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Abdul Majeed N, Zehnder B, Koh C, Heller T, Urban S. Hepatitis delta: Epidemiology to recent advances in therapeutic agents. Hepatology 2023; 78:1306-1321. [PMID: 36738087 DOI: 10.1097/hep.0000000000000331] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/19/2022] [Indexed: 02/05/2023]
Abstract
Hepatitis D virus (HDV) was first described in 1977 and is dependent on the presence of hepatitis B surface antigen (HBsAg) for its entry into cells and on the human host for replication. Due to the envelopment with the hepatitis B virus (HBV) envelope, early phases of HDV entry resemble HBV infection. Unlike HBV, HDV activates innate immune responses. The global prevalence of HDV is estimated to be about 5% of HBsAg positive individuals. However, recent studies have described a wide range of prevalence between 12 to 72 million individuals. Infection can occur as super-infection or co-infection. The diagnosis of active HDV infection involves screening with anti HDV antibodies followed by quantitative PCR testing for HDV RNA in those who are HBsAg positive. The diagnostic studies have evolved over the years improving the validity and reliability of the tests performed. HDV infection is considered the most severe form of viral hepatitis and the HDV genotype may influence the disease course. There are eight major HDV genotypes with prevalence varying by geographic region. HDV treatment has been challenging as HDV strongly depends on the host cell for replication and provides few, if any viral targets. Better understanding of HDV virology has led to the development of several therapeutic agents currently being studied in different phase II and III clinical trials. There is increasing promise of effective therapies that will ameliorate the course of this devastating disease.
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Affiliation(s)
- Nehna Abdul Majeed
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Benno Zehnder
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Stephan Urban
- Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany
- German Center for Infection Research (DZIF) - Heidelberg Partner Site, Heidelberg, Germany
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Sagnelli C, Pisaturo M, Curatolo C, Codella AV, Coppola N, Sagnelli E. Hepatitis B virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic. World J Gastroenterol 2021; 27:7271-7284. [PMID: 34876788 PMCID: PMC8611207 DOI: 10.3748/wjg.v27.i42.7271] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 06/20/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis D virus (HDV) is a defective liver-tropic virus that needs the helper function of hepatitis B virus (HBV) to infect humans and replicate. HDV is transmitted sexually or by a parenteral route, in co-infection with HBV or by super-infection in HBV chronic carriers. HDV infection causes acute hepatitis that may progress to a fulminant form (7%-14% by super-infection and 2%-3% by HBV/HDV co-infection) or to chronic hepatitis (90% by HDV super-infection and 2%-5% by HBV/HDV co-infection), frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma (HCC). Peg-interferon alfa the only recommended therapy, clears HDV in only 10%-20% of cases and, consequently, new treatment strategies are being explored. HDV endemicity progressively decreased over the 50 years from the identification of the virus, due to improved population lifestyles and economic levels, to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs. Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic, unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments, lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, University of Campania, Naples 80135, Italy
| | - Caterina Curatolo
- Department of Mental Health and Public Medicine, University of Campania, Naples 80135, Italy
| | - Alessio Vinicio Codella
- Department of Mental Health and Public Medicine, University of Campania, Naples 80135, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, University of Campania, Naples 80135, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
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Sagnelli C, Sagnelli E, Russo A, Pisaturo M, Occhiello L, Coppola N. HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges. Life (Basel) 2021; 11:169. [PMID: 33671730 PMCID: PMC7926847 DOI: 10.3390/life11020169] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/18/2021] [Accepted: 02/18/2021] [Indexed: 02/06/2023] Open
Abstract
Several investigations have been published on Hepatitis Delta Virus (HDV) infection in recent years, from which we have drawn the salient data to provide readers with useful information to improve their knowledge on the subject. HDV genotypes 5-8 have been recently imported to Western countries from central Africa, whose clinical relevance deserves further investigation. Ongoing HDV replication has been identified as an independent predictor of progression to cirrhosis and HCC for patients with HDV chronic hepatitis (HDV-CH). Long-term treatments of HDV-CH with standard or pegylated interferon alfa (peg-IFN-α) have all been unsatisfactory, leading to a sustained virological response (SVR) only in 20-30% of patients treated, faced with a poor tolerability and frequent serious adverse reactions; the addition of HBV nucleo(s)tide analogues to peg-IFN- α did not improve the rate of SVR. The improved knowledge of the HDV life cycle has allowed the development of direct acting agents towards key-points of the HDV life cycle, namely bulevirtide, lonafarnib and nucleic acid polymers. Preliminary data have shown that these drugs are more effective than interferon-based therapies, but adverse reactions are also common, which however seem toned down in combination therapy with other antivirals.
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Affiliation(s)
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (C.S.); (A.R.); (M.P.); (L.O.); (N.C.)
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Stockdale AJ, Kreuels B, Henrion MRY, Giorgi E, Kyomuhangi I, Geretti AM. Hepatitis D prevalence: problems with extrapolation to global population estimates. Gut 2020; 69:396-397. [PMID: 30567743 DOI: 10.1136/gutjnl-2018-317874] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 11/26/2018] [Accepted: 11/27/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Alexander J Stockdale
- Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.,Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
| | - Benno Kreuels
- Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.,Department of Tropical Medicine, 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marc R Y Henrion
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.,Liverpool School of Tropical Medicine, Liverpool, UK
| | - Emanuele Giorgi
- Centre for Health Informatics, Computing, and Statistics, University of Lancaster, Lancaster, UK
| | - Irene Kyomuhangi
- Centre for Health Informatics, Computing, and Statistics, University of Lancaster, Lancaster, UK
| | - Anna Maria Geretti
- Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
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Da BL, Heller T, Koh C. Hepatitis D infection: from initial discovery to current investigational therapies. Gastroenterol Rep (Oxf) 2019; 7:231-245. [PMID: 32477569 DOI: 10.1093/gastro/goz023] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 03/15/2019] [Accepted: 05/09/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis D is the most severe form of viral hepatitis associated with a more rapid progression to cirrhosis and an increased risk of hepatocellular carcinoma and mortality compared with hepatitis B mono-infection. Although once thought of as a disappearing disease, hepatitis D is now becoming recognized as a serious worldwide issue due to improvement in diagnostic testing and immigration from endemic countries. Despite these concerns, there is currently only one accepted medical therapy (pegylated-interferon-α) for the treatment of hepatitis D with less than desirable efficacy and significant side effects. Due to these reasons, many patients never undergo treatment. However, increasing knowledge about the virus and its life cycle has led to the clinical development of multiple promising new therapies that hope to alter the natural history of this disease and improve patient outcome. In this article, we will review the literature from discovery to the current investigational therapies.
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Affiliation(s)
- Ben L Da
- Digestive Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
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Jackson K, MacLachlan J, Cowie B, Locarnini S, Bowden S, Higgins N, Karapanagiotidis T, Nicholson S, Littlejohn M. Epidemiology and phylogenetic analysis of hepatitis D virus infection in Australia. Intern Med J 2019; 48:1308-1317. [PMID: 29761607 DOI: 10.1111/imj.13967] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 05/08/2018] [Accepted: 05/08/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND The incidence and trends of the hepatitis D virus (HDV) in Australia have not been recently assessed, and the circulating genotypes have never been determined. AIM To characterise the current virology and epidemiology of HDV. METHODS Notifiable disease surveillance and laboratory testing data were analysed to assess demographics, risk factors and trends. HDV serology and RNA testing were performed on requested samples from 2010 to 2016. Sequencing of a 500-nucleotide amplicon of the delta antigen and phylogenetic analysis of the strains from 2009 to 2016 were also conducted. RESULTS Ninety HDV notifications were reported to the Victorian Department of Health and Human Services between 2010 and 2016. The majority (64.4%) of those diagnosed were born overseas, most commonly in Sudan, Pakistan and Vietnam. Over the same period, 190 patients tested positive for anti-HDV serology and 166 for HDV RNA. Sequencing of isolates from 169 individuals between 2009 and 2016 found that 80.5% strains were genotype 1, 16% genotype 5 and 3.5% genotype 2. Phylogenetic analysis confirmed the relatedness of strains from birth country, demonstrated the presence of the 'Pacific Island' genotype 1 strain in Queensland and supported possible transmission in correctional facilities and within families. CONCLUSIONS This study demonstrates the ongoing need for routine HDV screening and engagement in clinical care for people living with HBV in Australia. Epidemiological findings highlight the diversity in those affected and provide insights into local and global geographic distribution and transmission patterns.
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Affiliation(s)
- Kathy Jackson
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Jennifer MacLachlan
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Benjamin Cowie
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Scott Bowden
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Nasra Higgins
- Department of Health and Human Services Victoria, Melbourne, Victoria, Australia
| | - Theo Karapanagiotidis
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Suellen Nicholson
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Margaret Littlejohn
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
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Howell J, Pedrana A, Cowie BC, Doyle J, Getahun A, Ward J, Gane E, Cunningham C, Wallace J, Lee A, Malani J, Thompson A, Hellard ME. Aiming for the elimination of viral hepatitis in Australia, New Zealand, and the Pacific Islands and Territories: Where are we now and barriers to meeting World Health Organization targets by 2030. J Gastroenterol Hepatol 2019; 34:40-48. [PMID: 30151932 DOI: 10.1111/jgh.14457] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 07/18/2018] [Accepted: 08/15/2018] [Indexed: 12/16/2022]
Abstract
Viral hepatitis affects more than 320 million people globally, leading to significant morbidity and mortality due to liver failure and hepatocellular carcinoma (HCC). More than 248 million people (3.2% globally) are chronically infected with hepatitis B virus (HBV), and an estimated 80 million people (1.1% globally) are chronically infected with hepatitis C virus (HCV). In 2015, more than 700 000 deaths were directly attributable to HBV, and nearly 500 000 deaths were attributable to HCV infection; 2-5% of HBV-infected people develop HCC per annum irrespective of the presence of cirrhosis, whereas 1-5% HCV-infected people with advanced fibrosis develop HCC per annum. The rapidly escalating global mortality related to HBV and HCV related viral hepatitis to be the 7th leading cause of death worldwide in 2013, from 10th leading cause in 1990. Australia, New Zealand, and Pacific Island Countries and Territories fall within the World Health Organization Western Pacific Region, which has a high prevalence of viral hepatitis and related morbidity, particularly HBV. Remarkably, in this region, HBV-related mortality is greater than for tuberculosis, HIV infection, and malaria combined. The region provides a unique contrast in viral hepatitis prevalence, health system resources, and approaches taken to achieve World Health Organization global elimination targets for HBV and HCV infection. This review highlights the latest evidence in viral hepatitis epidemiology and explores the health resources available to combat viral hepatitis, focusing on the major challenges and critical needs to achieve elimination in Australia, New Zealand, and Pacific Island Countries and Territories.
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Affiliation(s)
- Jess Howell
- Disease Elimination, Burnet Institute, Melbourne, Victoria, Australia.,School of Population Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.,Department of Gastroenterology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Alisa Pedrana
- Disease Elimination, Burnet Institute, Melbourne, Victoria, Australia
| | - Benjamin C Cowie
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.,WHO Collaborating Centre for Viral Hepatitis, Doherty Institute, Melbourne, Victoria, Australia.,Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Joseph Doyle
- Disease Elimination, Burnet Institute, Melbourne, Victoria, Australia.,Department of Infectious Diseases, Alfred Health, Melbourne, Victoria, Australia.,School of Population Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Aneley Getahun
- School of Public Health and Primary Care, Fiji National University, Suva, Fiji
| | - James Ward
- Head Aboriginal Health, Infection and Immunity, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.,Matthew Flinders Fellow, Flinders University Adelaide, Adelaide, South Australia, Australia
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, and Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Chris Cunningham
- Research Centre for Maõri Health and Development, Massey University, Wellington, New Zealand
| | - Jack Wallace
- Disease Elimination, Burnet Institute, Melbourne, Victoria, Australia.,Australian Research Centre in Sex, Health and Society, La Trobe University, Melbourne, Victoria, Australia
| | - Alice Lee
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, University of Sydney, Camperdown, New South Wales, Australia.,Hepatitis B Free, Australia
| | - Jioji Malani
- School of Public Health and Primary Care, Fiji National University, Suva, Fiji
| | - Alex Thompson
- Department of Gastroenterology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.,Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Margaret E Hellard
- Disease Elimination, Burnet Institute, Melbourne, Victoria, Australia.,Department of Infectious Diseases, Alfred Health, Melbourne, Victoria, Australia.,School of Population Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
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White SL, Rawlinson W, Boan P, Sheppeard V, Wong G, Waller K, Opdam H, Kaldor J, Fink M, Verran D, Webster A, Wyburn K, Grayson L, Glanville A, Cross N, Irish A, Coates T, Griffin A, Snell G, Alexander SI, Campbell S, Chadban S, Macdonald P, Manley P, Mehakovic E, Ramachandran V, Mitchell A, Ison M. Infectious Disease Transmission in Solid Organ Transplantation: Donor Evaluation, Recipient Risk, and Outcomes of Transmission. Transplant Direct 2019; 5:e416. [PMID: 30656214 PMCID: PMC6324914 DOI: 10.1097/txd.0000000000000852] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 08/15/2018] [Indexed: 12/11/2022] Open
Abstract
In 2016, the Transplantation Society of Australia and New Zealand, with the support of the Australian Government Organ and Tissue authority, commissioned a literature review on the topic of infectious disease transmission from deceased donors to recipients of solid organ transplants. The purpose of this review was to synthesize evidence on transmission risks, diagnostic test characteristics, and recipient management to inform best-practice clinical guidelines. The final review, presented as a special supplement in Transplantation Direct, collates case reports of transmission events and other peer-reviewed literature, and summarizes current (as of June 2017) international guidelines on donor screening and recipient management. Of particular interest at the time of writing was how to maximize utilization of donors at increased risk for transmission of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, given the recent developments, including the availability of direct-acting antivirals for hepatitis C virus and improvements in donor screening technologies. The review also covers emerging risks associated with recent epidemics (eg, Zika virus) and the risk of transmission of nonendemic pathogens related to donor travel history or country of origin. Lastly, the implications for recipient consent of expanded utilization of donors at increased risk of blood-borne viral disease transmission are considered.
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Affiliation(s)
- Sarah L White
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
| | - William Rawlinson
- Serology and Virology Division, NSW Health Pathology Prince of Wales Hospital, Sydney, Australia
- Women's and Children's Health and Biotechnology and Biomolecular Sciences, University of New South Wales Schools of Medicine, Sydney, Australia
| | - Peter Boan
- Departments of Infectious Diseases and Microbiology, Fiona Stanley Hospital, Perth, Australia
- PathWest Laboratory Medicine, Perth, Australia
| | - Vicky Sheppeard
- Communicable Diseases Network Australia, New South Wales Health, Sydney, Australia
| | - Germaine Wong
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Karen Waller
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
| | - Helen Opdam
- Austin Health, Melbourne, Australia
- The Organ and Tissue Authority, Australian Government, Canberra, Australia
| | - John Kaldor
- Kirby Institute, University of New South Wales, Sydney, Australia
| | - Michael Fink
- Austin Health, Melbourne, Australia
- Department of Surgery, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Deborah Verran
- Transplantation Services, Royal Prince Alfred Hospital, Sydney, Australia
| | - Angela Webster
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Kate Wyburn
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Lindsay Grayson
- Austin Health, Melbourne, Australia
- Department of Surgery, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Allan Glanville
- Department of Thoracic Medicine and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
| | - Nick Cross
- Department of Nephrology, Canterbury District Health Board, Christchurch Hospital, Christchurch, New Zealand
| | - Ashley Irish
- Department of Nephrology, Fiona Stanley Hospital, Perth, Australia
- Faculty of Health and Medical Sciences, UWA Medical School, The University of Western Australia, Crawley, Australia
| | - Toby Coates
- Renal and Transplantation, Royal Adelaide Hospital, Adelaide, Australia
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Anthony Griffin
- Renal Transplantation, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Greg Snell
- Lung Transplant, Alfred Health, Melbourne, Victoria, Australia
| | - Stephen I Alexander
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
| | - Scott Campbell
- Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Steven Chadban
- Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia
- Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
| | - Peter Macdonald
- Department of Cardiology, St Vincent's Hospital, Sydney, Australia
- St Vincent's Hospital Victor Chang Cardiac Research Institute, University of New South Wales, Sydney, Australia
| | - Paul Manley
- Kidney Disorders, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand
| | - Eva Mehakovic
- The Organ and Tissue Authority, Australian Government, Canberra, Australia
| | - Vidya Ramachandran
- Serology and Virology Division, NSW Health Pathology Prince of Wales Hospital, Sydney, Australia
| | - Alicia Mitchell
- Department of Thoracic Medicine and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
- Woolcock Institute of Medical Research, Sydney, Australia
- School of Medical and Molecular Biosciences, University of Technology, Sydney, Australia
| | - Michael Ison
- Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL
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Coghill S, McNamara J, Woods M, Hajkowicz K. Epidemiology and clinical outcomes of hepatitis delta (D) virus infection in Queensland, Australia. Int J Infect Dis 2018; 74:123-127. [PMID: 30003953 DOI: 10.1016/j.ijid.2018.07.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 07/03/2018] [Accepted: 07/04/2018] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES To investigate the epidemiology, clinical characteristics and outcomes of those with hepatitis delta virus (HDV) infection in Queensland, Australia. DESIGN Retrospective cohort study of individuals tested for HDV between 1997 and 2016 in the public healthcare system in Queensland. RESULTS 179 individuals recorded positive HDV serology between 1997 and 2016, with a total of 4407 individuals undergoing testing (seroprevalence 4.1%). The majority of HDV positive individuals were male and were born overseas. Those born in Africa had a higher risk ratio (RR) for HDV infection (RR, 1.55; 95% CI, 1.14-2.09); being born in Asia was associated with a relatively lower risk of HDV infection (RR, 0.36; 95% CI, 0.27-0.58). Positive hepatitis C virus (HCV) serology was significantly associated with positive HDV serology (RR, 2.98; 95% CI, 2.36-3.78). Of the HDV positive individuals born in Australia, the majority were HCV positive (69.8%). HDV positive individuals were less likely to be Hepatitis B e antigen (HBeAg) positive (RR, 0.64; 95% CI, 0.45-0.93) and recorded lower hepatitis B virus (HBV) viral loads. Positive HDV serology was associated with increased risk of liver cirrhosis (RR, 2.3; 95% CI 1.73-3.07) and liver transplantation (RR, 1.93; CI 1.31-2.85). Only 8% of HDV positive individuals underwent HDV treatment. CONCLUSIONS In Queensland, HDV seropositivity is associated with overseas birth, particularly in Africa. HDV infection is associated with decreased HBV viraemia and more advanced liver disease.
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Affiliation(s)
- Sarah Coghill
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia; School of Clinical Medicine, University of Queensland, Australia.
| | - John McNamara
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia
| | - Marion Woods
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia; School of Clinical Medicine, University of Queensland, Australia
| | - Krispin Hajkowicz
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia; School of Clinical Medicine, University of Queensland, Australia
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11
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Aftab M, Amin I, Idrees M, Ali A, Rafique S, Naz S. Molecular epidemiology of hepatitis delta and hepatitis B viruses circulating in two major provinces (East and North-West) of Pakistan. INFECTION GENETICS AND EVOLUTION 2018; 64:65-69. [PMID: 29906637 DOI: 10.1016/j.meegid.2018.06.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 06/05/2018] [Accepted: 06/09/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVES HBV and HDV are major public health problems with millions affected globally and Pakistan accounts for a significant proportion of the global Hepatitis burden. This cross sectional study was designed to assess the general epidemiological and virological features of HBV and HDV in the Punjab and Khyber Pakhtunkhawa (KP) provinces of Pakistan. METHODS A total of 1890 HBV patients from March 2016 to May 2017 were recruited in the study and the presence of HDV was retrospectively evaluated in all participants. Most participants were young adults (from 21 to 30 years). Genotyping was based on PCR amplification using primers specific for HBV genotypes A-F, and HDV. 405 nucleotide fragments of HDV were sequenced. MEGA was used for phylogenetic analysis. RESULTS Overall prevalence of HBV was 14.08% (266/1890). Higher prevalence was observed in males (66.85%) as compared to females (33.15%). Co-infection of HDV was found in 39 (14.66%) patients. HBV genotype-D was prevalent in dual infections followed by HDV/A (p < 0.05).While HDV genotype 1 was predominant in all HBV positive samples. Compared to Punjab, coinfection was higher in KP (14.3% versus15.2%; p < 0.05). CONCLUSION The prevalence of HBV and HDV is high in Pakistan. The description of HBV and HDV genotypes circulating in East and North-West Pakistan can contribute to a better understanding of their relevance in regional epidemics. These infections are highly endemic in the KP, where their control is confounded by its vast territorial dimension with small, hard-to-reach municipalities and diverse ethnic populations.
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Affiliation(s)
- Mahwish Aftab
- Department of Biotechnology, Lahore College For Women University, Lahore, Pakistan
| | - Iram Amin
- Division of Molecular Virology & Molecular Diagnostics, Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz, University Of The Punjab, Lahore, Pakistan
| | - Muhammad Idrees
- Division of Molecular Virology & Molecular Diagnostics, Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz, University Of The Punjab, Lahore, Pakistan; Hazara University, Mansehra, Pakistan.
| | - Amjad Ali
- Molecular Virology Laboratory, Centre for Applied Molecular Biology, 87 West Canal Bank Road, Thokar Niaz, University of the Punjab, Lahore, Pakistan.
| | - Shazia Rafique
- Division of Molecular Virology & Molecular Diagnostics, Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz, University Of The Punjab, Lahore, Pakistan.
| | - Shagufta Naz
- Department of Biotechnology, Lahore College For Women University, Lahore, Pakistan.
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Rizzetto M, Smedile A, Ciancio A. Hepatitis D. CLINICAL VIROLOGY 2016:1409-1423. [DOI: 10.1128/9781555819439.ch58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Abstract
The epidemiology of hepatitis B virus (HBV) infection is geographically diverse, with population prevalence, age and mode of acquisition, and likelihood of progression to chronic infection mutually interdependent. The burden of chronic HBV infection is increasingly being recognized, with cirrhosis and liver cancer attributable to HBV continuing to increase. The outcomes of chronic HBV infection are affected by a range of factors, including viral genotype, the presence of coinfections with other blood-borne viruses, and the impact of other causes of liver disease. The increased recognition of HBV infection as a leading cause of death globally has resulted in the development of new structures and policies at the international level; immediate attention to implementing these strategies is now required.
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Affiliation(s)
- Jennifer H MacLachlan
- Epidemiology Unit, Victorian Infectious Diseases Reference Laboratory, Doherty Institute, Melbourne, Victoria 3000, Australia Department of Medicine, University of Melbourne, Melbourne, Victoria 3050, Australia
| | - Benjamin C Cowie
- Epidemiology Unit, Victorian Infectious Diseases Reference Laboratory, Doherty Institute, Melbourne, Victoria 3000, Australia Department of Medicine, University of Melbourne, Melbourne, Victoria 3050, Australia Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia
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Crispim MAE, Fraiji NA, Campello SC, Schriefer NA, Stefani MMA, Kiesslich D. Molecular epidemiology of hepatitis B and hepatitis delta viruses circulating in the Western Amazon region, North Brazil. BMC Infect Dis 2014; 14:94. [PMID: 24555665 PMCID: PMC3936897 DOI: 10.1186/1471-2334-14-94] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Accepted: 02/14/2014] [Indexed: 02/07/2023] Open
Abstract
Background Hepatitis B virus (HBV) and hepatitis D virus (HDV) represent important public health problems in the Western Amazon region with reported cases of fulminant hepatitis. This cross sectional study describes HBV and HDV genotypes circulating in the Brazilian Amazon region. Methods HBsAg positive individuals (n = 224) were recruited in Manaus/Amazonas State (130 blood donors from the Hematology and Hemotherapy Foundation from Amazonas/HEMOAM; 60 subjects from outpatient clinic) and in Eirunepe city (n = 34) from 2003–2009. Most participants (n = 153) lived in Manaus, 63 were from 20 remote isolated municipalities, 8 lived outside Amazonas State. Genotyping was based on PCR products: HBV genotype A-F specific primers, restricted length polymorphism for HDV. HDV isolates were directly sequenced (delta antigen 405 nucleotide fragment) and phylogenetic analysis performed (MEGA; neighbor-joining, Kimura’s two parameter). Results Most participants were young adult males and HBV mono-infection predominated (70.5%, 158/224). Among blood donors, outpatient subjects and individuals from Eirunepe, HBV/A prevailed followed by HBV/D and F (p > 0.05). HBV/A was more frequent in blood donors (p < 0.05). HBV-HDV coinfection rate was 8.5% in blood donors (11/130), 65.0% (39/60) in outpatient subjects and 47.0% (16/34) in individuals from Eirunepe. Compared to blood donors, coinfection was higher in outpatient subjects (65.0% versus 8.5%; RR = 5.0; CI 3.4-7.9; p < 0.0001) and in subjects from Eirunepe (47.0% versus 8.5%; RR = 5.5; CI 3.0-9.9; p < 0.0001). HBV-HDV coinfection rates were higher in patients from highly endemic remote cities. Only HDV genotype 3 was detected, HBV/F-HDV/3 predominated (20/38; 52.7%), followed by HBV/A-HDV/3 (31.6%; 12/38) and HBV/D-HDV/3 (15.8%; 6/38). Conclusions The description of HBV and HDV genotypes circulating in the western Amazon can contribute to a better understanding of their relevance on the regional epidemics. These infections are highly endemic in the Amazon where their control is challenged by its vast territorial dimension with small, hard-to-reach municipalities dispersed into the jungle and populated by diverse ethnic groups.
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Noureddin M, Gish R. Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery. Curr Gastroenterol Rep 2014; 16:365. [PMID: 24293018 PMCID: PMC3918112 DOI: 10.1007/s11894-013-0365-x] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
With recent studies showing increased prevalence of hepatitis delta (HDV) even in the US, Australia, and some countries in Europe, and very high prevalence in endemic regions, HDV infection is far from being a disappearing disease. Although immigrants from endemic countries have been shown to have increased risk, studies have clearly shown that the disease is not solely appearing in traditional high-risk groups. Recent studies provide increasing evidence that sexual transmission may be an important factor in HDV infection spread. Based on the totality of evidence showing increased disease progression and substantially increased risk of cirrhosis in HDV-infected CHB patients, and the current studies showing higher than expected prevalence, it is time to call for HDV screening of all CHB patients. HDV viral load detection and measurement should be considered in all patients whether or not they are anti-HDV-positive. With universal screening of CHB patients for HDV, earlier diagnosis and consideration of treatment would be possible. Current treatment of HDV is IFN-based therapy with or without HBV antivirals, but current research indicates the possibility that prenylation inhibitors, entry inhibitors, HBsAg release inhibitors, or other therapies currently in the pipeline may provide more effective therapy in the future. In addition, universal screening would serve the important public health goal of allowing patients to be educated on their status and on the need for HDV-negative patients to protect themselves against superinfection and for HDV-infected patients to protect against transmission to others. Further studies and global awareness of HDV infection are needed.
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Affiliation(s)
- Mazen Noureddin
- Division of Gastroenterology and Hepatology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 101, Los Angeles, CA 90033 USA
| | - Robert Gish
- Robert G. Gish Consultants, LLC, San Diego, CA USA
- St. Joseph’s Hospital and Medical Center, Phoenix, AZ USA
- University of Nevada, Las Vegas, 6022 La Jolla Mesa Drive, San Diego, CA 92037 USA
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