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.
Citations
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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
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
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
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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TL;DR: It is suggested that HBV genotypes/subgenotypes have important influences on the outcome of chronic HBV infection, but more population-based prospective studies examining multiple genotypes are needed.
Abstract: Background
Chronic infection with hepatitis B virus (HBV) is associated with a high lifetime risk of developing hepatocellular carcinoma (HCC) and cirrhosis of the liver.
237 citations
"High prevalence of hepatitis B viru..." refers background in this paper
...Among the Asian patients from Vietnam, significantly higher associations were found between mixed genotype infections and acute hepatitis B, liver cirrhosis, and HCC although the specific combination was impossible to identify due to the different mixtures reported [20]....
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...7 years showed that the highest risk of developing HCC was in persons infected with HBV genotype C2, with the next highest being C1, followed by those infected with genotype B (presumably Ba) [20]....
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...The HBV genotype C is independently associated with a higher risk of HCC and associated with more rapid progression to cirrhosis than genotype B [8,20,23]....
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...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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...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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TL;DR: Hepatitis B Virus genotypes have come of age and there are still major gaps in knowledge about how variants and genotypes of HBV influence the spectrum of disease in people infected with HBV.
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.
222 citations
"High prevalence of hepatitis B viru..." refers background in this paper
...Thus, distinct HBV genotypes can be kept in societies living closely together even after migration over long distances [24]....
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...HBV genotypes may add additional support to anthropological data on ancient migration events [24]....
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...Differences between the Asian genotypes B and C appears to be influenced by the subgroup of genotype B, because in Japan where the genotype B1 (Bj) is prevalent, no differences in the development of HCC between genotypes B and C was observed [24]....
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TL;DR: While it is theoretically possible that hepatitis B infection could be eradicated by universal childhood immunisation, there are several biological and practical issues that make this extremely difficult, suggesting that, for the foreseeable future, control may be a more realisable goal.
Abstract: The Western Pacific and South East Asia regions are the largest and most populous of the six World Health Organisation regions and include more than 40 countries. More than 75% of the world's estimated 350 million carriers are located here. The region has therefore provided many insights into the epidemiology, natural history, and control of hepatitis B infection and has been home to the first national control programmes. Hepatitis B is hyperendemic in most countries of the region, with carrier rates ranging from 5-35% except in Australia, New Zealand, and Japan, where the mean carrier rate is less than 2%. Patterns of infection vary considerably from country to country, city to city, and even village to village, and can change with time. Most infections are acquired early in childhood or in early adult life. A variety of control measures are in place and many countries in the region have introduced widespread or universal childhood immunisation policies with significant success. While it is theoretically possible that hepatitis B infection could be eradicated by universal childhood immunisation, there are several biological and practical issues that make this extremely difficult, suggesting that, for the foreseeable future, control may be a more realisable goal.
205 citations
"High prevalence of hepatitis B viru..." refers background in this paper
...More than 75% of the 350 millions of HBV carriers are located in Western Pacific and South East Asia region [2]....
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TL;DR: A phylogenetic analysis of 19 hepatitis B virus strains from Laos that belonged to 2 subgenotypes of a new genotype I likely developed outside Southeast Asia and is now found in mixed infections and in recombinations with local strains in a geographically confined region.
Abstract: We conducted a phylogenetic analysis of 19 hepatitis B virus strains from Laos that belonged to 2 subgenotypes of a new genotype I. This emerging new genotype likely developed outside Southeast Asia and is now found in mixed infections and in recombinations with local strains in a geographically confined region.
195 citations
"High prevalence of hepatitis B viru..." refers background in this paper
...Ten HBV genotypes (A-J) have been identified [6,7], and each genotype can be further classified into subgenotypes [4]....
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TL;DR: There has been an explosion of knowledge in the literature on the epidemiology of HBV genotypes, and their association with hepatitis B e antigen (HBeAg) seroconversion, activity of liver disease, and treatment response, and subtypes have now been identified within some genotypes.
170 citations
"High prevalence of hepatitis B viru..." refers background in this paper
...HBV genotype B is associated with spontaneous HBeAg seroconversion at a younger age, with less active liver disease, and a slower rate of progression to cirrhosis compared with HBV genotype C [8,9]....
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