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Jargalsaikhan O, Shao W, Ichimura-Shimizu M, Ishimaru S, Koma T, Nomaguchi M, Ogawa H, Tachibana S, Chimeddorj B, Batchuluun K, Tseveenjav A, Magvan B, Enkhbat B, Lkhagvadorj S, Mendjargal A, Ganbaatar L, Irahara M, Akaike M, Boldbaatar D, Tsuneyama K. Histopathological Features of Hepatocellular Carcinoma in Patients with Hepatitis B and D Virus Infection: A Single-Institution Study in Mongolia. Cancers (Basel) 2025; 17:432. [PMID: 39941800 PMCID: PMC11815750 DOI: 10.3390/cancers17030432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 01/16/2025] [Accepted: 01/24/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Viral hepatitis, particularly hepatitis B (HBV) and hepatitis C (HCV), is highly prevalent in Mongolia. Moreover, Mongolia has the highest prevalence of hepatitis delta virus (HDV) globally, with over 60% of HBV-infected individuals also co-infected with HDV. Since HBV/HDV infections accelerate liver disease progression more compared to HBV infection alone, urgent national health measures are required. Method: This study presents a clinicopathological analysis of 49 hepatocellular carcinoma cases surgically resected at the Mongolia-Japan Hospital of the Mongolian National University of Medical Sciences. Results: HBV infection was found in 27 (55.1%) cases of all HCC cases. Immunohistochemical staining of the liver revealed that 14 (28.6%) cases were HDV antigen-positive in the HCC cases. HDV-positive cases exhibited significantly higher inflammatory activity compared to HDV-negative cases, with lymphocytic infiltrates predominantly composed of CD4-positive cells. Furthermore, HDV-positive cells were spatially distinct from HBs antigen-positive cells, suggesting that HDV-infected cells may interfere with HBV replication. No significant differences in fibrosis or in tumor characteristics were observed between the HDV-positive and negative cases. Early diagnosis of HBV/HDV infections is essential for appropriate treatment and to prevent further domestic transmission of the virus. However, routine testing for HDV infection is rarely conducted in Mongolia. Since HDV-positive cells are morphologically indistinguishable from surrounding HDV-negative cells, routine histopathological analysis may not be sufficient enough to detect HDV infection. Conclusions: Based on this clinicopathological study, CD4 and CD8 immunostaining can be considered an adjunctive diagnostic tool in cases with significant lymphocytic infiltration and hepatocellular damage. Additionally, HDV screening using blood and tissue samples may be recommended to ensure accurate diagnosis.
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Affiliation(s)
- Orgil Jargalsaikhan
- Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan; (O.J.); (S.I.); (H.O.); (S.T.); (K.T.)
| | - Wenhua Shao
- Department of Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan;
| | - Mayuko Ichimura-Shimizu
- Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan; (O.J.); (S.I.); (H.O.); (S.T.); (K.T.)
| | - Soichiro Ishimaru
- Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan; (O.J.); (S.I.); (H.O.); (S.T.); (K.T.)
| | - Takaaki Koma
- Department of Microbiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan; (T.K.); (M.N.)
| | - Masako Nomaguchi
- Department of Microbiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan; (T.K.); (M.N.)
| | - Hirohisa Ogawa
- Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan; (O.J.); (S.I.); (H.O.); (S.T.); (K.T.)
| | - Shotaro Tachibana
- Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan; (O.J.); (S.I.); (H.O.); (S.T.); (K.T.)
| | - Battogtokh Chimeddorj
- Institute of Biomedical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (K.B.); (A.T.)
- Department of Microbiology and Infection Prevention Control, School of Biomedicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia;
| | - Khongorzul Batchuluun
- Institute of Biomedical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (K.B.); (A.T.)
| | - Anujin Tseveenjav
- Institute of Biomedical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (K.B.); (A.T.)
| | - Battur Magvan
- Department of Microbiology and Infection Prevention Control, School of Biomedicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia;
| | - Bayarmaa Enkhbat
- Department of Pathology and Forensic Medicine, School of Biomedicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (B.E.); (S.L.)
| | - Sayamaa Lkhagvadorj
- Department of Pathology and Forensic Medicine, School of Biomedicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (B.E.); (S.L.)
- Surgery Department, Mongolia–Japan Hospital of Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (A.M.); (L.G.)
| | - Adilsaikhan Mendjargal
- Surgery Department, Mongolia–Japan Hospital of Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (A.M.); (L.G.)
| | - Lkhagvadulam Ganbaatar
- Surgery Department, Mongolia–Japan Hospital of Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia; (A.M.); (L.G.)
| | - Minoru Irahara
- Department of Obstetrics and Gynecology, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan;
| | - Masashi Akaike
- Department of Medical Education, Graduate School of Biomedical Sciences, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan;
| | - Damdindorj Boldbaatar
- Department of Physiology, School of Bio-Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia;
| | - Koichi Tsuneyama
- Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan; (O.J.); (S.I.); (H.O.); (S.T.); (K.T.)
- Department of Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan;
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2
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Giorgio M, Ramírez Ladino KA, López G, Sosa Rojas M, Outon E, Delfino CM. Frequency of hepatitis D virus with different hepatitis B virus serological markers and coinfections in hospital patients from Argentina: synchronous testing of anti-HDV antibodies and HDV RNA. Eur J Gastroenterol Hepatol 2024:00042737-990000000-00417. [PMID: 39373637 DOI: 10.1097/meg.0000000000002857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/08/2024]
Abstract
BACKGROUND Hepatitis D virus (HDV) RNA-positive cases with total anti-HDV antibodies nonreactive were documented. Moreover, HDV infection was observed in subjects with occult hepatitis B virus infection. The prevalence of HDV infection in Argentina is low; however, further research in different populations is needed. OBJECTIVE This study aimed to perform synchronous HDV detection in reactive hepatitis B virus patients treated in a public hospital in the province of Buenos Aires, Argentina, some of whom were coinfected with hepatitis C virus and/or HIV. A total of 189 hepatitis B virus-reactive serum samples with or without hepatitis C virus and/or HIV coinfection were synchronously analyzed for anti-HDV antibodies and HDV RNA. RESULTS HDV prevalence was 4.2% with HDV RNA found in 61 samples, most of which were nonreactive to anti-HDV antibodies and hepatitis B surface antigen. Genotype 1 was identified in all HDV sequences. Moreover, triple and quadruple infections were observed, showing a high frequency of HDV infection in hospitalized patients not following the recommended diagnostic algorithm. CONCLUSIONS This study is evidence that the synchronous testing of anti-HDV antibodies and HDV RNA is necessary for the diagnosis of HDV infection in Argentina. Finally, further research is necessary to identify high-risk populations and improve prevention and control strategies for triple and quadruple infections and their potential consequences.
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Affiliation(s)
- Marianela Giorgio
- Laboratorio de Virología, Hospital Interzonal General de Agudos 'Dr. Pedro Fiorito', Avellaneda, Buenos Aires, Argentina
| | - Kelly Alejandra Ramírez Ladino
- Universidad de Buenos Aires (UBA) - Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM). Ciudad Autónoma de Buenos Aires, Argentina
| | - Guido López
- Universidad de Buenos Aires (UBA) - Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM). Ciudad Autónoma de Buenos Aires, Argentina
| | - Maricel Sosa Rojas
- Universidad de Buenos Aires (UBA) - Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM). Ciudad Autónoma de Buenos Aires, Argentina
| | - Estela Outon
- Laboratorio de Virología, Hospital Interzonal General de Agudos 'Dr. Pedro Fiorito', Avellaneda, Buenos Aires, Argentina
| | - Cecilia María Delfino
- Universidad de Buenos Aires (UBA) - Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM). Ciudad Autónoma de Buenos Aires, Argentina
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3
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Tassachew Y, Belyhun Y, Abebe T, Mihret A, Teffera T, Ababi G, Shewaye A, Desalegn H, Aseffa A, Mulu A, Howe R, Liebert UG, Maier M. Magnitude and genotype of hepatitis delta virus among chronic hepatitis B carriers with a spectrum of liver diseases in Ethiopia. Ann Hepatol 2023; 28:100770. [PMID: 36220615 DOI: 10.1016/j.aohep.2022.100770] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 09/23/2022] [Accepted: 09/28/2022] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Chronic hepatitis D infection contributes substantially to the progression of chronic liver disease, especially in most low and middle-income countries, where hepatitis B virus-related chronic liver disease is endemic. Therefore, this study aimed to determine the magnitude and genotype of hepatitis delta virus (HDV) among patients with chronic hepatitis B (CHB)-related liver diseases in Ethiopia. PATIENTS AND METHODS In this cross-sectional study, 323 known HBsAg positive individuals comprising 220 patients with CHB-related liver diseases [121 advanced liver diseases (hepatocellular carcinoma /HCC/ and non-HCC) and 99 chronic hepatitis (CH)], and 103 symptomless blood donors (BD) were enrolled. An ELISA kit was employed to determine HDV infection, and quantitative real-time PCR was used to detect HDV RNA. In addition, a non-coding genomic RNA region was sequenced for genotyping and phylogenetic analysis. RESULTS Irrespective of the stage of liver disease, the overall magnitude of HDV was 7.7% (25/323). The frequency of anti-HDV increases with the severity of liver disease, 1.9%, 4%, 10%, and 21.3% among BD, CH, non-HCC, and HCC patients, respectively. HDV RNA has been detected in 1.54 %(5/323) cases with a mean viral load of 4,010,360 IU/ml. All isolates were found to be HDV genotype 1. CONCLUSIONS The magnitude of HDV infection increased with the severity of liver disease, indicating HDV infection is more common among patients with CHB-related liver diseases in Ethiopia.
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Affiliation(s)
- Yayehyirad Tassachew
- Department of Microbiology, Immunology, and Parasitology, School of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Institute of Virology, University of Leipzig, 04103 Leipzig, Germany; Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia; School of Medicine, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia.
| | - Yeshambel Belyhun
- Institute of Virology, University of Leipzig, 04103 Leipzig, Germany; School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Tamrat Abebe
- Department of Microbiology, Immunology, and Parasitology, School of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Adane Mihret
- Department of Microbiology, Immunology, and Parasitology, School of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia
| | - Tezazu Teffera
- School of Medicine, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia
| | - Girma Ababi
- School of Medicine, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia; Yanet Specialized Clinic, Hawassa, Ethiopia
| | - Abate Shewaye
- Department of Internal Medicine, School of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Adera Medical Center PLC, Addis Ababa, Ethiopia
| | - Hailemichael Desalegn
- Department of Internal Medicine, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Abraham Aseffa
- Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia
| | - Andargachew Mulu
- Institute of Virology, University of Leipzig, 04103 Leipzig, Germany; Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia
| | - Rawleigh Howe
- Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia
| | - Uwe G Liebert
- Institute of Virology, University of Leipzig, 04103 Leipzig, Germany
| | - Melanie Maier
- Institute of Virology, University of Leipzig, 04103 Leipzig, Germany
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Magvan B, Kloeble AA, Ptok J, Hoffmann D, Habermann D, Gantumur A, Paluschinski M, Enebish G, Balz V, Fischer JC, Chimeddorj B, Walker A, Timm J. Sequence diversity of hepatitis D virus in Mongolia. Front Med (Lausanne) 2023; 10:1108543. [PMID: 37035318 PMCID: PMC10077969 DOI: 10.3389/fmed.2023.1108543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 02/06/2023] [Indexed: 04/11/2023] Open
Abstract
Introduction The Hepatitis Delta Virus (HDV) is a defective, single-stranded RNA virusoid encoding for a single protein, the Hepatitis Delta Antigen (HDAg), which requires the hepatitis B virus (HBV) envelope protein (HBsAg) for its transmission. Currently, hepatitis D is the most aggressive form of viral hepatitis and treatment options are limited. Worldwide 12 million people are chronically infected with HDV being at high risk for progression to cirrhosis and development of liver cancer. Objectives Although it is well established that Mongolia is the country with the highest prevalence of HDV infections, the information on the molecular epidemiology and factors contributing to HDV sequence diversity are largely unclear. The aim of the study was to characterize the sequence diversity of HDV in rural areas from Mongolia and to determine the extent of HLA class I-associated selection pressure. Patients and methods From the HepMongolia cohort from rural areas in Mongolia, 451 HBsAg-positive individuals were selected and anti-HDV, HDV-RNA and the sequence of the large HDAg was determined. For all individuals the HLA class I locus was genotyped. Residues under selection pressure in the presence of individual HLA class I types were identified with the recently published analysis tool HAMdetector. Results Of 431 HBsAg positive patients, 281 were anti-HDV positive (65%), and HDV-RNA could be detected in 207 of 281 (74%) of patients. The complete large HDAg was successfully sequenced from 131 samples. Phylogenetic analysis revealed that all Mongolian HDV isolates belong to genotype 1, however, they separate into several different clusters without clear regional association. In turn, from phylogeny there is strong evidence for recent local transmission events. Importantly, we found multiple residues with strong support for HLA class I-associated selection pressure consistent with a functional CD8+ T cell response directed against HDV. Conclusion HDV isolates from Mongolia are highly diverse. The molecular epidemiology suggests circulation of multiple subtypes and provides evidence for ongoing recent transmissions.
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Affiliation(s)
- Battur Magvan
- Department of Microbiology and Infection Prevention and Control, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Anne Alina Kloeble
- Institute of Virology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Johannes Ptok
- Institute of Virology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Daniel Hoffmann
- Bioinformatics and Computational Biophysics, Faculty of Biology, University of Duisburg-Essen, Essen, Germany
| | - Daniel Habermann
- Bioinformatics and Computational Biophysics, Faculty of Biology, University of Duisburg-Essen, Essen, Germany
| | - Anuujin Gantumur
- Department of Microbiology and Infection Prevention and Control, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | | | - Gerelmaa Enebish
- Department of Microbiology and Infection Prevention and Control, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Vera Balz
- Institute for Transplant Diagnostics and Cell Therapeutics, University Hospital Dusseldorf, Dusseldorf, Germany
| | - Johannes C. Fischer
- Institute for Transplant Diagnostics and Cell Therapeutics, University Hospital Dusseldorf, Dusseldorf, Germany
| | - Battogtokh Chimeddorj
- Department of Microbiology and Infection Prevention and Control, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
- Institute of Biomedical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Andreas Walker
- Institute of Virology, University Hospital Düsseldorf, Düsseldorf, Germany
- *Correspondence: Andreas Walker,
| | - Jörg Timm
- Institute of Virology, University Hospital Düsseldorf, Düsseldorf, Germany
- Jörg Timm,
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5
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Dambadarjaa D, Radnaa O, Khuyag SO, Shagdarsuren OE, Enkhbayar U, Mukhtar Y, Tsogzolbaatar EO, Nyam G, Shaarii S, Singh P, Takahashi M, Namdag B, Okamoto H. Hepatitis B, C, and D Virus Infection among Population Aged 10-64 Years in Mongolia: Baseline Survey Data of a Nationwide Cancer Cohort Study. Vaccines (Basel) 2022; 10:1928. [PMID: 36423023 PMCID: PMC9696522 DOI: 10.3390/vaccines10111928] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 10/25/2022] [Accepted: 10/31/2022] [Indexed: 07/30/2023] Open
Abstract
Hepatitis B, C, and D virus infections are a major public health problem, and Mongolia has one of the highest prevalences of dual and triple infections in the world. We aimed to determine the seroprevalence of hepatitis infection and dual or triple hepatitis infections among 10-64-year-olds. A questionnaire was used to identify risk factors for hepatitis infection, and seromarkers were measured by the fully automated immunologic analyzer HISCL-5000. Among a total of 10,040 participants, 8.1% of the population aged 10-64 was infected with HBV, 9.4% with HCV, and 0.4% with HBV and HCV, and the prevalence of the disease varied by age, sex, and the area of residence. Young people were particularly unaware of their hepatitis infection status. A small proportion of children aged 10 to 19 years and the majority of adults younger than 30 years were unaware of their HBV and HCV infection. Men were also more likely to be unaware of their HBV and HCV infection status than women. The results suggested that the prevalence of infection in the general population is high and that most people are unaware that they are infected or have become chronic carriers. Identifying mono-, co-, or triple-infection status is critical to prevent the rapid progression of liver disease among the Mongolian population.
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Affiliation(s)
- Davaalkham Dambadarjaa
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Otgonbayar Radnaa
- School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Ser-Od Khuyag
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Oyu-Erdene Shagdarsuren
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Uranbaigali Enkhbayar
- School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Yerkyebulan Mukhtar
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Enkh-Oyun Tsogzolbaatar
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Gunchmaa Nyam
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Shatar Shaarii
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Pramil Singh
- Transdisciplinary Tobacco Research Program, Loma Linda University Cancer Center, Loma Linda, CA 92354, USA
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan
| | - Bira Namdag
- School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan
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6
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Torrens L, Puigvehí M, Torres-Martín M, Wang H, Maeda M, Haber PK, Leonel T, García-López M, Esteban-Fabró R, Leow WQ, Montironi C, Torrecilla S, Varadarajan AR, Taik P, Campreciós G, Enkhbold C, Taivanbaatar E, Yerbolat A, Villanueva A, Pérez-del-Pulgar S, Thung S, Chinburen J, Letouzé E, Zucman-Rossi J, Uzilov A, Neely J, Forns X, Roayaie S, Sia D, Llovet JM. Hepatocellular Carcinoma in Mongolia Delineates Unique Molecular Traits and a Mutational Signature Associated with Environmental Agents. Clin Cancer Res 2022; 28:4509-4520. [PMID: 35998012 PMCID: PMC7613712 DOI: 10.1158/1078-0432.ccr-22-0632] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/25/2022] [Accepted: 08/19/2022] [Indexed: 12/14/2022]
Abstract
PURPOSE Mongolia has the world's highest incidence of hepatocellular carcinoma (HCC), with ∼100 cases/100,000 inhabitants, although the reasons for this have not been thoroughly delineated. EXPERIMENTAL DESIGN We performed a molecular characterization of Mongolian (n = 192) compared with Western (n = 187) HCCs by RNA sequencing and whole-exome sequencing to unveil distinct genomic and transcriptomic features associated with environmental factors in this population. RESULTS Mongolian patients were younger, with higher female prevalence, and with predominantly HBV-HDV coinfection etiology. Mongolian HCCs presented significantly higher rates of protein-coding mutations (121 vs. 70 mutations per tumor in Western), and in specific driver HCC genes (i.e., APOB and TSC2). Four mutational signatures characterized Mongolian samples, one of which was novel (SBS Mongolia) and present in 25% of Mongolian HCC cases. This signature showed a distinct substitution profile with a high proportion of T>G substitutions and was significantly associated with a signature of exposure to the environmental agent dimethyl sulfate (71%), a 2A carcinogenic associated with coal combustion. Transcriptomic-based analysis delineated three molecular clusters, two not present in Western HCC; one with a highly inflamed profile and the other significantly associated with younger female patients. CONCLUSIONS Mongolian HCC has unique molecular traits with a high mutational burden and a novel mutational signature associated with genotoxic environmental factors present in this country.
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Affiliation(s)
- Laura Torrens
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Translational research in Hepatic Oncology, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Marc Puigvehí
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Hepatology Section, Gastroenterology Department, Parc de Salut Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Catalonia, Spain
| | - Miguel Torres-Martín
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Translational research in Hepatic Oncology, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | | | - Miho Maeda
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Philipp K. Haber
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Thais Leonel
- Liver Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Mireia García-López
- Liver Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Roger Esteban-Fabró
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Translational research in Hepatic Oncology, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Wei Qiang Leow
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
| | - Carla Montironi
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Translational research in Hepatic Oncology, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Sara Torrecilla
- Translational research in Hepatic Oncology, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | | | | | - Genís Campreciós
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Liver Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Chinbold Enkhbold
- Hepato-Pancreatico-Biliary Surgery Department, National Cancer Center, Ulaanbaatar, Mongolia
| | | | | | - Augusto Villanueva
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Sofía Pérez-del-Pulgar
- Liver Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Swan Thung
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | - Eric Letouzé
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Université Paris 13, Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France
| | - Jessica Zucman-Rossi
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Université Paris 13, Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France
| | - Andrew Uzilov
- Sema4, Stamford, Connecticut, USA
- Department of Genetics and Genomic Sciences and Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
| | - Jaclyn Neely
- Bristol Myers Squibb, Princeton, New Jersey, USA
| | - Xavier Forns
- Liver Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Sasan Roayaie
- Department of Surgery, White Plains Hospital, White Plains, New York, USA
| | - Daniela Sia
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Josep M. Llovet
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Translational research in Hepatic Oncology, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
- Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
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7
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Moussavou-Boundzanga P, Itoudi Bignoumba P, Mouinga-Ondeme A, Iroungou B, Bivigou-Mboumba B, Marchio A, Saibou M, Moussavou Kombila JB, Pineau P. Drastic sex-dependent etiological distribution in severe liver diseases from Gabon. Front Oncol 2022; 12:907554. [PMID: 36185278 PMCID: PMC9521596 DOI: 10.3389/fonc.2022.907554] [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: 03/29/2022] [Accepted: 08/22/2022] [Indexed: 12/15/2022] Open
Abstract
Chronic liver diseases still represent a worrying public health issue in Sub-Saharan Africa. In this region, emphasis is generally made on hepatocellular carcinoma (HCC) albeit liver cirrhosis (LC) is also responsible for an important death toll. Very few studies have compared the presentation and etiologies of cancer and cirrhosis of the liver in Middle Africa. We conducted a comparative retrospective analysis of 74 and 134 cases of patients with HCC and LC treated in Libreville, Gabon. Viral or lifestyle risk factors, clinical symptoms, and biological features were compared. We observed that ages of diagnosis were 53.2 ± 15.7 years and 48.6 ± 18.6 years for HCC and LC with remarkably low M:F sex ratios (1.3-1.8). Ethanol consumption was highly prevalent in both disease types (65.0%-70.0%). Chronic viral infections with hepatitis B (HBV) or C (HCV) virus were also widespread with slight domination of the former in both diseases (43.4% vs. 34.3%, and 35.9% vs. 28.5%). Patients with HCC were presenting very late with a mean diameter of the main nodule of 84 ± 50 mm and a multifocal pattern in 72.7% of cases. HCC developed on a cirrhotic liver in 91.7% of cases. Serum AFP was frankly elevated (>400 ng/ml) in only 35.8% of HCC cases. The most striking feature of the HCC series was the contrasted contribution of distinct pathogenic etiologies involving sex, viral, metabolic, and toxic factors. A frequently dysmetabolic condition synergizing with hepatitis C (anti-HCV, 73.8% vs 22.7%, p < 0.0001) in females and a male cancer promoted by recreational toxicants and chronic hepatitis B (HBsAg, 83.5% vs 35.9%, p < 0.0001) were observed. Men with HCC were considerably younger than women (46.8 ± 14.5 years vs. 62.2 ± 12.2 years, p < 0.0001). Further studies are now warranted to identify routes of HCV transmission and if they are still fueling reservoirs of future patients. Public policies to prevent alcohol-related harm have also to be urgently implemented in Gabon.
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Affiliation(s)
- Pamela Moussavou-Boundzanga
- Laboratoire de Biologie Moléculaire et Cellulaire (LABMC), Université des Sciences et Techniques de Masuku (USTM), Franceville, Gabon
- Unité des Infections Rétrovirales et Pathologies Associées, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
| | | | - Augustin Mouinga-Ondeme
- Unité des Infections Rétrovirales et Pathologies Associées, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
| | - Berthe Amelie Iroungou
- Unité Mixte de Recherche Centre International de Recherches Médicales de Franceville et Service de Santeí Militaire (CIRMF-SSM), Libreville, Gabon
| | - Berthold Bivigou-Mboumba
- Unité Mixte de Recherche Centre International de Recherches Médicales de Franceville et Service de Santeí Militaire (CIRMF-SSM), Libreville, Gabon
| | - Agnès Marchio
- Unité « Organisation nucléaire et oncogenèse », INSERM U993, Institut Pasteur, Paris, France
| | - Maryam Saibou
- Service de Gastroentérologie, Centre Hospitalier Universitaire de Libreville (CHUL), Libreville, Gabon
| | | | - Pascal Pineau
- Unité « Organisation nucléaire et oncogenèse », INSERM U993, Institut Pasteur, Paris, France
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8
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Dambadarjaa D, Mukhtar Y, Tsogzolbaatar EO, Khuyag SO, Dayan A, Oyunbileg NE, Shagdarsuren OE, Nyam G, Nakamura Y, Takahashi M, Okamoto H. Hepatitis B, C, and D virus infections and AFP tumor marker prevalence among elderly population in Mongolia: A nationwide survey. J Prev Med Public Health 2022; 55:263-272. [PMID: 35678000 PMCID: PMC9201085 DOI: 10.3961/jpmph.21.573] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 03/10/2022] [Indexed: 11/17/2022] Open
Abstract
Objectives Infections with hepatitis B, C, and D virus (HBV, HCV, and HDV) are a major public health problem and lead to serious complications such as cirrhosis and hepatocellular carcinoma. We aimed to determine the seroprevalence of hepatitis B surface antigen (HBsAg), anti-HCV, anti-HDV immunoglobulin G, alpha-fetoprotein (AFP), and dual and triple hepatitis virus infections in Mongolia. Methods A total of 2313 participants from urban and rural regions were randomly recruited for this cross-sectional study. A questionnaire was used to identify the risk factors for hepatitis virus infections, and the seromarkers were measured using immunoassay kits. Results Among all participants, the prevalence of HBV, HCV, and HDV was 15.6%, 36.6%, and 14.3%, respectively. The infection rates were significantly higher in females and participants with a lower education level, rural residence, older age, and a history of blood transfusion. HBV and HCV co-infection was found in 120 (5.2%) participants and HBV, HCV, and HDV triple infection was detected in 67 (2.9%) participants. The prevalence of elevated AFP was 2.7%, 5.5%, and 2.6% higher in participants who were seropositive for HBsAg (p=0.01), anti-HCV (p<0.001), and anti-HDV (p=0.022), respectively. Elevated AFP was more prevalent in participants co-infected with HBV and HCV (5.8%, p=0.023), HBV and HDV (6.0%, p<0.001), and triple-infected with HBV, HCV, and HDV (7.5%) than in uninfected individuals. Conclusions Nearly half (49.8%) of the study population aged ≥40 years were infected with HBV, HCV, or HDV, and 22.4% had dual or triple infections.
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Affiliation(s)
- Davaalkham Dambadarjaa
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar,
Mongolia
| | - Yerkyebulan Mukhtar
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar,
Mongolia
| | - Enkh-Oyun Tsogzolbaatar
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar,
Mongolia
| | - Ser-Od Khuyag
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar,
Mongolia
| | - Angarmurun Dayan
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar,
Mongolia
| | - Nandin-Erdene Oyunbileg
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar,
Mongolia
| | - Oyu-Erdene Shagdarsuren
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar,
Mongolia
| | - Gunchmaa Nyam
- School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar,
Mongolia
| | - Yosikazu Nakamura
- Department of Public Health, Jichi Medical University, Shimotsuke,
Japan
| | - Masaharu Takahashi
- Department of Public Health, Jichi Medical University, Shimotsuke,
Japan
| | - Hiroaki Okamoto
- Department of Public Health, Jichi Medical University, Shimotsuke,
Japan
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9
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Jacob R, Danta M. Pharmacotherapeutic strategies for hepatitis B and hepatitis C coinfection. Expert Opin Pharmacother 2021; 23:465-472. [PMID: 34937470 DOI: 10.1080/14656566.2021.2019708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
INTRODUCTION Hepatitis B (HBV) and Hepatitis C (HCV) infection place a significant burden on the global health system, with chronic carriage leading to cirrhosis and hepatocellular carcinoma. HBV/HCV coinfection can be seen in highly endemic areas and present a heterogenous group given varying virologic profiles. Coinfected patients have a greater risk of advanced liver disease; hence, diagnosis and early antiviral therapy (AVT) should be a priority. Optimal treatment regimens for coinfected patients remain unknown with differing recommendations, particularly relating to the risk of HBV reactivation whilst on AVT for HCV. AREAS COVERED This article summarizes the available data on HBV/HCV coinfection with regards to epidemiology, virologic interactions, and risk of HBV reactivation. The authors also provide a framework for the assessment and treatment of coinfected patients. EXPERT OPINION There is a moderate risk of HBV reactivation in hepatitis B surface antigen (HBsAg) positive patients undergoing HCV direct-acting antiviral (DAA) treatment; however, clinically significant events are rare. The risk of HBV reactivation in HBsAg negative patients undergoing HCV DAA treatment is negligible. Thus, prophylactic HBV treatment in both groups is not required. The authors recommend close monitoring with HBV treatment if there is evidence of HBV reactivation or elevated alanine aminotransferase levels.
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Affiliation(s)
- Rachael Jacob
- Department of Gastroenterology, St Vincent's Hospital, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, Unsw Sydney, St Vincent's Hospital, Sydney, Australia
| | - Mark Danta
- Department of Gastroenterology, St Vincent's Hospital, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, Unsw Sydney, St Vincent's Hospital, Sydney, Australia
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10
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Joseph K, Shabangu CS, Jang TY, Huang CF, Dai CY, Huang JF, Chuang WL, Yu ML, Wang SC. The Prevalence and Serological Association of Hepatitis D Virus Genotypes in Taiwan. Pathogens 2021; 10:1227. [PMID: 34684176 PMCID: PMC8541235 DOI: 10.3390/pathogens10101227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/17/2021] [Accepted: 09/19/2021] [Indexed: 11/16/2022] Open
Abstract
Hepatitis Delta Virus (HDV) is an RNA virus that requires the presence of hepatitis B surface antigen (HBsAg) to propagate into hepatocytes, with Genotype I being more prevalent globally. However, the prevalence of HDV genotypes in Taiwan is unknown. Accordingly, a cohort including 24 chronic HBV patients who received nucleos(t)ides (NUCs) between January 2002 and July 2018 was used to determine HDV genotypes and genotype specific serological association in chronic HBV carriers. HDV-positive genotypes in 18/24 (75%) males and 6/24 (25%) females were identified among chronic HBV patients. Viremia was lower in HDV-IV patients than in patients affected with other HDV genotypes (1.34 log10 copies/mL vs. 3.30 log10 copies/mL; p = 0.009). A logistics regression analysis revealed that HDV-IV was inversely proportional to HDV RNA (odds ratio [OR]/95% confidence intervals [CI]: 0.370/0.164-0.830; p = 0.017). The serologic association study indicated lower levels of creatinine (p = 0.047) and HDV-RNA (p = 0.009) in the HDV-IV group than the non-HDV-IV group but did not indicate any significant differences in the AST, ALT, bilirubin levels or other laboratory test factors. The three genotypes evident in Taiwan were HDV-I (4/24, 16.7%), HDV-II (6/24, 25.0%), and HDV-IV (14/24, 58.3%), and HDV-IV is the predominant HDV genotype in Taiwan. These results anticipate a clear understanding of HDV genotype serological association in chronic HBV carriers.
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Affiliation(s)
- Keva Joseph
- M. Sc. Program in Tropical Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | | | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (T.-Y.J.); (C.-F.H.); (C.-Y.D.); (J.-F.H.); (W.-L.C.); (M.-L.Y.)
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (T.-Y.J.); (C.-F.H.); (C.-Y.D.); (J.-F.H.); (W.-L.C.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (T.-Y.J.); (C.-F.H.); (C.-Y.D.); (J.-F.H.); (W.-L.C.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (T.-Y.J.); (C.-F.H.); (C.-Y.D.); (J.-F.H.); (W.-L.C.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (T.-Y.J.); (C.-F.H.); (C.-Y.D.); (J.-F.H.); (W.-L.C.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (T.-Y.J.); (C.-F.H.); (C.-Y.D.); (J.-F.H.); (W.-L.C.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Shu-Chi Wang
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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11
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Fong TL, Lee BT, Chang M, Nasanbayar K, Tsogtoo E, Boldbaatar D, Dashdorj ED, Clifford NE, Dashdorj AN, Bang BR, Chida T, Lim C, Sugiyama M, Mizokami M, Dashdorj NJ, Liu P, Glenn JS, Dashdorj ND, Saito T. High Prevalence of Chronic Viral Hepatitis and Liver Fibrosis Among Mongols in Southern California. Dig Dis Sci 2021; 66:2833-2839. [PMID: 32770488 PMCID: PMC7868472 DOI: 10.1007/s10620-020-06499-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 07/18/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Mongolia is a highly endemic region for chronic hepatitis B (HBV), hepatitis delta (HDV), and hepatitis C (HCV) infections. Aim of this study was to comprehensively characterize chronic viral hepatitis among Mongols living in Southern California. METHODS Three screening events were conducted between August and November 2018, with 528 adult Mongols tested for HBV and HCV. HBsAg (+) individuals (CHB) underwent additional testing for HDV RNA and anti-HDV. Liver tests, platelet count, and FibroScan™ were performed on CHB and chronic HCV (CHC) individuals. RESULTS Fifty-one out of 534 were HBsAg reactive (9.7%), and all were foreign-born. Mean age of CHB individuals was 37.8 (range 18-69) years. Forty-six out of 51 were HBeAg (-). HBV genotypes were exclusively D2 or A1. Twenty-one out of 51 (41.2%) were anti-HDV (+) and 17/51 (33.3%) were HDV RNA (+). HDV RNA (+) individuals had significantly higher ALT, fibrosis-4 score, and liver stiffness compared to HDV RNA (-) individuals. Incidence of advanced fibrosis was higher in HDV RNA (+) individuals (57% vs. 13%, p = 0.013). Forty-eight (9.1%) individuals were anti-HCV (+) and 19 (3.6%) were HCV RNA (+). Mean age of CHC individuals was 40.2 (range 28-71) years. Prevalence of anti-HCV (+) was higher among those born between 1945 and 1965 versus those born after 1965 (18.8% vs. 7.9%, p = 0.025). Genotype 1b was predominant. Incidence of cirrhosis was 7% among all participants. CONCLUSIONS Mongols living in the USA are at high risk for CHB and CHC infections. One-third of CHB individuals had CHD superinfection with advanced fibrosis. Universal screening for viral hepatitis in Mongols in the USA is mandatory.
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Affiliation(s)
- Tse-Ling Fong
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles California, USA,Asian Pacific Liver Center, St. Vincent Medical Center, Los Angeles, California, USA,Address correspondence to: Tse-Ling Fong, M.D., Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, 1510 San Pablo Street, 2nd floor, Los Angeles CA 90033 USA, Tel: +1-323-442-6171, Fax: +1-323-442-6169, , Naranbaatar D. Dashdorj, PhD, Co-Founder and Chairman of the Board, Onom Foundation, 3 Governance Academy Street, 15th Khoroo, Khan-Uul District, Ulaanbaatar 17013-0017, Mongolia, Phone: +976.7012.2006, Fax: +976.7013.2006, , Takeshi Saito, M.D., Ph.D., Associate Professor of Medicine, Molecular Microbiology & Immunology, and Pathology USC Research Center for Liver Diseases, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California2011 Zonal Avenue, HMR 801A, Los Angeles, CA 90033-9141, Phone: +1-323-442-2260, Fax:+1-323-442-5425,
| | - Brian T. Lee
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles California, USA
| | - Mimi Chang
- Asian Pacific Liver Center, St. Vincent Medical Center, Los Angeles, California, USA
| | | | | | | | | | | | | | - Bo Ram Bang
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles California, USA
| | - Takeshi Chida
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles California, USA
| | - Carolina Lim
- Asian Pacific Liver Center, St. Vincent Medical Center, Los Angeles, California, USA
| | - Masaya Sugiyama
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
| | - Masashi Mizokami
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
| | | | - Ping Liu
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Jeffrey S. Glenn
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Naranbaatar D. Dashdorj
- Onom Foundation, Ulaanbaatar, Mongolia,The Liver Center, Ulaanbaatar, Mongolia,Address correspondence to: Tse-Ling Fong, M.D., Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, 1510 San Pablo Street, 2nd floor, Los Angeles CA 90033 USA, Tel: +1-323-442-6171, Fax: +1-323-442-6169, , Naranbaatar D. Dashdorj, PhD, Co-Founder and Chairman of the Board, Onom Foundation, 3 Governance Academy Street, 15th Khoroo, Khan-Uul District, Ulaanbaatar 17013-0017, Mongolia, Phone: +976.7012.2006, Fax: +976.7013.2006, , Takeshi Saito, M.D., Ph.D., Associate Professor of Medicine, Molecular Microbiology & Immunology, and Pathology USC Research Center for Liver Diseases, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California2011 Zonal Avenue, HMR 801A, Los Angeles, CA 90033-9141, Phone: +1-323-442-2260, Fax:+1-323-442-5425,
| | - Takeshi Saito
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles California, USA,Address correspondence to: Tse-Ling Fong, M.D., Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, 1510 San Pablo Street, 2nd floor, Los Angeles CA 90033 USA, Tel: +1-323-442-6171, Fax: +1-323-442-6169, , Naranbaatar D. Dashdorj, PhD, Co-Founder and Chairman of the Board, Onom Foundation, 3 Governance Academy Street, 15th Khoroo, Khan-Uul District, Ulaanbaatar 17013-0017, Mongolia, Phone: +976.7012.2006, Fax: +976.7013.2006, , Takeshi Saito, M.D., Ph.D., Associate Professor of Medicine, Molecular Microbiology & Immunology, and Pathology USC Research Center for Liver Diseases, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California2011 Zonal Avenue, HMR 801A, Los Angeles, CA 90033-9141, Phone: +1-323-442-2260, Fax:+1-323-442-5425,
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12
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Chaabna K, Dashzeveg D, Shagdarsuren T, Al-Rifai RH. Prevalence and genotype distribution of hepatitis C virus in Mongolia: Systematic review and meta-analysis. Int J Infect Dis 2021; 105:377-388. [PMID: 33601031 DOI: 10.1016/j.ijid.2021.02.040] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 02/08/2021] [Accepted: 02/10/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To characterize hepatitis C virus (HCV) infection epidemiology in Mongolia. METHOD Publications on HCV antibody (Ab) and RNA prevalence, and/or genotypes/subtypes were systematically reviewed and reported following PRISMA guidelines. Random-effects meta-analyses and age adjustments were conducted to estimate the prevalence of Mongolians exposed to HCV (pooled HCV-Ab prevalence) by time period, sex, and at-risk populations; and to estimate the prevalence of chronically-infected HCV individuals. RESULTS The national pooled HCV-Ab prevalence was 12.3% in 2000-2009 and 11.2% in 2013. Sex-specific pooled prevalence appeared higher among females than males (14.0% versus 6.8%). Age-specific pooled prevalence significantly increased from 3.7% among children (aged 0-10 years) to 34.1% among people aged ≥50 years (p < 0.001). Among the adult general population (low-risk population), the national age-adjusted prevalence was 8.1%. Age-adjusted chronic infection prevalence in adults was 6.0%. Among healthcare workers, pooled prevalence was 18.0%. Among patients with liver diseases, pooled prevalence was 53.7%. Among individuals engaging in risky sexual behaviors, pooled prevalence was 11.1%. The identified circulating genotypes/subtypes were 1b (58.0%), 2a (21.7%), and 1a (20.2%). CONCLUSION The national HCV prevalence in Mongolia appeared to be among the highest worldwide. Higher prevalence in the clinical setting indicated potential ongoing HCV iatrogenic and occupational transmission. Additionally, HCV transmission in community settings should be investigated.
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Affiliation(s)
- Karima Chaabna
- Institute for Population Health, Weill Cornell Medicine-Qatar, Doha, Qatar.
| | - Delgermaa Dashzeveg
- Global Health Entrepreneurship Department, Tokyo Medical and Dental University, Tokyo, Japan; Head of Public Health Policy Implementation and Coordination, National Centre for Public Health, Ministry of Health, Mongolia
| | - Tserendulam Shagdarsuren
- Head of Public Health Policy Implementation and Coordination, National Centre for Public Health, Ministry of Health, Mongolia; Department of Mongolia and Healthy City Network of Mongolia, Mongolia
| | - Rami H Al-Rifai
- Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
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13
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Zhou K, Terrault NA. Treatment of HCV, HDV, or HIV Coinfections. HEPATITIS B VIRUS AND LIVER DISEASE 2021:339-373. [DOI: 10.1007/978-981-16-3615-8_15] [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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14
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Epidemiology of hepatitis B and C virus infections among patients who booked for surgical procedures at Felegehiwot referral hospital, Northwest Ethiopia. PLoS One 2020; 15:e0234822. [PMID: 32555634 PMCID: PMC7299365 DOI: 10.1371/journal.pone.0234822] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 06/02/2020] [Indexed: 01/17/2023] Open
Abstract
Background Hepatitis B virus(HBV) and hepatitis C virus(HCV) are the main causes of cirrhosis, liver cancer, and death. This study aimed to determine the seroprevalence and associated factors of HBV surface antigen(HBsAg) and anti-HCV among patients screened for surgery at Felegehiwot referral hospital, Northwest Ethiopia. Methods A hospital-based cross-sectional study was conducted among 433 patients in 2018. Data on socio-demographic and risk factors were collected by an exit interview using a pretested structured questionnaire. A venous blood sample of 5ml was collected from each participant, and serum was tested for HBsAg and anti-HCV using one-step rapid test kits and enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was computed to identify factors associated with HBV and HCV infections. The odds ratio with 95%CI was used to describe the strength of association and statistical significance. Results A total of 422 patients gave data and included in the analysis. The mean age of patients was 36±5 years. About two-thirds, 269(64%) and 274(65%) patients were males, and from rural areas, respectively. The seroprevalence of HBsAg was 34(8%) followed by 18(4.3%) anti-HCV and 4(0.9%) co-infections. Being single(AOR = 1.96, 95%CI = 1.12–3.10), rural residence (AOR = 2.68, 95%CI = 1.28–5.61), ever heard about HBV (AOR = 2.41, 95%CI = 1.18–5.20), having multiple sexual partners(AOR = 2.85, 95%CI = 1.30–5.58), HIV positive(AOR = 3.14, 95%CI = 1.31–7.61), history of tooth extraction(AOR = 3.0, 95%CI = 1.40–6.56), hospitalization history(AOR = 2.95, 95%CI = 1.26–5.81), sharing of sharp instruments (AOR = 3.86, 95%CI = 1.82–8.79), and had blood contact(AOR = 2.64, 95%CI = 1.14–5.42) were statistically significant factors to HBV infection. Similarly, sharing of sharp instruments(AOR = 4.65, 95%CI = 1.32–15.1), tooth extraction practice(AOR = 2.81, 95%CI = 1.12–6.56), surgical history (AOR = 3.68, 95%CI = 1.64–9.82), hospitalization history(AOR = 4.51, 95%CI = 1.62–8.35) and had blood contact(AOR = 3.2, 95%CI = 1.56–8.51) were significant factors to HCV infection. Conclusion The seroprevalence of HBsAg and ant-HCV was high compared to WHO and previous study findings. Giving special attention to awareness creation, rural settings, improving personal behaviors, infection prevention activities of health facilities, quality of healthcare procedures is crucial to prevent viral hepatitis infection.
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Sharafi H, Rezaee-Zavareh MS, Miri SM, Alavian SM. Global Distribution of Hepatitis D Virus Genotypes: A Systematic Review. HEPATITIS MONTHLY 2020; 20. [DOI: 10.5812/hepatmon.102268] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
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16
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Targeting the Host for New Therapeutic Perspectives in Hepatitis D. J Clin Med 2020; 9:jcm9010222. [PMID: 31947588 PMCID: PMC7019876 DOI: 10.3390/jcm9010222] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 01/09/2020] [Accepted: 01/10/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis D virus (HDV) is a small satellite virus of hepatitis B virus (HBV) requiring HBV infection to complete its life cycle. It has been recently estimated that 13% of chronic HBV infected patients (60 million) are co-infected with HDV. Chronic hepatitis D is the most severe form of viral hepatitis with the highest risk to develop cirrhosis and liver cancer. Current treatment is based on pegylated-interferon-alpha which rarely controls HDV infection and is complicated by serious side effects. The development of novel antiviral strategies based on host targeting agents has shown promising results in phase I/II clinical trials. This review summarizes HDV molecular virology and physiopathology as well as new therapeutic approaches targeting HDV host factors.
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Woldegiorgis AE, Erku W, Medhin G, Berhe N, Legesse M. Community-based sero-prevalence of hepatitis B and C infections in South Omo Zone, Southern Ethiopia. PLoS One 2019; 14:e0226890. [PMID: 31887192 PMCID: PMC6936792 DOI: 10.1371/journal.pone.0226890] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 12/08/2019] [Indexed: 12/22/2022] Open
Abstract
Background Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are the leading causes of liver-related morbidity and mortality throughout the world. The magnitude of HBV and HCV infections in Ethiopia has not been well studied at community level. This study aimed at investigating the sero-prevalence and associated risk factors of HBV and HCV among HBV unvaccinated community members in South Omo Zone, Southern Ethiopia. Methods A community-based cross-sectional study was conducted in three districts from March to May 2018. Structured questionnaire was used to collect relevant clinical and socio-demographic data. Three milliliter of blood sample was collected from each study participant and screened for HBV and HCV using one step hepatitis B surface antigen (HBsAg) test strip and one step HCV test strip, respectively. Samples found positive for HBsAg were further tested using immunoassay of Alere DetermineTM HBsAg (Alere Inc., USA). Data were analyzed using SPSS version 25.0. Results A total of 625 (51.4% males, age 6–80 years, mean age ± SD = 30.83 ± 13.51 years) individuals participated in the study. The sero-prevalence for HBV infection was 8.0% as detected using one step HBsAg test strip, while it was 7.2% using Alere DetermineTM HBsAg test. The sero-prevalence for HCV infection was 1.9%. Two (0.3%) of the participants were seropositive for both HBV and HCV infections. High sero-prevalence for HBV infection was associated with weakness and fatigue (AOR = 5.20; 95% CI: 1.58, 17.15), while high sero-prevalence of HCV infection was associated with age group between 46 and 65 years (AOR = 13.02; 95% CI: 1.11, 152.41). Conclusion This study revealed higher-intermediate endemicity level of HBV infection and low to intermediate endemicity level of HCV infection in the study area. Clinical symptoms like weakness and fatigue were found to be indictors for HBV infection, while individuals in the age group between 46 and 65 years were at higher risk for HCV infection. Provision of community- based health education; vaccination, mass screening and providing treatment would have utmost importance in reducing the transmission of these diseases in the present study area.
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Affiliation(s)
- Adugna Endale Woldegiorgis
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
- School of Medicine, College of Medicine and Health Sciences, Dire Dawa University, Dire Dawa, Ethiopia
- * E-mail:
| | - Woldearegay Erku
- Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Tikur Anbessa Hospital, Addis Ababa University, Addis Ababa, Ethiopia
| | - Girmay Medhin
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Nega Berhe
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Mengistu Legesse
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
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Gilman C, Heller T, Koh C. Chronic hepatitis delta: A state-of-the-art review and new therapies. World J Gastroenterol 2019; 25:4580-4597. [PMID: 31528088 PMCID: PMC6718034 DOI: 10.3748/wjg.v25.i32.4580] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 07/03/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Chronic delta hepatitis is the most severe form of viral hepatitis affecting nearly 65 million people worldwide. Individuals with this devastating illness are at higher risk for developing cirrhosis and hepatocellular carcinoma. Delta virus is a defective RNA virus that requires hepatitis B surface antigen for propagation in humans. Infection can occur in the form of a co-infection with hepatitis B, which can be self-limiting, vs superinfection in a patient with established hepatitis B infection, which often leads to chronicity in majority of cases. Current noninvasive tools to assess for advanced liver disease have limited utility in delta hepatitis. Guidelines recommend treatment with pegylated interferon, but this is limited to patients with compensated disease and is efficacious in about 30% of those treated. Due to limited treatment options, novel agents are being investigated and include entry, assembly and export inhibitors of viral particles in addition to stimulators of the host immune response. Future clinical trials should take into consideration the interaction of hepatitis B and hepatitis D as suppression of one virus can lead to the activation of the other. Also, surrogate markers of treatment efficacy have been proposed.
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MESH Headings
- Antiviral Agents/pharmacology
- Antiviral Agents/therapeutic use
- Coinfection/drug therapy
- Coinfection/epidemiology
- Coinfection/virology
- Drug Therapy, Combination/methods
- Global Burden of Disease
- Hepatitis B Surface Antigens/immunology
- Hepatitis B Surface Antigens/metabolism
- Hepatitis B virus/immunology
- Hepatitis B virus/pathogenicity
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/epidemiology
- Hepatitis B, Chronic/virology
- Hepatitis D, Chronic/drug therapy
- Hepatitis D, Chronic/epidemiology
- Hepatitis D, Chronic/virology
- Hepatitis Delta Virus/immunology
- Hepatitis Delta Virus/pathogenicity
- Humans
- Interferon-alpha/pharmacology
- Interferon-alpha/therapeutic use
- Lipopeptides/pharmacology
- Lipopeptides/therapeutic use
- Organic Anion Transporters, Sodium-Dependent/antagonists & inhibitors
- Organic Anion Transporters, Sodium-Dependent/metabolism
- Piperidines/pharmacology
- Piperidines/therapeutic use
- Pyridines/pharmacology
- Pyridines/therapeutic use
- Randomized Controlled Trials as Topic
- Review Literature as Topic
- Superinfection/drug therapy
- Superinfection/epidemiology
- Superinfection/virology
- Symporters/antagonists & inhibitors
- Symporters/metabolism
- Therapies, Investigational/methods
- Treatment Outcome
- Virus Assembly/drug effects
- Virus Internalization/drug effects
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Affiliation(s)
- Christy Gilman
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States
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Da BL, Heller T, Koh C. Hepatitis D infection: from initial discovery to current investigational therapies. Gastroenterol Rep (Oxf) 2019; 7:231-245. [PMID: 32477569 DOI: 10.1093/gastro/goz023] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 03/15/2019] [Accepted: 05/09/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis D is the most severe form of viral hepatitis associated with a more rapid progression to cirrhosis and an increased risk of hepatocellular carcinoma and mortality compared with hepatitis B mono-infection. Although once thought of as a disappearing disease, hepatitis D is now becoming recognized as a serious worldwide issue due to improvement in diagnostic testing and immigration from endemic countries. Despite these concerns, there is currently only one accepted medical therapy (pegylated-interferon-α) for the treatment of hepatitis D with less than desirable efficacy and significant side effects. Due to these reasons, many patients never undergo treatment. However, increasing knowledge about the virus and its life cycle has led to the clinical development of multiple promising new therapies that hope to alter the natural history of this disease and improve patient outcome. In this article, we will review the literature from discovery to the current investigational therapies.
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Affiliation(s)
- Ben L Da
- Digestive Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
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20
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National prevalence rate of hepatitis B and C in Pakistan and its risk factors. J Public Health (Oxf) 2019. [DOI: 10.1007/s10389-019-01081-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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21
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Turcanu A, Pitel E, Dumbrava VT, Tcaciuc E, Donscaia A, Peltec A, Pineau P. Profile of hepatocellular carcinoma in the Republic of Moldova: first-hand information on the presentation, distribution and etiologies. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2019; 57:37-46. [PMID: 30375353 DOI: 10.2478/rjim-2018-0026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Moldova is the European country with the highest incidence of hepatocellular carcinoma (HCC) in both sexes. There is, however, no data comprehensively describing the presentation and the risk factors of HCC in the country. We decided to analyze cases of HCC recently received in a tertiary healthcare Institution from Chisinau, the Moldovian capital. METHODS A series of 148 primary liver tumors including 139 cases of HCC were retrospectively analyzed for demographic features, serological and biochemical data, and clinical presentation. RESULTS The mean age of patients was 59 ± 10 years (range: 19-66) with a M:F sex ratio of 1.9. Tumors appeared on full-blown liver cirrhosis in 83% of cases and were composed of multiple nodules at diagnosis in 36% of patients. Serum Alpha-fetoprotein was exceeding 10ng/mL in 76% of cases. Liver tumor and hepatitis were co-discovered in 34% of cases. More than 81% of hepatocellular carcinomas were associated with at least one hepatitis virus. Carriers of anti-hepatitis C virus were predominating (55% of cases) over patients seropositive for hepatitis B virus surface antigen (36%). Half of the latter were also infected with hepatitis Delta virus. In total, dual or triple infections were present in 24% and 7% of cases. CONCLUSIONS The burden of infections with hepatitis viruses is particularly important in Moldova and corresponds to a situation commonly observed in countries of the Southern hemisphere. A pro-active policy of screening for persistent liver infection targeting population at risk of HCC (> 50 years) and coupled with the distribution of antivirals in positive cases should be rapidly implemented in Moldova to reduce incidence or primary liver cancer.
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Affiliation(s)
- Adela Turcanu
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Ecaterina Pitel
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Vlada-Tatiana Dumbrava
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Eugen Tcaciuc
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Ana Donscaia
- Institute of Oncology of the Republic of Moldova, str. Testemitanu 30,Chisinau
| | - Angela Peltec
- Department of Gastroenterology, Nicolae Testemitanu State University of Medicine and Pharmacy, Bd. Stefan cel Mare 165,Chisinau, Republic of Moldova
| | - Pascal Pineau
- Unité "Organisation nucléaire et Oncogenèse", INSERM U993, Institut Pasteur, 28, rue du Docteur Roux,75015 Paris, France
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Koh C, Heller T, Glenn JS. Pathogenesis of and New Therapies for Hepatitis D. Gastroenterology 2019; 156:461-476.e1. [PMID: 30342879 PMCID: PMC6340762 DOI: 10.1053/j.gastro.2018.09.058] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 09/21/2018] [Accepted: 09/25/2018] [Indexed: 12/13/2022]
Abstract
Hepatitis delta virus (HDV) infection of humans was first reported in 1977, and now it is now estimated that 15-20 million people are infected worldwide. Infection with HDV can be an acute or chronic process that occurs only in patients with an hepatitis B virus infection. Chronic HDV infection commonly results in the most rapidly progressive form of viral hepatitis; it is the chronic viral infection that is most likely to lead to cirrhosis, and it is associated with an increased risk of hepatocellular carcinoma. HDV infection is the only chronic human hepatitis virus infection without a therapy approved by the US Food and Drug Administration. Peginterferon alfa is the only recommended therapy, but it produces unsatisfactory results. We review therapeutic agents in development, designed to disrupt the HDV life cycle, that might benefit patients with this devastating disease.
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Affiliation(s)
- Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Jeffrey S. Glenn
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
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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] [MESH Headings] [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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Heller T, Koh C, Glenn JS. Hepatitis D. ZAKIM AND BOYER'S HEPATOLOGY 2018:501-511.e4. [DOI: 10.1016/b978-0-323-37591-7.00034-3] [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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25
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Chen X, Oidovsambuu O, Liu P, Grosely R, Elazar M, Winn VD, Fram B, Boa Z, Dai H, Dashtseren B, Yagaanbuyant D, Genden Z, Dashdorj N, Bungert A, Dashdorj N, Glenn JS. A novel quantitative microarray antibody capture assay identifies an extremely high hepatitis delta virus prevalence among hepatitis B virus-infected mongolians. Hepatology 2017; 66:1739-1749. [PMID: 27880976 PMCID: PMC5441964 DOI: 10.1002/hep.28957] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 11/09/2016] [Accepted: 11/22/2016] [Indexed: 12/12/2022]
Abstract
Hepatitis delta virus (HDV) causes the most severe form of human viral hepatitis. HDV requires a hepatitis B virus (HBV) coinfection to provide HDV with HBV surface antigen envelope proteins. The net effect of HDV is to make the underlying HBV disease worse, including higher rates of hepatocellular carcinoma. Accurate assessments of current HDV prevalence have been hampered by the lack of readily available and reliable quantitative assays, combined with the absence of a Food and Drug Administration-approved therapy. We sought to develop a convenient assay for accurately screening populations and to use this assay to determine HDV prevalence in a population with abnormally high rates of hepatocellular carcinoma. We developed a high-throughput quantitative microarray antibody capture assay for anti-HDV immunoglobulin G wherein recombinant HDV delta antigen is printed by microarray on slides coated with a noncontinuous, nanostructured plasmonic gold film, enabling quantitative fluorescent detection of anti-HDV antibody in small aliquots of patient serum. This assay was then used to screen all HBV-infected patients identified in a large randomly selected cohort designed to represent the Mongolian population. We identified two quantitative thresholds of captured antibody that were 100% predictive of the sample either being positive on standard western blot or harboring HDV RNA detectable by real-time quantitative PCR. Subsequent screening of the HBV+ cohort revealed that a remarkable 57% were RNA+ and an additional 4% were positive on western blot alone. CONCLUSION The quantitative microarray antibody capture assay's unique performance characteristics make it ideal for population screening; its application to the Mongolian HBV surface antigen-positive population reveals an apparent ∼60% prevalence of HDV coinfection among these HBV-infected Mongolian subjects, which may help explain the extraordinarily high rate of hepatocellular carcinoma in Mongolia. (Hepatology 2017;66:1739-1749).
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Affiliation(s)
- Xiaohua Chen
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| | | | - Ping Liu
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| | - Rosslyn Grosely
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| | - Menashe Elazar
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| | - Virginia D. Winn
- Department of Obstetrics and Gynecology, Stanford University School of Medicine, Palo Alto, California
| | - Benjamin Fram
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| | - Zhang Boa
- Department of Chemistry, Stanford University, Palo Alto, California
| | - Hongjie Dai
- Department of Chemistry, Stanford University, Palo Alto, California
| | - Bekhbold Dashtseren
- Liver Center, Ulaanbaatar, Mongolia
- Onom Foundation, Ulaanbaatar, Mongolia
- Mongolian National University of Health Sciences
| | - Dahgwahdorj Yagaanbuyant
- Liver Center, Ulaanbaatar, Mongolia
- Onom Foundation, Ulaanbaatar, Mongolia
- Mongolian National University of Health Sciences
| | - Zulkhuu Genden
- Liver Center, Ulaanbaatar, Mongolia
- Onom Foundation, Ulaanbaatar, Mongolia
| | | | | | | | - Jeffrey S. Glenn
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
- Department of Microbiology and Immunology, Stanford University School of Medicine, Palo Alto, California
- Veterans Administration Medical Center, Palo Alto, California
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Trad D, Bibani N, Sabbah M, Elloumi H, Gargouri D, Ouakaa A, Kharrat J. Known, new and emerging risk factors of hepatocellular carcinoma (review). Presse Med 2017; 46:1000-1007. [DOI: 10.1016/j.lpm.2017.09.025] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 08/30/2017] [Accepted: 09/20/2017] [Indexed: 12/24/2022] Open
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Tsatsralt-Od B, Primadharsini PP, Nishizawa T, Ohnishi H, Nagashima S, Takahashi M, Jirintai S, Nyamkhuu D, Okamoto H. Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis in Mongolia: The first report of the full genome sequence of a novel genotype 1 hepatitis E virus strain. J Med Virol 2017; 90:84-92. [PMID: 28776712 DOI: 10.1002/jmv.24907] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Accepted: 07/14/2017] [Indexed: 12/16/2022]
Abstract
In January 2012, Mongolia started a hepatitis A vaccination program, which has not yet been evaluated. The first occurrence of autochthonous acute hepatitis E in 2013, caused by genotype 4 hepatitis E virus (HEV), suggests the need for a routine study to monitor its prevalence. One hundred fifty-four consecutive patients who were clinically diagnosed with acute hepatitis between 2014 and 2015 in Ulaanbaatar, Mongolia were studied. By serological and molecular testing followed by sequencing and phylogenetic analysis, only one patient (0.6%) was diagnosed with acute hepatitis A, caused by genotype IA hepatitis A virus (HAV), and 32 (20.8%) patients were diagnosed with acute hepatitis E, caused by genotype 1 HEV. The 32 HEV isolates obtained in this study shared 99.5-100% nucleotide identity and were grouped into a cluster separated from those of subtypes 1a to 1f. Upon comparison of p-distances over the entire genome, the distances between one representative HEV isolate (MNE15-072) and 1a-1f strains were 0.071-0.137, while those between 1b and 1c were 0.062-0.070. In conclusion, the prevalence of acute hepatitis A has decreased in Mongolia since the start of the vaccination program, while the monophyletic genotype 1 HEV strain of a probably novel subtype has been prevalent.
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Affiliation(s)
- Bira Tsatsralt-Od
- National Center for Communicable Diseases, Ministry of Health, NCCD-Campus, Ulaanbaatar, Mongolia
| | - Putu Prathiwi Primadharsini
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Tsutomu Nishizawa
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Hiroshi Ohnishi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Suljid Jirintai
- Division of Pathology, Department of Basic Veterinary Medicine, Inner Mongolia Agricultural University College of Veterinary Medicine, Hohhot, Inner Mongolia, China
| | - Dulmaa Nyamkhuu
- National Center for Communicable Diseases, Ministry of Health, NCCD-Campus, Ulaanbaatar, Mongolia
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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Dashtseren B, Bungert A, Bat-Ulzii P, Enkhbat M, Lkhagva-Ochir O, Jargalsaikhan G, Enkhbat A, Oidovsambuu O, Klemen J, Dashdorj N, Dashdorj N, Genden Z, Yagaanbuyant D. Endemic prevalence of hepatitis B and C in Mongolia: A nationwide survey amongst Mongolian adults. J Viral Hepat 2017; 24:759-767. [PMID: 28211256 DOI: 10.1111/jvh.12697] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 02/07/2017] [Indexed: 12/19/2022]
Abstract
In this study, a representative group of Mongolian adults was tested for hepatitis B virus (HBV) and hepatitis C virus (HCV). Screening was conducted at 17 different locations on a randomly sampled group, representing the Mongolian adult population. A total of 1158 adults, 500 (43.1%) men and 659 (56.9%) women were included. The prevalence estimates of HBV and HCV amongst the general Mongolian adult population were found to be 11.1%±1% (SE) and 8.5%±0.7% or 207 418 and 160 228 cases, respectively. For HCV, the majority of cases are concentrated in older age groups with a prevalence of 25.8% amongst those aged 50 years and above, whilst the prevalence of HBV does not vary significantly amongst age groups. For both, HBV and HCV, the data indicate a higher risk of infection and a higher mortality because of the hepatitis amongst men than amongst women. This study represents the first nationwide estimate of the prevalence of HBV in Mongolia and also considered the first for HCV since 2005 and confirm the position of Mongolia as one of the hot-spots of chronic hepatitis infection in the world with about 19.4% of the adult population being infected with either HBV or HCV.
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Affiliation(s)
- B Dashtseren
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
- Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - A Bungert
- Onom Foundation, Ulaanbaatar, Mongolia
| | - P Bat-Ulzii
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
| | - M Enkhbat
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
| | - O Lkhagva-Ochir
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
| | - G Jargalsaikhan
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
| | - A Enkhbat
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
| | - O Oidovsambuu
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
- National University of Mongolia, Ulaanbaatar, Mongolia
| | - J Klemen
- Onom Foundation, Ulaanbaatar, Mongolia
| | | | - N Dashdorj
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
| | - Z Genden
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
| | - D Yagaanbuyant
- Onom Foundation, Ulaanbaatar, Mongolia
- Liver Centre, Ulaanbaatar, Mongolia
- Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
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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
| | - 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
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Chimed T, Sandagdorj T, Znaor A, Laversanne M, Tseveen B, Genden P, Bray F. Cancer incidence and cancer control in Mongolia: Results from the National Cancer Registry 2008-12. Int J Cancer 2017; 140:302-309. [PMID: 27716912 DOI: 10.1002/ijc.30463] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 09/27/2016] [Indexed: 12/19/2022]
Abstract
Mongolia has a high burden from noncommunicable diseases, with cancer now the second leading cause of mortality. Given the paucity of situation analyses from the country, this study reports cancer data based on new cases 2008-12 from the National Cancer Registry of Mongolia covering the entire population (2.87 million). New cancer cases of 21,564 were diagnosed over the 5-year period, with a slight predominance of cases (52%) in men. Liver cancer was the leading cancer site in both sexes (ASRs of 114.7 and 74.6 per 100,000 males and females), and responsible for almost two-fifths of all cancer diagnoses, followed by cancers of stomach, lung and oesophagus in men and cervix, stomach and oesophagus in women. The cumulative risk of incidence for all cancers (27.7% and 20.8% in men and women, respectively) positions Mongolia above China (20.2% and 13.3%), below the United States (34.1% and 28.5%) and similar to Russia (26.1% and 19.1%). These figures shed light on the considerable magnitude of cancer in the country and the large fraction of cancers that can be prevented by lifestyle modifications and vaccine implementation. An expansion of activities of the cancer registry and the continued development of research are necessary steps in support of national cancer control planning in Mongolia.
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Affiliation(s)
- Tuvshinjargal Chimed
- Cancer Surveillance Section, International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon CEDEX 08, 69372, France
| | | | - Ariana Znaor
- Cancer Surveillance Section, International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon CEDEX 08, 69372, France
| | - Mathieu Laversanne
- Cancer Surveillance Section, International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon CEDEX 08, 69372, France
| | - Badamsuren Tseveen
- Research Training and Information Department, National Cancer Center, Mongolia
| | - Purevsuren Genden
- Research Training and Information Department, National Cancer Center, Mongolia
| | - Freddie Bray
- Cancer Surveillance Section, International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon CEDEX 08, 69372, France
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Takyar V, Surana P, Kleiner DE, Wilkins K, Hoofnagle JH, Liang TJ, Heller T, Koh C. Noninvasive markers for staging fibrosis in chronic delta hepatitis. Aliment Pharmacol Ther 2017; 45:127-138. [PMID: 27813124 PMCID: PMC5135658 DOI: 10.1111/apt.13834] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 08/21/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Serum fibrosis markers are useful in staging chronic hepatitis B (HBV) and C (HCV) virus but have not been evaluated in chronic hepatitis D virus (HDV). AIM To evaluate the utility of serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, aspartate aminotransferase ratio (AAR), age-platelet index (API), AST-to-platelet-ratio-index (APRI) and Hui score] in HDV infection. METHODS Clinical and histologic laboratory data from HBV, HCV and HDV patients were evaluated and serum fibrosis markers were calculated. The ability of fibrosis markers to detect advanced fibrosis (Ishak ≥4) and cirrhosis (Ishak = 6) were evaluated and compared between viral infections. RESULTS A total of 1003 subjects (HCV = 701, HBV = 240 and HDV = 62) with mean age of 46 ± 11 and 66% male were evaluated. HDV subjects had higher ALT and AST than HCV and lower platelets than both HBV and HCV. Histologically, HDV had the greatest percentage of Ishak ≥4 and necroinflammation. FIB-4 performed best in detecting advanced fibrosis and cirrhosis in all viral cohorts. In HDV, area under the receiver operator curve (AUROC) 95% confidence intervals for detecting advanced fibrosis were: FIB-4 = 0.70 (0.55-0.84), API = 0.69 (0.55-0.82), APRI = 0.68 (0.54-0.82), Hui score = 0.63 (0.49-0.78), AAR = 0.63 (0.48-0.77). The AUROC for detecting cirrhosis in HDV were: FIB-4 = 0.83 (0.69-0.97), API = 0.80 (0.66-0.95), APRI = 0.75 (0.61-0.89), Hui score = 0.70 (0.49-0.91) and AAR = 0.70 (0.48-0.93). Adjustment of published cut-offs led to marginal improvements in FIB4 for advanced fibrosis and of APRI for cirrhosis in HDV. CONCLUSIONS Serum fibrosis markers have lower performance accuracy in chronic HDV infected patients compared to HBV and HCV patients. Other noninvasive fibrosis markers should be explored to assist in the management of these patients.
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Affiliation(s)
- Varun Takyar
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Pallavi Surana
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Kenneth Wilkins
- Office of the Director, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Jay H. Hoofnagle
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - T. Jake Liang
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Kim YA, Estevez J, Le A, Israelski D, Baatarkhuu O, Sarantuya T, Narantsetseg S, Nymadawa P, H Le R, Yuen MF, Dusheiko G, Rizzetto M, Nguyen MH. Screening and management of viral hepatitis and hepatocellular carcinoma in Mongolia: results from a survey of Mongolian physicians from all major provinces of Mongolia. BMJ Open Gastroenterol 2016; 3:e000119. [PMID: 27933202 PMCID: PMC5128837 DOI: 10.1136/bmjgast-2016-000119] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 09/08/2016] [Accepted: 09/22/2016] [Indexed: 12/11/2022] Open
Abstract
Background According to Globocan, Mongolia has the highest worldwide hepatocellular carcinoma (HCC) incidence (78.1/100 000, 3.5× higher than China). Aims and methods We conducted an anonymous survey of physicians from major provinces who attended an educational liver symposium, analysing their demography, practice, knowledge, perceptions and proposed solutions. Multivariate logistic regression was used to estimate OR relating demography and practice factors with higher provider knowledge and improvement. Results Of the 121 attendees, 44–95 (36–79%) responded to each question. Most were female (87%), young (79% age <50), subspecialists (81%), university-affiliated (74%), and practised in urban areas (61%). The mean pretest and post-test scores per physician were 60.4±20.4 and 65.6±21.3, with no observed significant predictors for baseline knowledge or improvement. Most (>80%) noted that <50% of patients who need hepatitis or HCC screening receive it. The main perceived barriers to screening were inability to pay for tests, lack of guidelines and poor patient awareness. Hepatitis treatment rates were low; 83% treated hepatitis C virus in <10 patients in the past year, and 86% treated hepatitis B virus in <10 patients/month. Treatment barriers were multifactorial, with cost as a principal barrier. Proposed solutions were universal screening policies (46%), removal of financial barriers (28%) and provider education (20%). Conclusions Physicians from major regions of Mongolia noted low screening for viral hepatitis, even lower treatment rates, financial barriers and the need for increased educational efforts. We advocate broad-based medical education tailored to local needs and based on needs assessment and outcome measurements.
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Affiliation(s)
- Yoona A Kim
- Division of Gastroenterology and Hepatology , Stanford University , Stanford, California , USA
| | - Jacqueline Estevez
- Division of Gastroenterology and Hepatology , Stanford University , Stanford, California , USA
| | - An Le
- Division of Gastroenterology and Hepatology , Stanford University , Stanford, California , USA
| | - Dennis Israelski
- Center for Innovation in Global Health, Stanford University, Stanford, California, USA; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California, USA
| | - Oidov Baatarkhuu
- Department of Infectious Diseases , Mongolian National University of Medical Sciences , Ulaanbaatar , Mongolia
| | - Tserenchimed Sarantuya
- Department of Internal Medicine , United Family Intermed Hospital , Ulaanbaatar , Mongolia
| | - Sonom Narantsetseg
- Shastin Memorial Third National General Hospital of Mongolia , Ulaanbaatar , Mongolia
| | - Pagbajabyn Nymadawa
- Public Health Branch , Mongolian Academy of Medical Sciences , Ulaanbaatar , Mongolia
| | - Richard H Le
- Division of Gastroenterology and Hepatology , Stanford University , Stanford, California , USA
| | - Man-Fung Yuen
- Division of Gastroenterology and Hepatology , Queen Mary Hospital, The University of Hong Kong , Hong Kong , Hong Kong
| | - Geoffrey Dusheiko
- Kings College Hospital and University College London School of Medicine , London , UK
| | - Mario Rizzetto
- Department of Gastroenterology , University of Turin , Turin , Italy
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA; Center for Innovation in Global Health, Stanford University, Stanford, California, USA
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Tsatsralt-Od B. Viral Hepatitis in Mongolia: Past, Present, and Future. Euroasian J Hepatogastroenterol 2016; 6:56-58. [PMID: 29201727 PMCID: PMC5578561 DOI: 10.5005/jp-journals-10018-1168] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 12/15/2015] [Indexed: 12/19/2022] Open
Abstract
Viral hepatitis is one of the major health concerns worldwide, particularly in Asian countries. Mongolia, which is located in northern Asia, between Russia and China, is confronting various infectious diseases, such as viral hepatitis and tuberculosis. As for healthy individuals in Mongolia, the reported prevalence of hepatitis B surface antigen (HBsAg) was 9 or 10% and the reported prevalence of anti-hepatitis C virus ranged from 11 to 25%. We reported a markedly high prevalence of hepatitis D virus RNA (83%) among apparently healthy individuals with HBsAg in Ulaanbaatar. Also due to lack of proper mechanisms to handle sewerage, disinfection, and lack of clean water supply across the country, hepatitis A is endemic in Mongolia. Moreover, Mongolia ranked in the high-prevalence zone for hepatitis B, D, and C. How to cite this article Tsatsralt-Od B. Viral Hepatitis in Mongolia: Past, Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):56-58.
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Affiliation(s)
- Bira Tsatsralt-Od
- National Institute of Medicine, Ministry of Health and Ministry of Science Education Mongolia, Ulaanbaatar, Mongolia
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PCR-Based Molecular Diagnosis of Hepatitis Virus (HBV and HDV) in HCV Infected Patients and Their Biochemical Study. J Pathog 2016; 2016:3219793. [PMID: 27366331 PMCID: PMC4913052 DOI: 10.1155/2016/3219793] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Revised: 04/21/2016] [Accepted: 05/11/2016] [Indexed: 12/12/2022] Open
Abstract
Seroprevalence of HCV indicates that HCV is found in more than 10% of HBV- or HDV-infected patients worldwide leading to liver disease. Here we show HBV and HDV coinfection association with HCV infected Pakistani patients, study of disease severity, and possible interpretation of associated risk factors in coinfected patients. A total of 730 liver diseased patients were included, out of which 501 were found positive for HCV infection via PCR. 5.1% of patients were coinfected with HBV while 1% were coinfected with HBV and HDV both. LFTs were significantly altered in dually and triply infected patients as compared to single HCV infection. Mean bilirubin, AST, and ALT levels were highest (3.25 mg/dL, 174 IU/L, and 348 IU/L) in patients with triple infection while dual infection LFTs (1.6 mg/dL, 61 IU/L, and 74 IU/L) were not high as in single infection (1.9 mg/dL, 76 IU/L, and 91 IU/L). The most prominent risk factor in case of single (22%) and dual infection (27%) group was “reuse of syringes” while in triple infection it was “intravenous drug users” (60%). It is concluded that HBV and HDV coinfections are strongly associated with HCV infected Pakistani patients and in case of severe liver disease the possibility of double and triple coinfection should be kept in consideration.
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Dantas LC, Genzini T, de Miranda MP, dos Santos RG, de Siqueira NG, Weirich J, Lobato CMDO. Liver transplantation in a patient with hepatitis B, C and D coinfection associated with hepatocellular carcinoma: a management strategy for a rare condition. Case report. SAO PAULO MED J 2015; 133:525-30. [PMID: 26176835 PMCID: PMC10496563 DOI: 10.1590/1516-3180.2015.8881501] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2014] [Revised: 09/25/2014] [Accepted: 10/20/2014] [Indexed: 02/07/2023] Open
Abstract
CONTEXT Orthotopic liver transplantation (OLT) is the treatment of choice for end-stage liver disease. Cirrhosis due to hepatitis C infection is the leading indication for liver transplantation worldwide. However, patients who are given transplants because of viral liver diseases often present clinical coinfections, including hepatitis B together with hepatitis D. Currently, different strategies exist for patient management before and after liver transplantation, and these are based on different protocols developed by the specialized transplantation centers. CASE REPORT We present a rare case of a 58-year-old man with chronic hepatitis B, C and D coinfection. The patient developed cirrhosis and hepatocellular carcinoma. His treatment comprised antiviral therapy for the three viruses and OLT. The patient's outcome was satisfactory. CONCLUSION OLT, in association with antiviral therapy using entecavir, which was administered before and after transplantation, was effective for sustained clearance of the hepatitis B and D viruses. A recurrence of hepatitis C infection after transplantation responded successfully to standard treatment comprising peginterferon alfa-2A and ribavirin.
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Affiliation(s)
- Lucas Carvalho Dantas
- MD. Physician, Health Sciences Center, Universidade Federal do Acre (UFAC), Rio Branco, Acre, Brazil
| | - Tércio Genzini
- MSc. Physician, Director and Founder, Liver Transplantation Group, Hospital Beneficência Portuguesa, São Paulo, São Paulo, Brazil
| | - Marcelo Perosa de Miranda
- MSc. Physician, Director and Founder, Liver Transplantation Group, Hospital Beneficência Portuguesa, São Paulo, São Paulo, Brazil
| | - Regina Gomes dos Santos
- MD. Physician, Liver Transplantation Group, Hospital Beneficência Portuguesa, São Paulo, São Paulo, Brazil.
| | | | - Judith Weirich
- MD, MSc. Physician, Hepatology and Tropical Diseases Unit, Hospital das Clínicas do Acre, Rio Branco, Acre, Brazil
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Wranke A, Heidrich B, Hardtke S, Wedemeyer H. Current Management of HBV/HDV Coinfection and Future Perspectives. ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s11901-015-0280-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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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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Tsatsralt-Od B, Baasanjav N, Nyamkhuu D, Ohnishi H, Takahashi M, Kobayashi T, Nagashima S, Nishizawa T, Okamoto H. Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013. J Med Virol 2015; 88:622-30. [PMID: 26369542 DOI: 10.1002/jmv.24380] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2015] [Indexed: 01/22/2023]
Abstract
Despite the high endemicity of hepatitis A virus (HAV) in Mongolia, the genetic information on those HAV strains is limited. Serum samples obtained from 935 patients with acute hepatitis in Ulaanbaatar, Mongolia during 2004-2013 were tested for the presence of HAV RNA using reverse transcription-PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 180 patients (19.3%) had detectable HAV RNA. These 180 isolates shared 94.6-100% identity and formed four phylogenetic clusters within subgenotype IA. One or three representative HAV isolates from each cluster exhibited 2.6-3.9% difference between clusters over the entire genome. Cluster 1 accounted for 65.0% of the total, followed by Cluster 2 (30.6%), Cluster 3 (3.3%), and Cluster 4 (1.1%). Clusters 1 and 2 were predominant throughout the observation period, whereas Cluster 3 was undetectable in 2009 and 2013 and Cluster 4 became undetectable after 2009. The Mongolian HAV isolates were closest to those of Chinese or Japanese origin (97.7-98.5% identities over the entire genome), suggesting the evolution from a common ancestor with those circulating in China and Japan. Further molecular epidemiological analyses of HAV infection are necessary to investigate the factors underlying the spread of HAV and to implement appropriate prevention measures in Mongolia.
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Affiliation(s)
- Bira Tsatsralt-Od
- National Institute of Medicine, Ministry of Health and Ministry of Science Education, Ulaanbaatar, Mongolia.,National Center for Communicable Diseases, Ministry of Health, Ulaanbaatar, Mongolia
| | - Nachin Baasanjav
- National Institute of Medicine, Ministry of Health and Ministry of Science Education, Ulaanbaatar, Mongolia
| | - Dulmaa Nyamkhuu
- National Center for Communicable Diseases, Ministry of Health, Ulaanbaatar, Mongolia
| | - Hiroshi Ohnishi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Tominari Kobayashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Tsutomu Nishizawa
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
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Kushner T, Serper M, Kaplan DE. Delta hepatitis within the Veterans Affairs medical system in the United States: Prevalence, risk factors, and outcomes. J Hepatol 2015; 63:586-92. [PMID: 25962883 PMCID: PMC4574953 DOI: 10.1016/j.jhep.2015.04.025] [Citation(s) in RCA: 125] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 04/24/2015] [Accepted: 04/27/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Low hepatitis delta prevalence estimates in the United States are likely biased due to low testing rates. The objectives of this study were to quantify the prevalence of testing and identify factors associated with hepatitis D positive status among chronic hepatitis B patients in the Veterans Health Administration. METHODS We performed a nationwide retrospective study of all veterans who tested positive for HBsAg from October 1999 to December 2013. Hepatitis D antibody testing results were used to stratify patients into three groups: HDV-positive, HDV-negative, and HDV-not tested. Demographics, comorbidities, additional laboratory data and clinical outcomes were compared across these groups of patients using standard statistical approaches. RESULTS Among 25,603 patients with a positive hepatitis B surface antigen, 2175 (8.5%) were tested for HDV; 73 (3.4%) patients tested positive. Receiving HDV testing was associated with receipt of testing for HBV, HIV, and HCV. Predictors of positive HDV results included substance abuse and cirrhosis. Fitting a predefined high-risk profile (abnormal ALT with suppressed HBV DNA titers) was strongly associated with testing positive for HDV (OR 3.2, 95%CI 1.4-7.5). Most (59%) of HDV-positive patients were HCV co-infected. HDV-positive subjects had higher risks of all-cause mortality. Incidence rates of HCC were 2.9 fold higher in HDV-positive relative to HDV-negative individuals (p=0.002). In adjusted analyses, HDV was independently associated with HCC (OR 2.1, 95%CI 1.1-3.9). CONCLUSIONS Testing rates for hepatitis delta in chronic hepatitis B patients in the United States are inappropriately low. Approaches to increase testing for HDV particularly in high-risk subsets should be explored.
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Affiliation(s)
- Tatyana Kushner
- Division of Gastroenterology, University of Pennsylvania, Philadelphia PA
| | - Marina Serper
- Division of Gastroenterology, University of Pennsylvania, Philadelphia PA,Department of Medicine Philadelphia VA Medical Center, Philadelphia PA
| | - David E. Kaplan
- Division of Gastroenterology, University of Pennsylvania, Philadelphia PA,Department of Medicine Philadelphia VA Medical Center, Philadelphia PA
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Tsatsralt-Od B, Baasanjav N, Nyamkhuu D, Ohnishi H, Takahashi M, Okamoto H. Prevalence of hepatitis viruses in patients with acute hepatitis and characterization of the detected genotype 4 hepatitis E virus sequences in Mongolia. J Med Virol 2015; 88:282-91. [PMID: 26147664 DOI: 10.1002/jmv.24319] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2015] [Indexed: 01/14/2023]
Abstract
Hepatitis E is considered to be a worldwide public health problem. Although the prevalence of hepatitis E virus (HEV) antibodies in healthy individuals is noted to be 11%, no patients with acute hepatitis E have previously been identified in Mongolia. Three hundred two consecutive patients (183 males and 119 females; median age of 22.0 [Interquartile range: 18.3-25.0] years) who were clinically diagnosed with sporadic acute hepatitis during 2012-2013 in Ulaanbaatar, Mongolia, were studied. By serological and/or molecular approaches, 77 (25.5%), 93 (30.8%), 19 (6.3%), 48 (15.9%), and 12 (4.0%) of the patients were diagnosed with acute hepatitis of types A, B, C, D (superinfection of hepatitis delta virus on a background of chronic hepatitis B virus infection) and E, respectively, while the cause of hepatitis was unknown in the remaining 53 patients (17.5%). The 12 hepatitis E patients had no history of travel abroad in the 3 months before the onset of disease, and lived separately in fixed or movable houses with water supplied via pipe, tank or well, denying transmission from a common water supply. The 12 HEV isolates obtained from the patients showed high nucleotide identities of 99.7-100%, and a representative HEV isolate, MNE13-227, was closest to the Chinese isolates of genotype 4, with the highest identity of 97.3% in the 304-nt ORF2 sequence and 92.1% over the entire genome. The present study revealed the occurrence of autochthonous acute hepatitis E in Mongolia, caused by a monophyletic genotype 4 HEV strain.
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Affiliation(s)
- Bira Tsatsralt-Od
- National Institute of Medicine, Ministry of Health and Ministry of Science Education, Ulaanbaatar, Mongolia.,National Center for Communicable Diseases, Ministry of Health, Ulaanbaatar, Mongolia
| | - Nachin Baasanjav
- National Institute of Medicine, Ministry of Health and Ministry of Science Education, Ulaanbaatar, Mongolia
| | - Dulmaa Nyamkhuu
- National Center for Communicable Diseases, Ministry of Health, Ulaanbaatar, Mongolia
| | - Hiroshi Ohnishi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi-Ken, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi-Ken, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi-Ken, Japan
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Tsatsralt Od B. Epidemiology of Viral Hepatitis and Liver Diseases in Mongolia. Euroasian J Hepatogastroenterol 2015; 5:37-39. [PMID: 29201684 PMCID: PMC5578518 DOI: 10.5005/jp-journals-10018-1127] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Accepted: 09/28/2014] [Indexed: 12/27/2022] Open
Abstract
Mongolia which is located in Northern Asia between Russia and China is endowed with one of lowest population density in the world. Acute hepatitis due all types of hepatitis virus has been reported in Mongolia. Also, dual and triple hepatitis viruses, HBV, HDV and HCV are highly prevalent among patients with chronic liver disease living in Mongolia. Due to these facts, liver cancer is the leading cause of cancer mortality in Mongolia. The national immunization program including vaccination against hepatitis B was started in 1991 and screening of blood donations for HBsAg and anti-HCV was introduced in 1993 and 1997 respectively. The incidence of hepatitis viruses showing a downhill course in some parts of Mongolia, but comprehensive efforts are needed to control hepatitis viruses and containment of hepatitis related liver diseases and liver cancer in Mongolia.
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Affiliation(s)
- Bira Tsatsralt Od
- Department of Gastroenterology, National Institute of Medicine, Ministry of Health, Education and Science, Ulaanbaatar, Mongolia
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42
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Hepatitis delta virus: a peculiar virus. Adv Virol 2013; 2013:560105. [PMID: 24198831 PMCID: PMC3807834 DOI: 10.1155/2013/560105] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Revised: 08/29/2013] [Accepted: 08/29/2013] [Indexed: 02/07/2023] Open
Abstract
The hepatitis delta virus (HDV) is distributed worldwide and related to the most severe form of viral hepatitis. HDV is a satellite RNA virus dependent on hepatitis B surface antigens to assemble its envelope and thus form new virions and propagate infection. HDV has a small 1.7 Kb genome making it the smallest known human virus. This deceivingly simple virus has unique biological features and many aspects of its life cycle remain elusive. The present review endeavors to gather the available information on HDV epidemiology and clinical features as well as HDV biology.
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Ghamari S, Alavian SM, Rizzetto M, Olivero A, Smedile A, Khedive A, Alavian SE, Zolfaghari MR, Jazayeri SM. Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B patients with unusual clinical pictures. HEPATITIS MONTHLY 2013; 13:e6731. [PMID: 24098308 PMCID: PMC3787685 DOI: 10.5812/hepatmon.6731] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Revised: 06/29/2013] [Accepted: 07/15/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone. OBJECTIVES The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates. PATIENTS AND METHODS 81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations. RESULTS 12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients. CONCLUSIONS HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group.
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Affiliation(s)
- Shiva Ghamari
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Seyed Moayed Alavian
- Baqiyatallah University of Medical Sciences, Baqiyatallah Research Centre for Gastroenterology and Liver Disease, Tehran, IR Iran
- Middle East Liver Diseases Center, Tehran, IR Iran
| | - Mario Rizzetto
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Antonella Olivero
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Antonina Smedile
- Department of Gastroenterology and Hepatology, San Giovanni Battista University Hospital (Molinette), Turin, Italy
| | - Abulfazl Khedive
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Seyed Ehsan Alavian
- Baqiyatallah University of Medical Sciences, Baqiyatallah Research Centre for Gastroenterology and Liver Disease, Tehran, IR Iran
- Middle East Liver Diseases Center, Tehran, IR Iran
| | | | - Seyed Mohammad Jazayeri
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
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Wedemeyer H, Hardtke S, Manns MP. Epidemiology and Natural History. VIRAL HEPATITIS 2013:403-409. [DOI: 10.1002/9781118637272.ch28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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45
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William Tong CY, Asher R, Toby M, Ngui SL, Tettmar K, Ijaz S, Tedder R, Kulasegaram R, Wilkinson M, Wong T. A re-assessment of the epidemiology and patient characteristics of hepatitis D virus infection in inner city London. J Infect 2013; 66:521-7. [PMID: 23466596 DOI: 10.1016/j.jinf.2013.02.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2012] [Revised: 01/26/2013] [Accepted: 02/09/2013] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To re-assess the prevalence and patient characteristics of hepatitis D virus (HDV) infection among hepatitis B patients in inner city London. METHODS All hepatitis B patients attending clinics over a 52 months period were tested for HDV antibody. All reactive samples were also tested for anti-HDV IgM and RNA. The characteristics of HDV seronegative patients first seen in the calendar year 2008 were compared with all HDV seropositive patients in the cohort. RESULTS Of 1048 hepatitis B patients, 11 had equivocal anti-HDV serology (1%) and 22 were HDV seropositive (2.1%, 95%CI 1.39-3.16%); 12 were anti-HDV IgM positive and 15 HDV RNA positive. No patient with equivocal anti-HDV serology had detectable HDV RNA. Five HDV seropositive patients were intravenous drug users (22.7%); 17/22 were from abroad with 11/22 (50%) from sub-Saharan Africa. HDV seropositive patients had poorer laboratory parameters and were more likely to have evidence of cirrhosis. Triple infected (HIV/HBV/HDV) patients were also more likely to have cirrhosis than HIV/HBV dually infected patients. CONCLUSIONS The prevalence of HDV in hepatitis B patients in inner city London was about 2%. The role of migration from endemic countries should be recognised.
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Affiliation(s)
- C Y William Tong
- Department of Infectious Diseases, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK.
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Popescu GA, Otelea D, Gavriliu LC, Neaga E, Popescu C, Paraschiv S, Fratila M. Epidemiology of hepatitis D in patients infected with hepatitis B virus in bucharest: a cross-sectional study. J Med Virol 2013; 85:769-74. [PMID: 23408537 DOI: 10.1002/jmv.23524] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2012] [Indexed: 12/18/2022]
Abstract
Epidemiological analyses indicate a decreasing level of hepatitis D (HDV) infections in most developed countries during the last 15 years. Romania, however, is one of the European countries that still has high morbidity from HDV; this study was performed in order to estimate the HDV prevalence in the Bucharest area. Three thousand four hundred sixty-one hepatitis B (HBV) infected patients were invited to participate and 1,094 were recruited. Serum anti-HDV IgG was detected in 223 patients indicating a hepatitis D seroprevalence of 20.4% (95% CI = 18.1-22.9) in patients chronically infected with HBV, less than that seen in previous studies. Seroprevalence was not gender related, but patients over 40 years were more likely to have anti-HDV antibodies, RR = 1.9 (1.2; 3.0). Detectable hepatitis D viraemia was found in 67.7% of the patients who were positive for anti-HDV. The HDV genotype was characterized for 40 isolates; all were very similar and belonged to genotype 1. Serum HBV-DNA was detectable less frequently in patients positive for anti-HDV than in patients infected with HBV alone: 68.5% versus 89.3%, OR 3.9 (1.7; 10.0), but the extent of this HDV replicative dominance varies with the sensitivity of the HBV-DNA detection. 19.3% of the subjects who tested positive for anti-HDV IgG had a HBV-DNA level higher than four logs. This high prevalence prompts the need for better HBV vaccination coverage and measures to prevent super infection with HDV in patients infected with HBV.
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Affiliation(s)
- G A Popescu
- Infectious Diseases Department, Prof. Dr. Matei Bals National Institute for Infectious Diseases, Str. Calistrat Grozovici, Nr.1, Sector 2, 021105 Bucharest, Romania
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Sunbul M, Sugiyama M, Kurbanov F, Leblebicioglu H, Khan A, Elkady A, Tanaka Y, Mizokami M. Specific mutations of basal core promoter are associated with chronic liver disease in hepatitis B virus subgenotype D1 prevalent in Turkey. Microbiol Immunol 2013; 57:122-129. [PMID: 23252849 DOI: 10.1111/1348-0421.12011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2012] [Revised: 11/12/2012] [Accepted: 11/23/2012] [Indexed: 12/13/2022]
Abstract
The role of hepatitis B virus (HBV) genetics in the clinical manifestations of infection is being increasingly recognized. Genotype D is one of eight currently recognized major HBV genotypes. The virus is ubiquitous worldwide, but shows different features in different regions. One hundred and ninety-eight patients with chronic HBV infection were enrolled in this study, 38 of whom had been diagnosed with cirrhosis of the liver and/or hepatocellular carcinoma. HBV DNA was isolated from the patients' blood samples and the entire genome and/or the basal core promoter/core promoter region sequenced. Phylogenetic analysis of the complete genomes revealed that subgenotype D1 is the most prevalent subgenotype in Turkey, but there was no definite phylogenetic grouping according to geography for isolates from different regions within Turkey, or for isolates in Turkey relative to other parts of the world. Turkish isolates tended to be genetically similar to European and central Asian isolates. Overall, HBV-infection in Turkey appears to be characterized by early HBeAg seroconversion, a high incidence of the A1896 core promoter mutation and a small viral load. Genotype D characteristic mutations A1757 and T1764/G1766 were found in the BCP region. T1773 was associated with T1764/G1766 and a larger viral load. In conclusion, infection with HBV genotype D in Turkey has a similar clinical outcome to that of Europe and central Asia. Genotypic mutations in genotype D may be linked with disease prognosis in Turkey, but further studies with higher sample numbers and balanced clinical groups are needed to confirm this.
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Affiliation(s)
- Mustafa Sunbul
- Department of Infectious Diseases, School of Medicine, Ondokuz Mayis University, Kurupelit, Samsun, Turkey
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Amini N, Alavian SM, Kabir A, Aalaei-Andabili SH, Saiedi Hosseini SY, Rizzetto M. Prevalence of hepatitis d in the eastern mediterranean region: systematic review and meta analysis. HEPATITIS MONTHLY 2013; 13:e8210. [PMID: 23554822 PMCID: PMC3609404 DOI: 10.5812/hepatmon.8210] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2012] [Revised: 09/01/2012] [Accepted: 09/22/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatitis D Virus (HDV) causes the most threatening form of chronic viral hepatitis. To date, there is no overall estimation of HDV prevalence in the Eastern Mediterranean Region Office of WHO (EMRO) countries. OBJECTIVES To provide a clear estimation of HDV prevalence in the aforementioned region. PATIENTS AND METHODS In the current systematic review, databases such as PubMed, Embase, Web of sciences and Google scholar were searched Until December 2010. The summary estimate of HDV prevalence in the EMRO region was calculated as an average of the pooled infection prevalence of each country weighted by the ratio of the country's HBV population to the study's sample size in the survey data analysis. RESULTS We included 62 eligible studies. The weighted mean of HDV prevalence in the EMRO region was 14.74% (95% CI: 14.73 - 14.77), 27.8% (95% CI: 27.78 - 27.82), 36.57% (95% CI: 36.55 - 36.59) and 16.44%. (95% CI: 16.42 - 16.46) in asymptomatic HBsAg positive carriers, chronic hepatitis patients, cirrhosis/ hepatocellular carcinoma, and high risk group, respectively. Among the asymptomatic HBsAg positive group, HDV prevalence was increased by years in older patients in Saudi Arabia but its prevalence was decreased in Iran. No specific pattern was seen according to chronological analysis during years among the EMRO countries. CONCLUSIONS HDV infection is endemic in the EMRO countries and it is more common among patients with severe forms of hepatitis. Due to the high HDV infection rates in the EMRO countries, we recommend blood screening for HDV infection in this region.
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Affiliation(s)
- Neda Amini
- Tehran University of Medical Sciences, Students' Scientific Research Centre, Tehran, IR Iran
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Ali Kabir
- Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
- Center for Educational Research in Medical Sciences, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Seyed Hossein Aalaei-Andabili
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Seyed Yasser Saiedi Hosseini
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Mario Rizzetto
- Division of Gastroenterology, Molinette – University of Turin, Corso Bramante, Turin, Italy
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Wedemeyer H, Hardtke S, Manns MP. Update on the Management of HBV-HDV Coinfection. CURRENT HEPATITIS REPORTS 2012; 11:95-101. [DOI: 10.1007/s11901-012-0129-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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50
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Jazag A, Puntsagdulam N, Chinburen J. Status quo of chronic liver diseases, including hepatocellular carcinoma, in Mongolia. Korean J Intern Med 2012; 27:121-7. [PMID: 22707881 PMCID: PMC3372793 DOI: 10.3904/kjim.2012.27.2.121] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 04/24/2012] [Indexed: 11/27/2022] Open
Abstract
Because Mongolia has much higher liver disease burden than any other regions of the world, it is necessary to provide information on real-time situation of chronic liver disease in Mongolia. In this article, we reviewed studies performed in Mongolia from 2000 to 2011 on seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among healthy individuals and patients with chronic liver diseases, and on the practice patterns for the management of liver cirrhosis and hepatocellular carcinoma (HCC). According to previous reports, the seroprevalence of HBV and HCV in general population in Mongolia is very high (11.8% and 15% for HBV and HCV, respectively). Liver cirrhosis is also highly prevalent, and mortality from liver cirrhosis remained high for the past decade (about 30 deaths per 100,000 populations per year). Among patients with cirrhosis, 40% and 39% are positive for HBsAg and anti-HCV, respectively, and 20% are positive for both. The seroprevalence is similar for HCC and more than 90% of HCC patients are positive for either HBV or HCV. The incidence of HCC in Mongolia is currently among the highest in the world. The mortality from HCC is also very high (52.2 deaths per 100,000 persons per year in 2010). Partly due to the lack of established surveillance systems, most cases of HCC are diagnosed at an advanced stage. The mortality from liver cirrhosis and HCC in Mongolia may be reduced by implementation of antiviral therapy program and control of alcohol consumption.
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Affiliation(s)
- Amarsanaa Jazag
- Mongolian National Research Institute, Ulaanbaatar, Mongolia.
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