. Viral Immunol 2015; 28:217-21. [PMID: 25714135 DOI: 10.1089/vim.2014.0147] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B infection is still a major global health problem even though safe and effective vaccines have been available for more than 30 years. Although development of protective antibody to hepatitis B surface antigen (anti-HBs) is a common phenomenon after vaccination as well as natural infection, sometimes it does not appear even after complete vaccination. In the present study, whether the impairment of the development of anti-HBs in naturally infected and/or vaccinated populations is associated with immunomodulating risk factors (i.e., age, gender, smoking, and diabetes) and/or other risk factors (i.e., socioeconomic status, dental, and saloon exposure) was investigated through a cross-sectional study. Among 204 nonvaccinated patients, 132 (64.7%) tested positive for anti-HBc, indicating that they had been exposed to hepatitis B virus (HBV) at least once in their lifetime. Exposure to HBV (anti-HBc positive) was significantly higher among low-income people, dental exposed, and saloon users. Among anti-HBc positive patients, only 44 (33.3%) developed natural immunity with anti-HBs. Impairment in anti-HBs formation was found to be significantly high among cigarette smokers. However, no significant association of anti-HBs development was observed with age, gender, socioeconomic status, diabetes, dental exposure, and using saloon. Consistently, the frequency of developing protective anti-HBs (≥10 IU/L) among a vaccinated population was almost nine times less among smokers. These data suggest that anti-HBs development, either naturally or after vaccination, is significantly lower among smokers. It emphasizes the need to check the anti-HBs status in smokers after vaccination, and a booster vaccination should be administered if the anti-HBs antibody titer decreases below the protective level.
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Affiliation(s)
- Modhusudon Shaha
- 1 Department of Microbiology, University of Dhaka , Dhaka, Bangladesh
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19
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Salemi JL, Whiteman VE, August EM, Chandler K, Mbah AK, Salihu HM. Maternal hepatitis B and hepatitis C infection and neonatal neurological outcomes. J Viral Hepat 2014; 21:e144-53. [PMID: 24666386 DOI: 10.1111/jvh.12250] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Accepted: 01/12/2014] [Indexed: 12/13/2022]
Abstract
To examine the associations between maternal hepatitis B (HBV) and hepatitis C (HCV) infection status and selected infant neurological outcomes diagnosed at birth, we conducted a population-based, retrospective cohort study on singleton live births in Florida from 1998 to 2009. Primary exposures included maternal HBV and HCV monoinfection. The neurological outcomes included brachial plexus injury, cephalhematoma, foetal distress, feeding difficulties, intraventricular h aemorrhage and neonatal seizures. Multivariable logistic regression models were used to generate odds ratios (OR) and 95% confidence intervals (CI) that were adjusted for socio-demographic characteristics, risky behaviours, pregnancy complications and pre-existing medical conditions, and timing of delivery. The risk of an adverse neurological outcome was higher in infants born to mothers with hepatitis viral infection (7.2% for HCV, 5.0% for HBV), compared with infants of hepatitis virus-free mothers (4.2%). After adjusting for potential confounders, women with HBV were twice as likely to have infants who suffered from brachial plexus injury (OR = 2.04, 95% CI = 1.15-3.60), while those with HCV had an elevated odds of having an infant with feeding difficulties (OR: 1.32, 95% CI = 1.06-1.64) and a borderline increased likelihood for neonatal seizures (OR = 1.74, 95% CI = 0.98-3.10). Additionally, HCV+ mothers had a 22% increased odds of having an infant with some type of adverse neurological outcome (OR: 1.22, 95% CI = 1.03-1.44). Our findings add to current understanding of the association between maternal HBV/HCV infections and infant neurological outcomes. Further research evaluating the role of maternal HBV and HCV infections (including viraemia, treatment) on pregnancy outcomes is warranted.
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Affiliation(s)
- J L Salemi
- Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL, USA
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20
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Kesel AJ, Huang Z, Murray MG, Prichard MN, Caboni L, Nevin DK, Fayne D, Lloyd DG, Detorio MA, Schinazi RF. Retinazone inhibits certain blood-borne human viruses including Ebola virus Zaire. Antivir Chem Chemother 2014; 23:197-215. [PMID: 23636868 DOI: 10.3851/imp2568] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2013] [Indexed: 10/26/2022] Open
Abstract
BACKGROUND Human HBV and HIV integrate their retro-transcribed DNA proviruses into the human host genome. Existing antiretroviral drug regimens fail to directly target these intrachromosomal xenogenomes, leading to persistence of viral genetic information. Retinazone (RTZ) constitutes a novel vitamin A-derived (retinoid) thiosemicarbazone derivative with broad-spectrum antiviral activity versus HIV, HCV, varicella-zoster virus and cytomegalovirus. METHODS The in vitro inhibitory action of RTZ on HIV-1 strain LAI, human HBV strain ayw, HCV-1b strain Con1, enhanced green fluorescent protein-expressing Ebola virus Zaire 1976 strain Mayinga, wild-type Ebola virus Zaire 1976 strain Mayinga, human herpesvirus 6B and Kaposi's sarcoma-associated herpesvirus replication was investigated. The binding of RTZ to human glucocorticoid receptor was determined. RESULTS RTZ inhibits blood-borne human HBV multiplication in vitro by covalent inactivation of intragenic and intraexonic viral glucocorticoid response elements, and, in close analogy, RTZ suppresses HIV-1 multiplication in vitro. RTZ disrupts the multiplication of blood-borne human HCV and Ebola Zaire virus at nanomolar concentrations in vitro. RTZ has the capacity to bind to human glucocorticoid receptor, to selectively and covalently bind to intraexonic viral glucocorticoid response elements, and thereby to inactivate human genome-integrated proviral DNA of human HBV and HIV. CONCLUSIONS RTZ represents the first reported antiviral agent capable of eradicating HIV and HBV proviruses from their human host. Furthermore, RTZ represents a potent and efficacious small-molecule in vitro inhibitor of Ebola virus Zaire 1976 strain Mayinga replication.
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21
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Ocho M, Togayachi A, Iio E, Kaji H, Kuno A, Sogabe M, Korenaga M, Gotoh M, Tanaka Y, Ikehara Y, Mizokami M, Narimatsu H. Application of a glycoproteomics-based biomarker development method: alteration in glycan structure on colony stimulating factor 1 receptor as a possible glycobiomarker candidate for evaluation of liver cirrhosis. J Proteome Res 2014; 13:1428-1437. [PMID: 24422531 DOI: 10.1021/pr400986t] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The importance of diagnosis and therapies for liver cirrhosis (LC) is indisputable. Thus, a reliable method for monitoring the progression of liver fibrosis and resultant LC is urgently needed. Previously, using a lectin-assisted glycoproteomic method, we identified 26 serum glycoproteins as promising glycobiomarker candidates for monitoring the progression of liver diseases. In this study, we identified colony stimulating factor 1 receptor (CSF1R) as a promising LC marker candidate and then established Wisteria floribunda agglutinin (WFA)-reactive CSF1R (WFA(+)-CSF1R) as a novel possible glycobiomarker candidate by utilizing a glycoproteomics-based strategy. The serum level of WFA(+)-CSF1R in patients with hepatitis C virus (HCV)-infected liver disease was measured by an antibody-lectin sandwich ELISA. In a proof-of-concept experiment of the strategy preceding to future clinical studies, LC patients showed a high serum WFA(+)-CSF1R level in selected samples (P = 1.3 × 10(-17)). This result suggests WFA(+)-CSF1R is a possible biomarker candidate for evaluation of LC. Our results verified feasibility of this strategy for glycobiomarker development.
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Affiliation(s)
- Makoto Ocho
- Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
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22
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Moucari R, Lada O, Marcellin P. Chronic hepatitis B: back to the future with HBsAg. Expert Rev Anti Infect Ther 2014; 7:633-6. [DOI: 10.1586/eri.09.57] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Cao ZH, Ma LN, Zhang HW, Liu YL, Chen XY. Extended treatment with peginterferon α-2a in combination with lamivudine or adefovir for 96 weeks yields high rates of HBeAg and HBsAg seroconversion. J Dig Dis 2013; 14:446-50. [PMID: 23615131 DOI: 10.1111/1751-2980.12065] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The study aimed to investigate the efficacy and safety of peginterferon α-2a (PEG IFNα-2a) in combination with lamivudine or adefovir in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). METHODS In total, 47 patients with HBeAg-positive CHB received either PEG IFNα-2a (135 μg once weekly) plus lamivudine (100 mg daily) or adefovir (10 mg daily). All patients completed 96 weeks of therapy and were followed up for a further 24 weeks. RESULTS Baseline characteristics and treatment efficacy of the two groups were similar. All patients achieved hepatitis B virus (HBV) DNA <500 copies/mL at 96 weeks, and none had a virological rebound after stopping the therapy. The rate of HBeAg seroconversion was 46.8% at 48 weeks, increased to 74.5% at 96 weeks, and kept at 72.3% at 120 weeks. Hepatitis B surface antigen (HBsAg) seroconversion rate was 6.4% at 48 weeks, increased to 21.3% at 96 weeks, and kept at 27.7% at 120 weeks. CONCLUSIONS Extended treatment with PEG IFNα-2a with lamivudine or adefovir for 96 weeks is a promising strategy to achieve high rates of sustainable HBeAg and HBsAg seroconversion and HBV DNA suppression in patients with HBeAg-positive CHB.
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Affiliation(s)
- Zhen Huan Cao
- International Medical Department, Beijing You'an Hospital, Capital Medical University, Beijing, China
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Lasher CD, Rajagopalan P, Murali TM. Summarizing cellular responses as biological process networks. BMC SYSTEMS BIOLOGY 2013; 7:68. [PMID: 23895181 PMCID: PMC3751784 DOI: 10.1186/1752-0509-7-68] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2012] [Accepted: 06/26/2013] [Indexed: 12/02/2022]
Abstract
Background Microarray experiments can simultaneously identify thousands of genes that show significant perturbation in expression between two experimental conditions. Response networks, computed through the integration of gene interaction networks with expression perturbation data, may themselves contain tens of thousands of interactions. Gene set enrichment has become standard for summarizing the results of these analyses in terms functionally coherent collections of genes such as biological processes. However, even these methods can yield hundreds of enriched functions that may overlap considerably. Results We describe a new technique called Markov chain Monte Carlo Biological Process Networks (MCMC-BPN) capable of reporting a highly non-redundant set of links between processes that describe the molecular interactions that are perturbed under a specific biological context. Each link in the BPN represents the perturbed interactions that serve as the interfaces between the two processes connected by the link. We apply MCMC-BPN to publicly available liver-related datasets to demonstrate that the networks formed by the most probable inter-process links reported by MCMC-BPN show high relevance to each biological condition. We show that MCMC-BPN’s ability to discern the few key links from in a very large solution space by comparing results from two other methods for detecting inter-process links. Conclusions MCMC-BPN is successful in using few inter-process links to explain as many of the perturbed gene-gene interactions as possible. Thereby, BPNs summarize the important biological trends within a response network by reporting a digestible number of inter-process links that can be explored in greater detail.
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Affiliation(s)
- Christopher D Lasher
- Genetics, Bioinformatics, and Computational Biology Ph.D. Program, Virginia Tech, Blacksburg, VA 24061 USA
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Tempestilli M, Milano E, D'Offizi G, Montalbano M, D'Avolio A, Gasperi T, Narciso P, Ascenzi P, Pucillo LP. Determination of telaprevir in plasma of HCV-infected patients by HPLC-UV. IUBMB Life 2013; 65:800-5. [DOI: 10.1002/iub.1197] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Revised: 05/30/2013] [Accepted: 06/24/2013] [Indexed: 11/11/2022]
Affiliation(s)
- Massimo Tempestilli
- Istituto Nazionale per le Malattie Infettive I.R.C.C.S., “Lazzaro Spallanzani,”; Roma; Italy
| | - Elisa Milano
- Istituto Nazionale per le Malattie Infettive I.R.C.C.S., “Lazzaro Spallanzani,”; Roma; Italy
| | - Gianpiero D'Offizi
- Istituto Nazionale per le Malattie Infettive I.R.C.C.S., “Lazzaro Spallanzani,”; Roma; Italy
| | - Marzia Montalbano
- Istituto Nazionale per le Malattie Infettive I.R.C.C.S., “Lazzaro Spallanzani,”; Roma; Italy
| | - Antonio D'Avolio
- Dipartimento di Scienze Mediche; Clinica Universitaria di Malattie Infettive, Ospedale Amedeo di Savoia, Università di Torino; Torino; Italy
| | - Tecla Gasperi
- Dipartimento di Scienze; Università Roma Tre; Roma; Italy
| | - Pasquale Narciso
- Istituto Nazionale per le Malattie Infettive I.R.C.C.S., “Lazzaro Spallanzani,”; Roma; Italy
| | | | - Leopoldo P. Pucillo
- Istituto Nazionale per le Malattie Infettive I.R.C.C.S., “Lazzaro Spallanzani,”; Roma; Italy
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Ikebuchi Y, Ishida C, Okamoto K, Murawaki Y. Association of TIMP-1 and TIMP-2 gene polymorphisms with progression of liver fibrosis in patients with type C chronic liver disease. Biochem Genet 2013; 51:564-74. [PMID: 23563628 DOI: 10.1007/s10528-013-9587-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2012] [Accepted: 09/21/2012] [Indexed: 12/16/2022]
Abstract
We examined the association of TIMP-1 and TIMP-2 gene polymorphisms with the progression of chronic liver disease related to the hepatitis C virus (HCV). We used PCR to analyze 188 patients with HCV-related liver disease (95 with chronic hepatitis and 93 with cirrhosis) for TIMP-1 372 T/C and TIMP-2 -418 G/C polymorphisms. Comparing chronic hepatitis and cirrhosis, there were no significant differences in TIMP-1 and TIMP-2 gene polymorphisms. Among chronic hepatitis patients, TIMP-2 -418 G homozygotes showed significantly faster fibrosis progression than C carriers. Among cirrhotic patients, males with the TIMP-1 372 T allele developed cirrhosis at a younger age, and patients who were homozygous for the higher-transcription TIMP-2 -418 G allele had significantly lower serum albumin concentrations. These results suggest that faster progression of liver fibrosis could be associated with TIMP-2 -418 G homozygotes.
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Affiliation(s)
- Yuichiro Ikebuchi
- Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Tottori University School of Medicine, Nishi-cho 36-1, Yonago 683-8504, Japan.
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Drexler JF, Corman VM, Müller MA, Lukashev AN, Gmyl A, Coutard B, Adam A, Ritz D, Leijten LM, van Riel D, Kallies R, Klose SM, Gloza-Rausch F, Binger T, Annan A, Adu-Sarkodie Y, Oppong S, Bourgarel M, Rupp D, Hoffmann B, Schlegel M, Kümmerer BM, Krüger DH, Schmidt-Chanasit J, Setién AA, Cottontail VM, Hemachudha T, Wacharapluesadee S, Osterrieder K, Bartenschlager R, Matthee S, Beer M, Kuiken T, Reusken C, Leroy EM, Ulrich RG, Drosten C. Evidence for novel hepaciviruses in rodents. PLoS Pathog 2013; 9:e1003438. [PMID: 23818848 PMCID: PMC3688547 DOI: 10.1371/journal.ppat.1003438] [Citation(s) in RCA: 164] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Accepted: 04/22/2013] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species); and sera from 2,939 bats (51 species). Three highly divergent rodent hepacivirus clades were detected in 27 (1.8%) of 1,465 European bank voles (Myodes glareolus) and 10 (1.9%) of 518 South African four-striped mice (Rhabdomys pumilio). Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%). Our data enable new hypotheses regarding HCV evolution and encourage efforts to develop rodent surrogate models for HCV.
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Affiliation(s)
- Jan Felix Drexler
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
| | - Victor Max Corman
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
| | | | | | - Anatoly Gmyl
- Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow, Russia
- Lomonosov Moscow State University, Moscow, Russia
| | - Bruno Coutard
- Architectures et Fonctions des Macromolécules Biologiques, UMR 7257 CNRS and Aix-Marseille University, Marseille, France
| | - Alexander Adam
- Institute of Pathology, University of Cologne Medical Centre, Cologne, Germany
| | - Daniel Ritz
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
| | | | - Debby van Riel
- Erasmus MC, Department of Viroscience, Rotterdam, The Netherlands
| | - Rene Kallies
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
| | - Stefan M. Klose
- Institute of Experimental Ecology, University of Ulm, Ulm, Germany
| | - Florian Gloza-Rausch
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
- Noctalis, Centre for Bat Protection and Information, Bad Segeberg, Germany
| | - Tabea Binger
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
| | - Augustina Annan
- Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana
| | - Yaw Adu-Sarkodie
- Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Samuel Oppong
- Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Mathieu Bourgarel
- Centre de Cooperation Internationale de Recherche en Agronomie pour le Développement, UPR AGIRs, Montpellier, France
| | - Daniel Rupp
- Department of Infectious Diseases, Molecular Virology, Medical Facility, Heidelberg University, Heidelberg, Germany
| | - Bernd Hoffmann
- Friedrich-Loeffler-Institut, Institute for Virus Diagnostics, Greifswald–Insel Riems, Germany
| | - Mathias Schlegel
- Friedrich-Loeffler-Institut, Institute for Novel and Emerging Infectious Diseases, Greifswald–Insel Riems, Germany
| | - Beate M. Kümmerer
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
| | - Detlev H. Krüger
- Institute of Medical Virology (Helmut Ruska Haus), Charité Medical School, Berlin, Germany
| | - Jonas Schmidt-Chanasit
- Bernhard Nocht Institute for Tropical Medicine, Department of Virology, Hamburg, Germany
| | - Alvaro Aguilar Setién
- Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, México DF, Mexico
| | | | - Thiravat Hemachudha
- Chulalongkorn University, Faculty of Medicine, Neuroscience Center for Research and Development, Bangkok, Thailand
| | - Supaporn Wacharapluesadee
- Chulalongkorn University, Faculty of Medicine, Neuroscience Center for Research and Development, Bangkok, Thailand
| | - Klaus Osterrieder
- Institute of Virology, Free University of Berlin, Department of Veterinary Medicine, Berlin, Germany
| | - Ralf Bartenschlager
- Department of Infectious Diseases, Molecular Virology, Medical Facility, Heidelberg University, Heidelberg, Germany
| | - Sonja Matthee
- Department of Conservation Ecology and Entomology, Stellenbosch University, Stellenbosch, South Africa
| | - Martin Beer
- Friedrich-Loeffler-Institut, Institute for Virus Diagnostics, Greifswald–Insel Riems, Germany
| | - Thijs Kuiken
- Erasmus MC, Department of Viroscience, Rotterdam, The Netherlands
| | - Chantal Reusken
- Netherlands Center for Infectious Disease Control, Bilthoven, The Netherlands
| | - Eric M. Leroy
- Centre International de Recherches Médicales de Franceville, Franceville, Gabon
- Institut de Recherche pour le Développement, UMR 224 (MIVEGEC), IRD/CNRS/UM1, Montpellier, France
| | - Rainer G. Ulrich
- Friedrich-Loeffler-Institut, Institute for Novel and Emerging Infectious Diseases, Greifswald–Insel Riems, Germany
| | - Christian Drosten
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
- * E-mail:
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Fujiki M, Aucejo F, Kim R. Adjuvant treatment of hepatocellular carcinoma after orthotopic liver transplantation: do we really need this? Clin Transplant 2012; 27:169-77. [PMID: 23216662 DOI: 10.1111/ctr.12042] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2012] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) continues to rise and is still a major cause of mortality. Orthotopic liver transplantation (OLT) continues to give patients the best chance for cure, but recurrence of the disease remains a problem. Even with the implementation of the Milan criteria, recurrence rates have been shown to be 8-15% in most studies and even higher in patients who are beyond the Milan criteria. Therefore, several investigators have looked into the value of adjuvant therapy using systemic cytotoxic chemotherapy in HCC after OLT. Unfortunately, most of the trials are very small, and the results have been disappointing. But trials using Licartin seem to be promising, and other drugs such as FOLFOX and sorafenib warrant further investigation based on their efficacy in the advanced disease. In this review, we will review the current data on efficacy and rationale of adjuvant treatment for HCC after OLT including novel biomarkers.
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Affiliation(s)
- M Fujiki
- Liver Transplantation and Hepatobiliary Surgery, Cleveland Clinic, Cleveland, OH, USA
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29
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The immunopathogenetic role of autoantibodies in canine autoimmune hepatitis: lessons to learn from human autoimmune hepatitis. AUTOIMMUNITY HIGHLIGHTS 2012; 3:87-93. [PMID: 26000131 PMCID: PMC4389077 DOI: 10.1007/s13317-012-0036-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Accepted: 09/24/2012] [Indexed: 02/08/2023]
Abstract
Autoimmune hepatitis (AIH) is not a disease entity restricted to man, but it can be found in other animals including canines. An increasing number of studies have focused on the immunopathogenesis of human autoimmune hepatitis (hAIH), but little is known of what triggers canine autoimmune hepatitis (cAIH). Several drugs, toxins, microbial and viral agents are able to induce autoantibodies and indeed immune-mediated chronic canine hepatitis with immunological and serological features similar of those seen in the human disease. We discuss the features of cAIH paying attention to the autoantibody profile of the disease in comparison to that seen in hAIH. We also discuss the immunomodulatory role of specific molecular signaling pathways such as those mediated by tumor growth factor and p38 mitogen-activated kinase in the induction of AIH, and the potential of these molecules to act as targets of specialized immunotherapeutic interventions. Review of the literature indicates that we have more to learn for the delineation of autoantibody profile and the antigen-specific immunoregulatory mechanisms involved in the pathogenesis of cAIH from the human disease, rather than the other way around.
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30
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Abdul F, Ndeboko B, Buronfosse T, Zoulim F, Kann M, Nielsen PE, Cova L. Potent inhibition of late stages of hepadnavirus replication by a modified cell penetrating peptide. PLoS One 2012; 7:e48721. [PMID: 23173037 PMCID: PMC3500254 DOI: 10.1371/journal.pone.0048721] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Accepted: 09/28/2012] [Indexed: 12/17/2022] Open
Abstract
Cationic cell-penetrating peptides (CPPs) and their lipid domain-conjugates (CatLip) are agents for the delivery of (uncharged) biologically active molecules into the cell. Using infection and transfection assays we surprisingly discovered that CatLip peptides were able to inhibit replication of Duck Hepatitis B Virus (DHBV), a reference model for human HBV. Amongst twelve CatLip peptides we identified Deca-(Arg)8 having a particularly potent antiviral activity, leading to a drastic inhibition of viral particle secretion without detectable toxicity. Inhibition of virion secretion was correlated with a dose-dependent increase in intracellular viral DNA. Deca-(Arg)8 peptide did neither interfere with DHBV entry, nor with formation of mature nucleocapsids nor with their travelling to the nucleus. Instead, Deca-(Arg)8 caused envelope protein accumulation in large clusters as revealed by confocal laser scanning microscopy indicating severe structural changes of preS/S. Sucrose gradient analysis of supernatants from Deca-(Arg)8-treated cells showed unaffected naked viral nucleocapsids release, which was concomitant with a complete arrest of virion and surface protein-containing subviral particle secretion. This is the first report showing that a CPP is able to drastically block hepadnaviral release from infected cells by altering late stages of viral morphogenesis via interference with enveloped particle formation, without affecting naked nucleocapsid egress, thus giving a view inside the mode of inhibition. Deca-(Arg)8 may be a useful tool for elucidating the hepadnaviral secretory pathway, which is not yet fully understood. Moreover we provide the first evidence that a modified CPP displays a novel antiviral mechanism targeting another step of viral life cycle compared to what has been so far described for other enveloped viruses.
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Affiliation(s)
- Fabien Abdul
- Université de Lyon 1, Lyon, France
- Institut National de la Santé et de la Recherche Medicale (INSERM) U1052, Centre de Recherche en Cancérologie de Lyon (CRCL), Lyon, France
- CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Bénédicte Ndeboko
- Université de Lyon 1, Lyon, France
- Institut National de la Santé et de la Recherche Medicale (INSERM) U1052, Centre de Recherche en Cancérologie de Lyon (CRCL), Lyon, France
- CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Thierry Buronfosse
- Université de Lyon 1, Lyon, France
- Institut National de la Santé et de la Recherche Medicale (INSERM) U1052, Centre de Recherche en Cancérologie de Lyon (CRCL), Lyon, France
- CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
- VetAgro-Sup, Marcy l'Etoile, France
| | - Fabien Zoulim
- Université de Lyon 1, Lyon, France
- Institut National de la Santé et de la Recherche Medicale (INSERM) U1052, Centre de Recherche en Cancérologie de Lyon (CRCL), Lyon, France
- CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Michael Kann
- Université de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France
- CNRS, Microbiologie fondamentale et Pathogénicité, UMR 5234, Bordeaux, France
- CHU de Bordeaux, Bordeaux, France
| | - Peter E. Nielsen
- Department of Cellular and Molecular Medicine and Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark
| | - Lucyna Cova
- Université de Lyon 1, Lyon, France
- Institut National de la Santé et de la Recherche Medicale (INSERM) U1052, Centre de Recherche en Cancérologie de Lyon (CRCL), Lyon, France
- CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
- * E-mail:
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Chandler DE, Penin F, Schulten K, Chipot C. The p7 protein of hepatitis C virus forms structurally plastic, minimalist ion channels. PLoS Comput Biol 2012; 8:e1002702. [PMID: 23028296 PMCID: PMC3447957 DOI: 10.1371/journal.pcbi.1002702] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2012] [Accepted: 07/27/2012] [Indexed: 12/20/2022] Open
Abstract
Hepatitis C virus (HCV) p7 is a membrane-associated oligomeric protein harboring ion channel activity. It is essential for effective assembly and release of infectious HCV particles and an attractive target for antiviral intervention. Yet, the self-assembly and molecular mechanism of p7 ion channelling are currently only partially understood. Using molecular dynamics simulations (aggregate time 1.2 µs), we show that p7 can form stable oligomers of four to seven subunits, with a bias towards six or seven subunits, and suggest that p7 self-assembles in a sequential manner, with tetrameric and pentameric complexes forming as intermediate states leading to the final hexameric or heptameric assembly. We describe a model of a hexameric p7 complex, which forms a transiently-open channel capable of conducting ions in simulation. We investigate the ability of the hexameric model to flexibly rearrange to adapt to the local lipid environment, and demonstrate how this model can be reconciled with low-resolution electron microscopy data. In the light of these results, a view of p7 oligomerization is proposed, wherein hexameric and heptameric complexes may coexist, forming minimalist, yet robust functional ion channels. In the absence of a high-resolution p7 structure, the models presented in this paper can prove valuable as a substitute structure in future studies of p7 function, or in the search for p7-inhibiting drugs.
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Affiliation(s)
- Danielle E. Chandler
- Department of Physics and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
| | - François Penin
- Bases Moléculaires et Structurales des Systèmes Infectieux, IBCP, Université Lyon 1, Univ Lyon, France; CNRS, UMR 5086, Lyon, France
| | - Klaus Schulten
- Department of Physics and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
| | - Christophe Chipot
- Beckman Institute, University of Illinois at Urbana-Champaign Urbana, Illinois, United States of America
- Équipe de Dynamique des Assemblages Membranaires UMR 7565, Université de Lorraine, Vanduvre-lès-Nancy, France
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Barth RE, Huijgen Q, Tempelman HA, Mudrikova T, Wensing AMJ, Hoepelman AIM. Presence of occult HBV, but near absence of active HBV and HCV infections in people infected with HIV in rural South Africa. J Med Virol 2012; 83:929-34. [PMID: 21503902 DOI: 10.1002/jmv.22026] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Human immunodeficiency (HIV), hepatitis B (HBV), and hepatitis C (HCV) viruses are endemic in Sub-Saharan Africa, but data regarding the prevalence of hepatitis co-infections in HIV-positive individuals residing there are limited. The aim of the study was to determine the prevalence of HBV, HCV, and occult HBV (presence of HBV-DNA in the absence of HBsAg) in a rural, South African cohort. The results were compared to various ethnic groups in a Dutch cohort of people infected with HIV. Antiretroviral-naïve individuals with HIV from both a rural South African clinic (n = 258), and a Dutch University hospital (n = 782), were included. Both serological (HBV and HCV) and molecular (occult HBV) assays were performed. Logistic regression analysis was used to define independent predictors of a hepatitis co-infection. HBV and HCV prevalence rates in the South African cohort were exceptionally low (0.4%, 1/242 and 0.8%, 2/242, respectively), compared to those observed in Caucasians (HBV 4.4% and HCV 10.9%) and African immigrants (HBV 8.9% and HCV 4.8%). Conversely, occult HBV was observed in a considerable proportion (10%, 6/60) of South African patients who were anti-HBc-positive but HBsAg-negative. Occult infections were less frequent in Caucasians and Africans in the Dutch cohort (3.2% and 1.4%, respectively). Independent predictors for occult HBV were not identified, but a trend towards more occult HBV at lower CD4 counts was observed. Local HBV/HCV prevalence data are needed to optimize vaccination and antiretroviral treatment strategies. Occult HBV in patients with HIV may be missed regularly when molecular analyses are not available.
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Affiliation(s)
- Roos E Barth
- Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands.
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Yano Y, Seo Y, Miki A, Saito M, Kato H, Hamano KI, Oya M, Ouchi S, Fujisawa T, Yamada H, Yamashita Y, Tani S, Hirohata S, Yoon S, Kitajima N, Kitagaki K, Kawara A, Nakashima T, Yu H, Maeda T, Azuma T, El-Shamy A, Hotta H, Hayashi Y. Mutations in non-structural 5A and rapid viral response to pegylated interferon-α-2b plus ribavirin therapy are associated with therapeutic efficacy in patients with genotype 1b chronic hepatitis C. Int J Mol Med 2012; 30:1048-52. [PMID: 22899224 DOI: 10.3892/ijmm.2012.1093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2012] [Accepted: 07/06/2012] [Indexed: 12/12/2022] Open
Abstract
For patients chronically infected with hepatitis C virus (HCV), mutations in the non-structural 5A (NS5A) gene are important predictive factors for the response to interferon (IFN) therapy. In the present study, factor analysis of the therapeutic response of patients following pegylated IFN and ribavirin combination therapy was assessed in a multicenter study. Chronic HCV-infected patients with genotype 1b and high viral load (n=96, mean age 56.5 years; 59 males, 68 females) treated with pegylated IFN-α-2b and ribavirin combination therapy were enrolled. This study was conducted at Kobe University Hospital and 25 affiliated hospitals in Hyogo prefecture. Sixty-five patients (68%) completed treatment with both pegylated IFN and ribavirin at >80% of the weight-based scheduled dosages. Patients who reduced or terminated therapy were frequently aged women (mean age 60.8 years; 11 males, 17 females). Overall, a sustained viral response (SVR) was achieved in 42 (44%) patients out of 96. Based on per-protocol-based (PPB) analysis, the SVR rate in patients with ≥6 amino acid (aa) mutations in the IFN resistance-determining region (IRRDR) (75%) or ≥1 aa mutation in the IFN sensitivity-determining region (ISDR) (61%) was significantly higher than that in patients with <5 aa mutations in IRRDR (30%) or no mutation in ISDR (29%). Multivariate analysis revealed that rapid viral response (RVR) (odds ratio, 18.1) and mutations of ≥6 in IRRDR (odds ratio, 15.5) were significantly associated with SVR. In conclusion, mutations in the NS5A region, particularly in patients with ≥6 aa mutations in IRRDR were strongly associated with a therapeutic response to pegylated IFN and ribavirin combination therapy.
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Affiliation(s)
- Yoshihiko Yano
- Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.
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Attia KA, Eholié S, Messou E, Danel C, Polneau S, Chenal H, Toni T, Mbamy M, Seyler C, Wakasugi N, N'dri-Yoman T, Anglaret X. Prevalence and virological profiles of hepatitis B infection in human immunodeficiency virus patients. World J Hepatol 2012; 4:218-23. [PMID: 22855697 PMCID: PMC3409356 DOI: 10.4254/wjh.v4.i7.218] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 07/12/2012] [Accepted: 07/21/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the prevalence of hepatitis B virus (HBV) in adult human immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm(3) and without antiretroviral therapy; to describe different HBV-HIV coinfection virological profiles; and to search for factors associated with HBs antigen (HBsAg) presence in these HIV positive patients. METHODS During four months (June through September 2006), 491 patients were received in four HIV positive monitoring clinical centers in Abidjan. INCLUSION CRITERIA HIV-1 or HIV-1 and 2 positive patients, age ≥ 18 years, CD4+ T-cell count < 500/mL and formal and signed consent of the patient. Realized blood tests included HIV serology, CD4+ T-cell count, quantitative HIV RNA load and HBV serological markers, such as HBsAg and HBc antibody (anti-HBcAb). We performed HBeAg, anti-HBe antibody (anti-HBeAb), anti-HBc IgM and quantitative HBV DNA load in HBsAg positive patients. Anti-HBsAb had been tested in HIV patients with HBsAg negative and anti-HBcAb-positive. HBV DNA was also tested in 188 anti-HBcAb positive patients with HBsAg negative status and without anti-HBsAb. Univariate analysis (Pearson χ(2) test or Fischer exact test) and multivariate analysis (backward step-wise selection logistic regression) were performed as statistical analysis. RESULTS Mean age of 491 patients was 36 ± 8.68 years and 73.3% were female. Type-1 HIV was found in 97% and dual-type HIV (type 1 plus type 2) in 3%. World Health Organization (WHO) clinical stage was 1, 2, 3 and 4 respectively in 61 (12.4%), 233 (47.5%), 172 (35%) and 25 patients (5.1%). Median CD4+ T-cell count was 341/mm(3) (interquartile range: 221-470). One hundred and twelve patients had less than 200 CD4+ T-cell/mm(3). Plasma HIV-1 RNA load was elevated (≥ 5 log(10) copies/mL) in 221 patients (45%). HBsAg and anti-HBcAb prevalence was respectively 13.4% and 72.9%. Of the 66 HBsAg positive patients, 22 were inactive HBV carriers (33.3%), 21 had HBeAg positive hepatitis (31.8%) and 20 had HBeAg negative hepatitis (30.3%). HBeAg and anti-HBeAb were indeterminate in 3 of them. Occult B infection prevalence (HBsAg negative, anti-HBcAb positive, anti-HBsAb negative and detectable HBV DNA) was 21.3%. Three parameters were significantly associated with the presence of HBsAg: male [odds ratio (OR): 2.2; P = 0.005; 95% confidence interval (CI): 1.3-3.8]; WHO stage 4 (OR: 3.2; P = 0.01; 95% CI: 1.3-7.9); and aspartate aminotransferase (AST) level higher than the standard (OR: 1.9; P = 0.04; 95% CI: 1.02-3.8). CONCLUSION HBV infection prevalence is high in HIV-positive patients. HBeAg positive chronic hepatitis and occult HBV infection are more frequent in HIV-positive patients than in HIV negative ones. Parameters associated with HBsAg positivity were male gender, AIDS status and increased AST level.
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Affiliation(s)
- Koffi Alain Attia
- Koffi Alain Attia, Thérèse N'dri-Yoman, Department of General Medicine and Hepato-Gastroenterology, Teaching Hospital of Yopougon, Abidjan 1021, Côte d'Ivoire
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Risk score based PEG Interferon alpha 2b and Ribavirin treatment response estimation model for genotype 1 chronic hepatitis C patients. Adv Med Sci 2012; 56:165-71. [PMID: 22130295 DOI: 10.2478/v10039-011-0056-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE Attempt to create simple practical algorithm for prospective assessment of PEG interferon/ribavirin related treatment response in individuals with chronic hepatitis C (CHC) basing on the risk factors defined prior to the treatment initiation. MATERIAL/METHODS Retrospective assessment of 45 female and 39 male previously untreated CHC patients aged 20 to 73 years, with genotype 1, undergoing standard treatment with PEG-IFNa2b+RBV was performed. For the final analysis 78 patients were included (38 effectively treated and 40 treatment failures). Thirty-six sustained virological response (SVR) related factors, which were routinely measured before treatment initiation were compared (including physical, biochemical, serologic and histopathologic). From this group the risk factors of the highest predictive value for treatment failure were selected. Cut-off values for statistical significance were defined for each parameter, with risk score (RS) calculated and compared in the group with and without SVR. RESULTS Seven factors related to treatment failure were identified: HCV>600000 IU/L, blood platelet count <150000/ul, GGTP>45 IU/ml, total serum protein<7.8 g/dl, glycaemia>105 mg/dl, detectable HBc IgG antibodies and cirrhosis. In the group with RS 1 the likelihood of SVR was 70% (p<0.028), while in patients with RS 3 the response was reduced to 23.8% (p<0.016), with no SVR achieved among patients with RS >3. CONCLUSIONS Low risk score (0-2) is associated with high probability of treatment success with scores >3 predictive for treatment failure. The presented model is a simple tool for prediction of treatment success for clinical use before PegIFN/RBV treatment initiation among genotype 1 CHC patients.
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Poordad F, Dieterich D. Treating hepatitis C: current standard of care and emerging direct-acting antiviral agents. J Viral Hepat 2012; 19:449-64. [PMID: 22676357 DOI: 10.1111/j.1365-2893.2012.01617.x] [Citation(s) in RCA: 140] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Summary. During the late 1990s and early 2000s, major advances were made in the treatment of patients with chronic hepatitis C virus (HCV) infection. Interferon, combination interferon plus ribavirin (RBV) and pegylated interferon plus RBV increased sustained virologic response (SVR) rates from ~5% to ~40-80%, depending on the genotype of HCV infection. Advances in molecular biology have allowed investigators to begin to understand the mechanisms of HCV infection and replication. Advances in understanding of viral kinetics have provided tools to identify patients who are most likely to attain SVR. With the advances in the science of HCV infection, the first part of the 21st century has seen the development and early introduction of a number of direct-acting antiviral (DAA) drugs. These novel medications interfere with critical steps in HCV replication and have the potential to significantly increase SVR rates. This article will review the key elements of HCV replication and evaluate the various classes of new and investigational DAA that have the potential to create a revolution in the management of patients with chronic hepatitis C.
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Affiliation(s)
- F Poordad
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
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Stern C, Martinot-Peignoux M, Ripault MP, Boyer N, Castelnau C, Valla D, Marcellin P. Impact of ribavirin dose on retreatment of chronic hepatitis C patients. World J Gastroenterol 2012; 18:2966-72. [PMID: 22736920 PMCID: PMC3380324 DOI: 10.3748/wjg.v18.i23.2966] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2011] [Revised: 02/15/2012] [Accepted: 02/26/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the efficacy and factors associated with a sustained virological response (SVR) in chronic hepatitis C (CHC) relapsing patients.
METHODS: Out of 1228 CHC patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV), 165 (13%) had a relapse. Among these, 62 patients were retreated with PEG-IFN-α2a or -α2b and RBV. Clinical, biological, virological and histological data were collected. Initial doses and treatment modifications were recorded. The efficacy of retreatment and predictive factors for SVR were analyzed.
RESULTS: An SVR was achieved in 42% of patients. SVR was higher in young (< 50 years) (61%) than old patients (27%) (P = 0.007), and in genotype 2 or 3 (57%) than in genotype 1 or 4 (28%) patients (P = 0.023). Prolonging therapy for at least 24 wk more than the previous course was associated with higher SVR rates (53% vs 28%, P = 0.04). Also, a better SVR rate was observed with RBV dose/body weight > 15.2 mg/kg per day (70% vs 35%, P = 0.04). In logistic regression, predictors of a response were age (P = 0.018), genotype (P = 0.048) and initial RBV dose/body weight (P = 0.022). None of the patients without a complete early virological response achieved an SVR (negative predictive value = 100%).
CONCLUSION: Retreatment with PEG-IFN/RBV is eff-ective in genotype 2 or 3 relapsers, especially in young patients. A high dose of RBV seems to be important for the retreatment response.
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Zafrir Y, Agmon-Levin N, Paz Z, Shilton T, Shoenfeld Y. Autoimmunity following hepatitis B vaccine as part of the spectrum of 'Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants' (ASIA): analysis of 93 cases. Lupus 2012; 21:146-52. [PMID: 22235045 DOI: 10.1177/0961203311429318] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVES In this study we analyzed the clinical and demographic manifestations among patients diagnosed with immune/autoimmune-mediated diseases post-hepatitis B vaccination. We aimed to find common denominators for all patients, regardless of different diagnosed diseases, as well as the correlation to the criteria of Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants (ASIA). PATIENTS AND METHODS We have retrospectively analyzed the medical records of 114 patients, from different centers in the USA, diagnosed with immune-mediated diseases following immunization with hepatitis-B vaccine (HBVv). All patients in this cohort sought legal consultation. Of these, 93/114 patients diagnosed with disease before applying for legal consultation were included in the study. All medical records were evaluated for demographics, medical history, number of vaccine doses, peri-immunization adverse events and clinical manifestations of diseases. In addition, available blood tests, imaging results, treatments and outcomes were recorded. Signs and symptoms of the different immune-mediated diseases were grouped according to the organ or system involved. ASIA criteria were applied to all patients. RESULTS The mean age of 93 patients was 26.5 ± 15 years; 69.2% were female and 21% were considered autoimmune susceptible. The mean latency period from the last dose of HBVv and onset of symptoms was 43.2 days. Of note, 47% of patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neuro-psychiatric (70%), fatigue (42%) mucocutaneous (30%), musculoskeletal (59%) and gastrointestinal (50%) complaints. Elevated titers of autoantibodies were documented in 80% of sera tested. In this cohort 80/93 patients (86%), comprising 57/59 (96%) adults and 23/34 (68%) children, fulfilled the required criteria for ASIA. CONCLUSIONS Common clinical characteristics were observed among 93 patients diagnosed with immune-mediated conditions post-HBVv, suggesting a common denominator in these diseases. In addition, risk factors such as history of autoimmune diseases and the appearance of adverse event(s) during immunization may serve to predict the risk of post-immunization diseases. The ASIA criteria were found to be very useful among adults with post-vaccination events. The application of the ASIA criteria to pediatric populations requires further study.
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Affiliation(s)
- Y Zafrir
- The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
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Albecka A, Belouzard S, Op de Beeck A, Descamps V, Goueslain L, Bertrand-Michel J, Tercé F, Duverlie G, Rouillé Y, Dubuisson J. Role of low-density lipoprotein receptor in the hepatitis C virus life cycle. Hepatology 2012; 55:998-1007. [PMID: 22121002 DOI: 10.1002/hep.25501] [Citation(s) in RCA: 131] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED Hepatitis C virus (HCV) particles are known to be in complex with lipoproteins. As a result of this interaction, the low-density lipoprotein (LDL) receptor (LDLR) has been proposed as a potential entry factor for HCV; however, its implication in virus entry remains unclear. Here, we reinvestigated the role of the LDLR in the HCV life cycle by comparing virus entry to the mechanism of lipoprotein uptake. A small interfering RNA targeting the LDLR in Huh-7 cells reduced HCV infectivity, confirming that this receptor plays a role in the life cycle of HCV generated in cell culture. However, kinetics of internalization were much faster for lipoproteins than for infectious HCV particles. Furthermore, a decrease in HCV RNA replication was observed by blocking the LDLR with a specific antibody, and this was associated with an increase in the ratio of phosphatidylethanolamine to phosphatidylcholine in host cells. Nevertheless, a soluble form of the LDLR inhibited both HCV entry into the hepatocytes and its binding to the LDLR expressed on Chinese hamster ovary cells, suggesting a direct interaction between the HCV particle and the LDLR. Finally, we showed that modification of HCV particles by lipoprotein lipase (LPL) reduces HCV infectivity and increases HCV binding to LDLR. Importantly, LPL treatment also induced an increase in RNA internalization, suggesting that LDLR, at least in some conditions, leads to nonproductive internalization of HCV. CONCLUSION The LDLR is not essential for infectious HCV particle entry, whereas the physiological function of this receptor is important for optimal replication of the HCV genome.
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Affiliation(s)
- Anna Albecka
- Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France
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Cunningham M, Foster GR. Efficacy and safety of telaprevir in patients with genotype 1 hepatitis C infection. Therap Adv Gastroenterol 2012; 5:139-51. [PMID: 22423262 PMCID: PMC3296085 DOI: 10.1177/1756283x11426895] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Chronic hepatitis C infection represents a significant and growing health problem worldwide. Patients with genotype 1 hepatitis C respond poorly to the current standard of care, pegylated interferon and ribavirin, which is frequently associated with unpleasant side effects. Consequently new agents with improved efficacy and tolerability are needed. The efficacy and safety of the direct-acting antiviral agent telaprevir in the treatment of genotype 1 hepatitis C infection have been demonstrated in a number of clinical trials. The addition of telaprevir to standard therapy considerably improves response rates and allows response-guided shortening of treatment duration in a substantial number of treatment-naïve patients. Side effects associated with telaprevir therapy include rash, anaemia, gastrointestinal disturbance and anorectal discomfort. Telaprevir-resistant variants have been identified in patients who have failed telaprevir-containing therapy, and whether selection of these variants will compromise future therapeutic options is currently unknown. The efficacy and safety of telaprevir in the treatment of the most challenging patients, including those with recurrent hepatitis C following liver transplantation and those co-infected with HIV, remains to be established.
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Affiliation(s)
- Morven Cunningham
- Queen Mary, University of London, Blizard Institute of Cell and Molecular Science, London, UK
| | - Graham R. Foster
- Queen Mary, University of London, Institute of Cell and Molecular Science, 4 Newark Street, London, E1 2AT, United Kingdom
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Chen X, Cao Z, Liu Y, Zhang H, Zhang Y, Ma L, Jin Y, Yu H, Ma B, Zheng Y, Wu H. Potent hepatitis B surface antigen response to treatment of hepatitis-B-e-antigen-positive chronic hepatitis B with α-interferon plus a nucleos(t)ide analog. J Gastroenterol Hepatol 2012; 27:481-6. [PMID: 22098411 DOI: 10.1111/j.1440-1746.2011.06970.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM Hepatitis B surface antigen (HBsAg) clearance is the closest cure outcome in hepatitis B. The goal of this study was to investigate clinical features in chronic hepatitis B patients achieving seroconversion of HBsAg after treatment with α-interferon (IFN-α) and a nucleos(t)ide analog. METHODS This retrospective study enrolled 38 chronic hepatitis B patients treated with IFN-α plus a nucleos(t)ide analog who achieved HBsAg seroconversion during the period from June 2001 to May 2009. Clinical and laboratory data of the patients were collected before and after treatment every 3 months. All patients with HBsAg seroconversion in this study were followed up for at least 12 months post-treatment. RESULTS A total of 38 out of 142 patients achieved HBsAg seroconversion after treatment with IFN-α and a nucleos(t)tide analog for a prolonged period of time (medium 31 months). The median time to hepatitis B e antigen seroconversion and to HBsAg seroconversion was 19.5 months (range 3-60 months) and 25.5 months (range 9-63 months), respectively. Thirty-six patients (95%) sustained HBsAg seroconversion during the post-treatment follow up. Three different HBsAg response patterns were observed with classical model accounting for 57.9% (22/38 cases), simultaneous transition mode accounting for 23.7% (9/38 cases), and HBsAg prior transition model accounting for 18.4% (7/38 cases). CONCLUSIONS Extended treatment with IFN-α in combination with a nucleos(t)ide analog in patients with hepatitis-B-e-antigen-positive appears to be a promising approach for achieving a high rate of HBsAg clearance-the closest outcome to cure.
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Affiliation(s)
- Xinyue Chen
- Beijing You'an Hospital, Capital Medical University, Beijing, China.
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Gong Y, Yang YS, Zhang XM, Su M, Wang J, Han JD, Guo MZ. ABO blood type, diabetes and risk of gastrointestinal cancer in northern China. World J Gastroenterol 2012; 18:563-9. [PMID: 22363124 PMCID: PMC3280403 DOI: 10.3748/wjg.v18.i6.563] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2010] [Revised: 03/14/2011] [Accepted: 03/21/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the potential risk factors related to gastrointestinal cancer in northern China.
METHODS: A total of 3314 cases of gastrointestinal cancer (esophageal, gastric, pancreatic and biliary) and 2223 controls (including healthy individuals, glioma and thyroid cancer) were analyzed by case-control study. Multivariable logistic regression analysis was applied to evaluate the association between different cancers and hepatitis B surface antigen, sex, age, blood type, diabetes, or family history of cancer.
RESULTS: Type 2 diabetes was significantly associated with gastric, biliary and pancreatic cancer with an OR of 2.0-3.0. Blood type B was significantly associated with esophageal cancer [odd ratio (OR) = 1.53, 95% confidence interval (CI) = 1.10-2.14] and biliary cancer (OR = 1.49, 95% CI = 1.09-2.05). The prevalence of type 2 diabetes was significantly higher in gastric, biliary and pancreatic cancers compared with other groups, with ORs ranging between 2.0 and 3.0. Family history of cancer was strongly associated with gastrointestinal compared with other cancers.
CONCLUSION: Blood type B individuals are susceptible to esophageal and biliary cancer. Type 2 diabetes is significantly associated with gastric, biliary and especially pancreatic cancer.
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Papamichalis P, Alexiou A, Boulbou M, Dalekos GN, Rigopoulou EI. Reactivation of resolved hepatitis B virus infection after immunosuppression: is it time to adopt pre-emptive therapy? Clin Res Hepatol Gastroenterol 2012; 36:84-93. [PMID: 21920838 DOI: 10.1016/j.clinre.2011.07.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2011] [Revised: 07/23/2011] [Accepted: 07/26/2011] [Indexed: 02/04/2023]
Abstract
New therapeutic options like monoclonal antibodies (anti-CD20/rituximab) and hematopoietic stem cell transplantation (HSCT) have increased both the effectiveness of therapies and the risk for reactivation of Hepatitis B virus (HBV). We describe two cases with serological evidence of resolved HBV infection (hepatitis B surface antigen (HBsAg) negative/antibody to hepatitis B core antigen (anti-HBc) and antibody to hepatitis B surface antigen (anti-HBs) positive), who developed reverse seroconversion (clearance of HBsAb/appearance of HBsAg) with active HBV infection after treatment with combination of conventional chemotherapy, rituximab and autologous HSCT for hematological malignancies. Review of the literature highlights the increasing incidence of HBV reactivation in patients with resolved infection and raises concerns as to whether current guidelines for pre-chemotherapy screening with sensitive HBV-DNA assays and serial monitoring for anti-HBs titres should be implemented also for patients with resolved infection. Future studies should aim at clarifying the cost-benefit from administration of nucleoside analogues in these patients.
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Affiliation(s)
- Panagiotis Papamichalis
- Department of Medicine, Medical School, University of Thessaly, Biopolis, 41110 Larissa, Greece
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Matsumoto A, Tanaka E, Suzuki Y, Kobayashi M, Tanaka Y, Shinkai N, Hige S, Yatsuhashi H, Nagaoka S, Chayama K, Tsuge M, Yokosuka O, Imazeki F, Nishiguchi S, Saito M, Fujiwara K, Torii N, Hiramatsu N, Karino Y, Kumada H. Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos(t)ide analogs in patients with chronic hepatitis B. Hepatol Res 2012; 42:139-149. [PMID: 22103237 DOI: 10.1111/j.1872-034x.2011.00910.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
AIM The factors associated with hepatitis recurrence after discontinuation of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B were analyzed to predict the risk of relapse more accurately. METHODS A total of 126 patients who discontinued NA therapy were recruited retrospectively. The clinical conditions of a successful discontinuation were set as alanine aminotransferase (ALT) below 30 IU/L and serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL. RESULTS Relapse of hepatitis B were judged to occur when maximal serum ALT became higher than 79 IU/L or when maximal serum HBV DNA surpassed 5.7 log copies/mL following NA discontinuation since these values corresponded with mean values of ALT (30 IU/L) and HBV DNA (4.0 log copies/mL), respectively. At least 90% of patients with either detectable hepatitis B e antigen or serum HBV DNA higher than 3.0 log copies/mL at the time of NA discontinuation relapsed within one year. In the remaining patients, higher levels of both hepatitis B surface and core-related antigens at the time of discontinuation, as well as a shorter course of NA treatment, were significantly associated with relapse by multivariate analysis. CONCLUSIONS It appears that negative results for hepatitis B e antigen and serum HBV DNA lower than 3.0 log copies/mL are essential for successful NA discontinuation, which may be attained by a longer treatment period. Levels of hepatitis B surface and core-related antigens are also significant factors independently associated with relapse of hepatitis.
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Affiliation(s)
- Akihiro Matsumoto
- Department of Medicine, Shinshu University School of Medicine, Matsumoto Department of Hepatology, Toranomon Hospital Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences Gastroenterology Section, Nagoya Daini Red Cross Hospital, Nagoya Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo The Clinical Research Center, NHO Nagasaki Medical Center, Omura Program for Biomedical Research, Division of Frontier Medical Science, Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba Division of Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo College of Medicine, Hyogo Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
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Zhou JY, Zhang L, Li L, Gu GY, Zhou YH, Chen JH. High hepatitis B virus load is associated with hepatocellular carcinomas development in Chinese chronic hepatitis B patients: a case control study. Virol J 2012; 9:16. [PMID: 22244446 PMCID: PMC3349554 DOI: 10.1186/1743-422x-9-16] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Accepted: 01/13/2012] [Indexed: 02/06/2023] Open
Abstract
Background Persistent hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC) development. This study aimed to clarify whether the high HBV DNA level is associated with HCC development by comparing HBV DNA levels between HBV infected patients with and without HCC. Results There were 78 male and 12 female patients in each group and there was no statistical difference between these two group patients' average ages. The HBV DNA level in the HCC patients was 4.73 ± 1.71 Log10 IU/ml while 3.90 ± 2.01 Log10 IU/ml in non-HCC patients (P < 0.01). The HBeAg positive rate was 42.2% (38/90) in the HCC group while 13.3% (12/90) in the non-HCC group (P < 0.001). Compared with patients with HBV DNA level of < 3 Log10 IU/ml, the patients with level of 3 to < 4, 4 to < 5, 5 to < 6, or ≥ 6 Log10 IU/ml had the odds ratio for HCC of 1.380 (95% CI, 0.544-3.499), 3.671 (95% CI, 1.363-9.886), 5.303 (95% CI, 1.847-15.277) or 3.030 (95% CI, 1.143-8.036), respectively. Conclusions HBV-related HCC patients had higher HBV DNA level than non-HCC counterparts. Our findings imply that active HBV replication is associated with the HCC development.
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Affiliation(s)
- Jin-Yong Zhou
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
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Morse DS, Schiff M, Levit S, Cohen-Moreno R, Williams GC, Neumark Y. A pilot training program for a motivational enhancement approach to hepatitis C virus treatment among individuals in Israeli methadone treatment centers. Subst Use Misuse 2012; 47:56-66. [PMID: 22216992 PMCID: PMC3305804 DOI: 10.3109/10826084.2011.628735] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Although hepatitis C virus (HCV) can be cleared, very few infected persons complete the treatment, resulting in disease progression and transmission. Motivational interventions effectively address health and substance-use-related conditions in many cultures. The research team piloted an HCV treatment motivational enhancement training and supervision for four counselors treating four patients in one (of 11) large methadone programs in Israel between 2007 and 2008. The counselors received a 3-day training followed by seven supervision sessions. Training included cultural and language adaptation from the original United States version to practice in Israel. Feasibility was assessed and demonstrated through training field notes and questionnaire feedback, review of taped intervention sessions for counselor proficiency and patient engagement, and patient completion of intervention sessions and piloted measures. While positive feasibility outcomes were noted, future studies should employ larger numbers of counselors and patients to assess the effectiveness of motivational enhancement in promoting HCV treatment in methadone patients.
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Affiliation(s)
- Diane S Morse
- Department of Psychiatry, University of Rochester Medical Center, Rochester, New York 14642, USA. diane
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Mahboobi N, Porter SR, Karayiannis P, Alavian SM. Oral fluid and hepatitis A, B and C: a literature review. J Oral Pathol Med 2011; 41:505-16. [PMID: 22188507 DOI: 10.1111/j.1600-0714.2011.01123.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Viral hepatitis is a significant global health problem that, depending upon the virus, affects individuals of the developing and/or developed world. In recent years, there has been renewed interest in whether oral fluids can be considered as a source of viral hepatitis transmission and whether oral fluid, in particular, whole saliva, may be a useful source for viral detection as part of the diagnosis and monitoring of viral hepatitis. The aim of this article was to review current data concerning the possible carriage of the hepatitis A, B and C viruses within saliva and gingival crevicular fluid. Such knowledge will indicate if (i) oral fluid is a possible source of infection and (ii) whether oral fluid can be used for diagnosis and monitoring of viral hepatitis. DATA AND SOURCES A literature search was conducted using PubMed (Medline), EMBASE/Excerpta medica, the Cochrane database and Scopus. The results were limited to published material after 2000. Relevant material was evaluated and reviewed. CONCLUSION There is some evidence that hepatitis viruses A, B and C are present in oral fluids, particularly whole saliva and gingival crevicular fluid and may thus be possible sources of viral detection in clinical diagnosis and monitoring. However, the data are inconsistent and warrant the need for well-planned longitudinal studies to explore the precise frequency of oral carriage of such viruses and to determine the virological and host factors that may influence the oral presence of hepatitis A, B and C viruses.
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Affiliation(s)
- Nima Mahboobi
- Department of Oral and Maxillofacial Surgery, Tehran University of Medical Sciences, Tehran, Iran
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Lee KI, Park KS, Seo HJ, Kim TY, Kim ES, Jang BK, Chung WJ, Cho KB, Hwang JS. [Shifting in seroprevalence of HBsAg and anti-HCV during recent 10 years in adults resident in Daegu and Gyeongbuk province]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2011; 58:82-7. [PMID: 21873822 DOI: 10.4166/kjg.2011.58.2.82] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
BACKGROUND/AIMS There have been only few studies on the population-adjusted seroprevalence of HBV and HCV and on the change of them for more than 10 years in Korea. Therefore, this study was performed to evaluate them at a single health center in Daegu and Gyeongbuk province considering the population composition ratio. METHODS We analyzed the seromarkers of HBV and HCV of 6,237 randomly sampled adults who had received health screening at the health promotion center in Dongsan hospital during the periods from year 1997 to 1999 (Period A) and from 2007 to 2009 (Period B). RESULTS The seroprevalences of HBsAg, anti-HBs, anti-HBc and anti-HCV were 4.8%, 70.2%, 47.4%, and 0.5%, respectively. There is no difference in the seroprevalence of HBsAg between period A and B. However, downward tendency of prevalence through A to B from 6.8% to 4.5% could be found in 40s, and upward tendency from 4.7% to 6.8% in 50s. As for the seroprevalence of anti-HCV, although there was no difference through A to B, for 50s, it decreasd from 2.0% to 0.3% (p=0.007). However, for 60s, it increased as much as decreasd for 50s. CONCLUSIONS The seroprevalence of HBsAg in Daegu/Gyeongbuk province was 4.8% and showed no difference through the time period of 10 years. The seroprevalence of anti-HCV was 0.5% and also showed no difference through the time periods.
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Affiliation(s)
- Kyung In Lee
- Department of Internal Medicine, Keimyung University College of Medicine, Daegu, Korea
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Alavian SM, Mahboobi N, Mahboobi N, Savadrudbari MM, Azar PS, Daneshvar S. Iranian Dental Students’ Knowledge of Hepatitis B Virus Infection and Its Control Practices. J Dent Educ 2011. [DOI: 10.1002/j.0022-0337.2011.75.12.tb05224.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah University of Medical Sciences; Research Center for Gastroenterology and Liver Disease; Tehran Iran
| | - Nima Mahboobi
- Students’ Scientific Research Center; Tehran University of Medical Sciences; Tehran Iran
| | | | | | | | - Sedigheh Daneshvar
- Faculty of Dentistry; Shahid Beheshti University of Medical Sciences; Tehran Iran
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