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Journal ArticleDOI

High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia

TL;DR: HBV/C with subgenotype C1 was the predominant HBV genotype among HBV carriers of Minangkabau ethnicity and the prevalence of pre-S, T1753V and A1762T/G1764A mutations was higher among the MinangKabau compared to IndonesianHBV carriers in general.
Abstract: The Minangkabau is one of the major ethnic groups in Indonesia. Previous studies with a limited number of samples have shown a different prevalence of HBV/C in the Minangkabau compared to the Indonesian population in general. The aim of this study was to assess the HBV genotype distribution pattern and the prevalence of pre-S, T1753V and A1762T/G1764A mutations among the Minangkabau HBV carriers. The samples were collected from Padang, West Sumatera and from western Java. Mixed primers for specific genotypes were used to determine the HBV genotype. Pre-S or S genes were amplified, sequenced and aligned with reference sequences from GenBank to derive a phylogenetic tree for subgenotyping. Pre-S genes were also analyzed for mutations. The basal core promoter (BCP) region was amplified and directly sequenced to analyze T1753V and A1762T/G1764A mutations. The predominant HBV genotype among the Minangkabau HBV carriers (n=117) was C (72.6%) followed by B (24.8%) and co-infection with B and C (2.6%). The prevalence of pre-S mutations, including both the pre-S deletion and pre-S2 start codon mutation, was 41.0%, and the T1753V and A1762T/G1764A mutations were found in 51.9% and 71.2% respectively. HBV/C1 was the predominant HBV subgenotype in the Minangkabau HBV carriers, and was found in 66.2%, followed by B3, B7, C8, B2, B9, C2, and C10 (18.3%, 7.0%, 2.8%, 1.4%, 1.4%, 1.4%, and 1.4% respectively). From samples that were found to be co-infected with HBV B and C, two samples were successfully cloned and subgenotyped, including one with mixed subgenotypes of B3 and C1, and another one with mixed subgenotypes of B7, C1, putative intergenotypic of B/A, and C/A. Furthermore, three samples from donors of non-Minangkabau ethnicity from Padang were found to be infected with an intragenotypic recombination form, including a putative recombinant of B8/B3 and B9/B7. HBV/C with subgenotype C1 was the predominant HBV genotype among HBV carriers of Minangkabau ethnicity. The prevalence of pre-S, A1762T/G1764A, and T1753V mutations was higher among the Minangkabau compared to Indonesian HBV carriers in general.

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Citations
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Journal ArticleDOI
TL;DR: Genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment, as pathogenic differences between HBV genotypes explain disease intensity, progression to LC, and HCC.
Abstract: At least 600000 individuals worldwide annually die of hepatitis B virus (HBV)-related diseases, such as chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Many viral factors, such as viral load, genotype, and specific viral mutations, are known to affect disease progression. HBV reverse transcriptase does not have a proofreading function, therefore, many HBV genotypes, sub-genotypes, mutants, and recombinants emerge. Differences between genotypes in response to antiviral treatment have been determined. To date, 10 HBV genotypes, scattered across different geographical regions, have been identified. For example, genotype A has a tendency for chronicity, whereas viral mutations are frequently encountered in genotype C. Both chronicity and mutation frequency are common in genotype D. LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes. Pathogenic differences between HBV genotypes explain disease intensity, progression to LC, and HCC. In conclusion, genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.

313 citations

Journal ArticleDOI
TL;DR: A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression and drug resistance to lamivudine, which is prominent in Indonesia, remains obscure.
Abstract: Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia.

49 citations

Journal ArticleDOI
TL;DR: Genetic variants of HLA-DP and the presence of anti-HBc are important predictors of OBI in Indonesian blood donors.
Abstract: Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the serum and/or liver in HBsAg-negative individuals. OBI is associated with the risk of viral transmission, especially in developing countries, and with progressive liver disease and reactivation in immunosuppressive patients. The objective of this study was to evaluate the relation of OBI to HLA-DP single nucleotide polymorphisms (SNPs) encoding antigen-binding sites for the immune response to HBV infection. As HLA-DP variants affect the mRNA expression of HLA-DPA1 and HLA-DPB1 in the liver, we hypothesised that high levels of HLA-DPA1 and HLA-DPB1 expression favour OBI development. The study enrolled 456 Indonesian healthy blood donors (HBsAg negative). OBI was defined as the presence of HBV-DNA in at least two of four open reading frames (ORFs) of the HBV genome detected by nested PCR. SNPs in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs2281388) were genotyped using real-time Taqman® genotyping assays. Of 122 samples positive for anti-HBs and/or anti-HBc, 17 were determined as OBI. The minor allele in rs3077 was significantly correlated with OBI [odds ratio (OR) = 3.87, 95% confidence interval (CI) = 1.58–9.49, p = 0.0015]. The prevalence of the minor allele (T) was significantly higher in subjects with OBI than in those without (59% and 33%, respectively). The combination of haplotype markers (TGA for rs3077–rs3135021–rs9277535) was associated with increased risk of OBI (OR = 4.90, 95%CI = 1.12–21.52 p = 0.038). The prevalence of OBI was highest in the isolated anti-HBc group among the three seropositive categories: anti-HBs <500 mIU/ml, anti-HBs ≥500 mIU/ml, and isolated anti-HBc (29.41%, p = 0.014). Genetic variants of HLA-DP and the presence of anti-HBc are important predictors of OBI in Indonesian blood donors. Ref: KE/FK/194/EC; registered 01 March 2013. Continuing approval Ref: KE/FK/536/EC; registered 12 May 2014.

11 citations


Cites result from "High prevalence of hepatitis B viru..."

  • ...This is in accordance with previous studies showing that in Indonesia the most common HBV genotype is HBV B3 (HBV/B3), followed by HBV/C1, especially in Java island [21, 33]....

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Journal Article
TL;DR: The development of multi-site mutations in the X gene may represent a strategy by which HBV can escape immune surveillance and thus contribute to hepatocarcinogenesis, even though the biological roles of some variants remain unclear.
Abstract: Multi-site mutations in the hepatitis B virus (HBV) X gene are often found in patients with advanced liver diseases such as liver cirrhosis and hepatocellular carcinoma. It has been reported that modifications in the X protein play crucial roles in the development of HBV-related severe liver disease. However, the prevalence of genetic variations in Indonesian strains has not been systematically assessed. In this study, we sought to investigate the profile of nonsynonymous mutations in the X gene. Overall, 114 Indonesian HBV strains, including 12 in-house samples, were retrieved from GenBank. The mutation frequency in the X gene was compared among strains obtained from patients with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The mutation frequencies of the domain and basal core promoter regions were significantly greater in advanced liver diseases compared with chronic hepatitis. In addition, the double mutation K130M/V131I and the triple mutation N88V/K130M/V131I were associated with a 2.5 times higher risk of advanced liver disease. However, the roles of two novel X gene mutations (A12S/T and L16F/P) on hepatocarcinogenesis are unclear relative to wild-type X gene. In conclusion, the development of multi-site mutations in the X gene may represent a strategy by which HBV can escape immune surveillance and thus contribute to hepatocarcinogenesis, even though the biological roles of some variants remain unclear.

4 citations

Journal ArticleDOI
TL;DR: It is concluded that all the samples have nucleotide variation and the mutation implying that molecular progression between the virus and the host at chronically infected patients is implied.
Abstract: Background: Hepatitis B is a health issue that become major problem worldwide with high morbidity. Hepatitis B is a liver infection that caused by Hepatitis B Virus. Chronic hepatitis B is a liver inflammation that lasted more than 6 months and it has the potential to progress to liver cirrhosis and hepatocellular cancer. The disease is influenced by Gene X and viral genotype. Mutations in the Gene X are suspected to having a role in disease progression. The aim of this study was to detect Gene X polymorphism and the phylogeny of HBV from Padang local clinical samples of chronic hepatitis B (CHB), West Sumatera, Indonesia.Method: The entire chronically HBV-infected patients were enrolled in this study: 38 CHB. The research samples were the entire Hepatitis B serum from Indonesian Red Cross Blood Bank than Gene X was amplified using nested PCR, which produced two fragments and aligned with X sequence database continued with mutation analysis. Results: In this study we found all the samples were having nucleotide variation. Of various mutations, we observed the presence of known liver cirrhosis and HCC-related HBx protein mutant i.e double mutations (HBx130 and HBx131) and two triple mutations (HBx5/HBx130/HBx131) and (HBx127/HBx130/HBx131) were high. The analysis also showed that patients were infected mainly by genotype C at 72,2% and followed by B at 27,8%.Conclusion: We conclude that all the samples have nucleotide variation and the mutation implying that molecular progression between the virus and the host at chronically infected patients.
References
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Journal ArticleDOI
TL;DR: The distribution of HBV genotypes/subgenotypes, including B8 and C7, seems to be associated with ethnological origins in Indonesia.
Abstract: Upon phylogenetic analysis of a partial S gene sequence [396 nucleotides (nt)], 928 hepatitis B virus (HBV) strains obtained from 899 viremic subjects in 28 major cities on 15 islands of Indonesia in 1989-2007 segregated into four HBV genotypes. Genotype B was predominant (66%), followed by genotype C (26%), genotype D (7%), and genotype A (0.8%). Comparative and phylogenetic analyses of the 396-nt S gene sequence of 928 HBV isolates and whole genomic sequences of 25 selected HBV isolates revealed a total of 14 subgenotypes within genotypes A-D: two (A1 and A2) in genotype A (HBV/A), five (B2, B3, B5, B7, and a novel subgenotype, tentatively designated B8) in HBV/B, five (C1, C2, C5, C6, and another novel subgenotype, C7) in HBV/C, and two (D1 and D3) in HBV/D. The distribution of HBV genotypes/subgenotypes, including B8 and C7, seems to be associated with ethnological origins in Indonesia.

87 citations


"High prevalence of hepatitis B viru..." refers background or result in this paper

  • ...Genotype B is the predominant HBV genotype in Indonesia, followed by genotypes C, D, and A [12-14]....

    [...]

  • ...Interestingly, in Minangkabau population of West Sumatra the predominant HBV genotype is HBV/C with subgenotype C1 [13,14]....

    [...]

  • ...HBV/C was found to be predominant in the eastern part of Indonesia (Papua and Papua-influenced populations of Moluccas) but of different subgenotypes than those found in the western Indonesia (C6 and C7) [13,14,22]....

    [...]

  • ...Furthermore, HBV strains circulating in an area can reflect the ethnic mix of its population [13,14,21]....

    [...]

  • ...They originated from and still mainly reside in the West Sumatra province of Sumatra Island [17]....

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Journal ArticleDOI
TL;DR: The result provides the first direct evidence that the distribution of HBV genotypes/subgenotypes in the Indonesian archipelago is related to the ethnic origin of its populations and suggests that the HBV distribution is associated with the ancient migratory events in the peopling of the archipelagos.
Abstract: The distribution of hepatitis B virus (HBV) in the populations of island Southeast Asia is of medical and anthropological interest and is associated with an unusually high genetic diversity. This study examined the association of this HBV genetic diversity with the ethnogeography of the populations of the Indonesian archipelago. Whole genome analysis of 21 HBV isolates from East Nusa Tenggara and Papua revealed two recently reported HBV/B subgenotypes unique to the former, B7 (7 isolates) and B8 (5 isolates), and uncovered a further novel subgenotype designated B9 (4 isolates). Further isolates were collected from 419 individuals with defined ethnic backgrounds representing 40 populations. HBV/B was predominant in Austronesian-language-speaking populations, whereas HBV/C was the major genotype in Papua and Papua-influenced populations of Moluccas; HBV/B3 was the predominant subgenotype in the western half of the archipelago (speakers of the Western Malayo-Polynesian [WMP] branch of Austronesian languages), whereas B7, B8 and B9 were specific to Nusa Tenggara (Central Malayo-Polynesian (CMP)). The result provides the first direct evidence that the distribution of HBV genotypes/subgenotypes in the Indonesian archipelago is related to the ethnic origin of its populations and suggests that the HBV distribution is associated with the ancient migratory events in the peopling of the archipelago.

60 citations


"High prevalence of hepatitis B viru..." refers background or result in this paper

  • ...HBV/C1 was commonly found in Southeast Asia (the western part of Indonesia, Malaysia, Thailand, Vietnam and Bangladesh) and Southern China [12,13,20,21,27]....

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  • ...HBV/B is predominant in the western part of Indonesia, whilst HBV/C is dominant on the eastern part [13,14]....

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  • ...Previous studies have shown that HBV genotype C is the most prevalent among HBV carriers in this population, which is different from other populations in Sumatra Island [12-14]....

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  • ...Genotype B is the predominant HBV genotype in Indonesia, followed by genotypes C, D, and A [12-14]....

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  • ...In the western Indonesian population, the HBV/C was exclusively high in Minangkabau population [13]....

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Journal ArticleDOI
TL;DR: Accumulating lines of evidence indicate a better response to interferon and lamivudine in patients with chronic hepatitis B who are infected with genotype B rather than C, and influence of genotypes on therapeutic response needs to be examined in patients infected with the other genotypes, particularly in those with genotypes A or D infection.
Abstract: Hepatitis B virus (HBV) has been classified into eight genotypes (A‐H) based on genome sequence divergence. Genotypes of HBV have distinct geographical distributions, and two genotypes account for most HBV worldwide. Hepatitis B e antigen expression lasts longer and liver disease is more severe with graver outcomes in carriers of genotype C than B in Asia. Accumulating lines of evidence indicate a better response to interferon and lamivudine in patients with chronic hepatitis B who are infected with genotype B rather than C. The therapeutic response may differ, however, in patients infected with HBV of the same genotype. For example, the response to lamivudine is poorer in patients infected with subtype Ba, which contains a recombination with genotype C, than in those with subtype Bj without such a recombination. Influence of genotypes on therapeutic response needs to be examined in patients infected with the other genotypes, particularly in those with genotype A or D infection.

56 citations


"High prevalence of hepatitis B viru..." refers background in this paper

  • ...Particular HBV genotypes are associated with the outcome of chronic HBV infection and the response to antiviral therapies [8,18-20]....

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Book
21 Aug 2003
TL;DR: In this article, the authors discuss the politics of ethnic classification in Thailand, Malaysia, and the Philippines, and discuss the importance of diversity in the classification of ethnic groups in these countries.
Abstract: 1. Introduction 2. Ethnicity in China 3. In Japan, but not of Japan 4. Ethnicity in Indonesia 5. Ethnicity and Class in Malaysia 6. Singapore: Multiracial harmony as public good 7. Vietnam 8. Ethnicity in the Philippines 9. Ethnicity and the Politics of Ethnic Classification in Thailand 10. Myanmar/Burma 11. Cambodia 12. Laos: Minorities

44 citations

Journal ArticleDOI
TL;DR: Investigation of the serologic status and virologic characteristics of hepatitis B virus among the children in East Java found a single amino substitution in the S region was frequently found.
Abstract: Universal childhood hepatitis B vaccination was introduced in Indonesia in 1997; by 2008, coverage was estimated to be 78% This study aimed to investigate the serologic status and virologic characteristics of hepatitis B virus (HBV) among the children in East Java A total of 229 healthy children born during 1994-1999 were enrolled in this study Overall, 31% were positive for hepatitis B surface antigen (HBsAg) and 236% were positive for antibody to HBsAg (anti-HBs) HBV DNA was detected in 5 of 222 HBsAg-negative carriers, which were suggested to be cases of occult HBV infection A single amino substitution (T126I) in the S region was frequently found HBV infection remains endemic, and the prevalence of anti-HBs remains insufficient among children in East Java, Indonesia

39 citations


"High prevalence of hepatitis B viru..." refers background in this paper

  • ...Indonesia has moderate to high endemicity for HBV infection, with a carrier rate of 5–20% in the general population [11]....

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