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Abdelhamed W, El-Kassas M. Hepatitis B virus in Egypt: the whole story. EGYPTIAN LIVER JOURNAL 2024; 14:56. [DOI: 10.1186/s43066-024-00362-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 07/03/2024] [Indexed: 04/03/2025] Open
Abstract
AbstractHepatitis B virus (HBV) infection is a significant global public health threat with variable geographical distribution. Chronic infection with HBV could be complicated by chronic hepatitis state, progression to liver cirrhosis, and the development of hepatocellular carcinoma (HCC). For years, the magnitude of HBV problem in Egypt was masked by the great prevalence of hepatitis C virus in the country. The exact epidemiological data regarding HBV in Egypt are defective. The prevalence rate of HBV in Egypt has declined after the universal immunization program introduced for infants in 1992. This review addresses the whole story of HBV in Egypt: the epidemiology, risk factors, vaccination programs, and treatment efforts.
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Basimane Bisimwa P, Koyaweda GW, Bihehe Masemo D, Ayagirwe RBB, Birindwa AB, Bisimwa PN, Kikuni Besulani G, Kashosi TM, Mugisho Matabishi C, Mitima Misuka B, Mukonkole JPM, Bisimwa Nachega J, Mukwege Mukengere D, Komas NPJ. High prevalence of hepatitis B and HIV among women survivors of sexual violence in South Kivu province, eastern Democratic Republic of Congo. PLoS One 2024; 19:e0292473. [PMID: 38959256 PMCID: PMC11221749 DOI: 10.1371/journal.pone.0292473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 05/08/2024] [Indexed: 07/05/2024] Open
Abstract
INTRODUCTION Limited data are available on the prevalence rates of hepatitis B and acquired immunodeficiency syndrome (AIDS) among women survivors of sexual violence (WSSV) in South Kivu province, in the eastern part of the Democratic Republic of Congo (DRC), where armed conflicts persist. Here, we aimed to assess the prevalence of these two infections in this vulnerable local population. METHODS A total of 1002 WSSV, aged from 18 to 70 years old were enrolled from May 2018 to May 2020 at three healthcare facilities (Panzi, Mulamba and Bulenga hospitals), which are called "The One-Stop Centre Care Model" for the management of sexual violence in South Kivu. Blood samples were collected and tested for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) antigens and antibodies using enzyme-linked immunoassay (ELISA) methods. Subsequently, viral load quantification for HBV and HIV were performed using the GeneXpert. Univariate and multivariate logistic regression models were used to assess factors associated with HIV-positive and HBV-positive status. RESULTS For HBV, overall prevalence was 8.9% (95% CI; 7.2-10.8%), 32.1% (95% CI; 29.3-35.0%), and 14.5% (95% CI; 12.3-16.8%) for HBsAg, anti-HBc and anti-HBs antibodies, respectively. Among the 89 HBsAg-positive patients, 17 (19.1%) were HBeAg-positive. The median age of individuals with a positive HBsAg test was higher than those with a negative test (median: 40 years (IQR 30-52) compared to 36 years (IQR 24-48)). Risk factors for HBV infection were age (≥35 years) (AOR = 1.83 [1.02-3.32]; p = 0.041), having no schooling (AOR = 4.14 [1.35-12.62]; p = 0.012) or only primary school-level (AOR = 4.88 [1.61-14.75]; p = 0.005), and multiple aggressors (AOR = 1.76 [1.09-2.84], p = 0.019). The prevalence of HIV was 4.3% [95% CI: 3.1-5.7%]. HIV/HBV co-infection occurred only in 5 individuals (0.5%). The HBV viral load was detectable (> 1 log10 UI/mL) in 61.8% of HBsAg-positive subjects and 64.8% HIV-positive subjects had a high viral load (≥ 3 log10 copies/mL). CONCLUSION This study revealed a high prevalence of HBV and HIV infections among WSSV in South Kivu. The results generated highlight the urgent need for systematic screening of HBV and HIV by integrating fourth-generation ELISA tests in HIV and HBV control programs.
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Affiliation(s)
- Parvine Basimane Bisimwa
- Viral Hepatitis Laboratory, Institut Pasteur de Bangui, Bangui, Central African Republic
- Faculty of Medecine, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
- Panzi General Referral Hospital, Internal Medicine, Bukavu, Democratic Republic of Congo
- Molecular Biology Laboratory, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
- International Center Advanced for Research and Training (ICART)/Panzi Fondation, Bukavu, Democratic Republic of Congo
| | | | - Dieudonné Bihehe Masemo
- Faculty of Medecine, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
- Panzi General Referral Hospital, Internal Medicine, Bukavu, Democratic Republic of Congo
| | | | - Ahadi Bwihangane Birindwa
- Molecular Biology Laboratory, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
| | - Patrick Ntagereka Bisimwa
- Molecular Biology Laboratory, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
| | - Georges Kikuni Besulani
- Faculty of Medecine, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
- Panzi General Referral Hospital, Internal Medicine, Bukavu, Democratic Republic of Congo
| | - Théophile Mitima Kashosi
- Faculty of Medecine, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
| | | | - Bienfait Mitima Misuka
- Faculty of Medecine, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
| | - Jean Paulin Mbo Mukonkole
- Faculty of Medecine, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
- Panzi General Referral Hospital, Internal Medicine, Bukavu, Democratic Republic of Congo
| | - Jean Bisimwa Nachega
- Departments of Epidemiology, Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, United States of America
- Departments of Epidemiology and International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
- Department of Medicine, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, South Africa
| | - Denis Mukwege Mukengere
- Faculty of Medecine, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
- Panzi General Referral Hospital, Internal Medicine, Bukavu, Democratic Republic of Congo
- Molecular Biology Laboratory, Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
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Bazie MM, Sanou M, Djigma FW, Compaore TR, Obiri-Yeboah D, Kabamba B, Nagalo BM, Simpore J, Ouédraogo R. Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review. World J Hepatol 2024; 16:843-859. [PMID: 38818293 PMCID: PMC11135261 DOI: 10.4254/wjh.v16.i5.843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 02/06/2024] [Accepted: 04/15/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND Occult hepatitis B infection (OBI) is a globally prevalent infection, with its frequency being influenced by the prevalence of hepatitis B virus (HBV) infection in a particular geographic region, including Africa. OBI can be transmitted through blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma (HCC). The associated HBV genotype influences the infection. AIM To highlight the genetic diversity and prevalence of OBI in Africa. METHODS This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed, Google Scholar, Science Direct, and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa. RESULTS The synthesis included 83 articles, revealing that the prevalence of OBI varied between countries and population groups, with the highest prevalence being 90.9% in patients with hepatitis C virus infection and 38% in blood donors, indicating an increased risk of HBV transmission through blood transfusions. Cases of OBI reactivation have been reported following chemotherapy. Genotype D is the predominant, followed by genotypes A and E. CONCLUSION This review highlights the prevalence of OBI in Africa, which varies across countries and population groups. The study also demonstrates that genotype D is the most prevalent.
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Affiliation(s)
- Michee M Bazie
- Department of Medicine, Transmissible Diseases Laboratory, Université Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso
| | - Mahamoudou Sanou
- Department of Medicine, Transmissible Diseases Laboratory, Université Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso
| | - Florencia Wendkuuni Djigma
- Department of Biochemistry and Microbiology, Molecular Biology and Genetics Laboratory, University Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso.
| | - Tegwinde Rebeca Compaore
- Infectious and parasitic disease Laboratory, Health Sciences Research Institute, IRSS/CNRST, National Center for Scientific and Technological Research, Ouagadougou 0000, Burkina Faso
| | - Dorcas Obiri-Yeboah
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, PMB, Cape Coast 0000, Ghana
| | - Benoît Kabamba
- Department of Clinical Biology, Virology Laboratory, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Bruxelles 0000, Belgium
| | | | - Jacques Simpore
- Department of Biochemistry and Microbiology, Molecular Biology and Genetics Laboratory, University Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso
| | - Rasmata Ouédraogo
- Department of Medicine, Transmissible Diseases Laboratory, Université Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso
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Anderson M, Phinius BB, Phakedi BK, Mudanga M, Bhebhe LN, Tlhabano GN, Motshosi P, Ratsoma T, Baruti K, Mpebe G, Choga WT, Marlink R, Glebe D, Blackard JT, Moyo S, Kramvis A, Gaseitsiwe S. Persistence and risk factors of occult hepatitis B virus infections among antiretroviral therapy-naïve people living with HIV in Botswana. Front Microbiol 2024; 15:1342862. [PMID: 38784816 PMCID: PMC11112038 DOI: 10.3389/fmicb.2024.1342862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 04/22/2024] [Indexed: 05/25/2024] Open
Abstract
Aim This study aimed to determine the kinetics of occult hepatitis B virus infections (OBI) among people with HIV (PWH). Methods The study used archived plasma samples from longitudinal HIV natural history studies. We identified new OBI cases and assessed risk factors for OBI using Cox proportional hazards regression analysis. Results At baseline, 8 of 382 [(2.1%) (95% CI: 1.06-4.1)] samples tested positive for hepatitis B surface antigen (HBsAg+). Of the 374 HBsAg-negative samples, 76 had sufficient sample volume for HBV DNA screening. OBI positivity (OBI+) at baseline was reported in 11 of 76 [14.7 95% CI (8.3-24.1)] HBsAg-negative (HBsAg-) participants. Baseline HBsAg-negative samples with sufficient follow-up samples (n = 90) were used for analysis of newly identified OBI cases. Participants contributed 129.74 person-years to the study and were followed for a median of 1.02 years (IQR: 1.00-2.00). Cumulatively, there were 34 newly identified OBI cases from the 90 participants, at the rate of 26.2/100 person-years (95% CI: 18.7-36.7). Newly identified OBI cases were more common among men than women (61.1% vs. 31.9%) and among participants with CD4+ T-cell counts ≤450 cells/mL (p-value = 0.02). Most of the newly identified OBI cases [55.9% (19/34)] were possible reactivations as they were previously HBV core antibody positive. Conclusion There was a high rate of newly identified OBI among young PWH in Botswana, especially in men and in participants with lower CD4+ T-cell counts. OBI screening in PWH should be considered because of the risk of transmission, possible reactivation, and risk factors for the development of chronic liver disease, including hepatocellular carcinoma.
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Affiliation(s)
- Motswedi Anderson
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
| | - Bonolo B. Phinius
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
- School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana
| | | | - Mbatshi Mudanga
- Botswana – University of Maryland School of Medicine Health Initiative, Gaborone, Botswana
| | - Lynnette N. Bhebhe
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
| | - Girlie N. Tlhabano
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
| | - Patience Motshosi
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
| | - Tsholofelo Ratsoma
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
| | - Kabo Baruti
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
- Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana
| | - Gorata Mpebe
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
| | - Wonderful T. Choga
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
- School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana
| | - Richard Marlink
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
- Rutgers Global Health Institute, Rutgers University, New Brunswick, NJ, United States
| | - Dieter Glebe
- Institute of Medical Virology, National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses, Justus Liebig University of Giessen, Giessen, Germany
| | - Jason T. Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Sikhulile Moyo
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
- School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Division of Medical Virology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa
- School of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
| | - Simani Gaseitsiwe
- Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States
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Ondigui JLN, Kenmoe S, Kengne-Ndé C, Ebogo-Belobo JT, Takuissu GR, Kenfack-Momo R, Mbaga DS, Tchatchouang S, Kenfack-Zanguim J, Fogang RL, Menkem EZ, Kame-Ngasse GI, Magoudjou-Pekam JN, Bowo-Ngandji A, Goumkwa NM, Esemu SN, Ndip L, Essama SHR, Torimiro J. Epidemiology of occult hepatitis B and C in Africa: A systematic review and meta-analysis. J Infect Public Health 2022; 15:1436-1445. [PMID: 36395668 PMCID: PMC7613883 DOI: 10.1016/j.jiph.2022.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 11/04/2022] [Accepted: 11/08/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Occult hepatitis B (OBI) and C (OCI) infections lead to hepatic crises including cases of liver cirrhosis and even hepatocellular carcinoma (HCC). OBI and OCI also pose a significant problem of their transmissibility. This study aimed to assess the overall prevalence of OBI and OCI in the African continent, a region highly endemic for classical hepatitis B and C viruses. METHODS For this systematic review and meta-analysis, we searched: PubMed, Web of Science, African Journal Online and African Index Medicus for published studies on the prevalence of OBI and OCI in Africa. Study selection and data extraction were performed by at least two independent investigators. Heterogeneity (I²) was assessed using the χ² test on the Cochran Q statistic and H parameters. Sources of heterogeneity were explored by subgroup analyses. This study was registered in PROSPERO, with reference number CRD42021252772. RESULTS We obtained 157 prevalence data for this meta-analysis, from 134 studies for OBI prevalence; 23 studies on OCI prevalence, and a single study on the OBI case fatality rate. The overall estimate for the prevalence of OBI was 14.8% [95% CI = 12.2-17.7] among 18579 participants. The prevalence of seronegative OBI and seropositive OBI was 7.4% [95% CI = 3.8-11.8] and 20.0% [95% CI = 15.3-25.1] respectively. The overall estimate for the prevalence of OCI was 10.7% [95% CI = 6.6-15.4] among 2865 participants. The pooled prevalence of seronegative OCI was estimated at 10.7% [95%CI = 4.8-18.3] and that of seropositive OCI at 14.4% [95%CI = 5.2-22.1]. In Sub-group analysis, patients with malignancies, chronic hepatitis C, and hemodialysis had a higher OCI prevalence. While those with malignancies, liver disorders, and HIV positive registered highest OBI prevalence. CONCLUSION This review shows a high prevalence of OBI and OCI in Africa, with variable prevalence between countries and population groups.
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Affiliation(s)
- Juliette Laure Ndzie Ondigui
- Department of Microbiology, The University of Yaounde I, Yaounde, Cameroon; Molecular Biology Laboratory, Chantal Biya International Reference Centre for AIDS Research (CIRCB), Yaounde, Cameroon
| | - Sebastien Kenmoe
- Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon.
| | - Cyprien Kengne-Ndé
- Epidemiological Surveillance, Evaluation and Research Unit, National AIDS Control Committee, Douala, Cameroon
| | - Jean Thierry Ebogo-Belobo
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | - Guy Roussel Takuissu
- Centre for Food, Food Security and Nutrition Research, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | - Raoul Kenfack-Momo
- Department of Biochemistry, The University of Yaounde I, Yaounde, Cameroon
| | | | | | | | | | | | - Ginette Irma Kame-Ngasse
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | | | - Arnol Bowo-Ngandji
- Department of Microbiology, The University of Yaounde I, Yaounde, Cameroon
| | - Nadège Mafopa Goumkwa
- Molecular Biology Laboratory, Chantal Biya International Reference Centre for AIDS Research (CIRCB), Yaounde, Cameroon
| | | | - Lucy Ndip
- Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon
| | | | - Judith Torimiro
- Molecular Biology Laboratory, Chantal Biya International Reference Centre for AIDS Research (CIRCB), Yaounde, Cameroon
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Maepa MB, Ely A, Kramvis A, Bloom K, Naidoo K, Simani OE, Maponga TG, Arbuthnot P. Hepatitis B Virus Research in South Africa. Viruses 2022; 14:v14091939. [PMID: 36146747 PMCID: PMC9503375 DOI: 10.3390/v14091939] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/11/2022] [Accepted: 08/26/2022] [Indexed: 11/18/2022] Open
Abstract
Despite being vaccine-preventable, hepatitis B virus (HBV) infection remains the seventh leading cause of mortality in the world. In South Africa (SA), over 1.9 million people are chronically infected with HBV, and 70% of all Black chronic carriers are infected with HBV subgenotype A1. The virus remains a significant burden on public health in SA despite the introduction of an infant immunization program implemented in 1995 and the availability of effective treatment for chronic HBV infection. In addition, the high prevalence of HIV infection amplifies HBV replication, predisposes patients to chronicity, and complicates management of the infection. HBV research has made significant progress leading to better understanding of HBV epidemiology and management challenges in the SA context. This has led to recent revision of the national HBV infection management guidelines. Research on developing new vaccines and therapies is underway and progress has been made with designing potentially curative gene therapies against HBV. This review summarizes research carried out in SA on HBV molecular biology, epidemiology, treatment, and vaccination strategies.
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Affiliation(s)
- Mohube B. Maepa
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, Infectious Diseases and Oncology Research Institute (IDORI), University of the Witwatersrand, Johannesburg 2000, South Africa
- Correspondence:
| | - Abdullah Ely
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, Infectious Diseases and Oncology Research Institute (IDORI), University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Anna Kramvis
- Hepatitis Diversity Research Unit, Department of Internal Medicine, Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Kristie Bloom
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, Infectious Diseases and Oncology Research Institute (IDORI), University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Kubendran Naidoo
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, Infectious Diseases and Oncology Research Institute (IDORI), University of the Witwatersrand, Johannesburg 2000, South Africa
- National Health Laboratory Service, Johannesburg 2000, South Africa
| | - Omphile E. Simani
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa
| | - Tongai G. Maponga
- Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7602, South Africa
| | - Patrick Arbuthnot
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, Infectious Diseases and Oncology Research Institute (IDORI), University of the Witwatersrand, Johannesburg 2000, South Africa
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Lalana Garcés M, Ortiz Pastor O, Solé Enrech G, Guerra-Ruiz AR, Casals Mercadal G, Almería Lafuente A, Ballesteros Vizoso MA, Medina PG, Salgüero Fernández S, Zamora Trillo A, Aured de la Serna I, Hurtado JC, Pérez-Del-Pulgar S, Forns X, Morales Ruiz M. Control of occult hepatitis B virus infection. ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO 2022. [DOI: 10.1515/almed-2022-0065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
Background
The diagnosis of hepatitis B virus (HBV) infection requires HBV DNA testing and serologic testing for detection of the surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). There is a population of patients with occult HBV infection (OBI), which is not detected by HBsAg or HBV DNA quantification in blood, despite the presence of active replication in the liver.
Scope
This document provides a definition of OBI and describes the diagnostic techniques currently used. It also addresses the detection of patients with risk factors and the need for screening for OBI in these patients.
Summary
Correct diagnosis of OBI prevents HBV reactivation and transmission. Diagnosis of OBI is based on the detection of HBV DNA in patients with undetectable HBsAg in blood.
Perspectives
A high number of patients with OBI may remain undiagnosed; therefore, screening for OBI in patients with factor risks is essential. For a correct diagnosis of OBI, it is necessary that new markers such as ultrasensitive HBsAg are incorporated, and a more comprehensive marker study is performed by including markers such as cccDNA.
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Affiliation(s)
- Marta Lalana Garcés
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Análisis Clínicos, Hospital de Barbastro , Huesca , Spain
| | - Oihana Ortiz Pastor
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet , Zaragoza , Spain
| | - Gemma Solé Enrech
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servei de laboratori, UDIAT-CD, Corporació Sanitaria Parc Taulí , Sabadell , Spain
| | - Armando R. Guerra-Ruiz
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Análisis Clínicos, Hospital Universitario Marqués de Valdecilla , Santander , Spain
| | - Gregori Casals Mercadal
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica y Genética Molecular, CDB, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , Spain
| | - Alejandro Almería Lafuente
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica Clínica, Hospital Royo Villanova , Zaragoza , Spain
| | - María Antonieta Ballesteros Vizoso
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Análisis Clínicos, Hospital Universitario Son Espases , Palma de Mallorca , Spain
| | - Pablo Gabriel Medina
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica Clínica, Hospital Universitari Vall d’Hebron , Barcelona , Spain
| | - Sergio Salgüero Fernández
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Análisis Clínicos, Hospital Universitario Fundación Alcorcón , Madrid , Spain
| | - Angielys Zamora Trillo
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica Clínica, Hospital General Universitario Gregorio Marañón , Madrid , Spain
| | | | - Juan Carlos Hurtado
- Servicio de Microbiología, CDB, Hospital Clínic de Barcelona, Universitat de Barcelona , Barcelona , Spain
- Instituto de Salud Global de Barcelona (ISGlobal) , Barcelona , Spain
| | - Sofía Pérez-Del-Pulgar
- Servicio de Hepatología, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , Spain
| | - Xavier Forns
- Servicio de Hepatología, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , Spain
| | - Manuel Morales Ruiz
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica y Genética Molecular, CDB, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , Spain
- Departamento de Biomedicina de la Facultad de Medicina y Ciencias de la Salud-Universidad de Barcelona , Barcelona , Spain
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Lalana Garcés M, Pastor OO, Solé Enrech G, Guerra-Ruiz AR, Mercadal GC, Almería Lafuente A, Ballesteros Vizoso MA, Medina PG, Salgüero Fernández S, Zamora Trillo A, Aured de la Serna I, Hurtado JC, Pérez-Del-Pulgar S, Forns X, Morales Ruiz M. Revisión de la infección oculta por el virus de la hepatitis B. ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO 2022. [DOI: 10.1515/almed-2021-0084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Resumen
Introducción
El diagnóstico actual del virus de la hepatitis B (VHB) está basado en la detección mediante técnicas moleculares de ADN de VHB y ensayos serológicos, como el antígeno de superficie (HBsAg) y anticuerpos frente al core VHB (anti-HBc). Existe un grupo de pacientes con infección oculta de VHB (OBI) en los que estos ensayos no son capaces de detectar el HBsAg ni la cuantificación de ADN de VHB en sangre, aunque exista replicación activa en hígado.
Contenido
El documento define la OBI, y los métodos actuales para su diagnóstico. También aborda la detección de pacientes con factores de riesgo y la necesidad de realizar el cribado de OBI en ellos.
Resumen
Un correcto diagnóstico de OBI, previene la reactivación del VHB y su transmisión. El diagnóstico de OBI actualmente está basado en la detección de ADN de VHB en pacientes con HBsAg indetectable en sangre.
Perspectivas
Un número elevado de pacientes con OBI puede permanecer sin diagnosticar. Es importante realizar el cribado de OBI en determinados pacientes con factores de riesgo. La introducción de nuevos marcadores, como el HBsAg ultrasensible, y estudios más profundos de marcadores, como el ADNccc hepático, serán necesarios para un correcto diagnóstico de OBI.
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Affiliation(s)
- Marta Lalana Garcés
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Análisis Clínicos , Hospital de Barbastro , Huesca , España
| | - Oihana Ortiz Pastor
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica Clínica , Hospital Universitario Miguel Servet , Zaragoza , España
| | - Gemma Solé Enrech
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servei de laboratori , UDIAT-CD. Corporació Sanitaria Parc Taulí , Sabadell , España
| | - Armando Raul Guerra-Ruiz
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Análisis Clínicos , Hospital Universitario Marqués de Valdecilla , Santander , España
| | - Gregori Casals Mercadal
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica y Genética Molecular, CDB , Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , España
| | - Alejandro Almería Lafuente
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica Clínica , Hospital Royo Villanova , Zaragoza , España
| | - María Antonieta Ballesteros Vizoso
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Análisis Clínicos , Hospital Universitario Son Espases , Palma de Mallorca , España
| | - Pablo Gabriel Medina
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica Clínica , Hospital Universitari Vall d’Hebron , Barcelona , España
| | - Sergio Salgüero Fernández
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Análisis Clínicos , Hospital Universitario Fundación Alcorcón , Madrid , España
| | - Angielys Zamora Trillo
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica Clínica , Hospital General Universitario Gregorio Marañón , Madrid , España
| | | | - Juan Carlos Hurtado
- Servicio de Microbiología, CDB, Hospital Clínic de Barcelona , Universitat de Barcelona , Barcelona , España
- Instituto de Salud Global de Barcelona (ISGlobal) , Barcelona , España
| | - Sofía Pérez-Del-Pulgar
- Servicio de Hepatología , Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , España
| | - Xavier Forns
- Servicio de Hepatología , Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , España
| | - Manuel Morales Ruiz
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica y Genética Molecular, CDB , Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , España
- Departamento de Biomedicina de la Facultad de Medicina y Ciencias de la Salud -Universidad de Barcelona , Barcelona , España
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9
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Saitta C, Pollicino T, Raimondo G. Occult Hepatitis B Virus Infection: An Update. Viruses 2022; 14:v14071504. [PMID: 35891484 PMCID: PMC9318873 DOI: 10.3390/v14071504] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 06/28/2022] [Accepted: 06/29/2022] [Indexed: 11/16/2022] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the "overt" infection, favoring the development of hepatocellular carcinoma.
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Affiliation(s)
- Carlo Saitta
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
| | - Teresa Pollicino
- Department of Human Pathology, University Hospital of Messina, 98124 Messina, Italy;
| | - Giovanni Raimondo
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
- Correspondence: ; Tel.: +39-(0)-902212392
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10
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Zaongo SD, Ouyang J, Chen Y, Jiao YM, Wu H, Chen Y. HIV Infection Predisposes to Increased Chances of HBV Infection: Current Understanding of the Mechanisms Favoring HBV Infection at Each Clinical Stage of HIV Infection. Front Immunol 2022; 13:853346. [PMID: 35432307 PMCID: PMC9010668 DOI: 10.3389/fimmu.2022.853346] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/14/2022] [Indexed: 11/25/2022] Open
Abstract
Human immunodeficiency virus (HIV) selectively targets and destroys the infection-fighting CD4+ T-lymphocytes of the human immune system, and has a life cycle that encompasses binding to certain cells, fusion to that cell, reverse transcription of its genome, integration of its genome into the host cell DNA, replication of the HIV genome, assembly of the HIV virion, and budding and subsequent release of free HIV virions. Once a host is infected with HIV, the host’s ability to competently orchestrate effective and efficient immune responses against various microorganisms, such as viral infections, is significantly disrupted. Without modern antiretroviral therapy (ART), HIV is likely to gradually destroy the cellular immune system, and thus the initial HIV infection will inexorably evolve into acquired immunodeficiency syndrome (AIDS). Generally, HIV infection in a patient has an acute phase, a chronic phase, and an AIDS phase. During these three clinical stages, patients are found with relatively specific levels of viral RNA, develop rather distinctive immune conditions, and display unique clinical manifestations. Convergent research evidence has shown that hepatitis B virus (HBV) co-infection, a common cause of chronic liver disease, is fairly common in HIV-infected individuals. HBV invasion of the liver can be facilitated by HIV infection at each clinical stage of the infection due to a number of contributing factors, including having identical transmission routes, immunological suppression, gut microbiota dysbiosis, poor vaccination immune response to hepatitis B immunization, and drug hepatotoxicity. However, there remains a paucity of research investigation which critically describes the influence of the different HIV clinical stages and their consequences which tend to favor HBV entrenchment in the liver. Herein, we review advances in the understanding of the mechanisms favoring HBV infection at each clinical stage of HIV infection, thus paving the way toward development of potential strategies to reduce the prevalence of HBV co-infection in the HIV-infected population.
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Affiliation(s)
- Silvere D. Zaongo
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Jing Ouyang
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Yaling Chen
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Yan-Mei Jiao
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Hao Wu
- Department of Infectious Diseases, You’an Hospital, Capital Medical University, Beijing, China
| | - Yaokai Chen
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
- *Correspondence: Yaokai Chen,
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11
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Cheng Z, Lin P, Cheng N. HBV/HIV Coinfection: Impact on the Development and Clinical Treatment of Liver Diseases. Front Med (Lausanne) 2021; 8:713981. [PMID: 34676223 PMCID: PMC8524435 DOI: 10.3389/fmed.2021.713981] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 08/23/2021] [Indexed: 02/05/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a common contributor to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Approximately 10% of people with human immunodeficiency virus (HIV) also have chronic HBV co-infection, owing to shared transmission routes. HIV/HBV coinfection accelerates the progression of chronic HBV to cirrhosis, end-stage liver disease, or hepatocellular carcinoma compared to chronic HBV mono-infection. HBV/HIV coinfection alters the natural history of hepatitis B and renders the antiviral treatment more complex. In this report, we conducted a critical review on the epidemiology, natural history, and pathogenesis of liver diseases related to HBV/HIV coinfection. We summarized the novel therapeutic options for these coinfected patients.
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Affiliation(s)
- Zhimeng Cheng
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Panpan Lin
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Nansheng Cheng
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, China
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12
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Challenges for hepatitis B virus cure in resource-limited settings in sub-Saharan Africa. Curr Opin HIV AIDS 2021; 15:185-192. [PMID: 32141888 DOI: 10.1097/coh.0000000000000619] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW The aim of this article is to highlight the unique challenges for hepatitis B virus (HBV) cure faced in resource-limited settings (RLS) in sub-Saharan Africa (SSA), where access to disease prevention measures, medical testing, and treatment are limited. RECENT FINDINGS SSA RLS face challenges, which need to be anticipated as HBV cure research advances. There is a paucity of data because of lack of HBV surveillance and limited access to laboratories. Interruption of transfusion-transmitted infections, perinatal mother-to-child-transmissions, and transmission in people-who-infect-drug networks has not been achieved fully. Although RLS in SSA are within the epicenter of the HIV pandemic, unlike for HIV, there is no population-based testing for HBV. Public health response to HBV is inadequate with concomitant political inertia in combatting HBV infection. SUMMARY A functional HBV cure will improve the diagnosis/treatment cascade, decrease costs and accelerate HBV elimination. There is a concerted effort to find a HBV cure, which will be finite, not require life-long treatment, adherence, and continued monitoring. Increased research, improved financial, infrastructural and human resources will positively impact on implementation of HBV cure, when available. We can emulate major strides made in tackling HIV and the strength of advocacy groups in soliciting policymakers to take action.
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Surial B, Wyser D, Béguelin C, Ramírez-Mena A, Rauch A, Wandeler G. Prevalence of liver cirrhosis in individuals with hepatitis B virus infection in sub-Saharan Africa: Systematic review and meta-analysis. Liver Int 2021; 41:710-719. [PMID: 33220137 PMCID: PMC8048614 DOI: 10.1111/liv.14744] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 10/26/2020] [Accepted: 11/17/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Chronic hepatitis B virus (HBV) infection accounts for 30%-50% of cirrhosis related deaths in sub-Saharan Africa (SSA). Since HBV-related cirrhosis is an indication for immediate antiviral therapy and cancer surveillance, we aimed to estimate the prevalence of cirrhosis among treatment-naïve patients with chronic HBV infection in SSA. METHODS We performed a systematic review of published articles which evaluated liver fibrosis stage among treatment-naïve HBV-infected individuals who presented to care in SSA. Our primary outcome was the prevalence of cirrhosis in HBsAg-positive persons, which was estimated using random-effects meta-analysis. Risk factors for cirrhosis were explored using subgroup-analyses and multivariable meta-regression. RESULTS Of 2129 articles identified, 17 met our eligibility criteria. The studies described 22 cohorts from 13 countries, including 13 cohorts (3204 patients) with chronic HBV mono-infection and nine cohorts (688 patients) with HIV/HBV-coinfection. Liver fibrosis was assessed using transient elastography (10 cohorts), APRI score (11 cohorts), and Fibrotest (one cohort). The pooled prevalence of cirrhosis was 4.1% (95% confidence interval [CI] 2.6-6.4) among studies from primary care facilities or general population, compared to 12.7% (95% CI 8.6-18.3) in studies performed in referral or tertiary care facilities (adjusted odds ratio 0.29, 95% CI 0.15-0.56). We found no association between cirrhosis and age, gender, fibrosis test used or HIV-coinfection. CONCLUSIONS Depending on the setting, between 4% and 13% of HBV-infected individuals in SSA have cirrhosis and need immediate antiviral therapy. These estimates should be considered when planning HBV treatment strategies and resource allocation.
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Affiliation(s)
- Bernard Surial
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Dominik Wyser
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Charles Béguelin
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Adrià Ramírez-Mena
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Andri Rauch
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Gilles Wandeler
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.,Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
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14
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Salyani A, Shah J, Adam R, Otieno G, Mbugua E, Shah R. Occult hepatitis B virus infection in a Kenyan cohort of HIV infected anti-retroviral therapy naïve adults. PLoS One 2021; 16:e0244947. [PMID: 33406137 PMCID: PMC7787452 DOI: 10.1371/journal.pone.0244947] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 12/18/2020] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Occult hepatitis B virus (HBV) infection (OBI) is a phase of HBV infection characterised by the presence of HBV DNA in the absence of detectable hepatitis B surface antigen (HBsAg). OBI is of concern in the HIV-infected due to high prevalence and risk of HBV reactivation. The prevalence and clinico-demographic characteristics of OBI in anti-retroviral therapy (ART) naïve HIV infected adults in Kenya is unknown. METHODS A cross sectional study carried was out at three sites in Kenya. HIV infected ART naïve adults were enrolled and demographic data collected. Blood samples were assayed for HBsAg, HBV DNA, alanine aminotransferase, aspartate aminotransferase, antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc). Data on CD4 count, HIV viral load and platelet count were obtained from medical records. RESULTS Of 208 patients, 199 (95.7%) did not report HBV vaccination, 196 (94.2%) were HBsAg negative, 119 (57.2%) had no HBV markers, 58 (27.9%) had previous HBV infection (anti-HBc positive) and 11 (5.3%) had OBI. All 11 (100%) OBI patients were anti-HBc positive. OBI patients comprised 19.0% of HBsAg negative, anti-HBc positive patients. There was no difference in clinico-demographic characteristics between the overt HBV, OBI and HBV negative patients. CONCLUSION This was the first study on OBI in ART naïve HIV infected adults in Kenya. The lower OBI prevalence compared to other sub-Saharan African countries could be attributed to lower HBV exposure. Most patients were HBV unexposed and unimmunized, outlining the need to implement guideline recommended immunization strategies.
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Affiliation(s)
- Adil Salyani
- Department of Medicine, Aga Khan University Hospital, Nairobi, Kenya
- * E-mail: (AS); (RS)
| | - Jasmit Shah
- Department of Medicine, Aga Khan University Hospital, Nairobi, Kenya
| | - Rodney Adam
- Department of Medicine, Aga Khan University Hospital, Nairobi, Kenya
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
| | - George Otieno
- Department of Medicine, Kijabe Hospital, Kijabe, Kenya
| | - Evelyn Mbugua
- Department of Medicine, Kijabe Hospital, Kijabe, Kenya
| | - Reena Shah
- Department of Medicine, Aga Khan University Hospital, Nairobi, Kenya
- * E-mail: (AS); (RS)
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15
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Ayana DA, Mulu A, Mihret A, Seyoum B, Aseffa A, Howe R. Occult Hepatitis B virus infection among HIV negative and positive isolated anti-HBc individuals in eastern Ethiopia. Sci Rep 2020; 10:22182. [PMID: 33335238 PMCID: PMC7747707 DOI: 10.1038/s41598-020-79392-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 12/02/2020] [Indexed: 01/05/2023] Open
Abstract
The absence of hepatitis B surface antigen (HBsAg) and the presence of antibody to hepatitis B core antigen (anti-HBc) in the blood of apparently healthy individuals may not indicate the absence of circulating hepatitis B virus (HBV) and might be infectious. Despite the risk of HBV transmission, there has been no report from Ethiopia examining this issue; therefore, this study determined occult HBV infection (OBI) among isolated anti-HBc (IAHBc) HIV negative and HIV positive individuals on ART in eastern Ethiopia. A total of 306 IAHBc individuals were included in this study. DNA was extracted, amplified, and detected from plasma using a commercially available RealTime PCR platform (Abbott m2000rt) following the manufacturer's instructions. Data were entered into EPI Data version 3.1, cleaned, and analyzed using Stata version 13. Descriptive analysis was used to calculate prevalence, summarize sociodemographic data and other factors. From the 306 IAHBc individuals (184 HIV positive and 122 HIV negative) included in the study, 183 (59.8%) were female of which 142 (77.6%) were within the reproductive age group. DNA extraction, amplified and detection was conducted in 224 individuals. The overall OBI prevalence was 5.8% (5.6% in HIV negative and 6% in HIV positive) among the IAHBc individuals. The HBV DNA concentration among the occult hepatitis B individuals was < 200 IU/mL, indicating a true occult. This study reported the burden of OBI, which pauses a significant public health problem due to the high burden of HBV infection in the country. OBI may cause substantial risk of HBV transmission from blood transfusion, organ transplantation as well as vertical transmission as screening is solely dependent on HBsAg testing.
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Affiliation(s)
- Desalegn Admassu Ayana
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia.
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
| | - A Mulu
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - A Mihret
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - B Seyoum
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - A Aseffa
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - R Howe
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
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16
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Patel NH, Meier-Stephenson V, Genetu M, Damtie D, Abate E, Alemu S, Aleka Y, Van Marle G, Fonseca K, Coffin CS, Deressa T. Prevalence and genetic variability of occult hepatitis B virus in a human immunodeficiency virus positive patient cohort in Gondar, Ethiopia. PLoS One 2020; 15:e0242577. [PMID: 33211768 PMCID: PMC7704059 DOI: 10.1371/journal.pone.0242577] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 11/04/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Occult hepatitis B (OHB) is a major concern in HIV infected patients as it associates with a high risk of HBV reactivation and disease progression. However, data on the prevalence of OHB among HIV positive patients in Ethiopia is lacking. This study aims to determine the prevalence of OHB in HBV/HIV co-infected patients from Gondar, Ethiopia. METHODS A total of 308 consented HIV positive patients were recruited from the University of Gondar Teaching Hospital, Ethiopia. Clinical and demographic data of the participants were recorded. Plasma was tested for HBsAg and anti-HBc using commercial assays (Abbott Architect). In HBsAg negative anti-HBc positive patient samples, total DNA was isolated and amplified using nested PCR with primers specific to HBV polymerase, surface and pre-core/core regions, followed by Sanger sequencing and HBV mutational analysis using MEGA 7.0. RESULTS Of the total study subjects, 62.7% were female, median age 38.4 years, interquartile range (IQR): 18-68, and 208 (67.5%) had lifestyle risk factors for HBV acquisition. Two hundred and ninety-one study subjects were HIV+/HBsAg-, out of which 115 (39.5%) were positive for anti-HBc. Occult hepatitis B was detected in 19.1% (22/115) of anti-HBc positive HIV patients. HBV genotype D was the predominant genotype (81%) among OHB positive patients. Mutations associated with HBV drug resistance, HBV reactivation, and HCC risk were detected in 23% (5/22), 14% (3/22) and 45.5% (10/22) of patients, respectively. CONCLUSION This study found a high rate of occult hepatitis B in HIV patients. Further, high rates of mutations associated with HBV reactivation, drug resistance, and HCC risk were detected in these patients. These data highlighted the need for integrating OHB screening for proper management of liver diseases in HIV patients.
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Affiliation(s)
- Nishi H. Patel
- Department of Microbiology, Immunology and Infectious Diseases, Cumming
School of Medicine, University of Calgary, Calgary, Alberta,
Canada
| | - Vanessa Meier-Stephenson
- Department of Microbiology, Immunology and Infectious Diseases, Cumming
School of Medicine, University of Calgary, Calgary, Alberta,
Canada
| | - Meaza Genetu
- Department of Immunology and Molecular Biology, School of Biomedical and
Laboratory Sciences, College of Medicine and Health Sciences, University of
Gondar, Gondar, Ethiopia
| | - Debasu Damtie
- Department of Immunology and Molecular Biology, School of Biomedical and
Laboratory Sciences, College of Medicine and Health Sciences, University of
Gondar, Gondar, Ethiopia
- Food Animal Health Research Program, CFAES, Ohio Agricultural Research
and Development Center, Department of Veterinary Preventive Medicine, The Ohio
State University, Wooster, OH, United States of America
- Global One Health LLC, Eastern African Regional Office, Addis Ababa,
Ethiopia
| | - Ebba Abate
- Department of Immunology and Molecular Biology, School of Biomedical and
Laboratory Sciences, College of Medicine and Health Sciences, University of
Gondar, Gondar, Ethiopia
- Ethiopian Public Health Institute, Addis Ababa,
Ethiopia
| | - Shitaye Alemu
- School of Medicine, College of Medicine and Health Sciences, University
of Gondar, Gondar, Ethiopia
| | - Yetework Aleka
- Department of Immunology and Molecular Biology, School of Biomedical and
Laboratory Sciences, College of Medicine and Health Sciences, University of
Gondar, Gondar, Ethiopia
| | - Guido Van Marle
- Department of Microbiology, Immunology and Infectious Diseases, Cumming
School of Medicine, University of Calgary, Calgary, Alberta,
Canada
| | - Kevin Fonseca
- Department of Microbiology, Immunology and Infectious Diseases, Cumming
School of Medicine, University of Calgary, Calgary, Alberta,
Canada
- Provincial Laboratory for Public Health, Alberta Health Services,
Calgary, Alberta, Canada
| | - Carla S. Coffin
- Department of Microbiology, Immunology and Infectious Diseases, Cumming
School of Medicine, University of Calgary, Calgary, Alberta,
Canada
- Division of Gastroenterology and Hepatology, Department of Medicine,
Cumming School of Medicine, University of Calgary, Calgary, Alberta,
Canada
| | - Tekalign Deressa
- Department of Immunology and Molecular Biology, School of Biomedical and
Laboratory Sciences, College of Medicine and Health Sciences, University of
Gondar, Gondar, Ethiopia
- Ethiopian Public Health Institute, Addis Ababa,
Ethiopia
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Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F, Lok AS. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol 2019; 71:397-408. [PMID: 31004683 DOI: 10.1016/j.jhep.2019.03.034] [Citation(s) in RCA: 335] [Impact Index Per Article: 55.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 03/20/2019] [Accepted: 03/28/2019] [Indexed: 02/06/2023]
Abstract
In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.
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Affiliation(s)
- Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
| | - Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory at the Doherty Institute, Melbourne, Victoria, Australia
| | - Teresa Pollicino
- Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy; Department of Human Pathology, University of Messina, Messina, Italy
| | - Massimo Levrero
- Cancer Research Center of Lyon, INSERM U1052, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Fabien Zoulim
- Cancer Research Center of Lyon, INSERM U1052, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
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18
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Msomi N, Ndlovu K, Giandhari J, Wilkinson E, Parboosing R, Zungu S, Mlisana K. High rate of occult hepatitis B virus infection in hemodialysis units of KwaZulu-Natal, South Africa. J Med Virol 2019; 91:1797-1803. [PMID: 31180137 DOI: 10.1002/jmv.25510] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 05/31/2019] [Accepted: 06/02/2019] [Indexed: 12/20/2022]
Abstract
Occult hepatitis B virus (HBV) infection (OBI) is defined as the presence of HBV DNA in the liver with or without detectable HBV DNA in the serum of individuals testing HBV surface antigen (HBsAg) negative using currently available assays. The prevalence of OBI among patients receiving hemodialysis (HD) treatment remains poorly characterized in South Africa despite the high prevalence of HBV. We sought to determine the prevalence of OBI in HD units in tertiary hospitals of KwaZulu-Natal and to characterize the HBV S gene mutations potentially responsible for OBI. A cross-sectional descriptive study of residual diagnostic plasma samples from 85 HBsAg-negative patients receiving HD treatment was included. The PreS/S gene was amplified with a nested HBV polymerase chain reaction for downstream next-generation sequencing, to determine the viral genotype and identify S gene mutations associated with OBI. Nine of the 85 samples had OBI, based on detectable HBV DNA. The point prevalence of OBI was 10.6% (95% control interval: 5.5%-19.1%). Phylogenetic analysis of the samples with OBI showed that all belonged to genotype A. Three (~33%) samples had mutations in the major hydrophilic region (MHR) within the S gene, three (~33%) had mutations within the S gene but outside the MHR, whilst the remaining three had no mutations observed. The prevalence of OBI in HBsAg-negative patients undergoing HD was 10.6%, suggesting that OBI is a clinically significant problem in patients with HD in this region. The screening methods for HBV infection need to be revised to include nucleic acid testing.
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Affiliation(s)
- Nokukhanya Msomi
- Department of Virology, School of Laboratory Medicine and Medical Sciences and National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa
| | - Kwazi Ndlovu
- Division of Nephrology and Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa
| | - Jennifer Giandhari
- KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.,Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa
| | - Eduan Wilkinson
- KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Raveen Parboosing
- Department of Virology, School of Laboratory Medicine and Medical Sciences and National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa
| | - Sabrina Zungu
- Department of Virology, School of Laboratory Medicine and Medical Sciences and National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa
| | - Koleka Mlisana
- National Health Laboratory Service (Academic Affairs, Research, and Quality Assurance), Johannesburg, South Africa
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19
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Prabdial-Sing N, Makhathini L, Smit SB, Manamela MJ, Motaze NV, Cohen C, Suchard MS. Hepatitis B sero-prevalence in children under 15 years of age in South Africa using residual samples from community-based febrile rash surveillance. PLoS One 2019; 14:e0217415. [PMID: 31150445 PMCID: PMC6544234 DOI: 10.1371/journal.pone.0217415] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 05/10/2019] [Indexed: 02/06/2023] Open
Abstract
Introduction and methods Hepatitis B is a vaccine preventable disease and is notifiable in South Africa. Hepatitis B vaccination was incorporated into the Expanded Programme on Immunisation in South Africa in 1995. We used a convenience sample from community-based febrile rash surveillance in 2013 to estimate hepatitis B sero-prevalence. Of samples serologically negative for acute measles infection, 450 samples spanning nine provinces of South Africa were tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc). Results Two children (2/450; 0.4%) tested positive for HBsAg. Three hundred and three children (67.3%) had evidence of vaccine induced immunity. Vaccine induced immunity was present in 80.2% of 1–5 year olds, but only 60.3% of 10–14 year olds. Natural immunity, indicating exposure to circulating hepatitis B, was present in 13/450 (2.9%) children. Conclusion Chronic hepatitis B in South African has decreased in prevalence from highly endemic levels prior to vaccine introduction to approximately 0.4% in this sample, demonstrating impact of a successful vaccination programme 18 years after introduction. Decreased vaccine-induced immunity with increasing age may reflect waning antibody titres over time.
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Affiliation(s)
- Nishi Prabdial-Sing
- Centre for Vaccines and Immunology, National Institute for Communicable Diseases (NICD), a division of the National Health Laboratory Service, Johannesburg, South Africa
- Department of Virology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Lillian Makhathini
- Centre for Vaccines and Immunology, National Institute for Communicable Diseases (NICD), a division of the National Health Laboratory Service, Johannesburg, South Africa
| | - Sheilagh Brigitte Smit
- Centre for Vaccines and Immunology, National Institute for Communicable Diseases (NICD), a division of the National Health Laboratory Service, Johannesburg, South Africa
| | - Morubula Jack Manamela
- Centre for Vaccines and Immunology, National Institute for Communicable Diseases (NICD), a division of the National Health Laboratory Service, Johannesburg, South Africa
| | - Nkengafac Villyen Motaze
- Centre for Vaccines and Immunology, National Institute for Communicable Diseases (NICD), a division of the National Health Laboratory Service, Johannesburg, South Africa
- Division of Epidemiology and Biostatistics, Department of Global Health,Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Cheryl Cohen
- Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa
- School of Public Health, University of the Witwatersrand, Johannesburg, South Africa
| | - Melinda Shelley Suchard
- Centre for Vaccines and Immunology, National Institute for Communicable Diseases (NICD), a division of the National Health Laboratory Service, Johannesburg, South Africa
- Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- * E-mail:
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20
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Boyd A, Moh R, Maylin S, Abdou Chekaraou M, Mahjoub N, Gabillard D, Anglaret X, Eholié SP, Danel C, Delaugerre C, Zoulim F, Lacombe K. Effect of hepatitis B virus (HBV) surface-gene variability on markers of replication during treated human immunodeficiency virus-HBV infection in Western Africa. Liver Int 2019; 39:280-289. [PMID: 30257068 DOI: 10.1111/liv.13975] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Revised: 08/18/2018] [Accepted: 09/19/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa. METHODS Seventy-three antiretroviral treatment (ART)-naïve human immunodeficiency virus (HIV)-HBV co-infected patients from Côte d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated. RESULTS Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B "e" antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5). CONCLUSION Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification.
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Affiliation(s)
- Anders Boyd
- INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Saint Antoine Hospital, AP-HP, Sorbonne Université, Paris, France
| | - Raoul Moh
- Programme PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.,Department of Infectious and Tropical Diseases, Treichville University Teaching Hospital, Abidjan, Côte d'Ivoire.,Medical School, University Felix Houphouet Boigny, Abidjan, Côte d'Ivoire
| | - Sarah Maylin
- Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.,Université Paris-Diderot, Paris, France
| | | | - Nadia Mahjoub
- Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France
| | - Delphine Gabillard
- INSERM U1219, Bordeaux, France.,ISPED, University of Bordeaux, Bordeaux, France
| | - Xavier Anglaret
- Programme PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.,INSERM U1219, Bordeaux, France.,ISPED, University of Bordeaux, Bordeaux, France
| | - Serge Paul Eholié
- Programme PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.,Department of Infectious and Tropical Diseases, Treichville University Teaching Hospital, Abidjan, Côte d'Ivoire.,Medical School, University Felix Houphouet Boigny, Abidjan, Côte d'Ivoire
| | - Christine Danel
- Programme PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.,INSERM U1219, Bordeaux, France.,ISPED, University of Bordeaux, Bordeaux, France
| | - Constance Delaugerre
- Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.,Université Paris-Diderot, Paris, France.,INSERM U941, Paris, France
| | - Fabien Zoulim
- INSERM U1052-Centre de Recherche sur le Cancer de Lyon (CRCL), Lyon, France.,UMR_S1052, CRCL, University of Lyon, Lyon, France.,Department of Hepatology, Hospices Civils de Lyon, Lyon, France
| | - Karine Lacombe
- INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Saint Antoine Hospital, AP-HP, Sorbonne Université, Paris, France.,Department of Infectious and Tropical Diseases, Saint-Antoine Hospital, AP-HP, Paris, France
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21
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Singh L, Bell TG, Yousif M, Kramvis A. Response of hepatitis B virus to antiretroviral treatment containing lamivudine in HBsAg-positive and HBsAg-negative HIV-positive South African adults. J Med Virol 2018; 91:758-764. [PMID: 30515847 DOI: 10.1002/jmv.25375] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 11/21/2018] [Indexed: 11/06/2022]
Abstract
Both hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection are highly endemic in sub-Saharan Africa. This study examined serological and clinical follow-up data from 39 HBV DNA-positive, HIV-positive black South African adults, who returned for follow-up at 3, 6, 12, and 18 months post-initiation of antiretroviral therapy (ART). Of the 39 participants, 10 experienced full suppression of HBV and 29 experienced no suppression, with 10 of these showing a virological breakthrough. All 10 patients who fully suppressed were HBsAg-negative, with 16 of the 29 who did not suppress being HBsAg-positive and 13 HBsAg-negative (P < 0.05). Participants fully suppressing the virus had significantly lower aminotransferase levels and were all HBsAg-negative compared to those who did not suppress (P < 0.05). HBV viral loads between HBsAg-positive and HBsAg-negative samples were similar at baseline and at the final time-point. In these South African patients with HBV/HIV coinfection, HBsAg-negative status at baseline was a predictor of the outcome of HBV suppression in response to ART containing lamivudine.
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Affiliation(s)
- Lanish Singh
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Trevor Graham Bell
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Mukhlid Yousif
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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22
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Boyd A, Moh R, Maylin S, Abdou Chekaraou M, Mahjoub N, Gabillard D, Anglaret X, Eholié SP, Delaugerre C, Danel C, Zoulim F, Lacombe K. Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co-infected patients from Western Africa. J Viral Hepat 2018; 25:1121-1131. [PMID: 29660214 DOI: 10.1111/jvh.12914] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Accepted: 03/20/2018] [Indexed: 12/22/2022]
Abstract
The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)-infected patients. Whether this mutation affects the therapeutic course of HIV-HBV co-infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)-naïve HIV-HBV co-infected patients from Côte d'Ivoire, initiating ARV-treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV-DNA, hepatitis B "e" antigen (HBeAg) seroclearance (in HBeAg-positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV-initiation, median HBV-DNA was 6.04 log10 copies/mL (IQR = 3.70-7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg-negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24-36). Cumulative proportion of undetectable HBV-DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV-DNA levels and anti-HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti-HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.
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Affiliation(s)
- A Boyd
- INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Paris, France
| | - R Moh
- Programme PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.,Department of Infectious and Tropical Diseases, Treichville University Teaching Hospital, Abidjan, Côte d'Ivoire.,Medical School, University Felix Houphouet Boigny, Abidjan, Côte d'Ivoire
| | - S Maylin
- Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.,Université Paris-Diderot, Paris, France
| | | | - N Mahjoub
- Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France
| | - D Gabillard
- INSERM, U1219, Bordeaux, France.,University of Bordeaux, ISPED, Bordeaux, France
| | - X Anglaret
- Programme PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.,INSERM, U1219, Bordeaux, France.,University of Bordeaux, ISPED, Bordeaux, France
| | - S P Eholié
- Programme PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.,Department of Infectious and Tropical Diseases, Treichville University Teaching Hospital, Abidjan, Côte d'Ivoire.,Medical School, University Felix Houphouet Boigny, Abidjan, Côte d'Ivoire
| | - C Delaugerre
- Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.,Université Paris-Diderot, Paris, France.,INSERM U941, Paris, France
| | - C Danel
- Programme PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.,INSERM, U1219, Bordeaux, France.,University of Bordeaux, ISPED, Bordeaux, France
| | - F Zoulim
- INSERM U1052- Cancer Research Center of Lyon (CRCL), Lyon, France.,University of Lyon, UMR_S1052, CRCL, Lyon, France.,Department of Hepatology, Hospices Civils de Lyon, Lyon, France
| | - K Lacombe
- Department of Infectious and Tropical Diseases, Saint-Antoine Hospital, AP-HP, Paris, France.,INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Hôpital Saint Antoine, AP-HP, Sorbonne Université, Paris, France
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23
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Anderson M, Choga WT, Moyo S, Bell TG, Mbangiwa T, Phinius BB, Bhebhe L, Sebunya TK, Makhema J, Marlink R, Kramvis A, Essex M, Musonda RM, Blackard JT, Gaseitsiwe S. In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm. Genes (Basel) 2018; 9:genes9090420. [PMID: 30134551 PMCID: PMC6162659 DOI: 10.3390/genes9090420] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 08/16/2018] [Indexed: 02/06/2023] Open
Abstract
Occult hepatitis B infections (OBI) represent a reservoir of undiagnosed and untreated hepatitis B virus (HBV), hence the need to identify mutations that lead to this phenotype. Functionally characterizing these mutations by in vitro studies is time-consuming and expensive. To bridge this gap, in silico approaches, which predict the effect of amino acid (aa) variants on HBV protein function, are necessary. We developed an algorithm for determining the relevance of OBI-associated mutations using in silico approaches. A 3 kb fragment of subgenotypes A1 and D3 from 24 chronic HBV-infected (CHB) and 24 OBI participants was analyzed. To develop and validate the algorithm, the effects of 68 previously characterized occult-associated mutations were determined using three computational tools: PolyPhen2, SNAP2, and PROVEAN. The percentage of deleterious mutations (with impact on protein function) predicted were 52 (76.5%) by PolyPhen2, 55 (80.9%) by SNAP2, and 65 (95.6%) by PROVEAN. At least two tools correctly predicted 59 (86.8%) mutations as deleterious. To identify OBI-associated mutations exclusive to Botswana, study sequences were compared to CHB sequences from GenBank. Of the 43 OBI-associated mutations identified, 26 (60.5%) were predicted by at least two tools to have an impact on protein function. To our knowledge, this is the first study to use in silico approaches to determine the impact of OBI-associated mutations, thereby identifying potential candidates for functional analysis to facilitate mechanistic studies of the OBI phenotype.
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Affiliation(s)
- Motswedi Anderson
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
- Faculty of Science, Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
| | | | - Sikhulile Moyo
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | - Trevor Graham Bell
- Hepatitis Virus Diversity Research Unit (HVDRU), Faculty of Health Sciences, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg 2050, South Africa.
| | - Tshepiso Mbangiwa
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
- Faculty of Allied Health Sciences, University of Botswana, Gaborone, Botswana.
| | - Bonolo B Phinius
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
| | - Lynette Bhebhe
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
| | - Theresa K Sebunya
- Faculty of Science, Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
| | - Joseph Makhema
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | - Richard Marlink
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
- Rutgers Global Health Institute, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08854, USA.
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit (HVDRU), Faculty of Health Sciences, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg 2050, South Africa.
| | - Max Essex
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | | | - Jason T Blackard
- College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
| | - Simani Gaseitsiwe
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
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24
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Mak D, Babb de Villiers C, Chasela C, Urban MI, Kramvis A. Analysis of risk factors associated with hepatocellular carcinoma in black South Africans: 2000-2012. PLoS One 2018; 13:e0196057. [PMID: 29718992 PMCID: PMC5931658 DOI: 10.1371/journal.pone.0196057] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 04/05/2018] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE The aims of this study were to determine the prevalence of risk factors associated with hepatocellular carcinoma (HCC) in black adult South Africans and to estimate the size of the associated risks. METHODS A case-control analysis of 150 black South African patients (aged 18-75 years) with HCC-who were a subset of patients recruited for the Johannesburg Cancer Case Control Study 2000 to 2012-was undertaken. The association between this tumour and hepatitis B/C virus infections, and human immunodeficiency virus (HIV) mono- and co-infections was investigated. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, year of diagnosis, marital status, place of birth and selected modifiable risk factors were calculated. RESULTS HCC was significantly associated with a rural birthplace (p<0.05), being male and living in an urban area for 14 years or less. The Odds Ratio (OR) for HCC increased significantly with HBV DNA+/HBsAg+ (OR 34.5; CI:16.26-73.13), HBV DNA+/HBsAg- (OR 3.76; CI:1.79-7.92), HBV DNA level >2000 IU/ml (OR 8.55; CI:3.00-24.54) to ≥200,000 (OR 16.93; CI:8.65-33.13), anti-HCV (OR 8.98; CI:3.59-22.46), HBV DNA+/HIV+ co-infection (OR 5.36; CI:2.59-11.11), but not with HBV DNA-/HIV+ (OR 0.34; CI:0.14-0.85). We did not find a synergistic interaction between HBV and HIV. Modifiable risk factors (alcohol consumption, tobacco smoking, number of sexual partners, diabetes and hormonal contraceptive use) were nonsignificant. DISCUSSION A considerable portion of the HCC burden in Johannesburg and surrounding provinces falls on rural migrants to urban areas, most of whom are men. The HBV will continue to contribute to HCC incidence in older age-groups and in others who missed vaccination. Although we did not find an increased risk for HCC in HIV positive individuals this may change as life expectancy increases due to greater access to antiretroviral therapies, necessitating the addition of hepatitis virus screening to preventive medical care.
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Affiliation(s)
- Daniel Mak
- Hepatitis Virus Diversity Research Unit (HVDRU), Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Chantal Babb de Villiers
- Cancer Epidemiology Research Group, National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa
- Division of Human Genetics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Charles Chasela
- Epidemiology and Strategic Information (ESI), HIV/AIDS, STIS and TB (HAST), Human Sciences Research Council (HSRC), Pretoria, South Africa
- Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Right to Care, EQUIP HEALTH, Centurion, South Africa
| | - Margaret I. Urban
- Cancer Epidemiology Research Group, National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit (HVDRU), Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Ambachew H, Zheng M, Pappoe F, Shen J, Xu Y. Genotyping and sero-virological characterization of hepatitis B virus (HBV) in blood donors, Southern Ethiopia. PLoS One 2018; 13:e0193177. [PMID: 29462187 PMCID: PMC5819820 DOI: 10.1371/journal.pone.0193177] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 02/06/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatitis B virus (HBV) prevalence is highest in Sub-Saharan Africa including Ethiopia. HBV genotypes have distinct geographic distributions and play a role in course of infection and treatment management. However, in Ethiopia there is paucity of information about distribution of HBV genotypes. This study was done to determine genotype, mutation and sero-virological profiles of HBV isolates in Southern Ethiopia. Cross-sectional, laboratory based study was conducted on 103HBsAg sero-positive samples from a total of 2,237 screened blood donors. HBV serological markers and biochemical assays were done. Serum viral load was measured using quantitative real-time PCR. Partial HBV S-gene was amplified with nested PCR and sequenced. Bioinformatics tools were utilized to determine genotypes, serotypes and mutations. Of 103 HBsAg reactive serum samples, 14.6% and 70.9% were sero-positive for HBeAg and HBeAb, respectively. Ninety-eight samples gave detectable viral load with a median of 3.46(2.62-4.82) log IU/ml. HBeAg sero-positive donors carried elevated levels of viral load. Eighty five isolates were successfully amplified, sequenced and genotyped into 58 (68.2%) genotype A (HBV/A) and 27 (31.8%) genotype D (HBV/D). HBV serotypes found were adw2 (74.1%), ayw2 (24.7%), and ayw3 (1.2%). In twenty-four (28.2%) samples mutations in the major hydrophilic region (MHR) were observed. Donors infected with HBV/A had higher viral load and more frequent MHR mutation than HBV/D infected donors. This study illustrated distribution of HBV genotype A and D among blood donors in southern Ethiopia. It also demonstrated occurrence HBV variants that may influence clinical aspects of HBV infection. The study contributes in narrowing the existing gap of HBV molecular study in Ethiopia.
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Affiliation(s)
- Henock Ambachew
- Department of Clinical Laboratory, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Clinical Laboratory Diagnostics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia
| | - Meijuan Zheng
- Department of Clinical Laboratory, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Clinical Laboratory Diagnostics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
| | - Faustina Pappoe
- Department of Immunology and Parasitology, Provincial Laboratory of Microbiology and Parasitology and the Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, Anhui, China
- Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Jilong Shen
- Department of Clinical Laboratory Diagnostics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Immunology and Parasitology, Provincial Laboratory of Microbiology and Parasitology and the Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, Anhui, China
| | - Yuanhong Xu
- Department of Clinical Laboratory, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Clinical Laboratory Diagnostics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Immunology and Parasitology, Provincial Laboratory of Microbiology and Parasitology and the Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, Anhui, China
- * E-mail:
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26
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Coffie PA, Egger M, Vinikoor MJ, Zannou M, Diero L, Patassi A, Kuniholm MH, Seydi M, Bado G, Ocama P, Andersson MI, Messou E, Minga A, Easterbrook P, Anastos K, Dabis F, Wandeler G. Trends in hepatitis B virus testing practices and management in HIV clinics across sub-Saharan Africa. BMC Infect Dis 2017; 17:706. [PMID: 29143625 PMCID: PMC5688463 DOI: 10.1186/s12879-017-2768-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Approximately 8% of HIV-infected individuals are co-infected with hepatitis B virus (HBV) in sub-Saharan Africa (SSA). Knowledge of HBV status is important to guide optimal selection of antiretroviral therapy (ART) and monitor/prevent liver-related complications. We describe changes in testing practices and management of HBV infection over a 3-year period in HIV clinics across SSA. Methods A medical chart review was conducted in large urban HIV treatment centers in Côte d’Ivoire (3 sites), Benin, Burkina Faso, Cameroon, Kenya, Senegal, South Africa, Togo, Uganda and Zambia (1 site each). Of the patients who started ART between 2010 and 2012, 100 per year were randomly selected from each clinic. Demographic, clinical and laboratory information as well as individual treatment histories were collected using a standardized questionnaire. We examined changes over time in the proportion of patients screened for HBV infection (HBV surface antigen [HBsAg]-positivity), identified predictors of HBV testing using logistic regression, and assessed the proportion of patients initiating a tenofovir (TDF)-containing ART regimen. Results Overall, 3579 charts of patients initiating ART (64.4% female, median age 37 years) were reviewed in 12 clinics. The proportion of patients screened for HBsAg increased from 17.8% in 2010 to 24.4% in 2012 overall, and ranged from 0.7% in Kenya to 96% in South Africa. In multivariable analyses, age and region were associated with HBsAg screening. Among 759 individuals tested, 88 (11.6%; 95% confidence interval [CI] 9.4–14.1) were HBV-infected, of whom 71 (80.7%) received a TDF-containing ART regimen. HBsAg-positive individuals were twice as likely to receive a TDF-containing first-line ART regimen compared to HBsAg-negative patients (80.7% vs. 40.3%, p < 0.001). The proportion of patients on TDF-containing ART increased from 57.9% in 2010 to 90.2% in 2012 in HIV/HBV-co-infected patients (Chi-2 test for trend: p = 0.01). Only 114 (5.0%) patients were screened for anti-HCV antibodies and one of them (0.9%, 95% CI 0.02–4.79) had a confirmed HCV infection. Conclusions The systematic screening for HBV infection in HIV-positive patients before ART initiation was limited in most African countries and its uptake varied widely across clinics. Overall, the prescription of TDF increased over time, with 90% of HIV/HBV-coinfected patients receiving this drug in 2012.
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Affiliation(s)
- Patrick A Coffie
- Programme PACCI, CHU Treichville, Site de Recherche ANRS, Abidjan, Côte d'Ivoire. .,Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, Abidjan, Côte d'Ivoire.
| | - Matthias Egger
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.,Centre for Infectious Disease Epidemiology and Research (CIDER), University of Cape Town, Cape Town, South Africa
| | - Michael J Vinikoor
- Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.,Department of Medicine at University of Alabama, Birmingham, AL, USA
| | - Marcel Zannou
- Service de Médecine Interne, CNHU Hubert Maga, Cotonou, Benin
| | - Lameck Diero
- Department of Medicine, Moi University, College of Health Sciences, School of Medicine, Eldoret, Kenya
| | - Akouda Patassi
- Service des Maladies Infectieuses et de Pneumologie, CHU Sylvanus Olympio, Lomé, Togo
| | - Mark H Kuniholm
- Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, NY, USA
| | - Moussa Seydi
- Department of Infectious Diseases, Fann University Hospital, Dakar, Senegal
| | - Guillaume Bado
- Hôpital de Jour, Service des Maladies Infectieuses et Tropicales, CHU Souro Sanou, Bobo Dioulasso, Burkina Faso
| | - Ponsiano Ocama
- Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Monique I Andersson
- Division of Medical Virology, Department of Pathology, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa
| | - Eugène Messou
- Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, Abidjan, Côte d'Ivoire.,Centre de Prise en charge de Recherche et de Formation. CePReF-Aconda-VS, Abidjan, Côte d'Ivoire
| | - Albert Minga
- Centre Médical de Suivi de Donneurs de Sang/ CNTS/PRIMO-CI, Abidjan, Côte d'Ivoire
| | - Philippa Easterbrook
- Global Hepatitis Programme, HIV Department, World Health Organization, Geneva, Switzerland.,Infectious Diseases Institute, Kampala, Uganda
| | - Kathryn Anastos
- Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA
| | - François Dabis
- ISPED, Université de Bordeaux, Bordeaux, France.,INSERM U1219, Bordeaux Population Health, Bordeaux, France
| | - Gilles Wandeler
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. .,Department of Infectious Diseases, Fann University Hospital, Dakar, Senegal. .,Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
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27
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Singh KP, Crane M, Audsley J, Avihingsanon A, Sasadeusz J, Lewin SR. HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment. AIDS 2017; 31:2035-2052. [PMID: 28692539 PMCID: PMC5661989 DOI: 10.1097/qad.0000000000001574] [Citation(s) in RCA: 163] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
: HIV infection has a significant impact on the natural history of chronic hepatitis B virus (HBV) infection, with increased levels of HBV DNA, accelerated progression of liver disease and increased liver-associated mortality compared with HBV monoinfection. Widespread uptake and early initiation of HBV-active antiretroviral therapy has substantially improved the natural history of HIV-HBV coinfection but the prevalence of liver disease remains elevated in this population. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease and seroconversion in HIV-HBV coinfection in the era of HBV-active antiretroviral therapy and the effects of HIV directly on liver disease. We also review novel therapeutics for the management of HBV with a particular emphasis on clinical strategies being developed for an HBV cure and an HIV cure and their impact on HIV-HBV coinfected individuals.
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Affiliation(s)
- Kasha P Singh
- aThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital bVictorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity cDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne Australia dThai Red Cross AIDS Research Center and Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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28
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Ryan K, Anderson M, Gyurova I, Ambroggio L, Moyo S, Sebunya T, Makhema J, Marlink R, Essex M, Musonda R, Gaseitsiwe S, Blackard JT. High Rates of Occult Hepatitis B Virus Infection in HIV-Positive Individuals Initiating Antiretroviral Therapy in Botswana. Open Forum Infect Dis 2017; 4:ofx195. [PMID: 29062862 PMCID: PMC5641381 DOI: 10.1093/ofid/ofx195] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 09/12/2017] [Indexed: 12/16/2022] Open
Abstract
Background Hepatitis B surface antigen (HBsAg)–negative but hepatitis B virus (HBV) DNA-positive infection—known as occult hepatitis B infection (OBI)—occurs in 1% to >15% of HIV-positive individuals in the United States and South Africa, respectively. However, there are no data on OBI from Botswana, a country known to be hyperendemic for chronic HBV infection and to have a significant HIV burden. Methods Two hundred seventy-two adults enrolled in an HIV treatment study of tenofovir/emtricitabine as the nucleoside backbone who were previously determined to be HBsAg negative were tested for HBV DNA at baseline and 1 year after initiation of highly active antiretroviral therapy (HAART). Results HBV DNA was detected in 72 of 272 (26.5%). Six individuals (8.3%) had HBV DNA levels greater than 200 IU/mL, and the highest viral load was 3280 IU/mL. Of 65 participants with OBI evaluated at 12 months after initiating HAART, only 1 (1.5%) had detectable HBV DNA. Conclusions Occult HBV infection is quite common in HIV-infected patients in Botswana, although its impact on the course of HIV disease progression is unknown. The suppression of occult HBV DNA levels by tenofovir/emtricitabine suggests an effective therapeutic option, although the long-term suppressive abilities remain unstudied.
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Affiliation(s)
- Kathleen Ryan
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Motswedi Anderson
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Biological Sciences, University of Botswana, Gaborone, Botswana
| | - Ivayla Gyurova
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| | | | - Sikhulile Moyo
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Teresa Sebunya
- Department of Biological Sciences, University of Botswana, Gaborone, Botswana
| | - Joseph Makhema
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Richard Marlink
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Max Essex
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Rosemary Musonda
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Simani Gaseitsiwe
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
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29
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Saha D, Pal A, Sarkar N, Das D, Blackard JT, Guha SK, Saha B, Chakravarty R. Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India. PLoS One 2017; 12:e0179035. [PMID: 28591184 PMCID: PMC5462430 DOI: 10.1371/journal.pone.0179035] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 05/23/2017] [Indexed: 12/13/2022] Open
Abstract
Occult HBV infection (OBI), defined by the presence of HBV DNA in absence of hepatitis B surface antigen (HBsAg), is a significant concern in the HIV-infected population. Of 441 HIV+/HBsAg- patients analyzed, the overall prevalence of OBI was 6.3% (28/441). OBI was identified in 21 anti-HBc positives (17.8%), as well as among those who lacked any HBV-specific serological markers (2.2%). Comparison with HIV/HBV co-infection revealed that the levels of CD4, ALT, and HBV DNA were significantly lower during occult infection. Discrete differences were also observed with respect to quasispecies divergence. Additionally, subgenotype D1 was most frequent in occult infection, while D2 was widespread during chronic infection. The majority (~90%) of occult D1 sequences had the sQ129R mutation in the surface gene. This study highlights several distinct features of OBI in India and underscores the need for additional HBV DNA screening in HIV-positive individuals.
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Affiliation(s)
- Debraj Saha
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Ananya Pal
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Neelakshi Sarkar
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Dipanwita Das
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Jason T. Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
| | | | - Bibhuti Saha
- Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
| | - Runu Chakravarty
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
- * E-mail:
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30
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Keechilot CS, Shenoy V, Kumar A, Biswas L, Vijayrajratnam S, Dinesh K, Nair P. Detection of occult hepatitis B and window period infection among blood donors by individual donation nucleic acid testing in a tertiary care center in South India. Pathog Glob Health 2016; 110:287-291. [PMID: 27788631 DOI: 10.1080/20477724.2016.1248171] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
With the introduction of highly sensitive hepatitis B surface antigen immunoassay, transfusion associated HBV infection have reduced drastically but they still tend to occur due to blood donors with occult hepatitis B infection (OBI) and window period (WP) infection. Sera from, 24338 healthy voluntary blood donors were screened for HBsAg, HIV and HCV antibody using Vitros Enhanced Chemiluminescent Immunoassay. The median age of the donor population was 30 (range 18-54) with male preponderance (98%). All serologically negative samples were screened by nucleic acid testing (NAT) for viral DNA and RNA. NAT-positive samples were subjected to discriminatory NAT for HBV, HCV, and HIV and all samples positive for HBV DNA were tested for anti-HBc, anti-HBs, HBeAg. Viral load was determined using artus HBV RG PCR Kit. Of the 24,338 donors screened, 99.81% (24292/24338) were HBsAg negative of which NAT was positive for HBV DNA in 0.0205% (5/24292) donors. Four NAT positive donors had viral load of <200 IU/ml making them true cases of OBI. One NAT positive donor was negative for all antibodies making it a case of WP infection. Among OBI donors, 75% (3/4) were immune and all were negative for HBeAg. Precise HBV viral load could not be determined in all (5/5) NAT positive donors due to viral loads below the detection limit of the artus HBV RG PCR Kit. The overall incidence of OBI and WP infections was found to be low at 1 in 6503 and 1 in 24214 donations, respectively. More studies are needed to determine the actual burden of WP infections in Indian blood donors.
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Affiliation(s)
- Cinzia S Keechilot
- a Amrita Institute of Medical Sciences and Research Center , Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Veena Shenoy
- b Department of Transfusion Medicine , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Anil Kumar
- c Department of Microbiology , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Lalitha Biswas
- d Department of Molecular Biology , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Sukhithasri Vijayrajratnam
- e Center for Nanoscience and Molecular medicine , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Kavitha Dinesh
- c Department of Microbiology , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Prem Nair
- f Department of Gastroenterology , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
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31
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Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol 2016; 22:8720-8734. [PMID: 27818588 PMCID: PMC5075547 DOI: 10.3748/wjg.v22.i39.8720] [Citation(s) in RCA: 105] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/13/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.
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32
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Powell EA, Boyce CL, Gededzha MP, Selabe SG, Mphahlele MJ, Blackard JT. Functional analysis of 'a' determinant mutations associated with occult HBV in HIV-positive South Africans. J Gen Virol 2016; 97:1615-1624. [PMID: 27031988 DOI: 10.1099/jgv.0.000469] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in the absence of hepatitis B surface antigen (HBsAg). Occult HBV is associated with the development of hepatocellular carcinoma, reactivation during immune suppression, and virus transmission. Viral mutations contribute significantly to the occult HBV phenotype. Mutations in the 'a' determinant of HBsAg are of particular interest, as these mutations are associated with immune escape, vaccine escape and diagnostic failure. We examined the effects of selected occult HBV-associated mutations identified in a population of HIV-positive South Africans on HBsAg production in vitro. Mutations were inserted into two different chronic HBV backbones and transfected into a hepatocyte-derived cell line. HBsAg levels were quantified by enzyme-linked immunosorbent assay (ELISA), while the detectability of mutant HBsAg was determined using an HA-tagged HBsAg expression system. Of the seven mutations analysed, four (S132P, C138Y, N146D and C147Y) resulted in decreased HBsAg expression in one viral background but not in the second viral background. One mutation (N146D) led to a decrease in HBsAg detected as compared to HA-tag, indicating that this mutation compromises the ability of the ELISA to detect HBsAg. The contribution of occult-associated mutations to the HBsAg-negative phenotype of occult HBV cannot be determined adequately by testing the effect of the mutation in a single viral background, and rigorous analysis of these mutations is required.
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Affiliation(s)
| | | | | | | | - M Jeffrey Mphahlele
- Sefako Makgatho Health Sciences University; South Africa Medical Research Council
| | - Jason T Blackard
- Division of Digestive Diseases ML 0595 231 Albert Sabin Way, University of Cincinnati, University of Cincinnati College of Medicine, USA
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Bivigou-Mboumba B, François-Souquière S, Deleplancque L, Sica J, Mouinga-Ondémé A, Amougou-Atsama M, Chaix ML, Njouom R, Rouet F. Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon. PLoS One 2016; 11:e0143869. [PMID: 26764909 PMCID: PMC4713159 DOI: 10.1371/journal.pone.0143869] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 11/09/2015] [Indexed: 12/20/2022] Open
Abstract
Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB.
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Affiliation(s)
- Berthold Bivigou-Mboumba
- Laboratoire de Rétrovirologie, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
- Unité Mixte de Recherche VIH et Maladies Infectieuses Associées (UMR-VIH-MIA), CIRMF, Libreville, Gabon
- * E-mail: ;
| | | | - Luc Deleplancque
- Laboratoire de Rétrovirologie, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
| | - Jeanne Sica
- Centre de Traitement Ambulatoire (CTA), Franceville, Gabon
| | - Augustin Mouinga-Ondémé
- Laboratoire de Rétrovirologie, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
| | | | - Marie-Laure Chaix
- Laboratoire de Virologie, AP-HP, Hôpital Saint Louis; INSERM U941, Université Paris Diderot; Laboratoire associé au Centre national de Référence du VIH, Paris, France
| | - Richard Njouom
- Service de Virologie, Centre Pasteur du Cameroun, Yaoundé, Cameroun
| | - François Rouet
- Laboratoire de Rétrovirologie, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
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Zampino R, Boemio A, Sagnelli C, Alessio L, Adinolfi LE, Sagnelli E, Coppola N. Hepatitis B virus burden in developing countries. World J Gastroenterol 2015; 21:11941-11953. [PMID: 26576083 PMCID: PMC4641116 DOI: 10.3748/wjg.v21.i42.11941] [Citation(s) in RCA: 190] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 07/23/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.
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Stabinski L, OʼConnor S, Barnhart M, Kahn RJ, Hamm TE. Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings. J Acquir Immune Defic Syndr 2015; 68 Suppl 3:S274-85. [PMID: 25768867 PMCID: PMC10426262 DOI: 10.1097/qai.0000000000000496] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS). METHODS We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed. RESULTS Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively. CONCLUSIONS Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS.
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Affiliation(s)
- Lara Stabinski
- *United States Department of State, Office of the US Global AIDS Coordinator and Health Diplomacy, Washington, DC; †Division of Viral Hepatitis, National Center for HIV/AIDS, STD, and TB Prevention, US Centers for Disease Control and Prevention, Atlanta, GA; ‡Office of HIV and AIDS, Bureau for Global Health, United States Agency for International Development, Washington, DC; §US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD; and ‖The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD
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Maldonado-Rodriguez A, Cevallos AM, Rojas-Montes O, Enriquez-Navarro K, Alvarez-Muñoz MT, Lira R. Occult hepatitis B virus co-infection in human immunodeficiency virus-positive patients: A review of prevalence, diagnosis and clinical significance. World J Hepatol 2015; 7:253-260. [PMID: 25729480 PMCID: PMC4342607 DOI: 10.4254/wjh.v7.i2.253] [Citation(s) in RCA: 18] [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: 08/29/2014] [Revised: 10/22/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
The prevalence of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection is high as they share similar mechanisms of transmission. The development and widespread use of highly sensitive tests for HBV diagnosis has demonstrated that a significant proportion of apparently healthy individuals with evidence of exposure to HBV continue to carry fully functional HBV DNA in their hepatocytes, a situation that predisposes them to the development of progressive liver disease and hepatocellular carcinoma. The presence of co-infections frequently influences the natural evolution of each of the participating infections present by either facilitating their virulence or competing for resources. Furthermore, the drugs used to treat these infections may also contribute to changes in the natural course of these infections, making the analysis of the impact of co-infection more difficult. The majority of studies has examined the impact of HIV on overt chronic hepatitis B, finding that co-infection carries an increased risk of progressive liver disease and the development of hepatocellular carcinoma. Although the effect of HIV on the natural history of occult hepatitis B infection (OBI) has not been fully assessed, all available data suggest a persisting risk of repeated flares of hepatitis and progressive liver disease. We describe studies regarding the diagnosis, prevalence and clinical significance of OBI in HIV-positive patients in this short review. Discrepancies in worldwide prevalence show the urgent need for the standardization of diagnostic criteria, as established by the Taormina statements. Ideally, standardized protocols for testing should be employed to enable the comparison of data from different groups. Additional studies are needed to define the differences in risk for OBI without HIV and in HIV-HBV co-infected patients with or without overt disease.
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Hepatitis B virus infection in post-vaccination South Africa: occult HBV infection and circulating surface gene variants. J Clin Virol 2014; 63:12-7. [PMID: 25600597 DOI: 10.1016/j.jcv.2014.11.032] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Revised: 11/19/2014] [Accepted: 11/24/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVE The aim of this study was to investigate the prevalence of occult hepatitis B virus (HBV) infection and the HBV surface (S) gene variants circulating in the South African population after nearly two decades of universal hepatitis B vaccination. STUDY DESIGN From a previous serosurvey, 201 serum samples with serological evidence of exposure to HBV were identified and these were stratified into post- and pre-vaccine introduction populations. For all samples, HBV DNA was screened and quantified using a real-time PCR assay and results analysed together with HBV serological markers. Where HIV results were available, subset analysis was performed. The HBV S gene was PCR-amplified and sequences analysed for a total of 37 isolates. RESULTS The prevalence of occult HBV infection reduced from 70.4% in the pre-vaccine introduction era to 66.0% post-vaccine introduction. There was an association between HIV infection and an increase in prevalence of occult HBV infection within the post-vaccine introduction population, although this was not statistically significant. Furthermore, sequence analysis revealed the following HBV subgenotypes; A1 (n=34), A2 (n=2) and a rare D4 isolate. HBV S gene variants, including diagnostic escape mutants were isolated. CONCLUSION There was a decline in the prevalence of occult HBV infection in post-vaccination South Africa, although the disease burden remains significant in the HIV co-infected population. After nearly two decades of a universal hepatitis B vaccination programme, no positive selection of vaccine escape mutants were observed.
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Mudawi H, Hussein W, Mukhtar M, Yousif M, Nemeri O, Glebe D, Kramvis A. Overt and occult hepatitis B virus infection in adult Sudanese HIV patients. Int J Infect Dis 2014; 29:65-70. [DOI: 10.1016/j.ijid.2014.07.004] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Revised: 03/31/2014] [Accepted: 07/03/2014] [Indexed: 12/14/2022] Open
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Yousif M, Mudawi H, Hussein W, Mukhtar M, Nemeri O, Glebe D, Kramvis A. Genotyping and virological characteristics of hepatitis B virus in HIV-infected individuals in Sudan. Int J Infect Dis 2014; 29:125-32. [PMID: 25449246 DOI: 10.1016/j.ijid.2014.07.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Revised: 06/19/2014] [Accepted: 07/02/2014] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common routes of blood-borne transmission. In HBV mono-infected Sudanese individuals, genotypes D, E, and A circulate. The objective of this study was to molecularly characterize HBV from HBV/HIV co-infected individuals. METHODS The polymerase overlapping the S region and the basic core promoter (BCP/PC) of HBV from 32 hepatitis B surface antigen (HBsAg)-positive and 18 HBsAg-negative serum samples were amplified and sequenced. RESULTS HBV from 37 samples was successfully genotyped and the genotype distribution was 46.0% D, 21.6% E, 18.9% A, and 13.5% D/E recombinant. Compared to mono-infected individuals, the frequencies of the D/E recombinant and genotype A were higher in HBV/HIV co-infected patients, as was the intra-group divergence of genotype E. BCP/PC mutations affecting hepatitis B e antigen (HBeAg) expression at the transcriptional and translational levels were detected. Two HBsAg-positive individuals had pre-S deletion mutants. The following mutations in the S region could account for the HBsAg negativity: sM133T, sE164G, sV168G, and sS174N. No primary drug resistance mutations were found. CONCLUSIONS In HBV/HIV co-infected Sudanese patients, the ratio of genotype A to non-A was higher than that in mono-infected patients. The genotype E intra-group divergence in HBV/HIV co-infected individuals was significantly higher than that in HBV mono-infected patients.
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Affiliation(s)
- Mukhlid Yousif
- Hepatitis Virus Diversity Research Programme, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, South Africa
| | - Hatim Mudawi
- Department of Medicine, Faculty of Medicine, University of Khartoum, Khartoum, Sudan
| | - Waleed Hussein
- Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan
| | - Maowia Mukhtar
- Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan
| | - Omer Nemeri
- College of Medicine, Bahri University, Khartoum, Sudan
| | - Dieter Glebe
- Institute of Medical Virology, National Reference Centre of Hepatitis B and D, Justus Liebig-University of Giessen, Giessen, Germany
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Programme, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, South Africa.
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Powell EA, Gededzha MP, Rentz M, Rakgole NJ, Selabe SG, Seleise TA, Mphahlele MJ, Blackard JT. Mutations associated with occult hepatitis B in HIV-positive South Africans. J Med Virol 2014; 87:388-400. [PMID: 25164924 DOI: 10.1002/jmv.24057] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/27/2014] [Indexed: 12/16/2022]
Abstract
Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV-positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult-associated mutations-those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references-were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult-associated mutations were identified. Ten occult-associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult-associated mutations at the same residue. Occult-associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro.
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Affiliation(s)
- Eleanor A Powell
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Musyoki AM, Msibi TL, Motswaledi MH, Selabe SG, Monokoane TS, Mphahlele MJ. Active co-infection with HBV and/or HCV in South African HIV positive patients due for cancer therapy. J Med Virol 2014; 87:213-21. [PMID: 25156907 DOI: 10.1002/jmv.24055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/27/2014] [Indexed: 01/20/2023]
Abstract
Human immunodeficiency virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) share routes of transmission. There is limited data on the incidence of active co-infection with HBV and/or HCV in cancer patients infected with HIV in Africa. This was a prospective study based on 34 patients with varied cancer diagnosis, infected with HIV and awaiting cancer therapy in South Africa. HIV viral load, CD4+ cell counts, Alanine-aminotransferase and aspartate aminotransferase levels were tested. Exposure to HBV and HCV was assessed serologically using commercial kits. Active HBV and/or HCV co-infection was detected using viral specific nested PCR assays. HCV 5'-UTR PCR products were sequenced to confirm active HCV infection. Active viral infection was detected in 64.7% of patients for HBV, 38.2% for HCV, and 29.4% for both HBV and HCV. Occult HBV infection was observed in 63.6% of the patients, while seronegative HCV infection was found in 30.8% of patients. In addition, CD4+ cell count < 350 cells/µl was not a risk factor for increased active HBV, HCV or both HBV and HCV co-infections. A total of 72.7%, 18.2% and 9.1% of the HCV sequences were assigned genotype 5, 1 and 4 respectively.The study revealed for the first time a high active HBV and/or HCV co-infection rate in cancer patients infected with HIV. The findings call for HBV and HCV testing in such patients, and where feasible, appropriate antiviral treatment be indicated, as chemotherapy or radiotherapy has been associated with reactivation of viral hepatitis and termination of cancer therapy.
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Affiliation(s)
- Andrew M Musyoki
- HIV and Hepatitis Research Unit, Department of Virology, University of Limpopo (Medunsa Campus) and National Health Laboratory Service, Pretoria, South Africa
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Matthews PC, Geretti AM, Goulder PJR, Klenerman P. Epidemiology and impact of HIV coinfection with hepatitis B and hepatitis C viruses in Sub-Saharan Africa. J Clin Virol 2014; 61:20-33. [PMID: 24973812 DOI: 10.1016/j.jcv.2014.05.018] [Citation(s) in RCA: 101] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2014] [Revised: 05/22/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023]
Abstract
Human immunodeficiency virus (HIV), Hepatitis B (HBV) and Hepatitis C (HCV) are blood-borne viruses with potentially shared routes of transmission. In high-income settings, the impact of antiretroviral therapy (ART) on survival has unmasked chronic liver disease from viral hepatitis B or hepatitis C as a leading cause of morbidity and mortality in individuals with HIV infection. It is now feared that progressive liver disease may threaten the success of ART programmes in developing countries, where HCV or HBV testing and monitoring are not yet systematic among HIV-infected patients and ART use is generally blind to these co-infections. We set out to review recent data from Sub-Saharan Africa, in order to build a detailed and up-to-date picture of the epidemiology and emerging impact of HBV and HCV coinfection in countries at the heart of the HIV pandemic. There is a preponderance of HIV/HBV coinfection compared to HIV/HCV in this region, and significant caveats exist regarding the accuracy of published HCV seroprevalence surveys. Morbidity and mortality of coinfection is significant, and may be further enhanced in African populations due to the influence of host, viral and environmental factors. Careful scrutiny of the coinfection problem is vital to inform an approach to directing resources, planning public health initiatives, providing clinical care, and guiding future research.
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Affiliation(s)
- Philippa C Matthews
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
| | - Anna Maria Geretti
- Institute of Infection and Global Health, University of Liverpool, 8 West Derby Street, Liverpool L69 7BE, UK
| | - Philip J R Goulder
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Department of Paediatrics, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK
| | - Paul Klenerman
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK; NIHR Biomedical Research Centre, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK
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Coffin CS, Mulrooney-Cousins PM, Osiowy C, van der Meer F, Nishikawa S, Michalak TI, van Marle G, Gill MJ. Virological characteristics of occult hepatitis B virus in a North American cohort of human immunodeficiency virus type 1-positive patients on dual active anti-HBV/HIV therapy. J Clin Virol 2014; 60:347-53. [PMID: 24881491 DOI: 10.1016/j.jcv.2014.04.021] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Revised: 03/10/2014] [Accepted: 04/25/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) is defined as low-level HBV DNA presence in serum, liver and/or peripheral blood mononuclear cells (PBMC) in individuals that lack serum hepatitis B virus surface antigen (HBsAg). HIV+ patients with OBI may be at risk for HBV reactivation, and often receive dual active anti-HBV/HIV therapy, such as lamivudine (LMV). OBJECTIVES To determine the presence of OBI in a North American cohort of HIV-1-positive patients. STUDY DESIGN/METHODS 45 HIV-1-positive, serum HBsAg-negative patients, reactive for antibodies to HBV core antigen (anti-HBc), were tested for HBV DNA in plasma and for HBV DNA and covalently closed circular DNA (cccDNA) in PBMC. Ten patients were re-tested after ∼5-10 years, including genotyping and clonal sequence analysis of the HBV polymerase (P) gene and overlapping HBV surface (S) gene from 8 PBMC samples. RESULTS Overall, 42% (19/45) tested HBV DNA positive, especially in PBMC (18/45), including 3/18 that were reactive for HBV cccDNA, compared to 17% (8/45) that were HBV DNA reactive in plasma. In 8 patients on LMV, sequence analysis in PBMC showed that all were HBV genotype C or D. Several carried HBV P region variants at residues associated with anti-HBV drug resistance and overlapping S gene region within the major HBsAg "a determinant". CONCLUSION OBI is common in HIV-positive, anti-HBc reactive patients on anti-HBV/HIV therapy, particularly in PBMC. HBV sequence analysis revealed that all had HBV genotype C or D and often had P/overlapping S gene variants possibly associated with dual-active anti-HIV/HBV therapy.
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Affiliation(s)
- Carla S Coffin
- Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
| | - Patricia M Mulrooney-Cousins
- Molecular Virology and Hepatology Research Group, Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada
| | - Carla Osiowy
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
| | - Frank van der Meer
- Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; Faculty of Veterinary Medicine, University of Calgary, AB, Canada
| | - Sandra Nishikawa
- Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Tomasz I Michalak
- Molecular Virology and Hepatology Research Group, Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada
| | - Guido van Marle
- Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - M John Gill
- Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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HBV whole-genome mutation profile in HIV-1/HBV coinfected patients in a long-term follow-up study. Infection 2014; 42:675-87. [PMID: 24700252 DOI: 10.1007/s15010-014-0616-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Accepted: 03/17/2014] [Indexed: 12/23/2022]
Abstract
PURPOSE Human immunodeficiency virus (HIV-1)-infected patients frequently harbour hepatitis B and C viruses (HBV and HCV, respectively). Possible modifications of the natural history of hepatitis B may occur. The aim of this study was to characterise HBV diversity and evolutionary and mutational viral genome profiles in HIV-1/HBV coinfections. METHODS HIV-1 and HBV markers determinations (Roche, FRG; Abbott, USA) and HBV genome-length retrospective analysis were performed in follow-up isolates from patients who were either stably HBsAg-negative with a low level of HBV DNA (occult hepatitis B infection, OBI) or HBsAg-positive with a high level of HBV DNA. Phylogenetic analysis (maximum likelihood method, MEGA5), statistical analysis and evolutionary rates calculation (d S/d N) were applied. RESULTS Positive selection pressures in the PreS/S region and a significantly higher number of mutations in this region including the major hydrophilic region (MHR) and the "a" determinant were shown in HBsAg-negative (possibly OBI) compared to stably HBsAg-positive HIV-1/HBV subgenotypes D3/A2 coinfected patients. Mutants previously described in HIV-1/HBV coinfected patients were found. Known mutants Y100C, P127T and P120A associated to Y134H and S143T and new S mutants, which may potentially affect HBsAg expression and secretion and anti-HBs binding, were detected in baseline sera persisting up to the end of 9 years follow-up. Known mutations of BCP, Pre-C, C and X regions were also characterised. Natural mutants strictly known as being involved in diagnostic failure were not detected; however, numerous corresponding sites showed amino acid variations. CONCLUSIONS Evolutionary and genotypic differences observed, particularly in the PreS/S region, between HBsAg-negative (OBI) and HBsAg-positive HIV-1/HBV coinfected patients, may contribute, in association with mutations of other genomic regions, to the HBsAg-negative phenotype.
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Prevalence of occult hepatitis B virus infection in a cohort of HIV-positive patients resident in Sicily, Italy. BIOMED RESEARCH INTERNATIONAL 2013; 2013:859583. [PMID: 24063015 PMCID: PMC3770005 DOI: 10.1155/2013/859583] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 07/12/2013] [Accepted: 07/25/2013] [Indexed: 12/18/2022]
Abstract
Occult hepatitis B virus (OBI) in HIV-infected groups is still debated, as well as the associated risk-factors and clinical significance.
In this paper, we examined a total of 405 HBsAg-negative/HIV-infected patients enrolled from January 2007 to December 2009. Overall, the prevalence of OBI was 5.9% (95% confidence interval (CI95%): 3.8–8.7%); it was more frequently associated with “anti-HBc alone” serological marker (11.3%; adjusted odds ratio = 3.7, CI95%: 1.4–9.8), although it was also detected in the absence of any HBV serological marker (4.9%; CI95%: 2.3–9.1%). A low prevalence of anti-HCV-positive patients with OBI was found (3.1%; CI95%: 0.6–8.7%). HIV RNA plasma levels or other immunological/clinical characteristics were not significantly associated with OBI. All but one occult HBV infections were sustained by genotype D viral strains. OBI is relatively frequent in HIV-infected patients, although it does not seem to exert a relevant clinical impact. Viral genotypes in occult HBV infections reflect those circulating in the Mediterranean area.
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Ochwoto M, Chauhan R, Gopalakrishnan D, Chen CY, Ng'ang'a Z, Okoth F, Kioko H, Kimotho J, Kaiguri P, Kramvis A. Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya. INFECTION GENETICS AND EVOLUTION 2013; 20:103-10. [PMID: 23978387 DOI: 10.1016/j.meegid.2013.08.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2013] [Revised: 08/15/2013] [Accepted: 08/18/2013] [Indexed: 12/17/2022]
Abstract
Hepatitis B virus (HBV) genotypes are important in both the clinical manifestation of disease and treatment response. Although Kenya belongs to the African Region (AFR-E) characterized by high mortality and hyperendemicity of HBV, there is a paucity of HBV genotyping data. The aim of this study was to molecularly characterize the basic core promoter/precore (BCP/PC) and complete surface (S) regions of HBV isolated from 61 HBsAg-positive liver disease patients attending Kenyatta National Hospital in Nairobi. HBsAg, HBeAg and viral loads were determined. HBV DNA was amplified and sequenced from 58/61 patients. In addition to the complete genome of two isolates, the BCP/PC and the complete S regions of 43 and 38 isolates, respectively were sequenced. Following phylogenetic analysis of the S region, 38 isolates clustered with subgenotype A1, whereas two isolates clustered with genotype D, one with subgenotype D1 and another as an outlier of the clade containing subgenotype D6 and the D/E recombinant. When the complete genome of the latter isolate was sequenced it clustered with D6. The majority of isolates belonged to serological subtype adw2 and only four to ayw2. Three distinct groups of subgenotype A1, distinguished by different amino acid motifs, circulate in Kenya: two in the African cluster and a monophyletic clade in the "Asian" cluster. HBeAg-negativity was a result of G1896A in genotype D isolates, whereas in subgenotype A1, the HBeAg-negativity was a result of mutations in the Kozak region (1809-1812) or precore start codon (1814-1816). Mutations at positions 1762 and 1764 occurred more frequently in HCC patients (p<0.05). In conclusion, subgenotypes A1, D1 and D6 circulate in liver disease patients in Kenya, with A1 predominating.
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Affiliation(s)
- Missiani Ochwoto
- Hepatitis Virus Diversity Research Programme (HVDRP), Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Kenya Medical Research Institute (KEMRI), Kenya; Jomo Kenyatta University of Agriculture and Technology (JKUAT), Kenya.
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Molecular characterization of hepatitis B virus in liver disease patients and asymptomatic carriers of the virus in Sudan. BMC Infect Dis 2013; 13:328. [PMID: 23865777 PMCID: PMC3722059 DOI: 10.1186/1471-2334-13-328] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Accepted: 07/16/2013] [Indexed: 12/12/2022] Open
Abstract
Background Hepatitis B virus is hyperendemic in Sudan. Our aim was to molecularly characterize hepatitis B virus from Sudanese individuals, with and without liver disease, because genotypes play an important role in clinical manifestation and treatment management. Methods Ninety-nine patients - 30 asymptomatic, 42 cirrhotic, 15 with hepatocellular carcinoma, 7 with acute hepatitis and 5 with chronic hepatitis- were enrolled. Sequencing of surface and basic core promoter/precore regions and complete genome were performed. Results The mean ± standard deviation, age was 45.7±14.8 years and the male to female ratio 77:22. The median (interquartile range) of hepatitis B virus DNA and alanine aminotransferase levels were 2.8 (2.2-4.2) log IU/ml and 30 (19–49) IU/L, respectively. Using three genotyping methods, 81/99 (82%) could be genotyped. Forty eight percent of the 99 patients were infected with genotype D and 24% with genotype E, 2% with putative D/E recombinants and 7% with genotype A. Patients infected with genotype E had higher frequency of hepatitis B e antigen-positivity and higher viral loads compared to patients infected with genotype D. Basic core promoter/precore region mutations, including the G1896A in 37% of HBeAg-negative individuals, could account for hepatitis B e antigen-negativity. Pre-S deletion mutants were found in genotypes D and E. Three isolates had the vaccine escape mutant sM133T. Conclusion Sudanese hepatitis B virus carriers were mainly infected with genotypes D or E, with patients infected with genotype E having higher HBeAg-positivity and higher viral loads. This is the first study to molecularly characterize hepatitis B virus from liver disease patients in Sudan.
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Makondo E, Bell TG, Kramvis A. Genotyping and molecular characterization of hepatitis B virus from human immunodeficiency virus-infected individuals in southern Africa. PLoS One 2012; 7:e46345. [PMID: 23029487 PMCID: PMC3460816 DOI: 10.1371/journal.pone.0046345] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2012] [Accepted: 08/30/2012] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) are hyperendemic in sub-Saharan Africa. The HBV genotypes prevailing in HIV-infected Africans are unknown. Our aim was to determine the HBV genotypes in HIV-infected participants and to identify clinically significant HBV mutations. From 71 HBV DNA+ve HIV-infected participants, 49 basic core promoter/precore (BCP/PC) and 29 complete S regions were successfully sequenced. Following phylogenetic analysis of 29 specimens in the complete S region, 28 belonged to subgenotype A1 and one to D3. Mutations affecting HBeAg expression at the transcriptional (1762T1764A), translational (Kozak 1809–1812, initiation 1814–1816, G1896A with C1858T), or post translational levels (G1862T), were responsible for the high HBeAg-negativity observed. The G1862T mutation occurred only in subgenotype A1 isolates, which were found in one third (7/21) of HBsAg−ve participants, but in none of the 18 HBsAg+ve participants (p<0.05). Pre-S deletion mutants were detected in four HBsAg+ve and one HBsAg−ve participant/s. The following mutations occurred significantly more frequently in HBV isolated in this study than in strains of the same cluster of the phylogenetic tree: ps1F25L, ps1V88L/A; ps2Q10R, ps2 R48K/T, ps2A53V and sQ129R/H, sQ164A/V/G/D, sV168A and sS174N (p<0.05). ps1I48V/T occurred more frequently in females than males (p<0.05). Isolates with sV168A occurred more frequently in participants with viral loads >200 IU per ml (p<0.05) and only sS174N occurred more frequently in HBsAg−ve than in HBsAg+ve individuals (p<0.05). Prior to initiation of ART, ten percent, 3 of 29 isolates sequenced, had drug resistance mutations rtV173L, rtL180M+rtM204V and rtV214A, respectively. This study has provided important information on the molecular characteristics of HBV in HIV-infected southern Africans prior to ART initiation, which has important clinical relevance in the management of HBV/HIV co-infection in our unique setting.
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Affiliation(s)
| | | | - Anna Kramvis
- Hepatitis Virus Diversity Research Programme, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa
- * E-mail:
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