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Aguilera A, Trastoy R, Rodríguez-Frias F, Muñoz-Bellido JL, Melón S, Suárez A, Orduña A, Viciana I, Bernal S, García-Bujalance S, Montiel N, Molina JM, Basaras M, Fernández-Cuenca F, García-Arata I, Reina G, Ocete MD, Fuentes A, Navarro-de la Cruz D, Nieto L, Blazquez de Castro A, Buti M, Álvarez M, García F. GEHEP 010 study: Prevalence and distribution of hepatitis B virus genotypes in Spain (2000-2016). J Infect 2020; 81:600-606. [PMID: 32711039 DOI: 10.1016/j.jinf.2020.07.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 06/29/2020] [Accepted: 07/17/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To study the prevalence and distribution of HBV genotypes in Spain for the period 2000-2016. METHODS Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded. RESULTS 1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR: 41-62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was: 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found. CONCLUSIONS We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups.
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Affiliation(s)
- Antonio Aguilera
- Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago IDIS, Spain
| | - Rocío Trastoy
- Hospital Universitario Vall d'Hebrón, Barcelona, Spain
| | | | | | - Santiago Melón
- Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Avelina Suárez
- Hospital Clínico Universitario San Carlos, Madrid, Spain
| | - Antonio Orduña
- Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Isabel Viciana
- Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Samuel Bernal
- Hospital Universitario Virgen de Valme, Sevilla, Spain
| | | | | | | | | | | | | | | | | | - Ana Fuentes
- Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Av. de la Innovación S/N, 18016 Granada, Spain
| | | | | | | | - María Buti
- Hospital Universitario Vall d'Hebrón, Barcelona, Spain
| | - Marta Álvarez
- Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Av. de la Innovación S/N, 18016 Granada, Spain
| | - Federico García
- Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Av. de la Innovación S/N, 18016 Granada, Spain.
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Rodríguez M, Buti M, Esteban R, Lens S, Prieto M, Suárez E, García-Samaniego J. Consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B virus infection (2020). GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:559-587. [PMID: 32778356 DOI: 10.1016/j.gastrohep.2020.03.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 03/31/2020] [Indexed: 12/14/2022]
Abstract
Hepatitis B virus (HBV) infection remains a global public health problem. HBV vaccination is the most effective tool to reduce the incidence of HBV disease. Despite there has not been new clinical developments for the treatment of chronic hepatitis B in the last few years, changing epidemiology and current insights on natural history, diagnostic tools and therapy indications make necessary an update of the former version of the consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B infection published in 2012. The current document updates the management of chronic hepatitis B. The treatment of choice is the long-term administration of a nucleos(t)ide analogue with high barrier to resistance (entecavir, tenofovir or tenofovir alafenamide). Pegylated interferon may be an option in patients with non-advanced liver disease, but its applicability is limited due to the low efficacy and poor tolerability. All patients must be monitored for the risk of progression to advanced liver disease and development of hepatocellular carcinoma.
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Affiliation(s)
- Manuel Rodríguez
- Sección de Hepatología, Servicio de Digestivo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, España.
| | - María Buti
- Servicio de Hepatología-Medicina Interna, Hospital Universitario Valle Hebrón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Barcelona, España
| | - Rafael Esteban
- Servicio de Hepatología-Medicina Interna, Hospital Universitario Valle Hebrón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Barcelona, España
| | - Sabela Lens
- Servicio de Hepatología, Hospital Clínic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Universidad de Barcelona, Barcelona, España
| | - Martín Prieto
- Sección de Hepatología, Servicio de Medicina Digestiva, Hospital Universitari ì Politècnic La Fe, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Valencia, España
| | - Emilio Suárez
- Unidad de Enfermedades Digestivas, Hospital Universitario Virgen de Valme, Sevilla, España
| | - Javier García-Samaniego
- Unidad de Hepatología, Hospital Universitario La Paz, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, España.
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Cornelissen M, Zorgdrager F, Bruisten SM, Bakker M, Berkhout B, van der Kuyl AC. Widespread hepatitis B virus genotype G (HBV-G) infection during the early years of the HIV epidemic in the Netherlands among men who have sex with men. BMC Infect Dis 2016; 16:268. [PMID: 27286832 PMCID: PMC4901482 DOI: 10.1186/s12879-016-1599-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 05/27/2016] [Indexed: 01/05/2023] Open
Abstract
Background Hepatitis B virus (HBV) variants belong to different genotypes, A-J, whose worldwide distribution is linked with geography, probably because viral spread was associated with ancient human migrations. HBV genotype G (HBV-G) is an aberrant genotype with little sequence divergence, suggesting a recent origin. HBV-G is strongly associated with certain risk groups such as intravenous drug users (IDUs) and men who have sex with men (MSM), but hardly with geography. The origin and epidemiology of HBV-G remain unresolved, as is the disease association. Methods To estimate the prevalence and possible time of introduction of HBV-G into the MSM community in Amsterdam, the Netherlands, we have retrospectively analysed 226 blood serum samples from HBsAg positive MSM enrolled in the Amsterdam Cohort Studies (ACS) on HIV infection and AIDS dating from 1984 to 1999 using genotype-specific PCR assays. Results Of the 226 HBsAg-positive samples, 149 were HBV DNA positive. Of those, 104 were positive for HBV genotype A (HBV-A) and five for HBV-G, and 40 showed a dual infection with both HBV-A and HBV-G. Being HIV-infected was significantly associated with a reduced HBV DNA viral load in blood, but not with the prevalence of HBV-G. Early virus already contained stop codons in the precore region and a 36 bp insertion in the core gene which are the characteristics of HBV-G. Conclusions HBV-G was introduced before 1985 into the Amsterdam MSM community. Early isolates show very limited sequence variation, confirming a low evolutionary rate. HBV-G acquisition was independent of HIV infection, but being HIV-infected was significantly associated with a reduced HBV viral load in blood, indicating a beneficial effect of early HIV infection in controlling HBV replication. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1599-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Marion Cornelissen
- Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands
| | - Fokla Zorgdrager
- Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands
| | - Sylvia M Bruisten
- Public Health Laboratory, GGD Amsterdam, Cluster Infectious Diseases, Nieuwe Achtergracht 100, Amsterdam, 1018 WT, The Netherlands
| | - Margreet Bakker
- Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands
| | - Ben Berkhout
- Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands
| | - Antoinette C van der Kuyl
- Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.
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Madejón A, Romero M, Hernández &A, García-Sánchez A, Sánchez-Carrillo M, Olveira A, García-Samaniego J. Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype. World J Gastroenterol 2016; 22:3165-3174. [PMID: 27003993 PMCID: PMC4789991 DOI: 10.3748/wjg.v22.i11.3165] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Revised: 11/04/2015] [Accepted: 01/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the hepatitis B virus (HBV) and hepatitis D virus (HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV genotypes.
METHODS: We conducted a transversal study including 68 chronic hepatitis delta (CHD) (37 HIV-positive) patients and a control group of 49 chronic hepatitis B (CHB) (22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B (HBsAg) serum titers were analyzed with the Monolisa HBsAg Ultra system (Bio-Rad), using as quantification standard a serial dilution curve of an international HBsAg standard. Serum HBV-DNA titers were analyzed using the Roche Cobas TaqMan (Roche, Barcelona, Spain), and the serum HDV-RNA using an in-house real-time qRT-PCR method, with TaqMan probes. HBV genotype was determined with the line immunoassay LiPA HBV genotyping system (Innogenetics, Ghent, Belgium). In those patients negative for LiPA assay, a nested PCR method of complete HBsAg coding region, followed by sequence analysis was applied.
RESULTS: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median (IQR): 1.25 (1.00-1.35) vs 2.95 (2.07-3.93) log10 (copies/mL), P = 0.013] and HIV positive patients [2.63 (1.24-2.69) vs 7.25 (4.61-7.55) log10 (copies/mL), P < 0.001]. This was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with LiPA assay. Finally, the HBsAg titers reflected no significant differences in CHD patients infected with HBV-A or D.
CONCLUSION: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E.
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Bihl F, Martinetti G, Wandeler G, Weber R, Ledergeber B, Calmy A, Battegay M, Cavassini M, Vernazza P, Caminada AP, Rickenbach M, Bernasconi E. HBV genotypes and response to tenofovir disoproxil fumarate in HIV/HBV-coinfected persons. BMC Gastroenterol 2015; 15:79. [PMID: 26152237 PMCID: PMC4495698 DOI: 10.1186/s12876-015-0308-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2014] [Accepted: 06/24/2015] [Indexed: 12/24/2022] Open
Abstract
Background Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood. Methods HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA <20 IU/mL) and the influence of HBV genotypes were determined. Results 143 HIV/HBV-coinfected participants with detectable HBV DNA were identified. The predominant HBV genotypes were A (82 patients, 57 %); and D (35 patients, 24 %); 20 patients (14 %) were infected with multiple genotypes (3 % A + D and 11 % A + G); and genotypes B, C and E were each present in two patients (1 %). TDF completely suppressed HBV DNA in 131 patients (92 %) within 6 months; and in 12 patients (8 %), HBV DNA suppression was delayed. No HBV resistance mutations to TDF were found in patients with delayed response, but all were infected with HBV genotype A (among these, 5 patients with genotype A + G), and all had previously been exposed to lamivudine. Conclusion In HIV/HBV-coinfected patients, infection with multiple HBV genotypes was more frequent than previously reported. The large majority of patients had an undetectable HBV viral load at six months of TDF-containing ART. In patients without viral suppression, no TDF-related resistance mutations were found. The role of specific genotypes and prior lamivudine treatment in the delayed response to TDF warrant further investigation.
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Affiliation(s)
- Florian Bihl
- Cantonal Hepatobiliary Unit, Ente Ospedaliera Cantonale, Ospedale San Giovanni Bellinzona,Switzerland and Gastroenterology and Hepatology Service, University Hospital of Geneva, Geneva, Switzerland.
| | - Gladys Martinetti
- Institute of Microbiology, Ente Ospedaliera Cantonale, Bellinzona, Switzerland.
| | - Gilles Wandeler
- Department of Infectious Diseases, University Hospital of Bern, and Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
| | - Rainer Weber
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
| | - Bruno Ledergeber
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
| | - Alexandra Calmy
- Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland.
| | - Manuel Battegay
- Division of Infectious Diseases, University Hospital of Basel, Basel, Switzerland.
| | - Matthias Cavassini
- Division of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland.
| | - Pietro Vernazza
- Division of Infectious Diseases, Cantonal Hospital of S. Gallen, St. Gallen, Switzerland.
| | - Anna-Paola Caminada
- Institute of Microbiology, Ente Ospedaliera Cantonale, Bellinzona, Switzerland.
| | | | - Enos Bernasconi
- Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland.
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Mousavi T, Haghshenas MR, Rafiei A, Navaei RA, khah ZH. Hepatitis B Virus Genotypes Distribution with HBsAg Positive in the North of Iran (Mazandaran) During 2011-2014. Med Arch 2014; 68:376-380. [PMID: 25648402 PMCID: PMC4314167 DOI: 10.5455/medarh.2014.68.376-380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Accepted: 10/10/2014] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND HBV infection is a major global health problem and ten genotypes (A to J) and multiples subtypes of HBV have been identified, and they show some distinct geographic distributions. The available data on HBV genotype in Iran are very heterogeneous and limited. Therefore in this study, we tried to identify the HBV genotypes by using polymerase chain reaction. METHODS In this cross-sectional study, HBV- positive serum samples of 122 patients with chronic hepatitis from 2011 to 2014 were studied. HBV-DNA was extracted from plasma samples using QIAamp(®) MiniElute(®) Virus Spin Kit (Qiagen). Plasma samples from HBsAg positive were confirmed the presence of HBV nucleic acid and determined the genotypes of HBV genome by PCR using the DNA PCR kit (Cinagene) with Taq-DNA polymerase enzyme and type of specific primers. All samples were examined in the virology laboratory of Sari Medical School. RESULTS The mean age of patients were 45 ± 25 (range, 20 to 70) year that 70 (57.37%) patients were male and 52 (42.62%) were female. The majority of HBV positive patients had a major surgery (44% patients) and then 32% patients followed by intra familial of hepatitis B virus infected and 11% of HBV positive patients had a history of blood transfusions. In this study, 91(74.59%) had genotype D, 7(5.73%) genotype B and 24(19.67%) genotype D and B. CONCLUSION This study indicates that the genotype D is the most frequent followed by the mixed genotypes D and B and genotype B in our region. Prevalence and incidence of HBV genotypes are with distributed among of areas and different genotypes may show different responses with antiviral therapy.
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Affiliation(s)
- Tahoora Mousavi
- Cell Molecular Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohammad Reza Haghshenas
- Department of Microbiology, Molecular and Cell-Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Alireza Rafiei
- Molecular and Cell Biology Research Center, Department of Immunology, Faculty of Medicine, Mazandaran Universityof Medical Sciences, Sari, Iran
| | - Reza Alizadeh Navaei
- Molecular and Cell-Biology, Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences Sari, Iran
| | - Zahra Hosseini khah
- Molecular and Cell-Biology, Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences Sari, Iran
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Mousavi T, Ziabakhsh-Tabary S, Ghaemiyan A, Haghshenas MR. Prevalence and genotypes of hepatitis B virus infection in patients underwent coronary angiography and coronary artery bypass grafting in mazandaran heart center, sari, iran. Med Arch 2014; 68:320-4. [PMID: 25568563 PMCID: PMC4269542 DOI: 10.5455/medarh.2014.68.320-324] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Accepted: 07/15/2014] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a major global health problem in the worldwide that associated with significant morbidity and mortality in cardiac surgery. The available data on HBV distribution and genotyping of HBV are very heterogeneous. Therefore in this study, we tried to indicate the prevalence of HBV infections in cardiac catheterization patients referred to health centers in the north of Iran and identified the HBV genotypes using polymerase chain reaction (PCR). METHODS In this cross-sectional study, we studied 2650 patients who underwent selective coronary artery angiography and coronary artery bypass grafting in Mazandaran heart center, Sari, Iran from 2011 to 2013. All serum samples were examined to detect HBsAg by ELISA test. HBV-DNA was extracted from HBsAg positive samples using Mini Elute Kit from Qiagen and determined the genotypes of HBV by PCR using the Master Mix kit with Taq-DNA polymerase enzyme and with type of specific primers. All samples were examined in the virology laboratory of Sari Medical School. RESULTS The mean age of patients was 59.7±10.9 (range, 20 to 81) year that 1590 (60%) patients were male and 1060 (40%) were female. Seventeen cases (0.08 %) were found with hepatitis B virus infection, and the highest rates of infection were reported among those aged 40-60 years old in this study. We found genotype D the predominant type in this study. CONCLUSION This study indicates that the prevalence of HBV endemicity in the north of Iran is low and genotype D is the only genotype in patients infected with HBV.
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Affiliation(s)
- Tahoora Mousavi
- Cell Molecular Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | | | - Ali Ghaemiyan
- Department of Cardiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohammad Reza Haghshenas
- Department of Microbiology, Molecular and Cell-Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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van der Kuyl AC, Zorgdrager F, Hogema B, Bakker M, Jurriaans S, Back NKT, Berkhout B, Zaaijer HL, Cornelissen M. High prevalence of hepatitis B virus dual infection with genotypes A and G in HIV-1 infected men in Amsterdam, the Netherlands, during 2000-2011. BMC Infect Dis 2013; 13:540. [PMID: 24225261 PMCID: PMC3840706 DOI: 10.1186/1471-2334-13-540] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Accepted: 11/12/2013] [Indexed: 12/11/2022] Open
Abstract
Background Hepatitis B virus (HBV) is divided into 8 definite (A-H) and 2 putative (I, J) genotypes that show a geographical distribution. HBV genotype G, however, is an aberrant genotype of unknown origin that demonstrates severe replication deficiencies and very little genetic variation. It is often found in co-infections with another HBV genotype and infection has been associated with certain risk groups such as intravenous drug users and men having sex with men (MSM). We aimed to estimate the prevalence of HBV-G in the Netherlands by analysing samples from HBV-positive patients visiting the Academic Medical Center in Amsterdam. Methods Ninety-six HBV-infected patients, genotyped as HBV-A or HBV-G infected, were retrieved from the clinical database. Blood plasma samples were analysed with a newly-developed real-time PCR assay that detects HBV-A and HBV-G. For three patients, the HBV plasma viral load (pVL) of both genotypes was followed longitudinally. In addition, three complete genomes of HBV-G were sequenced to determine their relationship to global HBV-G strains. Results Ten HBV-G infections were found in the selected Dutch patients. All concerned HIV-1 infected males with HBV-A co-infection. Dutch HBV-G strains were phylogenetically closely related to reference HBV-G strains. Conclusions In this study, HBV-G infection in the Netherlands is found exclusively in HIV-1 infected men as co-infection with HBV-A. A considerable percentage (37%) of men infected with HBV and HIV-1 are actually co- infected with two HBV genotypes.
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Affiliation(s)
- Antoinette C van der Kuyl
- Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, Amsterdam 1105, AZ, Netherlands.
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Role of genotype G hepatitis B virus mixed infection on the progression of hepatic fibrosis in HIV positive patients over 5 years of follow-up. J Clin Virol 2013; 58:408-14. [PMID: 23958588 DOI: 10.1016/j.jcv.2013.07.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2013] [Revised: 07/08/2013] [Accepted: 07/26/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND Due to common routes of transmission, HIV and HBV are frequently found as concomitant infections. The dynamic of liver disease in co-infected patients is important to understand for appropriate clinical management. Conflicting data surround the role played by genotype-G HBV (HBV-G) during the course of HIV co-infection. OBJECTIVES This study aims to assess, using non-invasive methods, liver disease progression in HIV-HBV genotype-G co-infected patients. STUDY DESIGN Co-infected patients with residual HBV replication (n=125) were screened for HBV-G infection by specific real-time PCR. The impact of HBV-G on liver fibrosis progression, as assessed by a non invasive biomarker (Fibrotest), was evaluated first, by a cross sectional analysis comparing fibrosis between HBV-G (n=23) and non-G (n=55) infected patients and second, by a longitudinal study performed over a 5 year period. RESULTS Selected patients were mostly male (90%), with homogenous characteristics between the HBV-G and non-G infected groups, in terms of age, known duration of HIV disease, immune and virological status and duration of HIV/HBV treatment. HBV-G infected patients were exclusively from Western Europe with homosexual intercourses (83%) as principal risk of transmission. Cross sectional analysis revealed comparable liver disease severity distribution between HBV-G and non-G infected patients. Co-infection with other hepatitis viruses and low CD4-nadir, but not HBV-G co-infection, were associated with a 5-year risk of fibrosis progression. CONCLUSIONS This study suggests that HBV-G infection is not significantly associated with a more severe liver disease and does not have a deleterious impact on fibrosis progression in efficiently treated HIV-HBV co-infected patients.
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Thibault V, Gaudy-Graffin C, Colson P, Gozlan J, Schnepf N, Trimoulet P, Pallier C, Saune K, Branger M, Coste M, Thoraval FR. Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study. Virol J 2013; 10:87. [PMID: 23497042 PMCID: PMC3602101 DOI: 10.1186/1743-422x-10-87] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Accepted: 02/26/2013] [Indexed: 01/08/2023] Open
Abstract
Background Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. Methods A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. Results Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. Conclusions Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.
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Buti M, García-Samaniego J, Prieto M, Rodríguez M, Sánchez-Tapias JM, Suárez E, Esteban R. Documento de consenso de la AEEH sobre el tratamiento de la infección por el virus de la hepatitis B (2012). GASTROENTEROLOGIA Y HEPATOLOGIA 2012; 35:512-28. [PMID: 22749508 DOI: 10.1016/j.gastrohep.2012.04.006] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2012] [Accepted: 04/23/2012] [Indexed: 12/13/2022]
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12
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Cassino L, Torres C, Mbayed V, Laufer N, Campos RH, Quarleri J. Comparative analysis of hepatitis B virus genotype a molecular evolution in patients infected with HBV and in patients co-infected with HBV and HIV. J Med Virol 2012; 84:562-569. [PMID: 22337294 DOI: 10.1002/jmv.23233] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
HIV infection has a significant impact on the natural progression of liver disease caused by infection with hepatitis B virus (HBV), but its role in the molecular evolution of HBV is unknown. It is difficult to study the molecular evolution of HBV longitudinally considering its genomic complexity, which implies the analysis of paired samples. This study aimed to analyze the difference in the evolutionary dynamics of HBV among patients with HIV and uninfected individuals. In this study, 17 patients infected chronically with HBV were recruited, 9 of them were co-infected with HIV. Patients were HBe antigen-positive and infected with HBV genotype A. Paired plasma samples were collected from each patient 3 years apart, and they were compared subsequently to each other. The HBV phylogenetic inference among isolates from patients infected with HBV and co-infected with HBV and HIV tends to cluster separately. Likewise, when comparing the HBV evolutionary rate and genetic distances, values were higher in the former in both preC/C and S genomic regions. Intra-host analyses of HBV isolates revealed high diversity and complexity of quasispecies among patients infected with HBV exhibiting high numbers of viral variants and genetic distance. In summary, after studying the HBV molecular evolution among isolates ascribed to genotype A at inter- and intra-host levels, HBV exhibited low quasispecies complexity and diversity as well as low evolutionary rates in the presence of HIV co-infection, suggesting that the co-infection may have an impact on the HBV molecular evolution most likely from the weakened cellular immune response.
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Affiliation(s)
- L Cassino
- Centro Nacional de Referencia para el SIDA, Departamento de Microbiologia, Universidad de Buenos Aires, Buenos Aires, Argentina
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13
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Pourkarim MR, Lemey P, Amini-Bavil-Olyaee S, Houspie L, Verbeeck J, Rahman M, Maes P, Vanwijngaerden E, Nevens F, Van Ranst M. Molecular characterization of hepatitis B virus strains circulating in Belgian patients co-infected with HIV and HBV: overt and occult infection. J Med Virol 2012; 83:1876-84. [PMID: 21915860 DOI: 10.1002/jmv.22174] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) have similar transmission routes, implying that patients infected with HIV are at particular risk for HBV infection. Patients who are co-infected with HIV and HBV progress more rapidly to end-stage liver disease and different HBV genotypes may have a distinct impact on disease progression. One hundred ninety-one anti-HBc-positive sera from Belgian patients co-infected with HIV and HBV were collected during 1998-2008. Full-length HBV genomes as well as large S or partial S genes were amplified and their molecular evolutionary history was analyzed. Clinically, 30 (65.8%) patients were categorized as "overt infection" and 16 (34.7%) cases were categorized as "occult infection." Five distinct HBV genotypes comprising A (69.6%), E (19.6%), followed by D, C, and G were detected. HBV genotype A was observed in all clinical groups and in patients with varying ethnical background. HBV genotype E could be detected in African patients who were mostly infected by heterosexual contacts. Several clinically important mutations at the HBs major hydrophilic region were detected in the new isolates but with no significant difference between occult and overt infection. The high prevalence of HBV genotype A in overt and occult cases, and in particular the detection of certain HBV subgenotypes in patients co-infected with HIV and HBV that carry diagnostic escape mutations, may provide useful information for national guidelines for prophylaxis and treatment.
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Affiliation(s)
- Mahmoud Reza Pourkarim
- Laboratory of Clinical Virology, Rega Institute for Medical Research, Katholieke Universiteit, Leuven, Belgium
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14
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Alvarado Mora MV, Romano CM, Gomes-Gouvêa MS, Gutierrez MF, Botelho L, Carrilho FJ, Pinho JRR. Molecular characterization of the Hepatitis B virus genotypes in Colombia: a Bayesian inference on the genotype F. INFECTION GENETICS AND EVOLUTION 2010; 11:103-8. [PMID: 20951841 DOI: 10.1016/j.meegid.2010.10.003] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2010] [Revised: 09/22/2010] [Accepted: 10/06/2010] [Indexed: 12/18/2022]
Abstract
Hepatitis B is a worldwide health problem affecting about 2 billion people and more than 350 million are chronic carriers of the virus. Nine HBV genotypes (A to I) have been described. The geographical distribution of HBV genotypes is not completely understood due to the limited number of samples from some parts of the world. One such example is Colombia, in which few studies have described the HBV genotypes. In this study, we characterized HBV genotypes in 143 HBsAg-positive volunteer blood donors from Colombia. A fragment of 1306 bp partially comprising HBsAg and the DNA polymerase coding regions (S/POL) was amplified and sequenced. Bayesian phylogenetic analyses were conducted using the Markov Chain Monte Carlo (MCMC) approach to obtain the maximum clade credibility (MCC) tree using BEAST v.1.5.3. Of all samples, 68 were positive and 52 were successfully sequenced. Genotype F was the most prevalent in this population (77%) - subgenotypes F3 (75%) and F1b (2%). Genotype G (7.7%) and subgenotype A2 (15.3%) were also found. Genotype G sequence analysis suggests distinct introductions of this genotype in the country. Furthermore, we estimated the time of the most recent common ancestor (TMRCA) for each HBV/F subgenotype and also for Colombian F3 sequences using two different datasets: (i) 77 sequences comprising 1306 bp of S/POL region and (ii) 283 sequences comprising 681 bp of S/POL region. We also used two other previously estimated evolutionary rates: (i) 2.60 × 10(-4)s/s/y and (ii) 1.5 × 10(-5)s/s/y. Here we report the HBV genotypes circulating in Colombia and estimated the TMRCA for the four different subgenotypes of genotype F.
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Affiliation(s)
- Mónica Viviana Alvarado Mora
- Laboratory of Gastroenterology and Hepatology, São Paulo Institute of Tropical Medicine and Department of Gastroenterology, School of Medicine, University of São Paulo, Brazil.
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15
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Soriano V, Mocroft A, Peters L, Rockstroh J, Antunes F, Kirkby N, de Wit S, Monforte AD, Flisiak R, Lundgren J, on behalf of EuroSIDA. Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients with chronic hepatitis B in Europe. J Antimicrob Chemother 2010; 65:548-555. [DOI: 10.1093/jac/dkp479] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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16
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Iacomi F, Vincenti D, Vairo F, Solmone M, Mariano A, Piselli P, Puro V, Capobianchi MR, Antonucci G. Effect of HIV co-infection on mutation patterns of HBV in patients with lamivudine-resistant chronic hepatitis B. J Med Virol 2009; 81:1151-6. [PMID: 19475624 DOI: 10.1002/jmv.21505] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
A retrospective review was performed comparing lamivudine-resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co-infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti-HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125-213 aa. Eighty-nine patients infected with HBV (29 co-infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co-infected with HIV/HBV. In this latter group, the prevalence of the rtV173L + rtL180M + rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D + sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co-infection (adjusted OR 11.2, 95% CI 2.0-61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5-34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co-infection were more likely to harbor the rtM204V mutation. Patients co-infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co-infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat.
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Affiliation(s)
- Fabio Iacomi
- Clinical Department of Infectious Diseases, National Institute for Infectious Disease, L. Spallanzani, Rome, Italy
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17
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Boot HJ, van der Waaij LA, Schirm J, Kallenberg CGM, van Steenbergen J, Wolters B. Acute hepatitis B in a healthcare worker: a case report of genuine vaccination failure. J Hepatol 2009; 50:426-31. [PMID: 19091440 DOI: 10.1016/j.jhep.2008.07.040] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2008] [Revised: 07/05/2008] [Accepted: 07/08/2008] [Indexed: 01/24/2023]
Abstract
BACKGROUND Individuals who reach the antibody threshold level of 10IU/l against the surface protein of the hepatitis B virus (HBV) after completion of a series of hepatitis B vaccination are considered to be long-term protected against a clinically manifest HBV infection. CASE REPORT Here we describe an acute hepatitis B infection in a patient who received five hepatitis B vaccinations. Although his initial response to vaccination was moderate, he finally reached an excellent hepatitis B surface antibody level (anti-HBs) titres of more than 1000 IU/l in response to a booster vaccination with a recombinant DNA vaccine. Nevertheless, he developed full-blown acute hepatitis due to an HBV infection 14years after this booster vaccination. A DNA analysis of the surface protein encoding region followed by phylogenetic analysis showed that our patient was infected with a normal HBV strain that is circulating among men who have sex with men. To our knowledge, this is the first report of a genuine hepatitis B vaccination failure in someone who acquired a high anti-HBs level in response to a recombinant DNA hepatitis B vaccine. CONCLUSION Healthcare workers whose response to the initial hepatitis B vaccination is moderate might be vulnerable to hepatitis B virus infection.
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Affiliation(s)
- Hein J Boot
- Centre for Infectious Disease Control, National institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
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18
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Barreiro P, Martín-Carbonero L, García-Samaniego J. [Hepatitis B in patients with HIV infection]. Enferm Infecc Microbiol Clin 2008; 26 Suppl 7:71-9. [PMID: 19100234 DOI: 10.1016/s0213-005x(08)76522-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Chronic hepatitis B virus infection affects approximately 10% of HIV-infected patients. There are an estimated 4 million patients with HIV/HBV coinfection. HIV infection has a deleterious effect on the natural history of chronic hepatitis B and increases the risk of progression to cirrhosis and terminal liver disease. Since the widespread use of highly active antiviral therapy (HAART), liver disease has emerged as one of the main causes of morbidity and mortality in HIV-positive patients. Therefore, all patients with HIV/HBV coinfection should be evaluated for treatment of hepatitis B, independently of the CD4 lymphocyte count. Six drugs are currently authorized for the treatment of chronic hepatitis B: standard interferon-alpha (2a and 2b), pegylated interferon alpha-2a, lamivudine, adefovir, entecavir and telbivudine. Other drugs with activity against HBV, such as tenofovir and emtricitabine, are used for the treatment of HIV infection. In patients not requiring HAART, treatment of hepatitis B should preferably consist of drugs without activity against HIV, such as pegylated interferon or adefovir. In contrast, in patients requiring HAART, a combination of drugs with activity against both viruses should be used, such as lamivudine, emtricitabine and tenofovir, with the aim of achieving maximal viral suppression and avoiding the development of resistance. Patients with HIV/HBV coinfection require periodic clinical and virological monitoring. Patients with cirrhosis should undergo ultrasonography and alphafetoprotein determination every 6 months for the early detection of hepatocellular carcinoma.
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Affiliation(s)
- Pablo Barreiro
- Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, España
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Trinks J, Cuestas ML, Tanaka Y, Mathet VL, Minassian ML, Rivero CW, Benetucci JA, Gímenez ED, Segura M, Bobillo MC, Corach D, Ghiringhelli PD, Sánchez DO, Avila MM, Peralta LAM, Kurbanov F, Weissenbacher MC, Simmonds P, Mizokami M, Oubiña JR. Two simultaneous hepatitis B virus epidemics among injecting drug users and men who have sex with men in Buenos Aires, Argentina: characterization of the first D/A recombinant from the American continent. J Viral Hepat 2008; 15:827-838. [PMID: 18507755 DOI: 10.1111/j.1365-2893.2008.00997.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Previous studies have revealed that hepatitis B virus (HBV)/D and HBV/F predominate among blood donors from Buenos Aires, Argentina. In the present study, blood samples from two high-risk groups were analysed: 160 corresponding to street- and hospital-recruited injecting drug users [81.2% showing the 'anti-hepatitis B core antigen (anti-HBc) only' serological pattern] and 20 to hepatitis B surface antigen (HBsAg)(+)/anti-HBc(+) men who have sex with men. HBV genotypes were assigned by polymerase chain reaction amplification followed by restriction fragment length polymorphism and confirmed by nucleotide sequencing of two different coding regions. HBV DNA was detected in 27 injecting drug users (16.9%, occult infection prevalence: 7.7%), and 14 men who have sex with men (70%). HBV/A prevailed among injecting drug users (81.8%) while HBV/F was predominant among men who have sex with men (57.1%). The high predominance of HBV/A among injecting drug users is in sharp contrast to its low prevalence among blood donors (P = 0.0006) and men who have sex with men (P = 0.0137). Interestingly, all HBV/A S gene sequences obtained from street-recruited injecting drug users encoded the rare serotype ayw1 and failed to cluster within any of the known A subgenotypes. Moreover, one of the HBV strains from a hospital-recruited injecting drug user was fully sequenced and found to be the first completely characterized D/A recombinant genome from the American continent. Data suggest that two simultaneous and independent HBV epidemics took place in Buenos Aires: one spreading among injecting drug users and another one sexually transmitted among the homosexual and heterosexual population.
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Affiliation(s)
- J Trinks
- Centro para el Estudio de Hepatitis Virales, Depto. de Microbiología, Fac. de Medicina, Universidad de Buenos Aires (UBA), Buenos Acres, Argentina
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20
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Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel. AIDS 2008; 22:1399-410. [PMID: 18614862 DOI: 10.1097/qad.0b013e3282f8b46f] [Citation(s) in RCA: 113] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nearly 10% of the estimated 36 million people having HIV worldwide suffer from chronic hepatitis B virus (HBV) infection. The advent of new antiviral agents against HBV and the recent availability of improved molecular diagnostic tools have revolutioned the management of HIV/HBV coinfected patients. The present study represents an update of the current knowledge about HBV/HIV coinfection and an intent to provide practical advise about how to give the best care to HIV-infected persons with chronic hepatitis B.
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21
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Hepatitis B virus genotypes : a retrospective survey in Southwestern France, 1999-2004. ACTA ACUST UNITED AC 2007; 31:1088-94. [PMID: 18176363 DOI: 10.1016/s0399-8320(07)78341-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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22
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Analysis of occult hepatitis B virus infection in liver tissue of HIV patients with chronic hepatitis C. AIDS 2007; 21:2171-5. [PMID: 18090043 DOI: 10.1097/qad.0b013e3282eea504] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Current data on the prevalence of occult hepatitis B virus (HBV) infection in HIV-positive individuals conflict. As occult HBV infection could have an impact on the outcome of liver disease in HIV-positive patients, we investigated a large number of HIV-positive/HBV-surface-antigen (HBsAg) negative subjects with hepatitis C virus (HCV) infection by using the 'gold standard' approach for occult HBV detection--analysis of liver DNA extracts. METHODS The presence or absence of HBV DNA was determined by PCR testing of four different viral genomic regions in DNA extracts of needle liver biopsy specimens of 101 HBsAg negative individuals with HIV/HCV co-infection. HBV genotyping was performed by sequencing analysis of the preS-S gene in occult HBV isolates from 18 cases. RESULTS Occult HBV infection was diagnosed in 42 of the 101 cases (41%). No clinically relevant difference was found between occult HBV-positive and -negative patients. HBV genotype D and A were detected, respectively, in 11 (61%) and 7 (39%) of 18 cases analysed. CONCLUSIONS Occult HBV infection frequently occurs in HIV/HCV co-infected patients indicating the importance of performing prospective studies able to clarify its clinical impact in these patients. HBV genotype A is highly prevalent in HIV-infected subjects with occult HBV infection in a similar way to HBsAg/HIV-positive individuals.
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Ramos B, Núñez M, Martín-Carbonero L, Sheldon J, Rios P, Labarga P, Romero M, Barreiro P, García-Samaniego J, Soriano V. Hepatitis B Virus Genotypes and Lamivudine Resistance Mutations in HIV/Hepatitis B Virus-Coinfected Patients. J Acquir Immune Defic Syndr 2007; 44:557-61. [PMID: 17224847 DOI: 10.1097/qai.0b013e3180314b46] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Differences in subtypes, hepatitis B early antigen (HBeAg)-negative variants, and drug resistance mutations all seem to influence the clinical and therapeutic outcome in patients with chronic hepatitis B virus (HBV) infection. Information available on the prevalence and distribution of distinct HBV variants in HIV-positive patients is scarce. METHODS All HIV-infected patients with persistent serum hepatitis B surface antigen and detectable HBV viremia were identified in a reference HIV clinic located in Madrid, Spain. HBV load, subtypes, precore (PC) and basal core promoter (BCP) variants, and lamivudine (LAM) resistance mutations were analyzed. RESULTS A total of 81 HBV/HIV-coinfected patients (4.1%) were identified in a population of 1968 HIV-positive patients. Plasma specimens with detectable HBV viremia could be obtained from 62 subjects, and this was the study population that underwent further virologic characterization. HBV genotype distribution was as follows: A (n = 27), D (n = 27), E (n = 1), F (n = 2), and G (n = 3). Two patients had mixed HBV genotypes (A/E and A/F). HBV subtype A was predominant (74%) among patients infected through sexual contact, whereas HBV-D was most frequent (74%) among intravenous drug users (P < 0.001). PC/BCP mutants were more frequent in patients with HBV-D than in those with HBV-A (63% vs. 18%; P < 0.01). Median time on LAM was 40 months; patients with HBV-A tended to show LAM resistance mutations more often (53% vs. 44%) and to develop them earlier (35 vs. 45 months) than patients with HBV-D. The dual L180M + M204V/I mutant was the predominant resistance pattern, although a triple rt173V + 180M + 204V, which acts as a vaccine escape mutant, was found in 1 individual. In the multivariate analysis, patients with LAM resistance mutations were significantly more frequently HBeAg-positive and older than individuals with wild-type HBV. Hepatitis-delta was recognized in 13 (21%) of these 62 HBV viremic patients, with no association with specific HBV variants. CONCLUSION Risk transmission group, age, and positive serum HBeAg are the main determinants of distinct HBV virologic variants, including HBV genotypes and LAM-resistant mutants, in HBV/HIV-coinfected patients.
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Affiliation(s)
- Belén Ramos
- Service of Infectious Diseases, Hospital Carlos III, Calle Sinesio Delgado 10, 28029 Madrid, Spain
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Sugiyama M, Tanaka Y, Sakamoto T, Maruyama I, Shimada T, Takahashi S, Shirai T, Kato H, Nagao M, Miyakawa Y, Mizokami M. Early dynamics of hepatitis B virus in chimeric mice carrying human hepatocytes monoinfected or coinfected with genotype G. Hepatology 2007; 45:929-937. [PMID: 17393501 DOI: 10.1002/hep.21584] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
UNLABELLED Of the 8 genotypes of HBV (genotypes A-H), genotype G is unique in that it has an insertion in the core gene and two stop codons in the precore region preventing the synthesis of hepatitis B e antigen. Most individuals with genotype G are coinfected with other genotypes, typically genotype A. Mice with severe combined immunodeficiency disease carrying human hepatocytes were infected with HBV particles propagated in Huh7 cells in culture. Mice monoinfected with genotype G did not raise detectable HBV DNA in serum, although products of the core gene emerged 4 to 8 weeks after inoculation. When they were superinfected with genotype A at week 10, however, HBV DNA of genotype A developed, which was replaced almost completely by that of genotype G within 10 weeks. Such a rapid takeover was also observed in mice initially infected with genotype A or C and superinfected with genotype G. Similar viral dynamics occurred in mice simultaneously coinfected with genotypes G and A. Takeover was markedly enhanced in mice inoculated with a serum passage containing genotype G with a trace of genotype A. Coinfection of mice with genotypes G and A induced abundant cellular steatosis along with increased fibrosis in the liver, which was not detected in mice monoinfected with genotype A or G. CONCLUSION Genotype G can monoinfect chimeric mice at very low levels, and its replication increases maredly when coinfected with other genotypes. Coinfection with genotype G could enhance fibrosis under immunocompromised states.
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Affiliation(s)
- Masaya Sugiyama
- Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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25
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Quarleri J, Moretti F, Bouzas MB, Laufer N, Carrillo MG, Giuliano SF, Pérez H, Cahn P, Salomon H. Hepatitis B virus genotype distribution and its lamivudine-resistant mutants in HIV-coinfected patients with chronic and occult hepatitis B. AIDS Res Hum Retroviruses 2007; 23:525-31. [PMID: 17506609 PMCID: PMC2894418 DOI: 10.1089/aid.2006.0172] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Hepatitis B virus (HBV) genotypes were examined in HIV-infected patients with chronic and occult HBV infection. From a total population of 593 HIV-infected patients, 22 individuals (prevalence 3.7%) were found to be HBsAg while 72 (12.1%) were found to be anti-HBc alone. From them, 20 and 4 were HBV DNA positive, respectively. These last four patients are therefore considered to be HBV infected in an occult form. The genotypes could be determined in all 24 HBV-infected patients. HBV-A was the most common (20/24; 83.3%), followed by HBV-D (2/24; 8.3%) and HBV-F (1/24; 4.2%). The remaining sample exhibited mixed infection involving genotypes A and D as pure ones, thus also forming part of three intergenotypic recombinant forms exhibiting different mosaic S gene patterns. The sexual route of transmission was predominant among HBV genotype A-infected patients. Among the 24 HBV DNA-positive patients, point mutations related to lamivudine resistance were found in four strains. These viral strains showed a methionine-to-valine substitution at codon 204 (rtM204V) in association with an upstream B-domain change at rtL180M. Additionally, two of them exhibited the additional rtV173L mutation. The value of HBV molecular monitoring including both HBV viral genomic characterization and genotypic resistance profile in HIV-HBV-coinfected individuals is discussed.
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Affiliation(s)
- J Quarleri
- Centro Nacional de Referencia para el SIDA, Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155-Piso 11 (1121) Buenos Aires, Argentina.
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26
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Sánchez LV, Tanaka Y, Maldonado M, Mizokami M, Panduro A. Difference of hepatitis B virus genotype distribution in two groups of mexican patients with different risk factors. High prevalence of genotype H and G. Intervirology 2006; 50:9-15. [PMID: 17164552 DOI: 10.1159/000096307] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2005] [Accepted: 10/26/2005] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) has been classified in eight genotypes, from A to H (HBV/A to HBV/H). HBV genotypes were determined in two groups with different risk factors. METHODS Group I consisted of 42 patients with chronic and acute hepatitis and group II with 25 men who have sex with men (MSM). HBV genotypes were determined by DNA sequencing of the S-gene. RESULTS Both groups differed with respect to genotype distribution (p < 0.001). In group I, there were 31 (74%), 9 (21%) and 2 patients (5%) with HBV/H, HBV/D and HBV/A; respectively. In group II, HBV/H, HBV/A, and HBV/G were found in 13 (52%), 8 (32%) and 4 (16%) cases, respectively. By using an HBV/G-specific PCR, 3 more cases of HBV/G were identified in group II, rising to a total 28%. All HBV/G strains were present in coinfection with other HBV genotypes, 86% with HBV/H, and 14% with HBV/A. CONCLUSIONS HBV/H predominated in both groups. A high frequency of HBV/G was found in MSM, which was always coinfected with HBV/H or HBV/A. Significant differences in HBV genotype distribution were also found, since HBV/D was present only in patients with liver disease, whereas HBV/G was present only in MSM.
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Affiliation(s)
- L V Sánchez
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, Health Sciences Center, University of Guadalajara, Guadalajara, Mexico
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27
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Alvarado-Esquivel C, Sablon E, Conde-González CJ, Juárez-Figueroa L, Ruiz-Maya L, Aguilar-Benavides S. Molecular analysis of hepatitis B virus isolates in Mexico: Predominant circulation of hepatitis B virus genotype H. World J Gastroenterol 2006; 12:6540-5. [PMID: 17072988 PMCID: PMC4100645 DOI: 10.3748/wjg.v12.i40.6540] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the genotypes in Mexican hepatitis B virus (HBV) isolates and characterize their precore and core promoter mutations.
METHODS: Forty-nine HBV isolates of Mexico obtained from sera of 15 hepatitis patients, 6 hemodialysis patients, 20 men seeking HIV testing, and 8 AIDS patients were analyzed. HBV isolates were amplified by PCR, and genotyped by line probe assay (INNO-LiPA HBV Genotyping; INNOGENETICS N V, Ghent, Belgium). HBV genotype confirmation was performed by DNA sequencing part of the sAg region. Precore and core promoter mutation characterization was performed by line probe assay (INNO-LiPA HBV PreCore; INNOGENETICS N V, Ghent, Belgium).
RESULTS: Overall, HBV genotype H was found in 37 (75.5%) out of the 49 isolates studied. HBV genotypes G, A, and D were found in 5 (10.2%), 4 (8.2%), and 3 (6.1%) isolates, respectively. HBV genotype H was predominant in isolates from hemodialysis patients (100%), hepatitis patients (80%), and men seeking HIV testing (75%), and accounted for half of infections in AIDS patients (50%). Six (12.2%) out of the 49 HBV isolates showed both wild type and mutant populations at precore codon 28. These mixed wild type and precore mutant populations were observed in one HBV genotype A isolate and in all HBV genotype G isolates. A dual variant core promoter mutation was observed in 1 (2%) of the isolates, which was genotype H.
CONCLUSION: HBV genotype H is highly predominant in HBV isolates of Mexico followed by genotypes G, A and D. A low frequency of precore and core promoter mutations is observed in HBV Mexican isolates.
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Soriano V. Tratamiento de la hepatitis crónica B en pacientes infectados por el VIH. GASTROENTEROLOGÍA Y HEPATOLOGÍA 2006; 29:82-85. [DOI: 10.1157/13097584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Affiliation(s)
- Jean-Pierre Allain
- Department of Transfusion Medicine, Department of Hematology, University of Cambridge, UK.
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Soriano V, Sheldon J, Ramos B, Núñez M. Confronting chronic hepatitis B virus infection in HIV: new diagnostic tools and more weapons. AIDS 2006; 20:451-3. [PMID: 16439880 DOI: 10.1097/01.aids.0000200538.25103.3a] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Lacombe K, Massari V, Girard PM, Serfaty L, Gozlan J, Pialoux G, Mialhes P, Molina JM, Lascoux-Combe C, Wendum D, Carrat F, Zoulim F. Major role of hepatitis B genotypes in liver fibrosis during coinfection with HIV. AIDS 2006; 20:419-27. [PMID: 16439876 DOI: 10.1097/01.aids.0000200537.86984.0e] [Citation(s) in RCA: 93] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Little is know about the determinants of liver fibrosis progression and genomic variability in hepatitis B virus (HBV) in HIV/HBV-coinfected patients. METHODS A cross-sectional analysis examined common characteristics of HBV infection in an ongoing cohort study of 308 patients with both HIV-1-positive Western blot and plasma HBV surface antigen (HBsAg) seropositivity. Risk factors for liver fibrosis were studied in a subset of 104 patients for whom liver biopsy and complete HBV genomic analysis were available. Analysis was performed by exact multiple regression analysis. RESULTS Mean age of the study population was 40.3 years, with a ratio male to female of 5.3 and a mean duration of HIV infection of 9.3 years. In the subset of 104 patients, plasma HBV e antigen (HBeAg) in HBV-replicative patients could not be detected in 28.4% and lamivudine-resistant mutants were detected in 67.8%. HBV genotype A was the most frequent genotype (73/104) and 25 patients were infected by the usually rare genotype G. METAVIR fibrosis score was rated F2-F4 in 70 patients. After adjustment for the most common known determinants of liver fibrosis, HBV genotype G [odds ratio (OR), 12.60; 95% confidence interval (CI), 1.72-infinite; P < 0.009], efavirenz exposure (OR, 3.55; 95% CI, 1.14-12.14; P < 0.03), and the duration of HIV infection (3.86; 95% CI, 1.27-12.64; P < 0.01) were strongly associated with the risk of grade F2-F4 fibrosis. CONCLUSION HBV genotype G is a determinant of liver fibrosis in HIV/HBV-coinfected patients and HBV genotyping should be considered as part of the management of patients with multiple risk factors for rapid progression of liver fibrosis.
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Pena-López MJ, Suárez-Bordón P, García-Bardeci D, Rodríguez-San Román JL, Pérez-González MC, Lafarga-Capuz B. Genotipos del virus de la hepatitis B en portadores crónicos en la isla de Gran Canaria. Características clinicoepidemiológicas. Enferm Infecc Microbiol Clin 2005; 23:415-8. [PMID: 16159541 DOI: 10.1157/13078800] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVE To investigate the prevalence of hepatitis B virus (HBV) genotypes in Spanish hepatitis B carriers, and to study the differences in epidemiological characteristics, e antigen (HBeAg) seroconversion, serum DNA viral levels (VL) and liver function alterations. METHODS This study included 108 patients. Genotyping was carried out in 84 with the INNO-LiPA HBV genotyping assay (Innogenetics). RESULTS There were 41 women and 67 men, with a mean age of 44.1 years. The source of transmission was family contact in 26 patients (24.1%); transfusions in 10 (9.3%); sexual promiscuity in 9 (8.3%), intravenous drug use in 3 (2.8%), health care accident in 2 (1.8%); and unknown causes in 58 (53.7%). Forty patients had chronic hepatitis and 68 (63%) were healthy carriers. The time of evolution of the infection was known in only in 45 patients, and was over 10 years in 42 of them. One hundred patients (92.6%) were HbeAg-negative and 90 (83.3%) had detectable viral DNA. Genotype A was present in 46 (54.8%), D in 20 (23.8%), F in 2 (2,4%), C in 1 (1.2%), A-G coinfection in 7 (8.3%), A-D in 4 (4.8%), D-G in 2 (2,4%), A-C in 1 (1.2%), and A-D-G in 1 (1.2%). There were no significant differences between genotypes. A trend towards an association was found between VL <or= 10(5) copies/mL and the presence of chronic hepatitis in genotype A (28.9%) as opposed to genotype D (7.7%) (p non significant). CONCLUSIONS HBV genotypes A and D, and coinfections with G are predominant in our area. Genotype A showed a tendency to produce greater inflammatory activity when VL was <or= 10(5) copies/mL.
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Affiliation(s)
- María José Pena-López
- Servicios de Microbiología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, España.
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