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Amin I, Rafique S, Ali A, Ahmed N, Shahid M, Afzal S, Tahir S, Waqas M, Bibi S, Elgorban AM, Idrees M, Shah M, Syed A. Improving Access to Anti-HDV Testing: Development and Validation of an Affordable In-House ELISA Assay. ACS OMEGA 2024; 9:17137-17142. [PMID: 38645367 PMCID: PMC11024977 DOI: 10.1021/acsomega.3c09843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 03/01/2024] [Accepted: 03/06/2024] [Indexed: 04/23/2024]
Abstract
In certain low-income nations, the hepatitis Delta virus and hepatitis B virus (HBV) pose a serious medical burden, where the prevalence of hepatitis B surface antigen (HBsAg) is greater than 8%. Especially in rural places, irregular diagnostic exams are the main restriction and reason for underestimation. Utilizing serum samples from a Pakistani isolate, an internal ELISA for the quick identification of anti-HDV was created, and the effectiveness of the test was compared to a commercial diagnostic kit. HDV-positive serum samples were collected, and a highly antigenic domain of HDAg antigen was derived from them. This antigenic HDAg was expressed in a bacterial expression system, purified by Ni-chromatography, and confirmed by SDS-PAGE and Western blot analysis. The purified antigen was utilized to develop an in-house ELISA assay for anti-HDV antibody detection of the patient's serum samples at very low cost. Purified antigens and positive and negative controls can detect anti-HDV (antibodies) in ELISA plates. The in-house developed kit's efficiency was compared with that of a commercial kit (Witech Inc., USA) by the mean optical density values of both kits. No significant difference was observed (a P value of 0.576) by applying statistical analysis. The newly developed in-house ELISA is equally efficient compared to commercial kits, and these may be useful in regular diagnostic laboratories, especially for analyzing local isolates.
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Affiliation(s)
- Iram Amin
- Centre
of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 54590, Pakistan
- Centre
of Applied Molecular Biology (CAMB), University
of the Punjab, Lahore 54590, Pakistan
| | - Shazia Rafique
- Centre
of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 54590, Pakistan
| | - Amjad Ali
- Department
of Biotechnology and Genetic Engineering, Hazara University Mansehra, Mansehra 2100, Pakistan
| | - Nadeem Ahmed
- Centre
of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 54590, Pakistan
| | - Muhammad Shahid
- Centre
of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 54590, Pakistan
| | - Samia Afzal
- Centre
of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 54590, Pakistan
| | - Saad Tahir
- Centre
of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 54590, Pakistan
| | - Muhammad Waqas
- Department
of Biotechnology and Genetic Engineering, Hazara University Mansehra, Mansehra 2100, Pakistan
| | - Sadia Bibi
- Department
of Botany, University of Malakand, Dir (Lower), Chakdara 18800, Khyber Pakhtunkhwa, Pakistan
| | - Abdallah M. Elgorban
- Department
of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Muhammad Idrees
- Centre
of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 54590, Pakistan
| | - Masaud Shah
- Department
of Physiology, Ajou University School of
Medicine, Suwon 16499, Republic
of Korea
| | - Asad Syed
- Department
of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
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Bansal SB, Ramasubramanian V, Prasad N, Saraf N, Soman R, Makharia G, Varughese S, Sahay M, Deswal V, Jeloka T, Gang S, Sharma A, Rupali P, Shah DS, Jha V, Kotton CN. South Asian Transplant Infectious Disease Guidelines for Solid Organ Transplant Candidates, Recipients, and Donors. Transplantation 2023; 107:1910-1934. [PMID: 36749281 DOI: 10.1097/tp.0000000000004521] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
These guidelines discuss the epidemiology, screening, diagnosis, posttransplant prophylaxis, monitoring, and management of endemic infections in solid organ transplant (SOT) candidates, recipients, and donors in South Asia. The guidelines also provide recommendations for SOT recipients traveling to this region. These guidelines are based on literature review and expert opinion by transplant physicians, surgeons, and infectious diseases specialists, mostly from South Asian countries (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) as well as transplant experts from other countries. These guidelines cover relevant endemic bacterial infections (tuberculosis, leptospirosis, melioidosis, typhoid, scrub typhus), viral infections (hepatitis A, B, C, D, and E; rabies; and the arboviruses including dengue, chikungunya, Zika, Japanese encephalitis), endemic fungal infections (mucormycosis, histoplasmosis, talaromycosis, sporotrichosis), and endemic parasitic infections (malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis, strongyloidiasis, and filariasis) as well as travelers' diarrhea and vaccination for SOT candidates and recipients including travelers visiting this region. These guidelines are intended to be an overview of each topic; more detailed reviews are being published as a special supplement in the Indian Journal of Transplantation .
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Affiliation(s)
- Shyam Bihari Bansal
- Department of Nephrology and Kidney Transplantation, Medanta Institute of Kidney and Urology Medanta-Medicity, Gurgaon, India
| | | | - Narayan Prasad
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta, Medicity, Gurgaon, India
| | - Rajeev Soman
- Department of Infectious Diseases, Jupiter Hospital, Pune, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Santosh Varughese
- Department of Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Manisha Sahay
- Department of Nephrology, Osmania Medical College, and Hospital, Hyderabad, India
| | - Vikas Deswal
- Department of Infectious Diseases, Medanta, Medicity, Gurgaon, India
| | - Tarun Jeloka
- Department of Infectious Diseases, Jupiter Hospital, Pune, India
| | - Sishir Gang
- Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujrat, India
| | - Ashish Sharma
- Department of Renal Transplant Surgery, PGIMER, Chandigarh, India
| | - Priscilla Rupali
- Department of Infectious Diseases, Christian Medical College, Vellore, Tamil Nadu, India
| | - Dibya Singh Shah
- Department of Nephrology and Transplant Medicine, Institute of Medicine, Tribhuvan University of Teaching hospital, Kathmandu, Nepal
| | | | - Camille Nelson Kotton
- Transplant and Immunocompromised Host Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Flower B, Du Hong D, Vu Thi Kim H, Pham Minh K, Geskus RB, Day J, Cooke GS. Seroprevalence of Hepatitis B, C and D in Vietnam: A systematic review and meta-analysis. THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2022; 24:100468. [PMID: 35573318 PMCID: PMC9096228 DOI: 10.1016/j.lanwpc.2022.100468] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/30/2022]
Abstract
Background Vietnam has one of the greatest disease burdens from chronic viral hepatitis. Comprehensive prevalence data are essential to support its elimination as a public health threat. Methods We searched Medline and Embase from 1990 to 2021 for seroprevalence data relating to Hepatitis B (HBV), C (HCV) and D (HDV) in Vietnam. We estimated pooled prevalence with a DerSimonian-Laird random-effects model and stratified study populations into i) low-risk ii) high-risk exposure and iii) liver disease. We further estimated prevalence by decade and region and rates of HIV-coinfection. Findings We analysed 72 studies, including 120 HBV, 114 HCV and 23 HDV study populations. Pooled HBV prevalence was low in blood donors (1.86% [1.82-1.90]) but high in antenatal populations (10.8% [10.1-11.6]) and adults in the general population (10.5% [10.0-11.0]). It was similar or modestly increased in groups at highest risk of exposure, suggesting the epidemic is largely driven by chronic infections acquired in childhood. HCV pooled prevalence in the general population was lower than historical estimates: 0.26% (0.09-0.51) have active infection defined by detectable antigen or HCV RNA. In contrast, there is an extremely high prevalence of active HCV infection in people who inject drugs (PWID) (57.8% [56.5-59.1]), which has persisted through the decades despite harm-reduction interventions. HDV appears mainly confined to high-risk groups. Interpretation Blood safety has improved, but renewed focus on HBV vaccination at birth and targeted HCV screening and treatment of PWID are urgently required to meet elimination targets. Large cross-sectional studies are needed to better characterize HDV prevalence, but mass screening may not be warranted. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Affiliation(s)
- Barnaby Flower
- Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam,Imperial College London, UK,Corresponding author. Barnaby Flower, Oxford University Clinical Research Unit, 764 Vo Van Kiet, Phuong 1, Quan 5, Ho Chi Minh City, Vietnam.
| | - Duc Du Hong
- Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
| | - Hang Vu Thi Kim
- Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
| | | | - Ronald B Geskus
- Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Jeremy Day
- Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
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Prevalence of Hepatitis D virus antibodies in Hepatitis B patients treated at tertiary care unit at Jabalpur Central India. Indian J Med Microbiol 2021; 40:132-134. [PMID: 34801290 DOI: 10.1016/j.ijmmb.2021.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 10/18/2021] [Accepted: 11/07/2021] [Indexed: 11/23/2022]
Abstract
Hepatitis Delta virus (HDV) infection amongst Hepatitis B virus (HBV) infected patients increases morbidity and mortality. The prevalence varies temporally and spatially. The present study aimed to evaluate the HDV prevalence in central India. Samples received from January 2018 to December 2019 were tested for viral hepatitis markers. Randomly picked 372 HBsAg positive samples were tested for the presence of HDV total antibodies using ELISA, of these 8 were found positive. This study for the first-time documents presence of HDV with 2.1% prevalence from central India. We recommend screening for better patient management and bringing down the disease burden.
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Hayashi T, Takeshita Y, Hutin YJF, Harmanci H, Easterbrook P, Hess S, van Holten J, Oru EO, Kaneko S, Yurdaydin C, Bulterys M. The global hepatitis delta virus (HDV) epidemic: what gaps to address in order to mount a public health response? Arch Public Health 2021; 79:180. [PMID: 34663473 PMCID: PMC8525025 DOI: 10.1186/s13690-021-00693-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 09/13/2021] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Co-infection between hepatitis B virus (HBV) and hepatitis delta virus (HDV) causes the severest chronic hepatitis and is associated with a high risk of cirrhosis and hepatocellular carcinoma (HCC). The Global Health Sector Strategy on Viral Hepatitis called for the elimination of hepatitis (- 65% mortality and - 90% incidence) by 2030. Our aims were to summarize key points of knowledge and to identify the gaps that need to be addressed to mount a public health response to HDV. METHODS We performed a current literature review in terms of epidemiology by WHO regions, genotypes distribution and their pathogenicity, factors associated with HDV infection, mortality due to HDV infection, testing strategies and treatment. RESULTS Prevalence of infection and genotypes are heterogeneous distributed, with highest prevalence in foci around the Mediterranean, in the Middle East, and in Central, Northern Asia and Eastern Asia. Persons who inject drugs (PWID) and migrants from highly endemic areas are highly affected. While antibody detection tests are available, HDV RNA tests of current infection are not standardized nor widely available. The few therapeutic options, including lofartinib, are not widely available; however several new and promising agents have entered clinical trials. CONCLUSION HDV infection is an poorly known cause of chronic liver disease. To mount a public health response, we need a better description of the HDV epidemic, standardized testing strategies and better treatment options.
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Affiliation(s)
- Tomoyuki Hayashi
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland.
- Department of Gastroenterology, Kanazawa University and WHO Collaborating Center for Chronic Hepatitis and Liver Cancer, Kanazawa, Ishikawa, Japan.
| | - Yumie Takeshita
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
- Department of Gastroenterology, Kanazawa University and WHO Collaborating Center for Chronic Hepatitis and Liver Cancer, Kanazawa, Ishikawa, Japan
| | - Yvan J-F Hutin
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Hande Harmanci
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | | | - Sarah Hess
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Judith van Holten
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Ena Oghenekaro Oru
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University and WHO Collaborating Center for Chronic Hepatitis and Liver Cancer, Kanazawa, Ishikawa, Japan
| | - Cihan Yurdaydin
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
- Hepatology Institute, University of Ankara, Ankara, Turkey
| | - Marc Bulterys
- Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
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Lee AU, Lee C. Hepatitis D Review: Challenges for the Resource-Poor Setting. Viruses 2021; 13:v13101912. [PMID: 34696341 PMCID: PMC8538672 DOI: 10.3390/v13101912] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 09/08/2021] [Accepted: 09/13/2021] [Indexed: 12/30/2022] Open
Abstract
Hepatitis D is the smallest virus known to infect humans, the most aggressive, causing the most severe disease. It is considered a satellite or defective virus requiring the hepatitis B surface antigen (HBsAg) for its replication with approximately 10–70 million persons infected. Elimination of hepatitis D is, therefore, closely tied to hepatitis B elimination. There is a paucity of quality data in many resource-poor areas. Despite its aggressive natural history, treatment options for hepatitis D to date have been limited and, in many places, inaccessible. For decades, Pegylated interferon alpha (Peg IFN α) offered limited response rates (20%) where available. Developments in understanding viral replication pathways has meant that, for the first time in over three decades, specific therapy has been licensed for use in Europe. Bulevirtide (Hepcludex®) is an entry inhibitor approved for use in patients with confirmed viraemia and compensated disease. It can be combined with Peg IFN α and/or nucleos(t)ide analogue for hepatitis B. Early reports suggest response rates of over 50% with good tolerability profile. Additional agents showing promise include the prenylation inhibitor lonafarnib, inhibitors of viral release (nucleic acid polymers) and better tolerated Peg IFN lambda (λ). These agents remain out of reach for most resource limited areas where access to new therapies are delayed by decades. strategies to facilitate access to care for the most vulnerable should be actively sought by all stakeholders.
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Affiliation(s)
- Alice U. Lee
- Concord Repatriation General Hospital, University of Sydney, Sydney, NSW 2139, Australia
- Hepatitis B Free, Sydney, NSW 2139, Australia
- Correspondence:
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7
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Rizzetto M, Hamid S, Negro F. The changing context of hepatitis D. J Hepatol 2021; 74:1200-1211. [PMID: 33484770 DOI: 10.1016/j.jhep.2021.01.014] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 01/04/2021] [Accepted: 01/09/2021] [Indexed: 12/18/2022]
Abstract
The global epidemiology of hepatitis D is changing with the widespread implementation of vaccination against hepatitis B. In high-income countries that achieved optimal control of HBV, the epidemiology of hepatitis D is dual, consisting of an ageing cohort of domestic patients with advanced liver fibrosis who represent the end stage of the natural history of HDV, and of a younger generation of immigrants from endemic countries who account for the majority of new infections. As observed in Europe in the 1980s, the distinctive clinical characteristic of chronic hepatitis D in endemic countries is the accelerated progression to cirrhosis and hepatocellular carcinoma. Despite some recent progress, the therapeutic management of HDV remains unsatisfactory, as most patients are not cured of HDV with currently available medicines. This review article describes the current epidemiology and clinical features of chronic hepatitis D, based on the literature published in the last 10 years.
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Affiliation(s)
- Mario Rizzetto
- Department of Medical Sciences, University of Turin, Turin, Italy.
| | - Saeed Hamid
- Department of Medicine, The Aga Khan University, Karachi, Pakistan
| | - Franco Negro
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland
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8
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Abbas Z, Qadeer MA, Mandviwalla HA, Abbas M. The Severity of Hepatitis D in Young Adults of Age 18-25 Years. Cureus 2020; 12:e10855. [PMID: 33052263 PMCID: PMC7546593 DOI: 10.7759/cureus.10855] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background Current literature on the prevalence and characteristics of hepatitis D virus (HDV) infection in young adults is limited. This study aims to determine the disease characteristics and severity in young adults. Methods The case records of HDV RNA positive patients of age 18-25 years were analyzed. Results Out of 119 patients, 105 (88%) patients were male. HBV-DNA was detectable in 83 (70%). Hepatitis B e-antigen (HBeAg) was non-reactive in 99 (83%). Cirrhosis was identified in 45 (37.8%) individuals; nine (7.5%) were classified as Child class B or Child class C. Twenty-four (20.2%) had a Model For End-Stage Liver Disease (MELD) score of ≥10, out of these 16 had a score of 15 or more. The risk of decompensation was calculated according to the Baseline-event-anticipation (BEA) score; eight (6.7%) patients were at BEA-A (mild risk), 105 (88.2%) were at BEA-B (moderate risk), and six (5.0%) were at BEA-C (severe risk). Notable findings in patients with cirrhosis included splenomegaly, low total leucocyte counts, low platelets, high bilirubin, elevated aspartate aminotransferase, gamma-glutamyl transferase and international normalization ratio, low albumin, high AST to Platelet Ratio Index (APRI), and high BEA score. The splenic size, platelet count, and albumin levels were independently associated with cirrhosis (p < 0.001, <0.001, and 0.003). A model using a combination of platelet count, albumin, and spleen size was developed to accurately predict cirrhosis in this cohort. It had an area under the receiver operating characteristics (AUROC) of 0.935. Conclusions HDV-infected young adults, age 18-25 years, were at moderate to severe risk of disease progression. About one-third of patients had already developed cirrhosis indicating the aggressive nature of the disease.
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Affiliation(s)
- Zaigham Abbas
- Gastroenterology and Hepatology, Dr. Ziauddin University Hospital Clifton, Karachi, PAK
| | - Muhammad Ali Qadeer
- Gastroenterology and Hepatology, Dr. Ziauddin University Hospital Clifton, Karachi, PAK
| | - Haider A Mandviwalla
- Gastroenterology and Hepatology, Dr. Ziauddin University Hospital Clifton, Karachi, PAK
| | - Minaam Abbas
- Gastroenterology and Hepatology, Dr. Ziauddin University Hospital Clifton, Karachi, PAK.,Gastroenterology and Hepatology, School of Clinical Medicine, University of Cambridge, Cambridge, GBR
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9
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Fouad HM, Ahmed A, Reyad EM, ElSadek SM, Khattab RA, El Damasy DA. Hepatitis D virus seroprevalence in Egyptian HBsAg-positive children: a single-center study. Arch Virol 2020; 165:2361-2365. [PMID: 32743697 DOI: 10.1007/s00705-020-04757-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Accepted: 06/25/2020] [Indexed: 11/24/2022]
Abstract
In this study, we investigated the seroprevalence of anti-hepatitis D virus (HDV) antibodies in hepatitis B surface antigen (HBsAg)-positive children after 25 years of obligatory vaccination of infants against hepatitis B virus. This cross-sectional study included 120 treatment-naïve HBsAg-positive children, with a male-to-female ratio of 1.8:1 and a mean age of 7.8 ± 3.8 years (range, 1-17 years). Mothers were positive for HBsAg in 96.6% of the cases. HBeAg-positive chronic infection was observed in 60% of the cases, HBeAg-positive chronic hepatitis in 12.5%, and HBeAg-negative chronic infection in 26.7%. Anti-HDV antibodies were not detected in any of the cases. Thus, there is a lack of anti-HDV antibodies in HBsAg-positive children, despite the current burden in adults.
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Affiliation(s)
- Hanan M Fouad
- Department of Pediatric, Faculty of Medicine, Helwan University, Cairo, Egypt.
| | - Amal Ahmed
- Biochemistry Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Ehab Mahfouz Reyad
- Clinical and Chemical Pathology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Sanaa Mohammed ElSadek
- Department of Pediatrics, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | | | - Dalia Ali El Damasy
- Microbiology Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
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The Prevalence of Hepatitis B and D Viruses and Evaluating YMDD Mutation in HBV-Suspected Patients in Qom Province, Iran. Jundishapur J Microbiol 2020. [DOI: 10.5812/jjm.100038] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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Fontana RJ, Avigan MI, Janssen HLA, Regev A, Mishra P, Gaggar A, Brown N, Wat C, Mendez P, Anderson RT, Given B, Miller V, Beumont M. Liver safety assessment in clinical trials of new agents for chronic hepatitis B. J Viral Hepat 2020; 27:96-109. [PMID: 31828894 DOI: 10.1111/jvh.13223] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/17/2019] [Accepted: 09/26/2019] [Indexed: 12/17/2022]
Abstract
Investigational agents that reduce or eliminate covalently closed circular DNA (cccDNA) or enhance host immunity against hepatitis B virus (HBV)-infected hepatocytes are intended to induce a durable off-treatment clearance of hepatitis B surface antigen (HBsAg) (referred to as functional cure). The aim of this paper was to highlight challenges in interpreting liver safety data in clinical trials of these agents when given alone or in combination regimens. The incidence, grading and management of spontaneous serum ALT flares in untreated chronic HBV patients are reviewed along with a summary of serum ALT flares observed during the registration trials for peginterferon and nucleos(t)ide reverse transcriptase inhibitors. Recommendations regarding the detection, management and interpretation of liver safety biomarker data in future clinical trials as well as suggested inclusion and exclusion criteria for phase 1/2 vs phase 3 studies are provided. Criteria to help classify liver safety signals as being due to the intended therapeutic response, emergence of drug-resistant HBV virions, or idiosyncratic drug-induced liver injury are provided along with a review of the role of an expert hepatic adjudication panel in assessing a compound's hepatotoxicity profile. Finally, an algorithmic approach to the differential diagnosis and recommended medical evaluation and management of individual clinical trial patients that develop a liver safety signal is provided along with the rationale to collect and test research blood samples for future mechanistic studies.
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Affiliation(s)
- Robert J Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Mark I Avigan
- Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, Toronto, Canada
| | - Arie Regev
- Eli Lilly and Company, Indianapolis, IN, USA
| | - Poonam Mishra
- Division of Antiviral Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | | | | | | | | | - Ryan T Anderson
- Forum for Collaborative Research, University of California, Berkeley
| | - Bruce Given
- Arrowhead Pharmaceuticals, Inc, Pasadena, CA, USA
| | - Veronica Miller
- Forum for Collaborative Research, University of California, Berkeley
| | - Maria Beumont
- Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium
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12
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Rizzetto M. Epidemiology of the Hepatitis D virus. WIKIJOURNAL OF MEDICINE 2020; 7:1. [DOI: 10.15347/wjm/2020.001.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/02/2023] Open
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13
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Dessordi R, Santana RDC, Navarro AM. Influence of antiretroviral therapy on bone metabolism of patients with chronic hepatitis B: a review. Rev Soc Bras Med Trop 2019; 52:e20180441. [PMID: 31596347 DOI: 10.1590/0037-8682-0441-2018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 08/21/2019] [Indexed: 11/21/2022] Open
Abstract
Hepatitis B is a major public health problem worldwide and associated with significant mortality. To prevent or delay the deleterious effects of chronic infection by the hepatitis B virus, patients should be carefully followed, and antiviral therapy indicated according to specific recommendations. Currently, available drugs inhibit viral replication and slow or stop the progression of inflammation and fibrosis of the liver. However, the drugs for oral use in the treatment of hepatitis B, jointly referred to as nucleoside/nucleotide analogs, are indicated for prolonged use and have potential side effects. The reduction in bone mineral density was associated with the use of tenofovir, already evaluated in patients infected with HIV because the drug is also part of the therapeutic arsenal for this viral infection. There are few studies on the effects of tenofovir in patients with mono hepatitis B. Therefore, this literature review proposes to examine how hepatitis B acts in the body and the mechanisms by which antiretroviral drugs (especially tenofovir) can affect bone metabolism.
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Affiliation(s)
- Renata Dessordi
- Universidade Estadual Paulista "Júlio de Mesquita Filho", Programa de Pós-Graduação Stricto Sensu em Alimentos e Nutrição, São Paulo, SP, Brasil.,Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas do Estado de São Paulo, Departamento de Alimentos e Nutrição, São Paulo, SP, Brasil
| | - Rodrigo de Carvalho Santana
- Universidade de São Paulo, Escola de Medicina de Ribeirão Preto, Departamento de Clínica Médica, Ribeirão Preto, SP, Brasil
| | - Anderson Marliere Navarro
- Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas do Estado de São Paulo, Departamento de Alimentos e Nutrição, São Paulo, SP, Brasil.,Universidade de São Paulo, Escola de Medicina de Ribeirão Preto, Departamento de Clínica Médica, Ribeirão Preto, SP, Brasil
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Rocco C, Bonavolta R, Vallefuoco L, Braschi U, Sorrentino R, Terracciano D, Portella G. Comparison of anti-hepatitis D virus (HDV) ETI-AB-DELTAK-2 assay and the novel LIAISON® XL MUREX anti-HDV assay in the diagnosis of HDV infection. Diagn Microbiol Infect Dis 2019; 95:114873. [PMID: 31473034 DOI: 10.1016/j.diagmicrobio.2019.114873] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 07/19/2019] [Accepted: 07/19/2019] [Indexed: 12/18/2022]
Abstract
Hepatitis B/D virus infection leads to severe liver disease. HDV infection is not routinely investigated since the diagnosis is based on enzyme immunoassays (EIAs), which are not available in all laboratories. This study investigates the performance of new automated assay for anti HDV Ab detection: LIAISON® XL Murex anti-HDV. HBsAg-positive samples were evaluated for HDV serology using the ETI-AB-DELTAK-2 and the new LIAISON® XL Murex with a concordance of 97.5% and 2.42% discordant results. The discordant specimens reacted negatively with EIA and positively with the new test. Dilutions of HDV-purified antibodies and HDV-positive samples were tested with both assays, showing a lower detection limit for the new assay. In conclusion, LIAISON® XL Murex showed a good concordance with the reference method and allowed a more rapid HDV detection. This new diagnostic tool may be useful for a more efficient approach to the HDV diagnosis and evaluation of HDV epidemiology.
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Affiliation(s)
- Caterina Rocco
- Dipartimento di Scienze Mediche Traslazionali, Università Federico II, U.O.S.D. Virologia A.O.U. Federico II, Napoli, Italy
| | - Raffaele Bonavolta
- Dipartimento di Scienze Mediche Traslazionali, Università Federico II, U.O.S.D. Virologia A.O.U. Federico II, Napoli, Italy
| | - Luca Vallefuoco
- Dipartimento di Scienze Mediche Traslazionali, Università Federico II, U.O.S.D. Virologia A.O.U. Federico II, Napoli, Italy
| | - Umberto Braschi
- Dipartimento di Scienze Mediche Traslazionali, Università Federico II, U.O.S.D. Virologia A.O.U. Federico II, Napoli, Italy
| | - Rosanna Sorrentino
- Dipartimento di Scienze Mediche Traslazionali, Università Federico II, U.O.S.D. Virologia A.O.U. Federico II, Napoli, Italy
| | - Daniela Terracciano
- Dipartimento di Scienze Mediche Traslazionali, Università Federico II, U.O.S.D. Virologia A.O.U. Federico II, Napoli, Italy
| | - Giuseppe Portella
- Dipartimento di Scienze Mediche Traslazionali, Università Federico II, U.O.S.D. Virologia A.O.U. Federico II, Napoli, Italy.
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15
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Husseini AA, Saeed KMI, Yurdcu E, Sertoz R, Bozdayi AM. Epidemiology of blood-borne viral infections in Afghanistan. Arch Virol 2019; 164:2083-2090. [PMID: 31134354 DOI: 10.1007/s00705-019-04285-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 04/20/2019] [Indexed: 12/30/2022]
Abstract
Although a few studies have been done on transmissible blood-borne viral infections in high-risk groups, little attention has been given to assessing the infection status of the general population in Afghanistan. To investigate the epidemiological status in the general population, we tested the serological markers of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus (HDV), human immunodeficiency virus 1 (HIV-1) and human T-cell leukemia virus (HTLV) infections. In total, 492 samples were selected randomly from Nangarhar, Herat, Mazar-e Sharif, Kandahar, and Kabul from subjects between 25 and 70 years old. The samples were tested for the presence of HBsAg, anti-HBs, anti-HBc, anti-HDV, anti-HCV, anti-HIV-1 and anti-HTLV I/II antibodies using chemiluminescent immunoassays on Abbott Architect automated platforms. In addition, 220 HBsAg-positive samples identified among 5897 samples from the general population of the same regions of Afghanistan were included in the study and tested for both HBsAg and anti-HDV to investigate HDV prevalence in the country. Viral loads of HBV, HCV and HDV were determined in all seropositive samples using Ampliprep/Cobas TaqMan HBV, HCV, Test Roche (CA, USA), and an in-house method, respectively. Out of 492 samples, 31 (6.3%), 136 (27.6%) and 149 (30.3%) were found to be positive for HBsAg, anti-HBs and anti-HBc, respectively. Anti-HDV positivity was detected in five (2.1%) out of 234 HBsAg-positive samples (including 14 of the randomly selected samples that were not among the 220 previously identified as HBsAg positive). Only eight out of 492 (1.6%) subjects were positive for anti-HCV antibodies. Seven out of 489 (1.4%) were positive for anti-HIV-1 antibodies, and three out of 466 cases (0.6%) were positive for anti-HTLV I/II antibodies. These results suggest that Afghanistan is an intermediate endemic region for HBV, HDV and HCV infection. The prevalence of HIV-1 seems to be significantly higher than the global prevalence and that of the eastern Mediterranean region. In addition, the HTLV I/II screening results suggest that these viruses should be monitored in Afghanistan to confirm the trend observed in the current study.
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Affiliation(s)
- Abbas Ali Husseini
- Institute of Hepatology, Ankara University, School of Medicine, Cebeci Hospitals, Dikimevi, 06620, Ankara, Turkey
| | - Khwaja Mir Islam Saeed
- Grant and Service Contract Management Unit (GCMU), Ministry of Public Health, Kabul, Afghanistan
| | - Esra Yurdcu
- Institute of Hepatology, Ankara University, School of Medicine, Cebeci Hospitals, Dikimevi, 06620, Ankara, Turkey
| | - Rüçhan Sertoz
- Department of Medical Microbiology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - A Mithat Bozdayi
- Institute of Hepatology, Ankara University, School of Medicine, Cebeci Hospitals, Dikimevi, 06620, Ankara, Turkey.
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16
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Te H, Doucette K. Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant 2019; 33:e13514. [DOI: 10.1111/ctr.13514] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 02/12/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Helen Te
- Center for Liver Diseases, Section of Gastroenterology, Hepatology and Nutrition University of Chicago Medicine Chicago Illinois
| | - Karen Doucette
- Division of Infectious Diseases University of Alberta Edmonton Alberta Canada
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17
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Evolution of Hepatitis B Virus Receptor NTCP Reveals Differential Pathogenicities and Species Specificities of Hepadnaviruses in Primates, Rodents, and Bats. J Virol 2019; 93:JVI.01738-18. [PMID: 30541833 DOI: 10.1128/jvi.01738-18] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 11/16/2018] [Indexed: 12/21/2022] Open
Abstract
Human hepatitis B virus (HBV) is a global health problem, affecting more than 250 million people worldwide. HBV-like viruses, named orthohepadnaviruses, also naturally infect nonhuman primates, rodents, and bats, but their pathogenicity and evolutionary history are unclear. Here, we determined the evolutionary history of the HBV receptors NTCP and GPC5 over millions of years of primate, rodent, and bat evolution. We use this as a proxy to understand the pathogenicity of orthohepadnaviruses in mammalian hosts and to determine the implications for species specificity. We found that NTCP, but not GPC5, has evolved under positive selection in primates (27 species), rodents (18 species), and bats (21 species) although at distinct residues. Notably, the positively selected codons map to the HBV-binding sites in primate NTCP, suggesting past genetic "arms races" with pathogenic orthohepadnaviruses. In rodents, the positively selected codons fall outside and within the presumed HBV-binding sites, which may contribute to the restricted circulation of rodent orthohepadnaviruses. In contrast, the presumed HBV-binding motifs in bat NTCP are conserved, and none of the positively selected codons map to this region. This suggests that orthohepadnaviruses may bind to different surfaces in bat NTCP. Alternatively, the patterns may reflect adaptive changes associated with metabolism rather than pathogens. Overall, our findings further point to NTCP as a naturally occurring genetic barrier for cross-species transmissions in primates, which may contribute to the narrow host range of HBV. In contrast, this constraint seems less important in bats, which may correspond to greater orthohepadnavirus circulation and diversity.IMPORTANCE Chronic infection with hepatitis B virus (HBV) is a major cause of liver disease and cancer in humans. Mammalian HBV-like viruses are also found in nonhuman primates, rodents, and bats. As for most viruses, HBV requires a successful interaction with a host receptor for replication. Cellular receptors are thus key determinants of host susceptibility as well as specificity. One hallmark of pathogenic virus-host relationships is the reciprocal evolution of host receptor and viral envelope proteins, as a result of their antagonistic interaction over time. The dynamics of these so-called "evolutionary arms races" can leave signatures of adaptive selection, which in turn reveal the evolutionary history of the virus-host interaction as well as viral pathogenicity and the genetic determinants of species specificity. Here, we show how HBV-like viruses have shaped the evolutionary history of their mammalian host receptor, as a result of their ancient pathogenicity, and decipher the genetic determinants of cross-species transmissions.
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18
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Scarponi CFDO, Silva RDND, Souza Filho JAD, Guerra MRL, Pedrosa MAF, Mol MPG. Hepatitis Delta Prevalence in South America: A Systematic Review and Meta-Analysis. Rev Soc Bras Med Trop 2019; 52:e20180289. [PMID: 30698197 DOI: 10.1590/0037-8682-0289-2018] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 12/18/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis delta virus (HDV) has been associated with acute or chronic hepatitis in Latin America, but there is no prevalence study covering South American countries. This meta-analysis aimed to estimate anti-HDV prevalence through a systematic review of published articles in English, Portuguese and Spanish until December 2017. Searches were conducted in Health Virtual Library, Capes, Lilacs, PubMed, and SciELO, according to defined criteria regarding participant selection and geographical setting. Study quality was assessed using the GRADE guidelines. Pooled anti-HDV prevalence was calculated using the DerSimonian-Laird random-effects model with Freeman-Tukey double arcsine transformation. Out of the 405 identified articles, only 31 met the eligibility criteria for inclusion in the meta-analysis. In South America, pooled anti-HDV prevalence among hepatitis B virus carriers was 22.37% (95% confidence interval: 13.72-32.26), though it appeared less frequently in some countries and populations, according to the data collection date. The findings indicated significant successive reductions in anti-HDV prevalence over thirty years. However, there was a scarcity of HDV epidemiological studies outside the Amazon Basin, notably in the Southwest continent and absence of target population standardization. There was a high HDV prevalence in South American countries, despite differences in methodological characteristics and outcomes, highlighting a drastic decline in the last decades. Future studies should identify HDV prevalence estimates in other regions of the continent and identify risk factors.
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Affiliation(s)
| | | | | | | | | | - Marcos Paulo Gomes Mol
- Diretoria de Pesquisa e Desenvolvimento. Fundação Ezequiel Dias, Belo Horizonte, MG, Brasil
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19
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Groc S, Abbate JL, Le Gal F, Gerber A, Tuaillon E, Albert JL, Nkoghé D, Leroy EM, Roche B, Becquart P. High prevalence and diversity of hepatitis B and hepatitis delta virus in Gabon. J Viral Hepat 2019; 26:170-182. [PMID: 30141209 DOI: 10.1111/jvh.12991] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 06/28/2018] [Accepted: 07/23/2018] [Indexed: 12/15/2022]
Abstract
Although central Africa is classified as having a high endemicity of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection, there is paucity of prevalence studies. For the first time on a country-wide level in Central Africa, we show in Gabon an overall 7.4% prevalence of Hepatitis B surface antigen (HBsAg) and that more than 25% of the HBsAg-positive population are infected by HDV. Although HBV prevalence did not differ significantly between provinces, there is a north-south split in the distribution of HDV seroprevalence, with the highest rates (>66.0%) correlating with the presence of specific ethnic groups in the northeastern provinces. Genotyping revealed high genetic diversity of the HBV and HDV strains circulating in Gabon, including many restricted to this region of the globe. This work confirmed that high exposure to HBV and HDV infection reported in selected regions of Gabon holds true across the whole country.
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Affiliation(s)
- Soraya Groc
- MIVEGEC, IRD/CNRS/Univ. Montpellier, Montpellier, France
| | - Jessica Lee Abbate
- MIVEGEC, IRD/CNRS/Univ. Montpellier, Montpellier, France.,UMR UMMISCO (UMI 209 IRD-UPMC), Bondy, France
| | - Frédéric Le Gal
- Laboratoire de Microbiologie Clinique, Hôpital Avicenne, Centre National de Référence des Virus des Hépatites B C et Delta, Bobigny, France.,Unité INSERM U955, Equipe 18, Créteil, France
| | - Athenaïs Gerber
- Laboratoire de Microbiologie Clinique, Hôpital Avicenne, Centre National de Référence des Virus des Hépatites B C et Delta, Bobigny, France
| | - Edouard Tuaillon
- Pathogenesis and Control of Chronic Infections, Inserm U1058, University of Montpellier, Montpellier, France.,CHU de Montpellier, Montpellier, France
| | - Jean-Louis Albert
- Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
| | - Dieudonné Nkoghé
- Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
| | - Eric M Leroy
- MIVEGEC, IRD/CNRS/Univ. Montpellier, Montpellier, France.,Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
| | - Benjamin Roche
- MIVEGEC, IRD/CNRS/Univ. Montpellier, Montpellier, France.,UMR UMMISCO (UMI 209 IRD-UPMC), Bondy, France
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20
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21
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SHARIFAN P, AMOUEIAN S. Histological and Serological Epidemiology of Hepatitis Delta Virus Coinfection among Patients with Chronic Active Hepatitis B Virus in Razavi Khorasan Province, Northeastern Iran. IRANIAN JOURNAL OF PUBLIC HEALTH 2018; 47:1906-1912. [PMID: 30788306 PMCID: PMC6379606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND Hepatitis delta virus (HDV), as well as hepatitis B virus (HBV), are regarded as one of the main public health issues in developing countries. This retrospective study described histological and serological features of HDV coinfection patients with chronic active HBV in Northeastern Iran. METHODS The frequency of HDV seropositivity and its impact on serum liver enzyme levels and pathological features were investigated by reviewing clinical and laboratory data. This study contained chronic active HBV-infected patients having admitted the department during 2009 and 2014. RESULTS The rate of HDV coinfection in chronic active carriers was 21.84%, with a male predominance. HDV seropositive carriers showed significantly higher concentrations of liver enzyme than chronic active HBV monoinfection. Moreover, there was a strong association between degrees of inflammation with HDV-positive patients' enzyme levels. CONCLUSION The HDV seroprevalence in northeastern Iran was higher than that reported from elsewhere in Iran while comparable to some regions in Middle East, which, in turn, requires more comprehensive tools for diagnosing and screening the blood.
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22
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Gourari S, Brichler S, Le Gal F, Abdou-Chekaraou M, Beloufa MA, Khelifa R, Djaballah H, Boufekane M, Nani A, Afredj N, Debzi N, Dény P, Gordien E, Tazir M. Hepatitis B virus and hepatitis delta virus subtypes circulating in Algeria and seroprevalence of HDV infection. J Med Virol 2018; 91:72-80. [PMID: 30168584 DOI: 10.1002/jmv.25301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Accepted: 06/15/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Little is known about molecular characteristics of HBV strains circulating in Algeria and there are few data regarding HDV infection. OBJECTIVES The aim of this study is to describe the genetic diversity of HBV and HDV strains existing in Algeria and to determine the seroprevalence of HDV infection. STUDY DESIGN Plasma samples from 134 patients were analyzed by enzyme immunoassay method for HBV and HDV serological markers. Genotyping of HBV and HDV strains were performed using direct sequencing followed by phylogenetic analyses of the PreS1 and R0 region of the HBV and HDV genome respectively. RESULTS The PreS1 gene was successfully amplified in 119 patients (82 males and 37 females). Phylogenetic analysis of HBV strains revealed the presence of genotypes D (86.5%) and A2 (11.76%). The subgenotypes D are distributed as follows: HBV/D7 (43.5%), HBV/D3 (24.75%), HBV/D1 (16.8%) and HBV/D2 (14.85%). A recombinant between genotypes A, E and D was found. The seroprevalence of HDV infection among HBV carriers was less than 5.35%. Only one isolate of HDV genotype 1 was identified. CONCLUSIONS Our data indicate the predominance of HBV subgenotype D7 and a low prevalence of HDV infection.
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Affiliation(s)
- Samir Gourari
- Service de Microbiologie, CHU Mustapha, Algiers, Algeria
| | - Ségolène Brichler
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | - Frédéric Le Gal
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | - Mariama Abdou-Chekaraou
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | | | - Rim Khelifa
- Service de Microbiologie, CHU Mustapha, Algiers, Algeria
| | | | | | | | - Nawel Afredj
- Service d'Hépatologie, CHU Mustapha, Algiers, Algeria
| | - Nabil Debzi
- Service d'Hépatologie, CHU Mustapha, Algiers, Algeria
| | - Paul Dény
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | - Emmanuel Gordien
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | - Mohamed Tazir
- Service de Microbiologie, CHU Mustapha, Algiers, Algeria
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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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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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25
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Wranke A, Pinheiro Borzacov LM, Parana R, Lobato C, Hamid S, Ceausu E, Dalekos GN, Rizzetto M, Turcanu A, Niro GA, Lubna F, Abbas M, Ingiliz P, Buti M, Ferenci P, Vanwolleghem T, Hayden T, Dashdorj N, Motoc A, Cornberg M, Abbas Z, Yurdaydin C, Manns MP, Wedemeyer H, Hardtke S. Clinical and virological heterogeneity of hepatitis delta in different regions world-wide: The Hepatitis Delta International Network (HDIN). Liver Int 2018; 38:842-850. [PMID: 28963781 DOI: 10.1111/liv.13604] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 09/19/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Chronic hepatitis D (delta) is a major global health burden. Clinical and virological characteristics of patients with hepatitis D virus (HDV) infection and treatment approaches in different regions world-wide are poorly defined. METHODS The Hepatitis Delta International Network (HDIN) registry was established in 2011 with centres in Europe, Asia, North- and South America. Here, we report on clinical/ virological characteristics of the first 1576 patients with ongoing or past HDV infection included in the database until October 2016 and performed a retrospective outcome analysis. The primary aim was to investigate if the region of origin was associated with HDV replication and clinical outcome. RESULTS The majority of patients was male (n = 979, 62%) and the mean age was 36.7 years (range 1-79, with 9% of patients younger than 20 years). Most patients were HBeAg-negative (77%) and HDV-RNA positive (85%). Cirrhosis was reported in 48.7% of cases which included 13% of patients with previous or ongoing liver decompensation. Hepatocellular carcinoma (HCC) developed in 30 patients (2.5%) and 44 (3.6%) underwent liver transplantation. Regions of origin were independently associated with clinical endpoints and detectability of HDV RNA. Antiviral therapy was administered to 356 patients with different treatment uptakes in different regions. Of these, 264 patients were treated with interferon-a and 92 were treated with HBV-Nucs only. CONCLUSIONS The HDIN registry confirms the severity of hepatitis delta but also highlights the heterogeneity of patient characteristics and clinical outcomes in different regions. There is an urgent need for novel treatment options for HDV infection.
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Affiliation(s)
- Anika Wranke
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Lourdes M Pinheiro Borzacov
- Research Centre for Tropical Medicine of Rondônia - CEPEM/SESAU, Federal University of Rondônia, Rondônia, Brazil
| | - Raymundo Parana
- Hepatology Centre of the University Hospital Professor Edgar Santos, Federal University of Bahia, Salvador, Brazil
| | | | - Saeed Hamid
- Department of Hepatogastroenterology, Aga Khan University, Karachi, Pakistan
| | - Emanoil Ceausu
- Infectious Diseases, Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | - Mario Rizzetto
- Department of Internal Medicine - Gastroenterology, University of Torino, Torino, Italy
| | - Adela Turcanu
- State University of Medicine "Nicolae Testemitanu", Chisinau, Republic of Moldova
| | - Grazia A Niro
- Divisione di Gastroenterologia, Ospedale Generale Regionale "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy
| | - Farheen Lubna
- Department of Hepatogastroenterology, Aga Khan University, Karachi, Pakistan
| | - Minaam Abbas
- Ziauddin University Hospital Karachi, Karachi, Pakistan
| | | | - Maria Buti
- Liver Unit, Valle d'Hebron University Hospital and Ciberhed del Instituto CarlosIII, Barcelona, Spain
| | - Peter Ferenci
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Thomas Vanwolleghem
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium
| | - Tonya Hayden
- Centres for Disease Control and Prevention/Div of viral hepatitis, Atlanta, USA
| | | | - Adriana Motoc
- Infectious Diseases, Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania
| | - Markus Cornberg
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Centre for Infection Research (DZIF), HepNet Study-House, Hannover, Germany
| | - Zaigham Abbas
- Ziauddin University Hospital Karachi, Karachi, Pakistan
| | | | - Michael P Manns
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Centre for Infection Research (DZIF), HepNet Study-House, Hannover, Germany
| | - Heiner Wedemeyer
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Centre for Infection Research (DZIF), HepNet Study-House, Hannover, Germany
| | - Svenja Hardtke
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Centre for Infection Research (DZIF), HepNet Study-House, Hannover, Germany
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Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67:1560-1599. [PMID: 29405329 PMCID: PMC5975958 DOI: 10.1002/hep.29800] [Citation(s) in RCA: 2715] [Impact Index Per Article: 387.9] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 01/11/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Norah A Terrault
- Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, CA
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska NativeTribal Health Consortium, Anchorage, AK
| | - Kyong-Mi Chang
- Division of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center & University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Jessica P Hwang
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | | | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Tufts University School of Medicine, Boston, MA
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Tong MJ, Pan CQ, Han SB, Lu DS, Raman S, Hu K, Lim JK, Hann HW, Min AD. An expert consensus for the management of chronic hepatitis B in Asian Americans. Aliment Pharmacol Ther 2018; 47:1181-1200. [PMID: 29479728 PMCID: PMC5900913 DOI: 10.1111/apt.14577] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 10/10/2017] [Accepted: 01/27/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM To generate recommendations for the management of Asian Americans infected with HBV. METHODS These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women. RESULTS Asian American patients, HBeAg positive or negative, with HBV DNA levels >2000 IU/mL (>104 copies/mL) and ALT values above normal are candidates for anti-viral therapy. HBeAg negative patients with HBV DNA >2000 IU/mL and normal ALT levels but who have either serum albumin <3.5 g/dL or platelet count <130 000 mm3 , basal core promoter (BCP) mutations, or who have first-degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive life-long anti-viral therapy. Indications for treatment include pregnant women with high viraemia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg positive patients with risk factors, life-long surveillance for HCC with alpha-fetoprotein (AFP) testing and abdominal ultrasound examination at 6-month intervals is required. In CHB patients receiving HCC treatments, repeat imaging with contrast CT scan or MRI at 3-month intervals is strongly recommended. These guidelines have been assigned to a Class (reflecting benefit vs. risk) and a Level (assessing strength or certainty) of evidence. CONCLUSIONS Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes.
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Affiliation(s)
- M. J. Tong
- Pfleger Liver InstituteDivision of Digestive DiseasesDavid Geffen School of Medicine at UCLALos AngelesCAUSA,Liver CenterHuntington Medical Research InstitutesPasadenaCAUSA
| | - C. Q. Pan
- Division of Gastroenterology and HepatologyNYU Langone Medical CenterNew York University School of MedicineNew YorkNYUSA
| | - S.‐H. B. Han
- Pfleger Liver InstituteDivision of Digestive DiseasesDavid Geffen School of Medicine at UCLALos AngelesCAUSA
| | - D. S.‐K. Lu
- Department of Radiological SciencesDavid Geffen School of Medicine at UCLALos AngelesCAUSA
| | - S. Raman
- Department of Radiological SciencesDavid Geffen School of Medicine at UCLALos AngelesCAUSA
| | - K.‐Q. Hu
- Division of GI/HepatologySchool of MedicineUniversity of California, IrvineOrangeCAUSA
| | - J. K. Lim
- Yale Liver Center and Section of Digestive DiseasesYale University School of MedicineNew HavenCTUSA
| | - H. W. Hann
- Liver Disease Prevention CenterDivision of Gastroenterology and HepatologySidney Kimmel Jefferson Medical College of Thomas Jefferson UniversityPhiladelphiaPAUSA
| | - A. D. Min
- Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNYUSA
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28
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Sanou AM, Benkirane K, Tinto B, Cissé A, Sagna T, Ilboudo AK, Dording C, Tarnagda Z, Muller CP, Hübschen JM. Prevalence of Hepatitis B virus and Hepatitis D virus Coinfection in Western Burkina Faso and molecular characterization of the detected virus strains. Int J Infect Dis 2018; 70:15-19. [PMID: 29432880 DOI: 10.1016/j.ijid.2018.02.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 02/01/2018] [Accepted: 02/02/2018] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES In this study, we monitored the seroprevalence of HBV-HDV co-infection in different population groups in the Western part of Burkina Faso, and described the genetic diversity of the detected virus strains. METHODS Between October 2013 and December 2014, venous blood samples were collected from different cohorts (blood donors, pregnant women, outpatients) in the western region of Burkina Faso. Samples were tested for HBsAg and total anti-HDV antibodies. Positive samples were further analysed for HBV-DNA and HDV-RNA. Genotyping of the detected virus strains was done by nucleotide sequencing and phylogenetic analyses. RESULTS A total of 841 participants were included in this study. The mean age was 27.45 years (range: 7-89 years). HBsAg was found in 117 (13.9%) participants. Of the HBsAg positive samples, 4 (3.4%) were positive for total anti-HDV antibodies and negative for HDV RNA. Phylogenetic analyses based on the HBV complete genome (n=10) and S fragment sequences (n=35) showed that all strains belonged to genotype E. CONCLUSIONS Our study showed a high HBsAg prevalence, but a low rate of HDV co-infection in HBsAg carriers from western Burkina Faso. The predominance of HBV genotype E in the country was confirmed. Our findings contribute to a better understanding of the burden of HBV and HDV infection in western Burkina Faso.
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Affiliation(s)
- Armel M Sanou
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Kenza Benkirane
- Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
| | - Bachirou Tinto
- Département des Sciences Biomédicales, Laboratoire National de Référence des Fièvres Hémorragiques Virales, Centre Muraz, Bobo-Dioulasso, Burkina Faso.
| | - Assana Cissé
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Tani Sagna
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Abdoul Kader Ilboudo
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Claire Dording
- Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
| | - Zekiba Tarnagda
- Unité des Maladies à potentiel épidémiques, Maladies émergentes et Zoonoses, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
| | - Claude P Muller
- Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Laboratoire national de santé, 1, rue Louis Rech • L-3555 Dudelange, Luxembourg.
| | - Judith M Hübschen
- Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
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Luma HN, Eloumou SA, Okalla C, Donfack-Sontsa O, Koumitana R, Malongue A, Nko’Ayissi GB, Noah DN. Prevalence and Characteristics of Hepatitis Delta Virus Infection in a Tertiary Hospital Setting in Cameroon. J Clin Exp Hepatol 2017; 7:334-339. [PMID: 29234199 PMCID: PMC5715454 DOI: 10.1016/j.jceh.2017.05.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 05/15/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS Hepatitis B virus (HBV) and hepatitis D virus (HDV) coinfection is associated with more severe liver disease than HBV alone. More knowledge on the epidemiology and clinical impact of HDV-infected individuals is needed in Cameroon.We aimed at determining the frequency of anti-HDV antibody testing in hepatitis B surface antigen (HBsAg) positive patients, the proportion of anti-HDV positivity, and the characteristics of anti-HDV positive compared to anti-HDV negative patients in a tertiary hospital setting in Cameroon. METHODS A cross-sectional study was conducted. Clinical records of chronic HBV-infected patients attending the gastroenterology unit at the Douala General Hospital from 2010 to 2014 were reviewed. RESULTS Of 365 files of HBsAg-positive patients defined as chronic HBV infection, 80.5% (294) were tested for anti-HDV antibodies, among whom 10.5% (31/294) were positive. Median aspartate aminotransferase (P < 0.0001), alanine aminotransferase (P < 0.0001), and gamma glutaryl transpeptidase (P < 0.0001) were significantly higher while platelets count (P < 0.002) and prothrombin time (P < 0.0001) were significantly lower in anti-HDV positive compared to anti-HDV negative patients. Liver necroinflammation (P < 0.0001), fibrosis score (P < 0.0001), and decompensated cirrhosis (P < 0.0001) were also significantly associated with anti-HDV positivity. CONCLUSION The proportion of anti-HDV antibody positivity remains high in this setting and was significantly associated with more severe liver disease compared to those who were anti-HDV negative. More studies are needed to evaluate rates of HDV testing in other centers in Cameroon and the subregion. Preventive strategies for HBV prevention, which also apply to HDV, must still be reinforced by healthcare providers and policy makers.
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Key Words
- AFP, alpha-fetoproteins
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- Cameroon
- ELISA, enzyme-linked immunosorbent assay
- GGT, gamma glutaryl transpeptidase
- HBV
- HBV, hepatitis B virus
- HBe ab, hepatitis B e antibody
- HBeAg, hepatitis B e antigen
- HBsAg, hepatitis B surface antigen
- HCC, hepatocellular carcinoma
- HDV
- HDV, hepatitis delta virus
- HIV, human immunodeficiency virus
- PT, prothrombin time
- fibrosis
- testing
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Affiliation(s)
- Henry N. Luma
- Internal Medicine Service, Douala General Hospital, Douala, Cameroon,Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon,Address for correspondence: Henry Namme Luma, P.O. Box 4856, Douala, Cameroon. Tel.: +237 699960059; fax: +237 243 37 01 46.Henry Namme Luma, P.O. Box 4856DoualaCameroon
| | - Servais A.F.B. Eloumou
- Internal Medicine Service, Douala General Hospital, Douala, Cameroon,Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
| | - Cécile Okalla
- Internal Medicine Service, Douala General Hospital, Douala, Cameroon,Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
| | | | - Ruth Koumitana
- Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
| | - Agnes Malongue
- Internal Medicine Service, Douala General Hospital, Douala, Cameroon
| | | | - Dominique N. Noah
- Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
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C Pak S, Alastal Y, Khan Z, Darr U. Viral Hepatitis in South Korea. Euroasian J Hepatogastroenterol 2017; 7:163-165. [PMID: 29201801 PMCID: PMC5670262 DOI: 10.5005/jp-journals-10018-1240] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2017] [Accepted: 07/19/2017] [Indexed: 12/27/2022] Open
Abstract
In South Korea (S. Korea), viral hepatitis is a major public health burden. Advances in healthcare policy, evidence-based medicine, and therapeutic strategies in S. Korea have brought a rapid change in the sociodemographic and clinical characteristics of viral hepatitis. This review discusses the innovative approaches that S. Korea has taken to curb the epidemic of viral hepatitis. In addition, the efficacy of various preventive and therapeutic modalities is discussed. This review aims to provide a brief overview to guide future research direction and healthcare policy changes. How to cite this article: Pak SC, Alastal Y, Khan Z, Darr U. Viral Hepatitis in South Korea. Euroasian J Hepato-Gastroenterol 2017;7(2):163-165.
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Affiliation(s)
- Stella C Pak
- Department of Medicine, University of Toledo Medical Center, Toledo, Ohio, USA
| | - Yaseen Alastal
- Department of Medicine, University of Toledo Medical Center, Toledo, Ohio, USA
| | - Zubair Khan
- Department of Medicine, University of Toledo Medical Center, Toledo, Ohio, USA
| | - Umar Darr
- Department of Medicine, University of Toledo Medical Center, Toledo, Ohio, USA
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31
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Ifeorah IM, Bakarey AS, Adeniji JA, Onyemelukwe FN. Seroprevalence of hepatitis B and delta viruses among HIV-infected population attending anti-retroviral clinic in selected health facilities in Abuja, Nigeria. J Immunoassay Immunochem 2017; 38:608-619. [PMID: 28854102 DOI: 10.1080/15321819.2017.1372474] [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] [Indexed: 01/15/2023]
Abstract
INTRODUCTION Triple infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis D virus (HDV) is rare. There is limited data on the seroprevalence of HIV/HBV/HDV tri-infection especially in Nigeria. The aim of this study was to determine the seroprevalences of HBsAg and HDV among HIV-infected individuals attending anti-retroviral (ARV) clinics in Abuja, Nigeria. METHODS In this cohort study, blood samples were collected from 1102 (male = 450; female = 652), with age range <20 to ≥51 years (mean age = 34.0; SD = 11.5), consenting HIV-infected population attending ARV clinics at selected health facilities in Abuja, Nigeria, between April and October 2016. A well-structured questionnaire was used to capture demographic information from the respondents. Enzyme-linked immunosorbent assay (ELISA) was used to determine the seroprevalence of hepatitis B surface antigen and anti-HDV. The result was interpreted according to manufacturer's instruction. Statistical data were analyzed using SPSS software version 21, and chi-square (χ2) test was used to determine association with P < 0.05 considered significant. RESULTS Overall seroprevalences of 10.3%, 7.1%, and 0.7% for HBV, HBV/HDV, and HIV/HBV/HDV, respectively, were found among the study population. The infection rate (13.3%) peaked at age range of 31-40 years for HBV (P = 0.002), 50% at <20 years for HBV/HDV (P = 0.049), and 1.5% at 31-40 years for HIV/HBV/HDV (P = 0.202). By gender, the rate was higher in males (10.9%, 10.2%, 1.1%) than females (9.8%, 4.9%, 0.5%) for HBV, HBV/HDV, and HIV/HBV/HDV infections, respectively. However, there was no significant association between infection rate and gender. CONCLUSION This study has established that HBV and HDV prevalence is still high in the population studied and that the rate of triple infection is low. We advocate for more robust control measures for HBV which should be extended to HDV in HIV population through screening and vaccination.
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Affiliation(s)
- I M Ifeorah
- a Department of Medical Laboratory Sciences , University of Nigeria , Enugu , Nigeria
| | - A S Bakarey
- b Institute for Advanced Medical Research and Training, College of Medicine , University of Ibadan , Ibadan , Nigeria
| | - J A Adeniji
- c Department of Virology, College of Medicine , University of Ibadan , Ibadan , Nigeria
| | - F N Onyemelukwe
- a Department of Medical Laboratory Sciences , University of Nigeria , Enugu , Nigeria
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32
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Rapid expression and purification of the hepatitis delta virus antigen using the methylotropic yeast Pichia pastoris. BMC Res Notes 2017; 10:340. [PMID: 28750657 PMCID: PMC5530947 DOI: 10.1186/s13104-017-2692-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 07/26/2017] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE Patients with dual hepatitis B (HBV) and hepatitis D (HDV) virus infection are at an increased risk of progression to liver cirrhosis and hepatocellular carcinoma than patients with a single viral infection. Treatment of viral hepatitis due to dual HBV/HDV infection represents a challenge. Currently there is no vaccine against HDV. Recombinant production of HDV antigen (HDAg) is the first step towards a potential vaccine candidate and the development of assays for HDV detection. RESULTS This study demonstrates the expression of one HDAg isoform, S-HDAg, in Pichia pastoris. A recombinant vector carrying a tagged gene encoding S-HDAg under the control of the methanol-inducible promoter AOX1 was designed and integrated into P. pastoris X33. The protein, which was purified using a Ni2+ affinity column and eluted at 100-150 mM imidazole, has potential as a recombinant antigen for further study.
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33
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Goyal A, Murray JM. Roadmap to control HBV and HDV epidemics in China. J Theor Biol 2017; 423:41-52. [PMID: 28442239 DOI: 10.1016/j.jtbi.2017.04.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 04/02/2017] [Accepted: 04/06/2017] [Indexed: 01/14/2023]
Abstract
PURPOSE Hepatitis B virus (HBV) is endemic in China. Almost 10% of HBV infected individuals are also infected with hepatitis D virus (HDV) which has a 5-10 times higher mortality rate than HBV mono-infection. The aim of this manuscript is to devise strategies that can not only control HBV infections but also HDV infections in China under the current health care budget in an optimal manner. METHODS Using a mathematical model, an annual budget of $10billion was optimally allocated among five interventions namely, testing and HBV adult vaccination, treatment for mono-infected and dually-infected individuals, second line treatment for HBV mono-infections, and awareness programs. RESULTS We determine that the optimal strategy is to test and treat both infections as early as possible while applying awareness programs at full intensity. Under this strategy, an additional 19.8million HBV, 1.9million HDV infections and 0.25million lives will be saved over the next 10years at a cost-savings of $79billion than performing no intervention. Introduction of second line treatment does not add a significant economic burden yet prevents 1.4million new HBV infections and 15,000 new HDV infections. CONCLUSION Test and treatment programs are highly efficient in reducing HBV and HDV prevalence in the population. Under the current health budget in China, not only test and treat programs but awareness programs and second line treatment can also be implemented that minimizes prevalence and mortality, and maximizes economic benefits.
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Affiliation(s)
- Ashish Goyal
- School of Mathematics and Statistics, UNSW Australia, Sydney, NSW 2052, Australia.
| | - John M Murray
- School of Mathematics and Statistics, UNSW Australia, Sydney, NSW 2052, Australia
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34
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Miyaaki H, Tamada Y, Hayashi K, Taura N, Miuma S, Shibata H, Soyama A, Hidaka M, Takatsuki M, Eguchi S, Nakao K. Recurrent Hepatitis B and D Virus Infection in a Liver Transplant Recipient. Transplant Proc 2017; 49:175-177. [PMID: 28104130 DOI: 10.1016/j.transproceed.2016.11.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 10/19/2016] [Accepted: 11/09/2016] [Indexed: 12/11/2022]
Abstract
Hepatitis B virus (HBV) and hepatitis delta virus (HDV) co-infections progress rapidly and lead to cirrhosis. In Japan, the prevalence of HBV and HDV co-infected patients is low. Therefore, there are few reports of patients with HBV and HDV co-infection having undergone liver transplantation. Herein, we report a rare case of recurrence of HBV and HDV in a 41-year-old man who underwent living donor liver transplantation 4 years prior.
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Affiliation(s)
- H Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
| | - Y Tamada
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - K Hayashi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - N Taura
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - S Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - H Shibata
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - A Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - M Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - M Takatsuki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - S Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - K Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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35
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Nguyen HM, Sy BT, Trung NT, Hoan NX, Wedemeyer H, Velavan TP, Bock CT. Prevalence and genotype distribution of hepatitis delta virus among chronic hepatitis B carriers in Central Vietnam. PLoS One 2017; 12:e0175304. [PMID: 28403190 PMCID: PMC5389633 DOI: 10.1371/journal.pone.0175304] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 03/23/2017] [Indexed: 02/07/2023] Open
Abstract
Hepatitis D virus (HDV) infection plays an important role in liver diseases. However, the molecular epidemiology and impact of HDV infection in chronic hepatitis B (CHB) remain uncertain in Vietnam. This cross-sectional study aimed to investigate the prevalence and genotype distribution of HDV among HBsAg-positive patients in Central Vietnam. 250 CHB patients were tested for HDV using newly established HDV-specific RT-PCR techniques. HDV genotypes were determined by direct sequencing. Of the 250 patients 25 (10%) had detectable copies of HDV viral RNA. HDV-2 was predominant (20/25; 80%) followed by HDV-1 (5/25; 20%). Proven HDV genotypes share the Asian nomenclature. Chronic hepatitis B patients with concomitant HDV-1 showed higher HBV loads as compared to HDV-2 infected patients [median log10 (HBV-DNA copies/ml): 8.5 vs. 4.4, P = 0.036]. Our findings indicate that HDV infection is highly prevalent and HDV-2 is predominant in Central Vietnam. The data will add new information to the management of HBsAg-positive patients in a highly HBV endemic region to in- or exclude HDV infection in terms of diagnostic and treatment options.
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Affiliation(s)
- Hung Minh Nguyen
- Center for Molecular Biology, Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
- * E-mail: (CTB); (HMN)
| | - Bui Tien Sy
- Department of Molecular Biology, 108 Military Central Hospital, Hanoi, Vietnam
| | - Nguyen Thanh Trung
- Center for Molecular Biology, Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
| | - Nghiem Xuan Hoan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Heiner Wedemeyer
- German Center for Infection Research, Department for Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
| | - Thirumalaisamy P. Velavan
- Center for Molecular Biology, Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - C-Thomas Bock
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
- * E-mail: (CTB); (HMN)
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Jamjoom GA, El-Daly MM, Azhar EI, Fallatah HI, Akbar HO, Babatin M, Alghamdi AS, Dgdgi MI, Hamid MA, Qari YA, El-Kafrawy SA. Prevalence and molecular characterization of hepatitis D virus in Saudi Arabia: A single-center study. Saudi J Gastroenterol 2017; 23:176-182. [PMID: 28611341 PMCID: PMC5470377 DOI: 10.4103/sjg.sjg_515_16] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIMS Hepatitis D virus (HDV) is a defective RNA virus that is dependent on hepatitis B surface antigen (HBsAg) for transmission and replication. HDV significance arises from the possibility of poor prognosis of hepatitis B virus (HBV) infection. In Saudi Arabia, HDV prevalence varied from 8 to 32% before the HBV vaccination program and ranged from 0 to 14.7% after the vaccination program was started. The last study, performed in 2004, showed a prevalence of 8.6% in hospital-based HBV cases and 3.3% in healthy donors. The aim of this study was to investigate the prevalence and molecular characterization of HDV in chronic hepatitis B (CHB) patients at the King Abdulaziz University Hospital in Jeddah, Saudi Arabia by molecular and serological techniques. To the best of our knowledge, this is the first study to detect HDV at the molecular level in Saudi Arabia. PATIENTS AND METHODS The study included samples from 182 CHB patients from Jeddah; 13 samples with HBsAg negative were excluded. Samples were tested for HDV-Ab, viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in the HDV L-Ag region and sequence analysis. RESULTS The mean age of the participants was 44.36 years; 75.1% of the participants were Saudi nationals, 58% were males. Nine samples were positive for HDV-Ab and four were borderline; all were subjected to RT-PCR amplification. Three of the positive HDV-Ab cases and 1 borderline case were positive by RT-PCR. All the positive cases had HBV genotype D, and the positive RT-PCR cases were positive for HBV DNA. One of the HDV viremic samples was of genotype 1 by sequencing. The prevalence of HDV in the study was 7.7%, which was lower in Saudis (6.3%) than in non-Saudis (11.9%). CONCLUSION HDV coinfection does not seem to have an effect on the clinical status of the recruited CHB cases in this study. More studies are needed to investigate the genetic diversity in other areas such as the southern parts of the Kingdom.
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Affiliation(s)
- Ghazi A. Jamjoom
- Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mai M. El-Daly
- Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Esam I. Azhar
- Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hind I. Fallatah
- Unit of Gastroenterology and Hepatology, Department of Internal Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hisham O. Akbar
- Unit of Gastroenterology and Hepatology, Department of Internal Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | | | | | - Mohammed I. Dgdgi
- Gastroenterology Department, King Fahd Central Hospital, Jizan, Saudi Arabia
| | - Mohamed A. Hamid
- Viral Hepatitis Research Laboratory, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt,Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Yousef A. Qari
- Department of Medicine, Section of Gastroenterology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Sherif A. El-Kafrawy
- Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia,Address for correspondence: Dr. Sherif A. El-Kafrawy, Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah - 21589, Saudi Arabia. E-mail:
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Wyles D, Lin J. Clinical Manifestations of Acute and Chronic Hepatitis. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00042-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Jalil I, Arshad M, Rafaque Z, Raziq F, Wazir R, Malik S, Dasti JI. Seroprevalence of HDV among non-hospitalized HBsAg positive patients from KPK-region of Pakistan. Asian Pac J Trop Biomed 2016. [DOI: 10.1016/j.apjtb.2016.05.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Goyal A, Murray JM. Cost-Effectiveness of Peg-Interferon, Interferon and Oral Nucleoside Analogues in the Treatment of Chronic Hepatitis B and D Infections in China. Clin Drug Investig 2016; 36:637-48. [DOI: 10.1007/s40261-016-0409-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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40
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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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Nomanee H, Rostami S, Taghi Shakeri M, Meshkat Z. Evidence of Hepatitis D Virus Infection in HBsAg Positive Subjects of Mashhad, North-East of Iran. Jundishapur J Microbiol 2015; 8:e7214. [PMID: 26568806 PMCID: PMC4639943 DOI: 10.5812/jjm.7214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Revised: 09/21/2012] [Accepted: 09/29/2012] [Indexed: 01/05/2023] Open
Affiliation(s)
- Hosain Nomanee
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Sina Rostami
- Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, IR Iran
| | - Mohammad Taghi Shakeri
- Department of Biostatistics, Public Health School, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Zahra Meshkat
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran
- Corresponding author: Zahra Meshkat, Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran. Tel: +98-5138012453, Fax: +98-5138002960, E-mail:
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Romeo R, Perbellini R. Hepatitis delta virus: Making the point from virus isolation up to 2014. World J Hepatol 2015; 7:2389-2395. [PMID: 26464754 PMCID: PMC4598609 DOI: 10.4254/wjh.v7.i22.2389] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2015] [Accepted: 09/18/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with hepatitis delta virus (HDV) has lately regained clinical importance because of the recent evidence of increasing prevalence in several European countries, due to immigration from highly endemic areas. HDV requires the mandatory presence of hepatitis B virus (HBV) for propagation to hepatocytes. It is transmitted by the same routes of HBV and it can be acquired either by co-infection (simultaneous transmission of the two viruses) or super-infection (acquisition of HDV by an already chronic carrier of HBV). As a consequence, every HBV carrier is potentially at risk for HDV superinfection. Since the clinical course of super-infection can be severe, early diagnosis of HDV infection is necessary.
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43
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Yacoubi L, Brichler S, Mansour W, Le Gal F, Hammami W, Sadraoui A, Ben Mami N, Msaddek A, Cheikh I, Triki H, Gordien E. Molecular epidemiology of hepatitis B and Delta virus strains that spread in the Mediterranean North East Coast of Tunisia. J Clin Virol 2015; 72:126-32. [PMID: 26513762 DOI: 10.1016/j.jcv.2015.10.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Revised: 09/28/2015] [Accepted: 10/04/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Tunisia is classified as an area of middle endemic for hepatitis B virus (HBV) infection, however little is known about hepatitis Delta virus (HDV) infection. OBJECTIVES This study aimed to address the prevalence of HDV infection, to identify possible risks factors, and to analyze the genetic diversity of HDV strains that are spreading in Tunisia. STUDY DESIGN A retrospective large-scale study including 1615 HBsAg positive patients, native of the North East coast of Tunisia, recruited from Gastroenterology departments, was conducted. Demographic, epidemiological, ethnical, clinical and biological data were recorded. HBV and HDV serological analyses and DNA and RNA viral load quantification were performed. Genotyping of HBV and HDV strains was performed using nucleotide sequencing followed by phylogenetic analyses. RESULTS The study population included 819 (50.7%) men and 796 (49.3%) women; aged 12-90 years (mean age 41±13 years). A very low prevalence of HDV infection, 2% was observed. No risk factor, except a history of hospitalization for surgery was found. All HDV strains belonged to genotype 1, with a wide distribution within the HDV-1 group. They all share the African amino acid marker, a serine at position 202 of the large Delta protein. HBV genotypes were distributed as follows: HBV/D1 (56.8%), HBV/D7 (40.9%), and HBV/A2 (2.3%). CONCLUSION Tunisia is a low endemic region for HDV infection, due to an efficient policy of HBV infection control. HDV-1 is the sole genotype found, with a high diversity within this group. Further studies are ongoing in order to better characterize and manage the HBV/HDV-infected patients according to the genetic variability of the viral strains.
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Affiliation(s)
- Lamia Yacoubi
- Laboratoire de Virologie Clinique, Institut Pasteur de Tunis, Tunisia; Carthage University, Tunis, Tunisia
| | - Ségolène Brichler
- Laboratoire de Bactériologie, Virologie, Hygiène, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, UFR Santé Médecine Biologie Humaine, Université Paris 13, Bobigny, France
| | - Wael Mansour
- Laboratoire de Bactériologie, Virologie, Hygiène, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, UFR Santé Médecine Biologie Humaine, Université Paris 13, Bobigny, France
| | - Frédéric Le Gal
- Laboratoire de Bactériologie, Virologie, Hygiène, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, UFR Santé Médecine Biologie Humaine, Université Paris 13, Bobigny, France
| | - Walid Hammami
- Laboratoire de Virologie Clinique, Institut Pasteur de Tunis, Tunisia
| | - Amel Sadraoui
- Laboratoire de Virologie Clinique, Institut Pasteur de Tunis, Tunisia
| | - Nabil Ben Mami
- Department of Gastroenterology B, La Rabta Hospital, Tunisia; Tunis El Manar University, Tunis, Tunisia
| | - Azouz Msaddek
- Department of Gastroenterology, Tahar Maamouri Hospital, Nabeul, Tunisia; Tunis El Manar University, Tunis, Tunisia
| | - Imed Cheikh
- Department of Gastroenterology, Habib Bougatfa Hospital, Bizerte, Tunisia; Tunis El Manar University, Tunis, Tunisia
| | - Henda Triki
- Laboratoire de Virologie Clinique, Institut Pasteur de Tunis, Tunisia; Tunis El Manar University, Tunis, Tunisia.
| | - Emmanuel Gordien
- Laboratoire de Bactériologie, Virologie, Hygiène, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, UFR Santé Médecine Biologie Humaine, Université Paris 13, Bobigny, France.
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Motamedifar M, Taheri M, Lankarani KB, Gholami M, Lari MA, Faramarzi H, Sarvari J. The Prevalence and Risk Factors of Hepatitis Delta Virus in HIV/HBV Co-Infected Patients in Shiraz, Iran, 2012. IRANIAN JOURNAL OF MEDICAL SCIENCES 2015; 40:448-53. [PMID: 26379352 PMCID: PMC4567605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 06/23/2014] [Accepted: 07/13/2014] [Indexed: 11/13/2022]
Abstract
Evidence has shown that liver disease caused by hepatitis viruses can be more aggressive and severe in HIV infected subjects. Therefore, the present cross-sectional study aimed to evaluate the seroprevalence of HDV infection among HIV/HBV co-infected clients in Shiraz, southwest Iran. In this study, 178 patients co-infected with HBV and HIV individuals were enrolled. The diagnosis of HIV infection was documented based on serological assays. The demographic and complementary data were collected by a questionnaire. HBsAg and HDV Ab were detected by commercial quantitative enzyme linked immunosorbent assay kits according to the manufacturer's instructions. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The mean age of the participants was 37.4±7.4 years (range 22-63). 175 (98.4 %) patients were male and 3 (1.6 %) were female. Among 178 patients co-infected with HIV/HBV, 35 cases (19.7%, 95% CI: 14%-25%) were anti-HDV positive and 143 (80.3%) were negative for anti-HDV. HDV exposure in HIV/HBV co-infected patients was associated with blood transfusion (P=0.002, OR: 14.3) and prison history (P=0.01, OR: 2.31) but not with age, marital status, unsafe sex contact, and injection drug abuse. Our data showed a relatively high prevalence of HDV infection in HIV infected population in Shiraz, Iran. The high frequency of HDV Ab in patients with blood transfusion and prison history reveals that HDV transmission occurs more frequently in the parental route than sexual contacts; therefore, blood screening for HDV diagnosis in the high-risk group is recommended.
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Affiliation(s)
- Mohammad Motamedifar
- Shiraz HIV/AIDS Research Center (SHARC), Shiraz University of Medical Sciences, Shiraz, Iran,Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Taheri
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kamran Bagheri Lankarani
- Health Policy Research Center (HPRC), School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mina Gholami
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahmood Amini Lari
- Shiraz HIV/AIDS Research Center (SHARC), Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Faramarzi
- Shiraz HIV/AIDS Research Center (SHARC), Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jamal Sarvari
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran,Correspondence: Jamal Sarvari, PhD; Assistant Professor of Virology, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71348- 45794, Shiraz, Iran Tel/Fax: +98 71 32304356
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Abbas Z, Abbas M. Management of hepatitis delta: Need for novel therapeutic options. World J Gastroenterol 2015; 21:9461-9465. [PMID: 26327754 PMCID: PMC4548107 DOI: 10.3748/wjg.v21.i32.9461] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Accepted: 06/10/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis D virus (HDV) is the smallest single stranded RNA virus infecting humans. The hepatitis B surface antigen envelope protein protects the HDV nucleocapsid antigen and provides a means for the virus to enter and exit the hepatocyte. Hepatitis B and D viruses exploit the human sodium taurocholate co-transporting polypeptide (NTCP), a receptor, for their entry into hepatocytes. Prenylation of the large delta antigen is a critical determinant of HDV particle assembly. Treatment with pegylated interferon results in sustained virological response six months post-treatment in one fourth of the patients. Nucleos(t)ide analogs (NAs) have been widely tested in hepatitis delta, but they appear to be ineffective. Combination treatment of NAs with interferon also proved to be disappointing so there is a need for novel therapeutic options. The receptor function of NTCP is blocked by Myrcludex B, a synthetic N-acylated preS1 lipopeptide that competes with infectious virions for receptor binding. There are already some approved drugs available, including irbesartan, ezetimibe, and ritonavir and cyclosporin A, with documented inhibitory effects on NTCP’s metabolic function. These drugs may have a role in HDV treatment. Interference with host-mediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation may become an important tool to control HDV infection and prevent replication. Lonafarnib, a prenylation inhibitor significantly reduces virus levels in hepatitis delta patients. Antisense oligodeoxynucleotides which are complementary to genomic HDV ribozyme self-cleavage site and stem I regions can inhibit genomic HDV ribozyme activity.
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Abstract
Hepatitis D is caused by the hepatitis D virus (HDV), a unique RNA pathogen that requires the hepatitis B surface antigen (HBsAg) to infect. Hepatitis D is transmitted by the parenteral route. The main susceptible group is patients with chronic HBsAg infection who become superinfected with the virus. Hepatitis D occurs throughout the globe, but control of hepatitis B virus (HBV) in the last two decades has consistently diminished the circulation of HDV in industrialized countries. However, hepatitis D remains a medical issue for injecting drug users (IDUs), as well as immigrants from endemic HDV areas, who are reintroducing the infection in Europe.
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Affiliation(s)
- Mario Rizzetto
- Division of Gastroenterology, University of Torino, 10126 Torino, Italy
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47
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Abbas Z, Ali SS, Shazi L. Interferon alpha versus any other drug for chronic hepatitis D. Hippokratia 2015. [DOI: 10.1002/14651858.cd011727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Zaigham Abbas
- Sindh Institute of Urology and Transplantation; Department of Hepatogastroenterology; Diwan Complex Chand Bibi Road Karachi Sindh Pakistan
| | | | - Lubna Shazi
- Aga Khan University Hospital; Bioethics; Kh-e-Saadi, Phase 7, DHA Karachi Pakistan M-98/3
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48
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Lin HH, Lee SSJ, Yu ML, Chang TT, Su CW, Hu BS, Chen YS, Huang CK, Lai CH, Lin JN, Wu JC. Changing hepatitis D virus epidemiology in a hepatitis B virus endemic area with a national vaccination program. Hepatology 2015; 61:1870-9. [PMID: 25677884 DOI: 10.1002/hep.27742] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2014] [Revised: 01/27/2015] [Accepted: 02/03/2015] [Indexed: 12/13/2022]
Abstract
UNLABELLED The emergence of hepatitis D virus (HDV) infection in the era of widespread HBV vaccination has not been described before. We aimed to investigate the changing epidemiology of HDV infection among high- and low-risk populations after an outbreak of human immunodeficiency virus (HIV) infection among injection drug users (IDUs) in Taiwan. A prospective, multicenter, cohort study of 2,562 hepatitis B surface antigen (HBsAg)-positive individuals was conducted to determine the prevalence, genotype, and risk factors of HDV infection from 2001 through 2012. The prevalence rates of HDV infection were 74.9%, 43.9%, 11.4%, 11.1%, and 4.4% among HIV-infected IDUs, HIV-uninfected IDUs, HIV-infected men who have sex with men, HIV-infected heterosexuals, and the general population of HBsAg-positive subjects, respectively. A significant increase in the trend of HDV prevalence from 38.5% to 89.8% was observed in HIV-infected IDUs (odds ratio = 3.06; 95% confidence interval: 1.68-5.56; P = 0.0002). In multivariate analysis, injection drug use, hepatitis C virus infection, HIV infection, serum HBsAg level ≧250 IU/mL, duration of drug use, and older age were significant factors associated with HDV infection. HDV genotype IV (72.2%) was the prevalent genotype circulating among IDUs, whereas genotype II was predominant in the non-IDU populations (73.3%). In the HIV cohort born after 1987 who were HBsAg negative, over half (52.9%) had antibody to hepatitis B surface antigen antibody levels of <10 mIU/mL and there was a significantly higher HBsAg seroprevalence in the HIV cohort, compared to the control group (8.1% vs. 0.0%; P = 0.02). CONCLUSION In the era of HBV vaccination, IDUs and HIV-infected individuals have emerged as high-risk groups and a reservoir for HDV infection. Effective strategies are needed to curb the reemerging epidemic of HDV infection in these high-risk groups.
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Affiliation(s)
- Hsi-Hsun Lin
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Medicine and Infection Control, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Susan Shin-Jung Lee
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.,Department of Medicine, Medical College of National Cheng Kung University, Tainan, Taiwan
| | - Chien-Wei Su
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Bor-Shen Hu
- Section of Infectious Diseases, Taipei City Hospital, Taipei City Government, Taipei, Taiwan
| | - Yaw-Sen Chen
- Department of General Surgery, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chun-Kai Huang
- Department of Medicine and Infection Control, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chung-Hsu Lai
- Department of Medicine and Infection Control, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Jiun-Nong Lin
- Department of Medicine and Infection Control, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Translational Research Division, Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan
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Abbas Z, Abbas M, Abbas S, Shazi L. Hepatitis D and hepatocellular carcinoma. World J Hepatol 2015; 7:777-786. [PMID: 25914778 PMCID: PMC4404383 DOI: 10.4254/wjh.v7.i5.777] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Revised: 10/05/2014] [Accepted: 01/19/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis D virus (HDV) is a defective circular shape single stranded HDV RNA virus with two types of viral proteins, small and large hepatitis D antigens, surrounded by hepatitis B surface antigen. Superinfection with HDV in chronic hepatitis B is associated with a more threatening form of liver disease leading to rapid progression to cirrhosis. In spite of some controversy in the epidemiological studies, HDV infection does increase the risk of hepatocellular carcinoma (HCC) compared to hepatitis B virus (HBV) monoinfection. Hepatic decompensation, rather than development of HCC, is the first usual clinical endpoint during the course of HDV infection. Oxidative stress as a result of severe necroinflammation may progress to HCC. The large hepatitis D antigen is a regulator of various cellular functions and an activator of signal transducer and activator of transcription (STAT)3 and the nuclear factor kappa B pathway. Another proposed epigenetic mechanism by which HCC may form is the aberrant silencing of tumor suppressor genes by DNA Methyltransferases. HDV antigens have also been associated with increased histone H3 acetylation of the clusterin promoter. This enhances the expression of clusterin in infected cells, increasing cell survival potential. Any contribution of HBV DNA integration with chromosomes of infected hepatocytes is not clear at this stage. The targeted inhibition of STAT3 and cyclophilin, and augmentation of peroxisome proliferator-activated receptor γ have a potential therapeutic role in HCC.
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Prevalence of hepatitis D virus infection among hepatitis B virus-infected individuals in India. Indian J Gastroenterol 2015; 34:164-8. [PMID: 25902955 DOI: 10.1007/s12664-015-0555-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 03/30/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND The prevalence of hepatitis D virus (HDV) infection among persons with hepatitis B virus (HBV) infection shows geographic variation and has declined in recent times in several regions. In India, studies during the 1990s showed highly variable anti-HDV prevalence rates among HBV-infected persons; however, data using molecular testing and recent data are not available. We therefore studied the prevalence of HDV infection in HBV-infected patients using tests for anti-HDV and HDV ribonucleic acid (RNA). METHODS Two cohorts of patients with HBV infection were enrolled (cohort A, n = 150, January to December 2012; cohort B, n = 168, October 2013 to April 2014). Sera from cohort A were tested for IgG anti-HDV using three enzyme immunoassays and those from cohort B for IgG anti-HDV using an enzyme immunoassay and for HDV RNA using a real-time amplification assay. RESULTS Of the 318 subjects (259 male; mean age 36.9 years), 161 (50.6 %) had chronic hepatitis B, 101 (31.8 %) had cirrhosis, 52 (16.3 %) had acute viral hepatitis, and 4 (1.3 %) had acute liver failure. In cohort A, all specimens tested negative for anti-HDV antibodies using all the three assays. In cohort B, all specimens tested negative for anti-HDV IgG as well as HDV RNA. CONCLUSION Our data indicate that HDV infection is uncommon in northern India.
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