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Kim DH, Choi YM, Jang J, Kim Z, Kim BJ. Distinct phylogeographic distributions and frequencies of precore and basal core promoter mutations between HBV subgenotype C1 rt269L and rt269I types. Sci Rep 2025; 15:9315. [PMID: 40102552 PMCID: PMC11920224 DOI: 10.1038/s41598-025-94286-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 03/12/2025] [Indexed: 03/20/2025] Open
Abstract
Hepatitis B virus (HBV) genotype C exhibits two distinct polymorphisms in its viral polymerase: rt269I and rt269L. Recently, we reported that there are distinct virological and clinical profiles between chronic patients with subgenotype C2 with the rt269I polymorphism and those with the rt269L polymorphism, with the latter being more closely related to liver disease severity. This study explored the phylogenetic and geographic distributions, as well as the mutation frequencies, of precore (T1858C/G1896A) and basal core promoter (BCP) (A1762T/G1764A) mutations between these two types within the HBV subgenotype C1. Analysis of 408 HBV/C1 full-genome sequences from GenBank revealed clear phylogenetic separation between rt269L and rt269I in subgenotype C1. Geographically, rt269I strains within subgenotype C1 are predominant in Southwest Asia (e.g., Thailand and Bangladesh), whereas rt269L strains are more common in East Asia and Southeast Asia (e.g., Vietnam, China, and Hong Kong). Notably, compared with rt269L in subgenotype C2, rt269I presented higher frequencies of the C1858 and BCP mutations but lower frequencies of the G1896A mutation. These findings suggest significantly distinct phylogeographic and mutational characteristics of the rt269L and rt269I types of subgenotype C1, impacting clinical outcomes and evolutionary trajectories.
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Affiliation(s)
- Dong Hyun Kim
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Yu-Min Choi
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Junghwa Jang
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
- BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ziyun Kim
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
- BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Bum-Joon Kim
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
- BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Institute of Endemic Disease, Seoul National University Medical Research Center (SNUMRC), Seoul, Republic of Korea.
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Sirilert S, Khamrin P, Kumthip K, Malasao R, Tongsong T, Maneekarn N. Hepatitis B virus genotypes associated with pregnant women in Northern Thailand. J Infect Public Health 2024; 17:406-411. [PMID: 38262076 DOI: 10.1016/j.jiph.2023.12.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 12/17/2023] [Accepted: 12/26/2023] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Mother-to-child transmission of hepatitis B virus (HBV) is the major route of transmission causing persistent infection. The prevalence of HBV infection and HBV genotypes found in different geographical areas varies from country to country. Therefore, this study was conducted to identify the HBV genotypes in HBV-infected pregnant women in Northern Thailand. METHODS Stored blood samples that were collected from 145 HBsAg-positive pregnant women who gave birth at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand from 2017 to 2020 were analyzed. The partial nucleotide sequence of the S gene of HBV was amplified by nested PCR and sequenced. All sequences were analyzed phylogenetically together with the reference strains to define the HBV genotypes. RESULTS A total of 31 blood samples from 145 HBsAg-positive pregnant women were positive for HBV by nested PCR. The detected HBV strains were identified as presumptive subgenotypes C1 (77.4%; 24/31), B9 (9.7%; 3/31), C2 (3.2%; 1/31), B2 (3.2%; 1/31), B4 (3.2%; 1/31), and presumptive B4/C2 recombinant subgenotype (3.2%; 1/31). CONCLUSIONS The findings revealed that presumptive subgenotype C1 was the most common subgenotype circulating in pregnant women in Northern Thailand and accounted for 77.4% of cases, followed by presumptive subgenotypes B9, C2, B2, and B4. Furthermore, this study reported, for the first time in Thailand, the HBV genotypes and presumptive subgenotypes, particularly subgenotype B9 circulating in pregnant women.
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Affiliation(s)
- Sirinart Sirilert
- Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pattara Khamrin
- Department of Microbiology, Faculty of Medicine, and Emerging and Re-emerging Diarrheal Viruses Cluster, Chiang Mai University, Chiang Mai, Thailand
| | - Kattareeya Kumthip
- Department of Microbiology, Faculty of Medicine, and Emerging and Re-emerging Diarrheal Viruses Cluster, Chiang Mai University, Chiang Mai, Thailand
| | - Rungnapa Malasao
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Theera Tongsong
- Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Niwat Maneekarn
- Department of Microbiology, Faculty of Medicine, and Emerging and Re-emerging Diarrheal Viruses Cluster, Chiang Mai University, Chiang Mai, Thailand.
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Bello KE, Mat Jusoh TNA, Irekeola AA, Abu N, Mohd Amin NAZ, Mustaffa N, Shueb RH. A Recent Prevalence of Hepatitis B Virus (HBV) Genotypes and Subtypes in Asia: A Systematic Review and Meta-Analysis. Healthcare (Basel) 2023; 11:healthcare11071011. [PMID: 37046937 PMCID: PMC10094200 DOI: 10.3390/healthcare11071011] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/24/2023] [Accepted: 03/27/2023] [Indexed: 04/05/2023] Open
Abstract
Background and Aim: Despite introducing the hepatitis B virus (HBV) vaccine, the incidence of the Hepatitis B virus globally is still a major health concern. This systematic review and meta-analysis were conducted to provide detailed information on the prevalence of HBV genotypes and subtypes in circulation in Asia. Methods: A systematic search for articles describing the prevalence of HBV genotypes and subtypes in Asia was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Results: Our search returned 207 eligible articles involving 49,279 genotypes and 7457 subtypes representing 28 Asian countries. A meta-analysis was performed on our eligible studies using the Random effect Model. The pooled prevalence of HBV genotypes showed that genotype C (30.9%) (95% CI, 27.5–34.5%; I2 = 97.57%; p < 0.001) was the most common HBV genotype in Asia, followed by genotype B (17.8%) (95% CI, 15.5–20.4%; I2 = 97.26%; p < 0.001) and genotype D (15.4%) (95% CI, 11.8–19.8%). Vietnam had the highest prevalence of genotype B, Lebanon had the highest prevalence of genotypes C, and Jordan had the highest prevalence of genotype D. There was variation in genotypic prevalence with respect to the target genes for HBV genotyping. Reverse dot blot hybridization had the highest estimate of genotypes B and C. HBV subtype C2 (40.0%) (95% CI, 33.3–47.0) is the most prevalent HBV subtype. Conclusion: Evidence from this study reveals that HBV genotypes C and B are the most dominant HBV genotypes in Asia, and HBV subtype C2 is more endemic in Asia.
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Affiliation(s)
- Kizito Eneye Bello
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
- Department of Microbiology, Faculty of Natural Science, Kogi State University (Prince Abubakar Audu University), Anyigba 1008, Kogi State, Nigeria
| | - Tuan Nur Akmalina Mat Jusoh
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
| | - Ahmad Adebayo Irekeola
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
- Microbiology Unit, Department of Biological Sciences, College of Natural and Applied Sciences, Summit University Offa, Offa 4412, Kwara State, Nigeria
| | - Norhidayah Abu
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
- Advanced Materials Research Centre (A.M.R.E.C.), Lot 34 Jalan Hi-Tech 2/3, Kulim Hi-Tech Park, Kulim 09000, Kedah, Malaysia
| | - Nur Amalin Zahirah Mohd Amin
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
| | - Nazri Mustaffa
- Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
- Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Rafidah Hanim Shueb
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
- Institute for Research in Molecular Medicine (I.N.F.O.R.M.M.), Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
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Hepatitis B Virus Genotypes in the Kingdom of Bahrain: Prevalence, Gender Distribution and Impact on Hepatic Biomarkers. ACTA ACUST UNITED AC 2019; 55:medicina55100622. [PMID: 31547539 PMCID: PMC6843804 DOI: 10.3390/medicina55100622] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 09/09/2019] [Accepted: 09/16/2019] [Indexed: 12/17/2022]
Abstract
Background: Approximately 400 million people are infected with Hepatitis B virus (HBV) around the world, which makes it one of the world’s major infectious diseases. The prevalence of HBV genotypes and predictive factors for risk are poorly known in the Kingdom of Bahrain. Objectives: The aim of the present study was to investigate the prevalence of HBV genotypes, its correlation with demographic factor sand impacts on hepatic biomarkers. Materials and Methods: Venous blood samples were collected from 82 HBV positive patients (48 males, 34 females). The extraction of HBV DNA, PCR amplification, and genotyping were done to classify different genotypes (A, A/D, B, B/D, C, D, D/E, E). HBV genotypes association with gender, nationality, mode of transmission, and liver cirrhosis complication was determined by descriptive statistic and univariate analysis of variance (ANOVA). For liver function test, unpaired t-test and ANOVA were performed. Results: The predominant genotype among patients under study was genotype D (61%), followed by genotype A (10%), and lowest frequency was found for undetermined genotype (1%). In general, there was no significant association between the different genotypes and some demographical factors, serological investigations, and liver function test. The prevalence of HBV genotypes was higher in male patients as compared to female patients and higher in non-Bahraini than in Bahraini. Patients with the dominant genotype D showed higher than the normal maximum range for alanine aminotransferase (ALT) (mean = 45.89) and Gamma-glutamyl transferase (GGT) (mean = 63.36). Conclusions: The most common HBV genotype in Bahrain was genotype D, followed by genotype A. Further studies involving the sources of transmission and impact of hepatic biomarker in Bahrain are required to enhance the control measures of HBV infections.
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Kim BG, Park NH, Lee SB, Jeon S, Park JH, Jung SW, Jeong ID, Bang SJ, Shin JW. The risk of hepatocellular carcinoma within and beyond the first 5 years of entecavir in Korean patients with chronic hepatitis B. Liver Int 2018; 38:2269-2276. [PMID: 30052303 DOI: 10.1111/liv.13938] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 07/05/2018] [Accepted: 07/23/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS The development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) has decreased due to potent antiviral agents. However, it remains uncertain whether the risk of HCC will diminish after long-term antiviral therapy in Asia, where CHB is endemic and vertical transmission is common. This study aimed to compare the incidence of HCC within and beyond the first 5 years of entecavir (ETV) in treatment-naïve Korean patients with CHB. METHODS We performed a retrospective observational analysis of data from 894 consecutive, adult patients with CHB undergoing ETV treatment at a tertiary referral hospital in Ulsan, Korea from January 1, 2007 through April 31, 2017. We compared the HCC incidence rates per 100 person-years within and beyond the first 5 years. Univariate and multivariate analyses for factors predictive of HCC were performed. RESULTS The incidence rate of HCC in patients with CHB did not differ statistically when we compared within and beyond the first 5 years of ETV therapy (2.29% vs 1.66% per person-year, P = 0.217). Failure to achieve maintained virological response (MVR) was a major independent risk factor for HCC in patients at a follow-up of <5 years. In contrast, in patients with a follow-up of ≥5 years, achieving MVR was not significantly associated with HCC development. CONCLUSIONS The incidence rate of HCC may not change significantly before and after 5 years of ETV therapy in Korean CHB patients. The risk of HCC in Asian CHB patients may remain in the long-term.
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Affiliation(s)
- Byung Gyu Kim
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Neung Hwa Park
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Seung Bum Lee
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Soyoung Jeon
- Statistical Consulting Laboratory, Department of Mathematical Sciences, University of Texas at El Paso, El Paso, Texas
| | - Jae Ho Park
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Seok Won Jung
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - In Du Jeong
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Sung-Jo Bang
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Jung Woo Shin
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
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Nwe Win N, Nakamoto S, Myint Sein M, Moriyama M, Kanda T, Shirasawa H. Hepatitis B Virus Genotype C is Predominant in Myanmar. Diseases 2017; 6:3. [PMID: 29278399 PMCID: PMC5871949 DOI: 10.3390/diseases6010003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 12/23/2017] [Accepted: 12/25/2017] [Indexed: 12/12/2022] Open
Abstract
Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis B virus (HBV) infections is 6.5% and accounts for 60% of hepatocellular carcinoma. HBV has nine genotypes that have been identified by molecular genetic analysis. HBV genotypes are associated with several clinical features. We reviewed the prevalence of HBV genotypes in Myanmar and neighboring countries. We also reviewed HBV genotypes in refugees from Myanmar. HBV subgenotype C1 is predominant in Myanmar. As HBV genotype C is associated with hepatocellular carcinoma (HCC), it is important to screen for cirrhosis and HCC and to prevent their development in HBV-infected individuals of Myanmar.
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Affiliation(s)
- Nan Nwe Win
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan.
| | - Shingo Nakamoto
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan.
| | - Myint Myint Sein
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan.
| | - Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
| | - Hiroshi Shirasawa
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan.
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Gao S, Joshi SS, Osiowy C, Chen Y, Coffin CS, Duan ZP. Chronic hepatitis B carriers with acute on chronic liver failure show increased HBV surface gene mutations, including immune escape variants. Virol J 2017; 14:203. [PMID: 29065883 PMCID: PMC5655973 DOI: 10.1186/s12985-017-0870-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 10/13/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The pathogenesis of acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is not well understood. The aim of this study was to investigate whether there is an association between HBV polymerase (P)/overlapping surface (S) gene and basal core promoter (BCP)/precore (PC) variants and development of ACLF in CHB. METHODS Two CHB patient cohorts were compared: (i) ACLF (N = 12) (11/12 M, median age 52 yrs., 5/9 genotype C, 6/12 HBeAg+), (ii) 27 treatment native CHB carriers (15/27 M, median age 44 yrs., 9 genotype B, 10 genotype C, 1 genotype A, 5 genotype D, 2 genotype E). Clonal sequencing of PCR-amplified HBV P/S and BCP/PC gene fragments was done and HBV diversity, frequency of immune escape (IE) and drug resistance (DR) mutations and mutations in BCP/PC gene (G1896A and A1762T/G1764A), were compared between each group. RESULTS Our data showed the incidence of IE and clusters of mutations in the HBV S region was significantly greater in ACLF patients vs. treatment naïve CHB patients (p < 0.05). Additionally, a significantly higher frequency of G1896A and A1762T/G1764A mutations were found in HBeAg negative than in ACLF patients (p < 0.0001). CONCLUSION In our study, ACLF was not associated with a specific genomic mutation. However, higher frequency of IE mutations along with various mutations clustering in the HBV S region could contribute to or be an outcome of ACLF in CHB infection. (words 226).
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Affiliation(s)
- Shan Gao
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing, 100069, China
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary 6D21, Teaching, Research and Wellness Building, 3280 Hospital Drive N.W, Calgary, AB, T2N 4Z6, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Shivali S Joshi
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary 6D21, Teaching, Research and Wellness Building, 3280 Hospital Drive N.W, Calgary, AB, T2N 4Z6, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Carla Osiowy
- Bloodborne Pathogens and Hepatitis Laboratory of the National Microbiology Laboratory, Winnipeg, MB, Canada
| | - Y Chen
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing, 100069, China
| | - Carla S Coffin
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary 6D21, Teaching, Research and Wellness Building, 3280 Hospital Drive N.W, Calgary, AB, T2N 4Z6, Canada.
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
| | - Z-P Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing, 100069, China.
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Park CH, Kim HY, Lee SW, Song DS, Song MJ, Kwon JH, You CR, Jang JW, Kim CW, Choi SW, Bae SH, Choi JY, Yoon SK. On-treatment and off-treatment efficacy of entecavir in a real-life cohort of chronic hepatitis B patients. Eur J Gastroenterol Hepatol 2016; 28:1179-1187. [PMID: 27428552 DOI: 10.1097/meg.0000000000000691] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Entecavir (ETV) is a potent nucleoside analogue with high genetic barrier to resistance. In this study, real-life clinical experiences in the long-term use of ETV and the durability of its off-treatment effectiveness were analyzed. MATERIALS AND METHODS This study was based on a large real-life cohort of 2240 chronic hepatitis B patients treated with ETV between January 2006 and December 2012 using a centralized electronic data repository. RESULTS Among 2240 patients, 804 patients were treatment naive and underwent ETV monotherapy. Their mean treatment duration was 712±493 days, with a cumulative proportion of patients achieving HBV DNA less than 300 copies/ml in 85.8, 95.7, and 97.6% at years 1, 2, and 3, respectively. Predictors for earlier virologic response were female sex, lower HBV DNA, higher alanine transaminase, lower platelet count, and HBeAg negativity at baseline. In patients who achieved virologic response and HBeAg loss, the cumulative relapse rate was 91.3% in 2 years after the cessation of treatment. During the treatment, 34 patients developed hepatocellular carcinoma, among whom 30 patients had cirrhosis before treatment initiation. ETV treatment showed efficient virologic response as the treatment duration was extended, but off-treatment efficacy was not durable, and the antiviral treatment showed some limitation in preventing hepatocellular carcinoma among liver cirrhosis patients, implying that treatment cessation should be taken into consideration more carefully. CONCLUSION This study from a real-life cohort may provide data on treating chronic hepatitis B patients more close to everyday clinical practice.
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Affiliation(s)
- Chung-Hwa Park
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Keshvari M, Alavian SM, Sharafi H. Comparison of Serum Hepatitis B Virus DNA and HBsAg Levels Between HBeAg-Negative and HBeAg-Positive Chronic Hepatitis B Patients. Jundishapur J Microbiol 2015; 8:e21444. [PMID: 25973160 PMCID: PMC4426187 DOI: 10.5812/jjm.21444] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2014] [Revised: 08/20/2014] [Accepted: 09/06/2014] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Chronic hepatitis B consists of different clinical phases. Laboratory and histological assessments can help differentiate the clinical phases of this disease and thus lead to better management. OBJECTIVES This study was conducted to determine laboratory and histological characteristics of HBeAg-negative and HBeAg-positive chronic hepatitis B patients. PATIENTS AND METHODS In this study, we evaluated 151 treatment naive chronic hepatitis B patients and grouped them according to their HBeAg status. Serum hepatitis B virus (HBV) DNA and HBsAg levels were measured, and liver function tests, and liver biopsy were performed for the study population. RESULTS There was a significant difference in age, and HBV DNA and HBsAg levels between HBeAg-negative and HBeAg-positive groups yet there was no statistically significant difference in sex, liver function tests, grading and staging of liver biopsy between the groups. Hepatitis B virus DNA and HBsAg levels were correlated in both HBeAg-negative and HBeAg-positive chronic hepatitis B patients. CONCLUSIONS We concluded that chronic hepatitis B patients had different HBV DNA and HBsAg levels according to their HBeAg status.
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Affiliation(s)
- Maryam Keshvari
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
- Iran Hepatitis Network, Tehran, IR Iran
| | - Seyed Moayed Alavian
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
- Iran Hepatitis Network, Tehran, IR Iran
| | - Heidar Sharafi
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
- Iran Hepatitis Network, Tehran, IR Iran
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Louisirirotchanakul S, Olinger CM, Arunkaewchaemsri P, Poovorawan Y, Kanoksinsombat C, Thongme C, Sa-Nguanmoo P, Krasae S, Theamboonlert A, Oota S, Fongsatitkul L, Puapairoj C, Promwong C, Weber B. The distribution of hepatitis B virus genotypes in Thailand. J Med Virol 2012; 84:1541-1547. [PMID: 22930500 DOI: 10.1002/jmv.23363] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Phylogenetic analysis was performed on hepatitis B virus (HBV) strains obtained from 86 hepatitis B surface antigen (HBsAg) positive donors from Thailand originating throughout the country. Based on the S gene, 87.5% of strains were of genotype C while 10.5% were of genotype B, with all genotype B strains obtained from patients originating from the central or the south Thailand. No genotype B strains were found in the north of Thailand. Surprisingly, one patient was infected with a genotype H strain while another patient was infected with a genotype G strain. Complete genome sequencing and recombination analysis identified the latter as being a genotype G and C2 recombinant with the breakpoint around nucleotide position 700. The origin of the genotype G fragment was not identifiable while the genotype C2 fragment most likely came from strains circulating in Laos or Malaysia. The performance of different HBsAg diagnostic kits and HBV nucleic acid amplification technology (NAT) was evaluated. The genotype H and G/C2 recombination did not interfere with HBV detection.
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11
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Nabuco LC, Mello FCDA, Gomes SDA, Perez RM, Soares JAS, Coelho HSM, Nogueira CAV. Hepatitis B virus genotypes in Southeast Brazil and its relationship with histological features. Mem Inst Oswaldo Cruz 2012; 107:785-789. [PMID: 22990965 DOI: 10.1590/s0074-02762012000600013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2011] [Accepted: 03/22/2012] [Indexed: 12/27/2022] Open
Abstract
Data concerning the relationship between hepatitis B virus (HBV) genotypes and liver histology are scarce. The aim of this study was to compare HBV non-B and non-C genotypes according to demographic features, clinical status, HBV-DNA levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive chronic HBV-infected patients were enrolled during two-year period and data were prospectively collected. Sera were tested for HBV genotyping using restriction fragment length polymorphism. Liver biopsy was obtained from patients with either increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17 (14%), B in one (1%) and C in two (2%). There was no association between HBV genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p = 0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p = 0.01). Genotype A was the most prevalent in chronic HBV-infected patients and genotype D patients presented with less intense liver disease.
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Affiliation(s)
- Leticia Cancella Nabuco
- Divisão de Hepatologia, [corrected] Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
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Ali L, Idrees M, Ali M, Rehman IU, Hussain A, Afzal S, Butt S, Saleem S, Munir S, Badar S. An overview of treatment response rates to various anti-viral drugs in Pakistani hepatitis B virus infected patients. Virol J 2011; 8:20. [PMID: 21235813 PMCID: PMC3027132 DOI: 10.1186/1743-422x-8-20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2010] [Accepted: 01/15/2011] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) is one of the leading health problem with up to 350 million affected people worldwide including 4.5 million only in Pakistan. It has mortality rate of 0.5 to 1.2 million per year worldwide. Pakistan lies in the endemic region with 3-5% HBV carrier rate in the country. The present article reviews the literature on the treatment response of HBV prevalent in Pakistani population. The average treatment response of Lamivudine and interferon-α is 25.81% and 47.95%, respectively. Peg-Interferon was shown to be not effective against the HBV/HCV (hepatitis C virus)/HDV (hepatitis Delta virus) co-infection. The present study reveals that interferon-α is the most effective therapy available for HBV infection prevalent in Pakistani population. Genotype C & D are the most common HBV genotypes in Pakistan and are associated with increased severity and less response to interferon therapy. This poses a great challenge for physicians and researchers and further studies are needed to describe the outcome of the current therapies recommended against HBV infection in Pakistani population.
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Affiliation(s)
- Liaqat Ali
- Division of Molecular Virology, National Centre of Excellence in Molecular Biology, University of the Punjab, 87-West Canal Bank Road, Thoker Niaz Baig, Lahore 53700, Pakistan.
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Aung MN, Leowattana W, Tangpukdee N, Kittitrakul C. Nucleos(t)ide analogues treatment outcome in genotype B and C chronic hepatitis B. NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2010; 2:365-370. [PMID: 22737674 PMCID: PMC3339060 DOI: 10.4297/najms.2010.2365] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatitis B genotypes influence the course and severity of the disease. AIM To compare the treatment outcome of chronic hepatitis B genotype B and C patients after treating with nucleos(t)ide analogues for six months. PATIENTS AND METHODS Forty chronic hepatitis B patients attending the liver clinic of Hospital for Tropical diseases, Bangkok, were studied in retrospective cohort design. Six genotype B patients (15%) and thirty-four genotype C patients (85%) were treated. Serum hepatitis B viral load, serum alanine amino transferase level, HBeAg status and alpha-feto protein level were measured at the time of starting nucleos(t) analogues therapy, and six months later. Besides, achievement of undetectable viral load was assessed in patients with normal serum alanine amino transferase compared to patients with high serum alanine amino transferase level. RESULTS After six months of nucleos (t) analogues treatment, achievement of undetectable hepatitis B viral load was higher in genotype B patients (66.7%) than in genotype C patients (42.4%) (Relative Risk=1.57, 0.79-3.14). Biochemical remission, HBeAg seroconversion and tumor marker levels between the two groups were not significantly different. Moreover, achievement of undetectable hepatitis B viral load was significantly higher in normal alanine amino transferase level (75%) than in patients with high serum alanine amino transferase level (33.3%) on nucleos(t)ide analogue treatment (Relative Risk=2.25, 1.20- 4.20). CONCLUSION Chronic hepatitis B treatment outcome between genotype B and C were not significantly different. Patients with normalized serum alanine amino transferase level tend to achieve undetectable viral load after nucleoside analogues treatment.
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Affiliation(s)
- Myo Nyein Aung
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Department of Pharmacology, University of Medicine Mandalay, Myanmar
| | - Wattana Leowattana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Noppadon Tangpukdee
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Chatporn Kittitrakul
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Huang WJ, Zhou C, Wang YC, Zhang HY, Wu X, Liang ZL, Li HM. Cloning and sequence analysis of complete genome of hepatitis B virus isolates of genotypes B, C, D/C and A from Chinese patients with chronic hepatitis B. Shijie Huaren Xiaohua Zazhi 2009; 17:2978-2983. [DOI: 10.11569/wcjd.v17.i29.2978] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To clone and sequence the complete genome of hepatitis sequence of hepatitis B virus (HBV) isolates of genotypes B, C, D/C and A from the sera of Chinese patients with chronic hepatitis B (CHB).
METHODS: Long-distant polymerase chain reaction (L-PCR) technique was used to amplify the complete genome of HBV isolates from Chinese patients with CHB. After the resulting amplicons were cloned into the TA vector and sequenced, the complete sequences of HBV isolates of genotypes B, C, D/C and A were analyzed using the DNAStar and Simpot software.
RESULTS: The complete genome sequences of HBV isolates of genotypes B, C, D/C and A, which had been deposited into GenBank, were composed of 3215, 3215, 3215 and 3182 bp, respectively. A 33-bp deletion mutation at position 2853-2885 and two point mutations at positions 1762A-T and 1764G-A were observed in one of four clones of sample H3. The coexistence of wild-type and mutant HBV strains in a patient with chronic hepatitis B may provide a molecular basis for the development of drug resistance during antiviral therapy.
CONCLUSION: The complete genome sequences of HBV isolates of genotypes B, C, D/C and A are successfully cloned and can be used as reference sequences for the study of HBV in Chinese patients with chronic hepatitis B.
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Comparison and significance of specific and non-specific cellular immunity in patients with chronic hepatitis B caused by infection with genotypes B or C of hepatitis B virus. ACTA ACUST UNITED AC 2009; 52:719-23. [PMID: 19727589 DOI: 10.1007/s11427-009-0098-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2009] [Accepted: 05/05/2009] [Indexed: 10/20/2022]
Abstract
The present study was designed to investigate possible relationships between the genotypes of hepatitis B virus (HBV) and the HBV-specific cytotoxic T lymphocyte (CTL) responses. HBV genotypes, HBV specific CTL HBV DNA and other markers of HBV infection were determined in 138 patients with chronic hepatitis B. The results showed that the patients infected with genotype C (n=62) had a significantly lower HBV-specific CTL response than those who were infected with HBV genotype B (P<0.01). HBV DNA titer was higher in patients infected with HBV genotype C than in those infected with HBV genotype B (P<0.01). Both alanine aminotransferase (ALT) and total bilirubin (TBIL) were higher in HBV genotype C infected patients than in those infected with genotype B (P<0.01 and <0.05, respectively). These results suggest that compared with CHB patients infected with HBV genotype B, the higher HBV DNA level and more severe liver damages in the patients infected with genotype C of HBV may be associated with genotype C of the virus.
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16
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Panessa C, Hill WD, Giles E, Yu A, Harvard S, Butt G, Andonov A, Krajden M, Osiowy C. Genotype D amongst injection drug users with acute hepatitis B virus infection in British Columbia. J Viral Hepat 2009; 16:64-73. [PMID: 19192159 DOI: 10.1111/j.1365-2893.2008.01045.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The eight genotypes of hepatitis B virus (HBV) exhibit distinct geographical distributions. This study identified HBV genotypes and transmission modes associated with acute infection in British Columbia (BC), Canada, from 2001 to 2005. Seventy cases of acute HBV in BC were identified from laboratory reports using a standardized case definition. Interviews for risk factors and hepatitis history were conducted for each case. HBV genotypes were determined by BLAST comparison analysis of the surface (S) or preS gene sequence. To illustrate the distribution of genotypes identified amongst acute cases in BC, an annotated map was produced showing the global occurrence of HBV genotypes. The majority of acute HBV cases occurred in Caucasian, Canadian-born males, with 30% of cases reporting injection drug use (IDU) and 21% reporting incarceration. The most common genotype observed was genotype D (62.9%), followed by genotypes A (18.6%), C (11.4%), B (4.3%), and E (1.4%). A significant association was observed between Genotype D and IDU (P = 0.0025) and previous incarceration (P = 0.0067). Phylogenetic analysis of the S gene sequence demonstrated identical or high genetic relatedness amongst genotype D viral strains (86% sub-genotype D3), thus verifying transmission clustering amongst BC injection drug users. The association between acute HBV genotype and reported transmission modes has not been previously described in North America. Tracking of genotypes can help identify disease transmission patterns and target at-risk populations for preventive immunization.
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Affiliation(s)
- C Panessa
- BC Centre for Disease Control, Vancouver, BC, Canada
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17
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Suwannakarn K, Tangkijvanich P, Thawornsuk N, Theamboonlers A, Tharmaphornpilas P, Yoocharoen P, Chongsrisawat V, Poovorawan Y. Molecular epidemiological study of hepatitis B virus in Thailand based on the analysis of pre-S and S genes. Hepatol Res 2008; 38:244-251. [PMID: 17711443 DOI: 10.1111/j.1872-034x.2007.00254.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
AIMS This study was undertaken to determine the prevalence and characteristics of hepatitis B virus (HBV) genotypes, antigen subtypes, "a" determinant variants and pre-S gene mutations circulating on a large scale in Thailand. METHODS The sequences of the Pre-S1, Pre-S2 and S regions were determined in serum samples of 147 HBsAg and HBV DNA-positive subjects who had been enrolled from the nationwide seroepidemiological survey conducted on 6213 individuals in 2004. RESULTS The results showed that genotypes C, B and A accounted for 87.1%, 11.6% and 1.3%, respectively. The distribution of the HBV antigen subtypes was: adr (84.4%), adw (14.2%) and ayw (1.4%). Regarding the "a" determinant, 2/43 (4.65%) and 2/104 (1.92%) samples of vaccinated and non-vaccinated subjects, respectively, displayed mutations, all ofwhich were Thr126Asn. Sequencing analysis showed the pre-S mutations in 14 (9.5%) samples, with pre-S2 deletion as the most common mutant (4.1%) followed by pre-S2 start codon mutation (2.9%), both pre-S2 deletion and start codon mutation (2.0%), and pre-S1 deletion (0.7%). The pre-S mutations were associated with older age and higher mean serum HBsAg level. CONCLUSION This study demonstrated that HBV genotype/subtype C/adr and B/adw were the predominant strains circulating in Thailand. The "a" determinant variants seemed to be uncommon, and might not be attributed to vaccine-induced mutation.
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Affiliation(s)
- Kamol Suwannakarn
- Center of Excellence in Viral Hepatitis Research, Department of Pediatrics, Chulalongkorn University, Bankok, Thailand
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18
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Hepatitis B virus genotypes : a retrospective survey in Southwestern France, 1999-2004. ACTA ACUST UNITED AC 2007; 31:1088-94. [PMID: 18176363 DOI: 10.1016/s0399-8320(07)78341-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Baig S, Siddiqui AA, Ahmed W, Qureshi H, Arif A. The association of complex liver disorders with HBV genotypes prevalent in Pakistan. Virol J 2007; 4:128. [PMID: 18042293 PMCID: PMC2212638 DOI: 10.1186/1743-422x-4-128] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2007] [Accepted: 11/27/2007] [Indexed: 02/06/2023] Open
Abstract
Background Genotyping of HBV is generally used for determining the epidemiological relationship between various virus strains and origin of infection mostly in research studies. The utility of genotyping for clinical applications is only beginning to gain importance. Whether HBV genotyping will constitute part of the clinical evaluation of Hepatitis B patients depends largely on the availability of the relevance of the evidence based information. Since Pakistan has a HBV genotype distribution which has been considered less virulent as investigated by earlier studies from south East Asian countries, a study on correlation between HBV genotypes and risk of progression to further complex hepatic infection was much needed Methods A total of 295 patients with HBsAg positive were selected from the Pakistan Medical Research Council's (PMRC) out patient clinics. Two hundred and twenty six (77%) were males, sixty nine (23%) were females (M to F ratio 3.3:1). Results Out of 295 patients, 156 (53.2%) had Acute(CAH), 71 (24.2%) were HBV Carriers, 54 (18.4%) had Chronic liver disease (CLD) Hepatitis. 14 (4.7%) were Cirrhosis and HCC patients. Genotype D was the most prevalent genotype in all categories of HBV patients, Acute (108), Chronic (39), and Carrier (53). Cirrhosis/HCC (7) were HBV/D positive. Genotype A was the second most prevalent with 28 (13%) in acute cases, 12 (22.2%) in chronics, 14 (19.7%) in carriers and 5 (41.7) in Cirrhosis/HCC patients. Mixed genotype (A/D) was found in 20 (12.8%) of Acute patients, 3 (5.6%) of Chronic and 4 (5.6%) of carriers, none in case of severe liver conditions. Conclusion Mixed HBV genotypes A, D and A/D combination were present in all categories of patients except that no A/D combination was detected in severe conditions. Genotype D was the dominant genotype. However, genotype A was found to be more strongly associated with severe liver disease. Mixed genotype (A/D) did not significantly appear to influence the clinical outcome.
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Affiliation(s)
- Saeeda Baig
- Department of Biochemistry, Ziauddin Medical College, Ziauddin University, Karachi, Pakistan.
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20
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Hou J, Schilling R, Janssen HLA, Hansen BE, Heijtink R, Sablon E, Williams R, Lau GKK, Schalm SW, Naoumov NV. Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearance. J Med Virol 2007; 79:1055-63. [PMID: 17596838 DOI: 10.1002/jmv.20935] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon-alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO-LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16-weeks interferon-alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P = 0.014), or genotype D alone (P = 0.05). The HBV genome analysis revealed that: (i) after 16-weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P < 0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P = 0.001; odds ratio 6.19, 95 confidence interval 1.94-19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon-alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon-based therapies in chronic hepatitis B may vary between different HBV genotypes.
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Affiliation(s)
- Jinlin Hou
- Institute of Hepatology, University College London, London WC1E 6HX, UK
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Wen ZL, Tan DM, Cheng J, Yang YF, Liu GZ, Liu HB. Comparison of effect on hepatocellular apoptosis between core proteins of hepatitis B virus genotype B and C. Shijie Huaren Xiaohua Zazhi 2006; 14:3228-3232. [DOI: 10.11569/wcjd.v14.i33.3228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the proapoptosis effect of hepatitis B virus (HBV) genotype B and C core proteins on liver cells, and explore the pathogenesis of HBV infection with different genotypes.
METHODS: Four serum samples infected by HBV (2 for type B and C, respectively) were used to amplify HBV core fragment using polymerase chain reaction (PCR). After recombination, cloning, and subcloning, four eucaryotic plasmids with different genotypes and clinical phenotypes were obtained. Then the plasmids were transfected into hepatocellular carcinoma cell line HepG2, and MTT assay and flow cytometry were used to detect the proliferation and apoptosis of HepG2 cells.
RESULTS: All the four recombinant eucaryotic plasmids were constructed successfully, and HBV core protein expression was confirmed by internal reference for transfection. The proliferation of HepG2 cells was not significantly different between the four plasmids, but the apoptosis rate in C-type (C2) group was markedly higher than that in B-type (B1) group (8.8% ± 2.0%vs 6.4% ± 0.8%, P < 0.05).
CONCLUSION: C-type HBV can induce more severe cell apoptosis than B-genotype HBV.
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Tran N, Berne R, Chann R, Gauthier M, Martin D, Armand MA, Ollivet A, Teo CG, Ijaz S, Flichman D, Brunetto M, Bielawski KP, Pichoud C, Zoulim F, Vernet G. European multicenter evaluation of high-density DNA probe arrays for detection of hepatitis B virus resistance mutations and identification of genotypes. J Clin Microbiol 2006; 44:2792-800. [PMID: 16891494 PMCID: PMC1594645 DOI: 10.1128/jcm.00295-06] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Polymorphisms along the hepatitis B virus (HBV) genome have an impact on disease outcome, sensitivity to antiviral treatment, escape from vaccination, and laboratory diagnosis. We have designed a diagnostic tool based on duplex amplification of the whole HBV genome and a high-density DNA chip designed to detect 245 mutations, 20 deletions, and 2 insertions at 151 positions and to determine the genotype of the virus in serum. Assay performances were evaluated with 170 samples, characterized by determination of viral load and sequencing of the Pol, S, and precore genes and the basal core promoter. One hundred fifty-three samples (90%) could be amplified and analyzed by the chip. Only two samples with more than 10(3) genome copies/ml could not be analyzed. Genotype had no impact on analytical sensitivity. Reproducibility studies showed no difference between repeats for codon and genotype determination. Genotype determination by sequencing and the chip were concordant in 148 of 151 samples. Twelve thousand one hundred sixty-one codons were analyzed by both techniques. Only 89.4% could be determined by sequencing, and among the remaining 11,335 codons, 92.8% were identical by sequencing and the chip. Failures to identify an amino acid by the chip were mainly due to reduced hybridization efficiency attributed to unexpected polymorphisms. Optimization of the chip-based reagent for the analysis of the HBV genome is ongoing. This first evaluation showed that DNA chip technology can provide important information in relation to the clinical management of chronic hepatitis B.
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Affiliation(s)
- N Tran
- bioMerieux, Emerging Pathogens Department, Marcy-l'Etoile, France
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Banerjee A, Kurbanov F, Datta S, Chandra PK, Tanaka Y, Mizokami M, Chakravarty R. Phylogenetic relatedness and genetic diversity of hepatitis B virus isolates in Eastern India. J Med Virol 2006; 78:1164-1174. [PMID: 16847957 DOI: 10.1002/jmv.20677] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatitis B virus (HBV) has been classified into eight genotypes, and several subgenotypes, distinctly distributed geographically. The genotypes A and D were previously reported to be predominant in India. Recent studies indicated evidence of circulation of genotype C in Eastern part of India. With the aim to confirm the phylogenetic relation and molecular genetic characteristics of the HBV circulating in Kolkata, the most populous city in Eastern India, 11 strains were isolated and the complete genome sequences were analyzed. Phylogenetic analysis determined; three genotype C (adr-serotype) isolates closely related with C1 (Cs) subgenotype references from South East Asia, and three genotype A (adw2-serotype) isolates, related to Asia-variant references of subgenotype A1 (Aa). Whereas, five genotype D (ayw2, ayw3 serotype) isolates were highly divergent; one was related to subgenotype D1, two to subgenotype D3, and the remaining two clustered with a single genotype D isolate from Japan belonging to an unclassified subgenotype. Together, these two isolates differed from HBV D1-D4 subgenotypes by nucleotide differences ranging from 5.0 to 5.49%, probably indicating a new subgenotype, which we designate as D5. All serotype ayw3 of genotype D isolates had specific amino acid substitution Threonine at codon 118 and Methionine at codon 125 in antigenic determinant of surface gene that has not been reported previously in isolates from other parts of India. In conclusion; using the complete genome analyses this study has confirmed circulation of the genotype C in Eastern part of India and demonstrated considerable genotypic heterogeneity of the Indian genotype D.
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Affiliation(s)
- Arup Banerjee
- ICMR Virus Unit, ID & BG Hospital Campus, Kolkata, West Bengal, India
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Alavian SM, Keyvani H, Rezai M, Ashayeri N, Sadeghi HM. Preliminary report of hepatitis B virus genotype prevalence in Iran. World J Gastroenterol 2006; 12:5211-3. [PMID: 16937535 PMCID: PMC4088022 DOI: 10.3748/wjg.v12.i32.5211] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the prevalence of hepatitis B virus (HBV) genotypes in Iranian hepatitis B surface antigen (HBsAg) carriers, chronic hepatitis B and cirrhotic patients.
METHODS: A total of 109 HBsAg-positive patients were included in this study. HBV genotypes were determined by using INNO-LiPA methodology which is based on the reverse hybridization principle.
RESULTS: The distribution of patients with different stages of liver disease was as follows: 95 (86.4%) chronic hepatitis, 11 (10%) liver cirrhosis, and 3 (2.7%) inactive carrier. Of the chronic hepatitis and liver cirrhosis patients, 26.4% were HBeAg-positive while 70% were HBeAg-negative. Genotype D was the only detected type found in all patients.
CONCLUSION: Classifying HBV into genotypes has to be cost-effective and clinically relevant. Our study indicates that HBV genotype D prevails in the Mediterranean area, Near and Middle East, and South Asia. Continued efforts for understanding HBV genotype through international co-operation will reveal further virological differences of the genotypes and their clinical relevance.
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Affiliation(s)
- Seyed-Moayed Alavian
- Department of Internal Medicine, Baqiatollah Medical University, Tehran Hepatitis Center, Iran.
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Dzierzanowska-Fangrat K, Woynarowski M, Szczygielska I, Jozwiak P, Cielecka-Kuszyk J, Dzierzanowska D, Madalinski K. Hepatitis B virus genotypes in children with chronic hepatitis B in Poland. Eur J Gastroenterol Hepatol 2006; 18:655-8. [PMID: 16702856 DOI: 10.1097/00042737-200606000-00013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVES To analyse the distribution of HBV genotypes in Polish children with chronic hepatitis B, and to assess the relation between the viral genotype and the severity of liver damage. METHODS Serum samples from children with chronic hepatitis B were used for biochemical and serological testing, and for determination of HBV genotypes by a nested-multiplex-polymerase chain reaction. Liver biopsies were obtained for histological assessment, which was performed according to the Batts and Ludwig scoring system of chronic hepatitis. RESULTS Of 78 children with chronic hepatitis B, 74 had an identifiable HBV genotype: 86.5% were infected with genotype A, and 13.5% were carriers of genotype D. The frequency of HBeAg clearance and the levels of alanine aminotransferase and serum aspartate transaminase were comparable in both genotype groups. There was no correlation between the HBV genotype and either activity of liver inflammation or liver fibrosis. CONCLUSIONS This study shows that the distribution of HBV genotypes in Polish children with chronic HBV infection reflects the general prevalence of HBV genotypes in Europe. The course of chronic hepatitis B in children is not significantly influenced by viral genotypes A or D.
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Song BC, Cui XJ, Kim HU, Cho YK. Sequential accumulation of the basal core promoter and the precore mutations in the progression of hepatitis B virus-related chronic liver disease. Intervirology 2006; 49:266-73. [PMID: 16714855 DOI: 10.1159/000093456] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2005] [Accepted: 08/08/2005] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVES Despite the pathogenic role of the basal core promoter (BCP) and the precore mutations in chronic hepatitis B virus (HBV) infection, their role in the progression of liver disease is still controversial. We analyzed whether the accumulation of these mutations might enhance the progression of HBV-related chronic liver disease. METHODS Forty consecutive patients at each clinical status were analyzed. Clinical statuses were as follows: HBeAg-positive asymptomatic carrier (HBeAg(+) ASC) (defined as HBeAg(+), anti-HBe(-), HBV-DNA(+) by hybridization, normal ALT); inactive HBsAg carrier; chronic hepatitis B; liver cirrhosis. The genotype and the BCP/precore regions were determined by PCR using genotype specific primers and direct sequencing, respectively. RESULTS All patients except one were infected with genotype C. The A to T mutation at nucleotide 1762 and/or G to A mutation at nucleotide 1764 were found in 30% in HBeAg(+) ASC, 65.7% in inactive HBsAg carrier, 95% in chronic hepatitis B, and 90% in liver cirrhosis (p < 0.001). The prevalence of the G to A mutation at nucleotide 1896 was 5% in HBeAg(+) ASC, 22.5% in inactive HBsAg carrier, 32.5% in chronic hepatitis B, and 50% in liver cirrhosis, respectively (p < 0.001). The T to C/A mutation at nucleotide 1753 in the BCP and G to A mutation at nucleotide 1899 in the precore were more frequent in liver cirrhosis than in the other clinical statuses (p < 0.05). CONCLUSION Sequential accumulation of mutations in the BCP/precore has an important role in the progression of HBV-related liver disease.
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Affiliation(s)
- Byung-Cheol Song
- Department of Internal Medicine, Cheju National University College of Medicine, Cheju National University Hospital, Jeju, Republic of Korea.
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Abstract
Hepatitis B virus (HBV) is a major human health problem as approximately 8% of the world’s population are chronic carriers and there are over a million HBV-related deaths annually. Treatment of HBV is extremely difficult, as the unique viral replication strategy results in both a continual source of stable DNA molecules that are the template for viral replication and gene expression, and a pool of viral quasispecies from which different isolates may emerge as selection pressures alter. Although the use of antiviral therapies has improved outcomes significantly for many chronically infected individuals, the emergence of drug-resistant and immune/vaccine-escape viruses ensures there is a continuing need for the development of new and imaginative approaches to control and eventually eradicate HBV.
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Affiliation(s)
- Peter Revill
- Victorian Infectious Diseases Reference Laboratory, Research and Molecular Development, 10 Wreckyn Street, North Melbourne, Victoria 3051, Australia
| | - Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory, Research and Molecular Development, 10 Wreckyn Street, North Melbourne, Victoria 3051, Australia
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Ganne-Carrié N, Williams V, Kaddouri H, Trinchet JC, Dziri-Mendil S, Alloui C, Hawajri NA, Dény P, Beaugrand M, Gordien E. Significance of hepatitis B virus genotypes A to E in a cohort of patients with chronic hepatitis B in the Seine Saint Denis District of Paris (France). J Med Virol 2006; 78:335-40. [PMID: 16419113 DOI: 10.1002/jmv.20545] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The aim of this study was to examine the genetic variability of the hepatitis B virus (HBV) and its significance. HBV genotypes, core promoter and precore mutants were characterized in 109 consecutive patients with biopsy-proven HBV chronic hepatitis. Genotypes A (26.6%), B (12.8%), C (18.3%), D (18.3%), and E (14.7%) indicate a wide genotypic distribution. Patients were from Asia (30.3%), Europe (28.4%), Sub Saharan Africa (23.9%), the Caribbean (10.1%), North Africa (5.5%), and Madagascar (1.8%). HBV genotypes A and D (HBV/A and /D) infected all subgroups except Asian patients. HBV/B or /C were found in 97% of Asian patients, whereas HBV/E only infected sub-Saharan African and Caribbean patients. Differences according to genotypes were: an increased prevalence of anti-HBe antibodies in patients infected with HBV/D (P = 0.003), higher serum transaminases in patients infected with HBV/A and/D (P = 0.043), more severe liver fibrosis in patients infected with HBV/A, /C and/D (P = 0.02). Precore and core promoter mutants were found in 87% of anti-HBe positive patients, and were associated with HBV/D (P = 0.04) and severe liver fibrosis (P = 0.002). It is concluded that HBV genotypes A, B, C, D, and E circulate in the Seine Saint Denis District, reflecting the geographical origin of patients. HBV/A, /C and/D seem to be associated with more severe hepatic disease.
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Affiliation(s)
- Nathalie Ganne-Carrié
- Service d'Hépato-Gastroentérologie, Hôpital Jean Verdier (Bondy), Assistance Publique-Hôpitaux de Paris, UPRES 3409, UFR Santé Médecine Biologie Humaine, Université Paris 13, France.
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29
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Lim CK, Tan JTM, Khoo JBS, Ravichandran A, Low HM, Chan YC, Ton SH. Correlations of HBV genotypes, mutations affecting HBeAg expression and HBeAg/ anti-HBe status in HBV carriers. Int J Med Sci 2006; 3:14-20. [PMID: 16421626 PMCID: PMC1332200 DOI: 10.7150/ijms.3.14] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2005] [Accepted: 12/15/2005] [Indexed: 12/12/2022] Open
Abstract
This study was carried out to determine the effects of hepatitis B virus genotypes, core promoter mutations (A1762G1764-->T1762A1764) as well as precore stop codon mutations (TGG-->TAG) on HBeAg expression and HBeAg/ anti-HBe status. Study was also performed on the effects of codon 15 variants (C1858/ T1858) on the predisposition of precore stop codon mutations (TGG-->TAG). A total of 77 sera samples were analyzed. Fifty one samples were successfully genotyped of which the predominant genotype was genotype B (29/ 51, 56.9 %), followed by genotype C (16/ 51, 31.4 %). Co-infections by genotypes B and C were observed in four samples (7.8 %). To a lesser degree, genotypes D and E (2.0 % each) were also observed. For core promoter mutations, the prevalence was 68.8 % (53/ 77) for A1762G1764 wild-type and 14.3 % (11/ 77) for T1762A1764 mutant while 9.1 % (7/ 77) was co-infected by both strains. The prevalence of codon 15 variants was found to be 42.9 % (33/ 77) for T1858 variant and 16.9 % (13/ 77) for C1858 variant. No TAG mutation was found. In our study, no associations were found between genotypes (B and C) and core promoter mutations as well as codon 15 variants. Also no correlation was observed between HBeAg/ anti-HBe status with genotypes (B and C) and core promoter mutations.
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Affiliation(s)
- Chee Kent Lim
- 1. School of Arts and Sciences, Monash University Malaysia, Petaling Jaya 46150, Malaysia
- 2. Faculty of Biotechnology, Malaysia University of Science and Technology, Petaling Jaya 47301, Malaysia
| | - Joanne Tsui Ming Tan
- 3. Discipline of Medicine, Blackburn Building D06, University of Sydney, NSW 2006, Australia
| | - Jason Boo Siang Khoo
- 4. Institute of Molecular and Cell Biology, 61 Biopolis Drive (Proteos), 138673, Singapore
| | - Aarthi Ravichandran
- 5. Department of Biological Sciences, Faculty of Sciences, National University of Singapore, 10 Kent Ridge Crescent, 119260, Singapore
| | - Hsin Mei Low
- 6. Faculty of Medicine, Nursing and Health Sciences, Monash Immunology and Stem Cell Laboratories, Level 3, STRIP 1 - Building 75, Monash University, Wellington Road, Clayton, VIC 3800, Australia
| | - Yin Chyi Chan
- 1. School of Arts and Sciences, Monash University Malaysia, Petaling Jaya 46150, Malaysia
| | - So Har Ton
- 1. School of Arts and Sciences, Monash University Malaysia, Petaling Jaya 46150, Malaysia
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30
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Thuy LTT, Ryo H, Van Phung L, Furitsu K, Nomura T. Distribution of genotype/subtype and mutational spectra of the surface gene of hepatitis B virus circulating in Hanoi, Vietnam. J Med Virol 2005; 76:161-9. [PMID: 15834887 DOI: 10.1002/jmv.20337] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
In order to ascertain the molecular epidemiological features and mutational spectra of hepatitis B virus (HBV) in Hanoi, Vietnam, direct sequencing of the 219-nucleotide fragment of the surface (S) gene of HBV from the sera of 40 patients mostly with chronic hepatitis were carried out. The samples were classified into genotypes by phylogenetic and genotype-specific analysis, and subtypes by the deduced amino acid sequences. The results showed that genotype B with ayw1 was predominant genotype/subtype (63%), followed by genotype C with adr (18%). The quasi-species nature of the HBV in the sera was observed in 24 of 40 samples examined. One sample (HN109) showed mixture of genotypes B and C. Among 26 amino acid substitutions, 16 were the variants and the remainders were mutations. In the "a" determinant region, three mutations with methionine to leucine (L) changes at the 133 amino acid residue were in the first loop and no mutations were in the second loop. A new mutation, threonine to methionine at 126 amino acid residue, was observed in one sample. In conclusion, the analysis of the S gene region of HBV showed that in Hanoi, genotype B with ayw1 was prevalent and the quasi-species nature of HBV was also common.
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Affiliation(s)
- Le Thi Thanh Thuy
- Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, Suita, Japan
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31
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Kramvis A, Kew MC. Relationship of genotypes of hepatitis B virus to mutations, disease progression and response to antiviral therapy. J Viral Hepat 2005; 12:456-64. [PMID: 16108759 DOI: 10.1111/j.1365-2893.2005.00624.x] [Citation(s) in RCA: 145] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Phylogenetic analysis has led to the classification of hepatitis B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show heterogeneity in their global distribution. These attributes of the genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also be responsible for differences in the clinical outcome and response to antiviral treatment in different population groups.
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Affiliation(s)
- A Kramvis
- MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
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32
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Yotsuyanagi H, Okuse C, Yasuda K, Orito E, Nishiguchi S, Toyoda J, Tomita E, Hino K, Okita K, Murashima S, Sata M, Hoshino H, Miyakawa Y, Iino S. Distinct geographic distributions of hepatitis B virus genotypes in patients with acute infection in Japan. J Med Virol 2005; 77:39-46. [PMID: 16032734 DOI: 10.1002/jmv.20411] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Genotypes of hepatitis B virus (HBV) were determined in 145 patients with acute hepatitis B from various districts in Japan to establish their geographic distribution and evaluating the influence on the clinical illness and outcome. Genotypes were A in 27 (19%) patients, B in 8 (5%), C in 109 (75%) and mixed with B and C in the remaining one (1%). Genotype A was more frequent in metropolitan than the other areas (21/69 (30%) vs. 6/76 (8%), P < 0.001). On phylogenetic analysis, seven of the nine (78%) HBV/A isolates selected at random clustered with those from Europe and the United States, while the remaining two with those of subgroup A' prevalent in Asia and Africa. Maximum ALT levels were lower (2069 +/- 1075 vs. 2889 +/- 1867 IU/L, P = 0.03) and baseline HBV DNA titers were higher (5.90 +/- 1.45 vs. 5.13 +/- 1.36 log genome equivalents (LGE)/ml, P = 0.002) in patients infected with genotype A than C. Hepatitis B surface antigen persisted longer in patients infected with genotype A than C (1.95 +/- 1.09 vs. 1.28 +/- 1.42 months, P = 0.02). HBV infection became chronic in one (4%) patient with genotype A and one (1%) with genotype C infection. Fulminant hepatic failure developed in none of the patients with genotype A, one (13%) with genotype B and five (5%) with genotype C. The point mutation in the precore region (A1896) or the double mutations in the basic core promoter (BCP) region (T1762/A1764) were detected in none of the patients with genotype A, two (25%) with genotype B and 27 (26%) with genotype C. In conclusion, genotype A is frequent in patients with acute hepatitis B in metropolitan areas of Japan, probably reflecting particular transmission routes, and associated with longer and milder clinical course than genotype C.
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Affiliation(s)
- Hiroshi Yotsuyanagi
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan.
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Song BC, Cui XJ, Kim H. Hepatitis B virus genotypes in Korea: an endemic area of hepatitis B virus infection. Intervirology 2005; 48:133-7. [PMID: 15812186 DOI: 10.1159/000081740] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2004] [Accepted: 05/17/2004] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVES It has been reported that distribution of hepatitis B virus (HBV) genotypes shows geographic difference and are associated with clinical outcomes of HBV infection, including response to antiviral therapy and progression of chronic liver diseases. In this study, we analyzed the distribution of HBV genotypes according to the various clinical outcomes of chronic HBV infection in Korea, which is one of the most endemic areas of HBV infection. METHODS A total of 200 patients with chronic HBV infection were enrolled. Clinical diagnoses of the 200 patients with chronic liver diseases were as follows: hepatitis B e antigen (HBeAg)-positive healthy carrier (defined as HBeAg(+), anti-HBe(-), HBV DNA(+) by hybridization, normal transaminase; n = 40); inactive HBsAg carrier (n = 40); chronic hepatitis B (n = 40); liver cirrhosis (n = 40); hepatocellular carcinoma (n = 40). HBV genotypes were determined by nested polymerase chain reaction using genotype-specific primers. RESULTS All patients except 2 (inactive HBsAg carriers) were positive for nested PCR and they have genotype C regardless of clinical outcomes. CONCLUSIONS HBV genotype was genotype C regardless of various clinical outcomes of chronic HBV infection in Korea. Considering that HBV genotypes have clinical relevance, distribution of HBV genotype in each area should be monitored when management for chronic HBV infection is planned.
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Affiliation(s)
- Byung-Cheol Song
- Department of Internal Medicine, College of Medicine, Cheju National University, Jeju, Korea
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34
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35
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Tangkijvanich P, Mahachai V, Komolmit P, Fongsarun J, Theamboonlers A, Poovorawan Y. Hepatitis B virus genotypes and hepatocellular carcinoma in Thailand. World J Gastroenterol 2005; 11:2238-2243. [PMID: 15818732 PMCID: PMC4305805 DOI: 10.3748/wjg.v11.i15.2238] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2004] [Revised: 08/31/2004] [Accepted: 10/06/2004] [Indexed: 02/06/2023] Open
Abstract
AIM The role of hepatitis B virus (HBV) genotypes on the clinical features and prognosis of patients with hepatocellular carcinoma (HCC) is currently unknown. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Thai patients. METHODS HBV genotypes were determined by PCR-RFLP in stored sera of 93 asymptomatic carriers, 103 patients with chronic hepatitis, 60 patients with cirrhosis and 76 patients with HCC. The clinical data were analyzed in relation to the HBV genotype. RESULTS HBV genotypes C and B were predominant in Thailand, accounting for 73% and 21%, respectively. The distributions of genotypes B and C were similar in HCC patients compared to the other groups. Genotype C was significantly more common in HCC patients who were under 40 years old than genotype B (18% vs 0%, P = 0.03), but was significantly less common in patients older than 60 years (26% vs 56.5%, P = 0.01). The positive rate of hepatitis B e antigen (HBeAg) in patients with genotype C was significantly higher than that in patients with genotype B (71.6% vs 44.4%, P = 0.03 in chronic hepatitis; 56.8% vs 11.1%, P = 0.01 in cirrhosis). There were no differences between HCC patients with genotypes B and C regarding tumor staging by CLIP criteria and the overall median survival. Multivariate analyses showed that HBV genotype was not an independent prognostic factor of survival in HCC patients. CONCLUSION Patients with genotype C had a higher positive rate of HBeAg and exhibited earlier progression of cirrhosis and HCC than those with genotype B. However, there were no differences in the risk of developing HCC and its prognosis between patients with these genotypes.
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Affiliation(s)
- Pisit Tangkijvanich
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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36
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Abstract
Hepatitis B Virus (HBV) genotypes have come of age. The concept that HBV genotypes may influence the course of disease and relevant biological differences has now been recognised. However, there are still major gaps in our knowledge. Most clinical data come from Asia and describe findings in patients infected with genotypes B and C. Large scale studies with genotypes A and D as found in Europe or A, D and E from Africa are urgently needed to broaden our understanding. Experimental data which explain in vivo findings in terms of differences in molecular biology in vitro are still in the beginning. The succeeding years will see many interesting studies which will aid our understanding of how variants and genotypes of HBV influence the spectrum of disease in people infected with HBV.
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Affiliation(s)
- S Schaefer
- Abteilung Virologie, Institut für Mikrobiologie, Universität Rostock, Rostock, Germany.
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37
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Kramvis A, Kew M, François G. Hepatitis B virus genotypes. Vaccine 2005; 23:2409-23. [PMID: 15752827 DOI: 10.1016/j.vaccine.2004.10.045] [Citation(s) in RCA: 262] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2004] [Revised: 09/27/2004] [Accepted: 10/14/2004] [Indexed: 12/17/2022]
Abstract
Eight genotypes of hepatitis B virus (A-H) are currently recognized, and subgenotypes have recently been described in four of these genotypes (A, B, C and F). The genotypes show a distinct geographical distribution between and even within regions, and are proving to be an invaluable tool in tracing the molecular evolution and patterns and modes of spread of hepatitis B virus. Structural and functional differences between genotypes can influence the severity, course and likelihood of complications, and response to treatment of hepatitis B virus infection and possibly vaccination against the virus. Although the number of studies on these genotypes has increased dramatically during recent years, much remains to be learnt about their full implications.
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Affiliation(s)
- Anna Kramvis
- MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193 Johannesburg, South Africa.
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Norder H, Couroucé AM, Coursaget P, Echevarria JM, Lee SD, Mushahwar IK, Robertson BH, Locarnini S, Magnius LO. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology 2005; 47:289-309. [PMID: 15564741 DOI: 10.1159/000080872] [Citation(s) in RCA: 649] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2004] [Accepted: 07/22/2004] [Indexed: 02/06/2023] Open
Abstract
Sequences of 234 complete genomes and 631 hepatitis B surface antigen genes were used to assess the worldwide diversity of hepatitis B virus (HBV). Apart from the described two subgenotypes each for A and F, also B, C, and D divided into four subgenotypes each in the analysis of complete genomes supported by significant bootstrap values. The subgenotypes of B and C differed in their geographical distribution, with B1 dominating in Japan, B2 in China and Vietnam, B3 confined to Indonesia, and B4 confined to Vietnam, all strains specifying subtype ayw1. Subgenotype C1 was common in Japan, Korea, and China; C2 in China, South-East Asia, and Bangladesh, and C3 in the Oceania comprising strains specifying adrq-, and C4 specifying ayw3 is encountered in Aborigines from Australia. This pattern of defined geographical distribution was less evident for D1-D4, where the subgenotypes were widely spread in Europe, Africa, and Asia, possibly due to their divergence having occurred a longer time ago than for genotypes B and C, with D4 being the first split and still the dominating subgenotype of D in the Oceania. The genetic diversity of HBV and the geographical distribution of its subgenotypes provide a tool to reconstruct the evolutionary history of HBV and may help to complement genetic data in the understanding of the evolution and past migrations of man.
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Affiliation(s)
- Helene Norder
- Swedish Institute for Infectious Disease Control, Solna, Sweden.
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Guettouche T, Hnatyszyn HJ. Chronic hepatitis B and viral genotype: the clinical significance of determining HBV genotypes. Antivir Ther 2005; 10:593-604. [PMID: 16152753 DOI: 10.1177/135965350501000501] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The global health challenge posed by the hepatitis B virus (HBV) centres around the widespread distribution and the serious complications as a result of persistent infection with the virus. As with other chronic diseases mediated by pathogens such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV), clinicians are searching for epidemiological, pathological and viral characteristics of HBV infection that may lead to more effective management of patients with chronic infection. Unlike HCV, the role of HBV genotype in disease progression, severity, response to therapy and drug resistance is still under investigation and just beginning to be clarified. This review examines the potential role of HBV genotype determination in the clinic with emphasis on how this genetic information may used to provide effective management for the treatment of patients with chronic hepatitis B.
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Affiliation(s)
- Toumy Guettouche
- Bayer Institute for Clinical Investigation, Bayer Healthcare-Diagnostics, Berkeley, CA, USA
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40
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Wai CT, Fontana RJ. Clinical significance of hepatitis B virus genotypes, variants, and mutants. Clin Liver Dis 2004; 8:321-52, vi. [PMID: 15481343 DOI: 10.1016/j.cld.2004.02.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Emerging evidence suggests that hepatitis B virus (HBV) genotypes may influence the rate of spontaneous and interferon-induced hepatitis B e antigen (HBeAg) seroconversion as well as the natural history of liver disease. In contrast, the dinical significance of precore and core promoter variants associated with HBeAg negative liver disease is less certain in light of the many competing host and virologic factors noted in reported studies. HBV surface mutants are primarily associated with prior vaccine or hepatitis B immune globulin exposure and do not appear to have untoward virulence or association with occult HBV infection. Polymerase mutants with reduced drug sensitivity and phenotypic resistance are commonly detected in patients receiving prolonged antiviral therapy and have a variable impact on disease outcomes. The introduction of additional nucleoside/nucleotide analog agents will likely lead to the development of further unique polymerase mutants with varying pathogenicity and cross-resistance to existing drugs.
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Affiliation(s)
- Chun-Tao Wai
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, 3912 Taubman Center, Ann Arbor, MI 48109-0362, USA
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Vivekanandan P, Abraham P, Sridharan G, Chandy G, Daniel D, Raghuraman S, Daniel HD, Subramaniam T. Distribution of hepatitis B virus genotypes in blood donors and chronically infected patients in a tertiary care hospital in southern India. Clin Infect Dis 2004; 38:e81-6. [PMID: 15127358 DOI: 10.1086/383144] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2003] [Accepted: 12/15/2003] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) genotypes differ in their potential for causing disease. Consecutive patients with chronic HBV infection (CHBV) (n=122) and blood donors (n=67) positive for hepatitis B surface antigen and HBV DNA were genotyped using polymerase chain reaction-restriction fragment-length polymorphism. The ratio of male to female subjects was significantly higher in the blood donor group than in the group of patients with CHBV (P=.0004). Among patients with CHBV, genotype D was detected in 57.3%, genotype A was detected in 18%, and genotype C was detected in 11.5%. Only genotypes D and A were detected in blood donors. The difference between the detection rate of genotype C in patients with CHBV and in blood donors was significant (11.5% vs. 0%; P=.009). Patients with CHBV who had genotype C had higher alanine transaminase (ALT) levels than those who had genotype A (P=.044) or genotype D (P=.014). Detection of genotype C in patients with CHBV and the association of genotype C with higher ALT levels may predict that this genotype has a greater potential for causing disease than other genotypes.
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Affiliation(s)
- Perumal Vivekanandan
- Department of Clinical Virology, Christian Medical College, Vellore-632004, India
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Abstract
In 1988, hepatitis B virus (HBV) was classified into four genotypes by a sequence divergence in the entire genome exceeding 8%, and designated by capital letters of the alphabet from A to D. There are seven genotypes of HBV (A-G) at present, and an eighth is on the horizon. They have an uneven geographical distribution, and only a few of them are prevalent in a given area of the world. Thus genotype A is frequent in northwest Europe, Sub-Saharan Africa, India and the North, Central and South America, B as well as C are common in Southeast Asia and Oceania, and D is prevalent in the Mediterranean area, Central Asia and South America. Genotype E is restricted to West Africa, and F is localized in Central and South America. The distribution of genotype G added to the alphabet list very recently has yet to be determined. Coinfection with HBV of distinct genotypes is not infrequent and found in about 10% of infected individuals, and is responsible for intertypic recombination of HBV genomes. The mutation for a stop codon in the precore region (G1896A) for aborting the translation of hepatitis B e antigen (HBeAg) is prohibited in HBV genomes of genotype A, as well as some of genotypes C and F, because they possess C at position 1858 that makes a Watson-Crick pair with G at position 1896. Hence, seroconversion to antibody to HBeAg is forbidden or delayed in individuals who carry them. Evidence is accumulating as regards the influence of HBV genotypes on the progression of chronic hepatitis B and response to antiviral therapies. HBV isolates even of the same genotype can differ in virological and clinical characteristics, and therefore, the genotype needs to be classified further into subtypes, especially if they are clinically relevant.
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Affiliation(s)
- Yuzo Miyakawa
- Miyakawa Memorial Research Foundation, Minami-Aoyama 2-19-8, Minato-ku, Tokyo 107-0062, Japan.
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Sugauchi F, Kumada H, Acharya SA, Shrestha SM, Gamutan MTA, Khan M, Gish RG, Tanaka Y, Kato T, Orito E, Ueda R, Miyakawa Y, Mizokami M. Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A. J Gen Virol 2004; 85:811-820. [PMID: 15039524 DOI: 10.1099/vir.0.79811-0] [Citation(s) in RCA: 111] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Complete nucleotide sequences of 19 hepatitis B virus (HBV) isolates of genotype A (HBV/A) were determined and analysed along with those of 20 previously reported HBV/A isolates. Of the 19 HBV/A isolates, six including three from Japan and three from the USA clustered with the 14 HBV/A isolates from Western countries. The remaining 13 isolates including four from The Philippines, two from India, three from Nepal and four from Bangladesh clustered with the six HBV/A isolates reported from The Philippines, South Africa and Malawi. Due to distinct epidemiological distributions, genotype A in the 20 HBV isolates was classified into subtype Ae (e for Europe), and that in the other 19 into subtype Aa (a for Asia and Africa) provisionally. The 19 HBV/Aa isolates had a sequence variation significantly greater than that of the 20 HBV/Ae isolates (2.5+/-0.3 % vs 1.1+/-0.6 %, P<0.0001); they differed by 5.0+/-0.4 % (4.1-6.4 %). The double mutation (T1762/A1764) in the core promoter was significantly more frequent in HBV/Aa isolates than in HBV/Ae isolates (11/19 or 58 % vs 5/20 or 25 %, P<0.01). In the pregenome encapsidation (epsilon) signal, a point mutation from G to A or T at nt 1862 was detected in 16 of the 19 (84 %) HBV/Aa isolates but not in any of the 20 HBV/Ae isolates, which may affect virus replication and translation of hepatitis B e antigen. Subtypes Aa and Ae of genotype A deserve evaluation for any clinical differences between them, with a special reference to hepatocellular carcinoma prevalent in Africa.
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Affiliation(s)
- Fuminaka Sugauchi
- Departments of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiromitsu Kumada
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Subrat A Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | | | | | - Mobin Khan
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Robert G Gish
- Hepatology and Gastroenterology, California Pacific Medical Center, San Francisco, USA
| | - Yasuhito Tanaka
- Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takanobu Kato
- Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Etsuro Orito
- Departments of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Ryuzo Ueda
- Departments of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | | | - Masashi Mizokami
- Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Huy TTT, Ushijima H, Quang VX, Win KM, Luengrojanakul P, Kikuchi K, Sata T, Abe K. Genotype C of hepatitis B virus can be classified into at least two subgroups. J Gen Virol 2004; 85:283-292. [PMID: 14769886 DOI: 10.1099/vir.0.19633-0] [Citation(s) in RCA: 106] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
A genomic characterization of hepatitis B virus (HBV) was done for 56 pre-S1/pre-S2 genes and 10 full-length HBV genotype C isolates from five Asian countries. Phylogenetic analysis of the pre-S1/pre-S2 genes revealed two major groups within genotype C: one for isolates from southeast Asia including Vietnam, Myanmar and Thailand (named HBV/C1) and the other for isolates from Far East Asia including Japan, Korea and China (named HBV/C2). This finding was confirmed by phylogenetic analysis based on the full-length sequence of 32 HBV genotype C isolates, including 22 from database entries. Two isolates from Okinawa, the island off the southern end of Japan, formed a different branch. Specific amino acid sequence changes were identified in the large S protein (amino acids 51, 54, 60, 62 and 73) and P protein (amino acids 231, 233, 236, 248, 252 and 304). Our results indicate that genotype C of HBV can be classified into at least two subgroups.
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Affiliation(s)
- Tran Thien-Tuan Huy
- Department of Gastroentero-Hepatology, Cho Ray Hospital, Ho Chi Minh City, Vietnam
- Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
- Department of Pathology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
| | - Hiroshi Ushijima
- Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Vo Xuan Quang
- Department of Gastroentero-Hepatology, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | - Khin Maung Win
- Department of Hepatology, Yangon General Hospital, Yangon, Myanmar
| | - Pairoj Luengrojanakul
- Department of Gastroenterology, Mahidol University Siriraj Hospital, Bangkok, Thailand
| | - Kaoru Kikuchi
- Gastroenterology Section, Okinawa Chubu Hospital, Okinawa, Japan
| | - Tetsutaro Sata
- Department of Pathology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
| | - Kenji Abe
- Department of Pathology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
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45
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Saudy N, Sugauchi F, Tanaka Y, Suzuki S, Aal AA, Zaid MA, Agha S, Mizokami M. Genotypes and phylogenetic characterization of hepatitis B and delta viruses in Egypt. J Med Virol 2003; 70:529-536. [PMID: 12794714 DOI: 10.1002/jmv.10427] [Citation(s) in RCA: 84] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatitis B virus (HBV) and hepatitis D virus (HDV) sequences among HBV carriers from Egypt have not been evaluated sufficiently. The genotypes of HBV isolated from 105 serum samples from Egyptian carriers were determined. Four complete genomes and 11 entire preS1/S2/S genes were sequenced and evaluated. All serum samples were classified into HBV genotype D using serologic and genetic methods. The length of four complete nucleotide sequences was 3,182 bp. In all 15 samples, the common 33 nucleotides (11 amino acids) deletions in the preS1 region specific for HBV genotype D were observed. In the phylogenetic analysis based on the complete nucleotide sequences, all samples were clustered with the HBV isolates reported from previously Western and Mediterranean countries with nucleotide homology ranging from 96.0-98.0%. Of 75 HBsAg positive samples, anti-HDV was found in 15 (20%), and HDV RNA was detected in 9 of 15 (60%). The proportion of the patients with liver disease was higher in HBV carriers of anti-HDV positive with HDV RNA than in HBV carriers of anti-HDV positive without HDV RNA (P < 0.05). In the phylogenetic analysis based on the sequences in nucleotide position 853-1267 of HDV, nine samples were classified into HDV genotype I with the nucleotide homology ranging from 88.3-92.1% (mean; 90.5%) and clustered with HDV strains reported previously from Ethiopia, Somalia, Egypt, and Lebanon. These results indicate that HBV genotype D and HDV genotype I are most prevalent in Egypt, and HDV co-infection in HBV carriers is related to severity of liver disease.
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Affiliation(s)
- Niveen Saudy
- Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Arankalle VA, Murhekar KM, Gandhe SS, Murhekar MV, Ramdasi AY, Padbidri VS, Sehgal SC. Hepatitis B virus: predominance of genotype D in primitive tribes of the Andaman and Nicobar islands, India (1989-1999). J Gen Virol 2003; 84:1915-1920. [PMID: 12810887 DOI: 10.1099/vir.0.18943-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
To understand the possible origin of hepatitis B virus (HBV), three of the four hyperendemic, primitive accessible tribes of the Andaman and Nicobar islands, India, were investigated. The Nicobarese tribe was investigated in 1989 and 1999. The S gene from 65 HBV isolates was amplified by PCR and sequenced. Genotyping and serotyping were carried out on the basis of phylogenetic and amino acid analyses of S gene. All 20 Nicobarese-89 isolates, nine Onges-99 isolates and the single Andamanese-99 HBV isolate were classified as genotype D. Of the Nicobarese-99 isolates, 32 (91.4 %) and three (8.6 %) were genotypes D and A, respectively. Per cent nucleotide identity between the S sequences representing different tribes varied from 98.06 to 98.59 % and varied from mainland isolates by 1.6-2.0 %. Although southeast Asian origin is postulated for the Nicobarese tribe, the presence of different genotypes suggests introduction of HBV after migration to these islands, probably from mainland India, 200 years back, when these islands became inhabited as a part of penal settlement during the British regimen.
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Affiliation(s)
- V A Arankalle
- National Institute of Virology, 20-A Dr Ambedkar Road, 411001 Pune, India
| | - K M Murhekar
- Regional Medical Research Center, Port Blair, Andaman and Nicobar islands, India
| | - S S Gandhe
- National Institute of Virology, 20-A Dr Ambedkar Road, 411001 Pune, India
| | - M V Murhekar
- Regional Medical Research Center, Port Blair, Andaman and Nicobar islands, India
| | - A Y Ramdasi
- National Institute of Virology, 20-A Dr Ambedkar Road, 411001 Pune, India
| | - V S Padbidri
- National Institute of Virology, 20-A Dr Ambedkar Road, 411001 Pune, India
| | - S C Sehgal
- Regional Medical Research Center, Port Blair, Andaman and Nicobar islands, India
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47
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Suzuki S, Sugauchi F, Orito E, Kato H, Usuda S, Siransy L, Arita I, Sakamoto Y, Yoshihara N, El-Gohary A, Ueda R, Mizokami M. Distribution of hepatitis B virus (HBV) genotypes among HBV carriers in the Cote d'Ivoire: complete genome sequence and phylogenetic relatedness of HBV genotype E. J Med Virol 2003; 69:459-65. [PMID: 12601751 DOI: 10.1002/jmv.10331] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The characteristics of hepatitis B virus (HBV) genotype E are not well known because only a few studies have been carried out by complete genome analysis. The aim of this study was to elucidate the distribution of HBV genotypes in Cote d'Ivoire, and to clarify the genotype-related characteristics of genotype E. The distribution of HBV genotypes among 48 HBV carriers in Cote d'Ivoire was determined using serological and genetic methods. The characteristics of genotype E were evaluated by complete genome sequences, and further investigations of small S gene, basic core promoter (BCP) mutation, and precore mutation were undertaken. HBV genotype distribution among the 48 carriers was 6.3% for genotype A, 6.3% for genotype D, and 87.4% for genotype E. Complete genomes of two genotype E strains were sequenced, and found to have 98.2% to 99.2% homology at the nucleotide level when compared with genotype E strains reported previously. In 24 genotype E carriers, the precore mutation was detected in 75% of the patients without HBeAg, in contrast to only 25% of the patients with HBeAg (P < 0.05). All 24 strains have T at nucleotide 1858 in the precore region. In contrast, BCP double mutation was detected in 17% of the patients with HBeAg, and 33% of the patients without HBeAg. These results indicated as the following: (1) genotypes A, D, and E of HBV exist in Cote d'Ivoire and genotype E is the most prevalent; (2) genotype E spread with low genetic diversity over the complete genome in West Africa; (3) HBV precore and/or BCP double variants were common among the patients with genotype E infections.
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Affiliation(s)
- Seiji Suzuki
- Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Japan
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