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  1. Fulltext Universal Primers for Detection and Sequencing of Hepatitis B Virus Genomes across Genotypes A to G
    Chook JB, Teo WL, Ngeow YF, Tee KK, Ng KP, Mohamed R
    J Clin Microbiol, 2015 Jun;53(6):1831-5.
    PMID: 25788548 DOI: 10.1128/JCM.03449-14
    Hepatitis B virus (HBV) has been divided into 10 genotypes, A to J, based on an 8% nucleotide sequence divergence between genotypes. The conventional practice of using a single set of primers to amplify a near-complete HBV genome is hampered by its low analytical sensitivity. The current practice of using overlapping conserved primer sets to amplify a complete HBV genome in a clinical sample is limited by the lack of pan-primers to detect all HBV genotypes. In this study, we designed six highly conserved, overlapping primer sets to cover the complete HBV genome. We based our design on the sequences of 5,154 HBV genomes of genotypes A to I downloaded from the GenBank nucleotide database. These primer sets were tested on 126 plasma samples from Malaysia, containing genotypes A to D and with viral loads ranging from 20 to >79,780,000 IU/ml. The overall success rates for PCR amplification and sequencing were >96% and >94%, respectively. Similarly, there was 100% amplification and sequencing success when the primer sets were tested on an HBV reference panel of genotypes A to G. Thus, we have established primer sets that gave a high analytical sensitivity for PCR-based detection of HBV and a high rate of sequencing success for HBV genomes in most of the viral genotypes, if not all, without prior known sequence data for the particular genotype/genome.
    Matched MeSH terms: Hepatitis B/virology
  2. Comparative analysis of viral genomes from acute and chronic hepatitis B reveals novel variants associated with a lower rate of chronicity
    Chook JB, Ngeow YF, Khang TF, Ng KP, Tiang YP, Mohamed R
    J Med Virol, 2013 Mar;85(3):419-24.
    PMID: 23297244 DOI: 10.1002/jmv.23500
    Infection with the hepatitis B virus (HBV) may lead to an acute or chronic infection. It is generally accepted that the clinical outcome of infection depends on the balance between host immunity and viral survival strategies. In order to persist, the virus needs to have a high rate of replication and some immune-escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non-fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut-off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five-fold cross-validation. The average prediction accuracy was 61% ± 1%, with a sensitivity of 24% ± 1%, specificity of 98% ± 1%, positive predictive value of 92% ± 4% and negative predictive value of 56% ± 1%. BCP/X, enhancer I and surface/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non-progression to chronic hepatitis.
    Matched MeSH terms: Hepatitis B/virology*
  3. The distribution of hepatitis B virus genotypes in Thailand
    Louisirirotchanakul S, Olinger CM, Arunkaewchaemsri P, Poovorawan Y, Kanoksinsombat C, Thongme C, et al.
    J Med Virol, 2012 Oct;84(10):1541-7.
    PMID: 22930500 DOI: 10.1002/jmv.23363
    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.
    Matched MeSH terms: Hepatitis B/virology*
  4. Polydimethylsiloxane-Paper Hybrid Lateral Flow Assay for Highly Sensitive Point-of-Care Nucleic Acid Testing
    Choi JR, Liu Z, Hu J, Tang R, Gong Y, Feng S, et al.
    Anal Chem, 2016 06 21;88(12):6254-64.
    PMID: 27012657 DOI: 10.1021/acs.analchem.6b00195
    In nucleic acid testing (NAT), gold nanoparticle (AuNP)-based lateral flow assays (LFAs) have received significant attention due to their cost-effectiveness, rapidity, and the ability to produce a simple colorimetric readout. However, the poor sensitivity of AuNP-based LFAs limits its widespread applications. Even though various efforts have been made to improve the assay sensitivity, most methods are inappropriate for integration into LFA for sample-to-answer NAT at the point-of-care (POC), usually due to the complicated fabrication processes or incompatible chemicals used. To address this, we propose a novel strategy of integrating a simple fluidic control strategy into LFA. The strategy involves incorporating a piece of paper-based shunt and a polydimethylsiloxane (PDMS) barrier to the strip to achieve optimum fluidic delays for LFA signal enhancement, resulting in 10-fold signal enhancement over unmodified LFA. The phenomena of fluidic delay were also evaluated by mathematical simulation, through which we found the movement of fluid throughout the shunt and the tortuosity effects in the presence of PDMS barrier, which significantly affect the detection sensitivity. To demonstrate the potential of integrating this strategy into a LFA with sample-in-answer-out capability, we further applied this strategy into our prototype sample-to-answer LFA to sensitively detect the Hepatitis B virus (HBV) in clinical blood samples. The proposed strategy offers great potential for highly sensitive detection of various targets for wide application in the near future.
    Matched MeSH terms: Hepatitis B/virology
  5. Fulltext Naturally occurring hepatitis B virus surface antigen mutant variants in Malaysian blood donors and vaccinees
    Hudu SA, Harmal NS, Saeed MI, Alshrari AS, Malik YA, Niazlin MT, et al.
    Eur J Clin Microbiol Infect Dis, 2015 Jul;34(7):1349-59.
    PMID: 25792010 DOI: 10.1007/s10096-015-2358-1
    Hepatitis B virus surface mutants are of enormous importance because they are capable of escaping detection by serology and can infect both vaccinated and unvaccinated populations, thus putting the whole population at risk. This study aimed to detect and characterise hepatitis B-escaped mutants among blood donors and vaccinees. One thousand serum samples were collected for this study from blood donors and vaccinees. Hepatitis B surface antigen, antibodies and core antibodies were tested using a commercial enzyme-linked immunosorbent assay (ELISA) kit. DNA detection was performed via nested polymerase chain reaction (PCR), and the S gene was sequenced and analysed using bioinformatics. Of the 1,000 samples that were screened, 5.5% (55/1,000) were found to be HBsAg-negative and anti-HBc- and HBV DNA-positive. All 55 isolates were found to belong to genotype B. Several mutations were found across all the sequences from synonymous and non-synonymous mutations, with the most nucleotide mutations occurring at position 342, where adenine was replaced by guanine, and cytosine at position 46 was replaced by adenine in 96.4% and 98% of the isolates, respectively. Mutation at position 16 of the amino acid sequence was found to be common to all the Malaysian isolates, with 85.7% of the mutations occurring outside the major hydrophilic region. This study revealed a prevalence of 5.5% for hepatitis B-escaped mutations among blood donors and vaccinated undergraduates, with the most common mutation being found at position 16, where glutamine was substituted with lysine.
    Matched MeSH terms: Hepatitis B/virology*
  6. Fulltext Knowledge and awareness of hepatitis B among households in Malaysia: a community-based cross-sectional survey
    Rajamoorthy Y, Taib NM, Munusamy S, Anwar S, Wagner AL, Mudatsir M, et al.
    BMC Public Health, 2019 Jan 10;19(1):47.
    PMID: 30630464 DOI: 10.1186/s12889-018-6375-8
    BACKGROUND: Hepatitis B (HepB) is a major public health concern in Malaysia yet little is known about knowledge and awareness of this infection in the country. Such information is essential for designing effective intervention strategies for HepB prevention and control. The aim of this study was to characterize knowledge and awareness regarding HepB in Malaysia and to identify their associated sociodemographic determinants.

    METHODS: A community-based cross-sectional survey was conducted between January and May 2016 in Selangor state of Malaysia. A two-stage cluster random sampling design was used and one adult member of selected households was interviewed face-to-face. Logistic regression was used to estimate the differences in knowledge and awareness between groups.

    RESULTS: A total of 764 households completed the interviews and were included in the final analysis. Only 36.9 and 38.8% of the participants had good knowledge and awareness, respectively. The factors associated with good knowledge were being in the 35-44 year age group, Malay ethnicity, high educational attainment and high family income. Being Chinese, being older and having high educational attainment were determinants of having good awareness towards HepB. Participants who had good knowledge were 2.5 times more likely to also have good awareness (OR: 2.41, 95% CI: 1.78-3.26, p B virus transmission and achieve the governmental target of eliminating viral hepatitis as a public health concern by 2030.

    Matched MeSH terms: Hepatitis B/virology
  7. Fulltext Willingness to pay for hepatitis B vaccination in Selangor, Malaysia: A cross-sectional household survey
    Rajamoorthy Y, Radam A, Taib NM, Rahim KA, Munusamy S, Wagner AL, et al.
    PLoS One, 2019;14(4):e0215125.
    PMID: 30964934 DOI: 10.1371/journal.pone.0215125
    BACKGROUND: In Malaysia, one million individuals are estimated to be infected with the hepatitis B virus. A vaccine for infants has been compulsory since 1989, whereas those born before 1989 need to spend their own money to be vaccinated in private clinics or hospitals. The aim of this study was to investigate and ascertain the determinants of willingness to pay (WTP) for adult hepatitis B vaccine in Selangor, Malaysia.

    METHODS: In 2016, 728 households were selected through a stratified, two stage cluster sample and interviewed. Willingness to pay for hepatitis B vaccine was estimated using the Contingent Valuation Method, and factors affecting WTP were modelled with logit regression.

    RESULTS: We found that 273 (37.5%) of the households were willing to pay for hepatitis B vaccination. The mean and median of WTP was estimated at Ringgit Malaysia (RM)303 (approximately US$73) for the three dose series. The estimated WTP was significantly greater in those with higher levels of education, among Malays and Chinese (compared to others, predominantly Indians), and for those with greater perceived susceptibility to hepatitis B virus infection. Other factors-perceived severity, barriers, benefits and cues to action-were not significantly associated with WTP for adult hepatitis B vaccination.

    CONCLUSION: Additional resources are needed to cover the households that are not willing to pay for hepatitis B vaccination. More awareness (particularly in regards to hepatitis B virus susceptibility) could change the national perception towards self-paid hepatitis B virus vaccination and increase hepatitis B vaccine coverage.

    Matched MeSH terms: Hepatitis B/virology
  8. Fulltext Practical approach in hepatitis B e antigen-negative individuals to identify treatment candidates
    Azmi AN, Tan SS, Mohamed R
    World J Gastroenterol, 2014 Sep 14;20(34):12045-55.
    PMID: 25232242 DOI: 10.3748/wjg.v20.i34.12045
    The natural history of chronic hepatitis B is characterized by different phases of infection, and patients may evolve from one phase to another or may revert to a previous phase. The hepatitis B e antigen (HBeAg)-negative form is the predominant infection worldwide, which consists of individuals with a range of viral replication and liver disease severity. Although alanine transaminase (ALT) remains the most accessible test available to clinicians for monitoring the liver disease status, further evaluations are required for some patients to assess if treatment is warranted. Guidance from practice guidelines together with thorough investigations and classifications of patients ensure recognition of who needs which level of care. This article aims to assist physicians in the assessment of HBeAg-negative individuals using liver biopsy or non-invasive tools such as hepatitis B s antigen quantification and transient elastography in addition to ALT and hepatitis B virus DNA, to identify who will remain stable, who will reactivate or at risk of disease progression hence will benefit from timely initiation of anti-viral therapy.
    Matched MeSH terms: Hepatitis B/virology
  9. Gold nanoparticle-decorated reduced-graphene oxide targeting anti hepatitis B virus core antigen
    Abd Muain MF, Cheo KH, Omar MN, Amir Hamzah AS, Lim HN, Salleh AB, et al.
    Bioelectrochemistry, 2018 Aug;122:199-205.
    PMID: 29660648 DOI: 10.1016/j.bioelechem.2018.04.004
    Hepatitis B virus core antigen (HBcAg) is the major structural protein of hepatitis B virus (HBV). The presence of anti-HBcAg antibody in a blood serum indicates that a person has been exposed to HBV. This study demonstrated that the immobilization of HBcAg onto the gold nanoparticles-decorated reduced graphene oxide (rGO-en-AuNPs) nanocomposite could be used as an antigen-functionalized surface to sense the presence of anti-HBcAg. The modified rGO-en-AuNPs/HBcAg was then allowed to undergo impedimetric detection of anti-HBcAg with anti-estradiol antibody and bovine serum albumin as the interferences. Upon successful detection of anti-HBcAg in spiked buffer samples, impedimetric detection of the antibody was then further carried out in spiked human serum samples. The electrochemical response showed a linear relationship between electron transfer resistance and the concentration of anti-HBcAg ranging from 3.91ngmL-1 to 125.00ngmL-1 with lowest limit of detection (LOD) of 3.80ngmL-1 at 3σm-1. This established method exhibits potential as a fast and convenient way to detect anti-HBcAg.
    Matched MeSH terms: Hepatitis B/virology
  10. Fulltext PreS1 Mutations Alter the Large HBsAg Antigenicity of a Hepatitis B Virus Strain Isolated in Bangladesh
    Hossain MG, Mahmud MM, Nazir KHMNH, Ueda K
    Int J Mol Sci, 2020 Jan 15;21(2).
    PMID: 31952213 DOI: 10.3390/ijms21020546
    Mutations in the hepatitis B virus (HBV) genome can potentially lead to vaccination failure, diagnostic escape, and disease progression. However, there are no reports on viral gene expression and large hepatitis B surface antigen (HBsAg) antigenicity alterations due to mutations in HBV isolated from a Bangladeshi population. Here, we sequenced the full genome of the HBV isolated from a clinically infected patient in Bangladesh. The open reading frames (ORFs) (P, S, C, and X) of the isolated HBV strain were successfully amplified and cloned into a mammalian expression vector. The HBV isolate was identified as genotype C (sub-genotype C2), serotype adr, and evolutionarily related to strains isolated in Indonesia, Malaysia, and China. Clinically significant mutations, such as preS1 C2964A, reverse transcriptase domain I91L, and small HBsAg N3S, were identified. The viral P, S, C, and X genes were expressed in HEK-293T and HepG2 cells by transient transfection with a native subcellular distribution pattern analyzed by immunofluorescence assay. Western blotting of large HBsAg using preS1 antibody showed no staining, and preS1 ELISA showed a significant reduction in reactivity due to amino acid mutations. This mutated preS1 sequence has been identified in several Asian countries. To our knowledge, this is the first report investigating changes in large HBsAg antigenicity due to preS1 mutations.
    Matched MeSH terms: Hepatitis B/virology
  11. HBV and HIV co-infection: Prevalence and clinical outcomes in tertiary care hospital Malaysia
    Akhtar A, Khan AH, Sulaiman SA, Soo CT, Khan K
    J Med Virol, 2016 Mar;88(3):455-60.
    PMID: 26255632 DOI: 10.1002/jmv.24347
    According to WHO, Malaysia has been classified as a concentrated epidemic country due to progression of HIV infection in the population of injecting drug users. The main objectives of current study are to determine the prevalence of HBV among HIV-positive individuals in a tertiary care hospital of Malaysia and to assess the predictors involved in the outcomes of HIV-HBV co-infected patients. A retrospective, cross-sectional study is conducted at Hospital Palau Pinang, Malaysia. The collection of socio-demographic data as well as clinical data is done with the help of data collection form. Data were analyzed after putting the collected values of required data by using statistical software SPSS version 20.0 and P > 0.05 is considered as significant. Results show that the overall prevalence of HBV was 86 (13%) including 495 (74.5%) males and 169 (25.5%) females among a total of 664 HIV-infected patients. It was observed that there is a high prevalence of HIV-HBV co-infection in males 76 (11.4%) as compared to females 10 (1.5%) (P = 0.002). The median age of the study population was 39 years. The statistical significant risk factors involved in the outcomes of HIV-HBV co-infected patients were observed in the variables of gender, age groups, and injecting drug users. The findings of the present study shows that the prevalence of HBV infection among HIV-positive patients was 13% and the risk factors involved in the outcomes of HIV-HBV co-infected patients were gender, age, and intravenous drug users.
    Matched MeSH terms: Hepatitis B/virology
  12. Diversity of hepatitis B virus infecting Malaysian candidate blood donors is driven by viral and host factors
    Meldal BH, Bon AH, Prati D, Ayob Y, Allain JP
    J Viral Hepat, 2011 Feb;18(2):91-101.
    PMID: 20196797 DOI: 10.1111/j.1365-2893.2010.01282.x
    Malaysia is a medium endemic country for hepatitis B virus (HBV) infection but little is known about HBV strains circulating in Malaysian blood donors. Viral load, HBsAg concentrations and nested PCR products from 84 HBV surface antigen (HBsAg) positive samples were analysed in detail. Median viral load was 3050 IU/mL and median HBsAg 1150 IU/mL. Fifty-six full genome, 20 pre-S/S, 1 S gene and six basic core promoter/precore-only sequences were obtained. Genotypes B and C were present at a ratio of 2:1, and two genotype D samples were obtained, both from donors of Indian background. Phylogenetically, genotype B was more diverse with subgenotypes B2-5, B7 and B8 present, while most genotype C strains were from subgenotype C1. Genotypes B and C were equally frequent in ethnic Malays, but 80% of strains from Chinese were genotype B. HBsAg concentrations were higher in genotype C than in genotype B, in Chinese than Malays and in donors under the age of 30. HBV vaccine escape substitutions (P120S/T, I126N and G145G) were present in six strains. In the large surface protein, immuno-inactive regions were more mutated than CD8 epitopes and the major hydrophilic region. Strains of genotype B or from ethnic Malays had higher genetic diversity than strains of genotype C or from Chinese donors. Hence HBV strains circulating in Malaysia are phylogenetically diverse reflecting the ethnic mix of its population. Ethnic Malays carry lower HBsAg levels and higher genetic diversity of the surface antigen, possibly resulting in more effective immune control of the infection.
    Matched MeSH terms: Hepatitis B/virology*
  13. Fulltext High possibility of hepatocarcinogenesis in HBV genotype C1 infected Cambodians is indicated by 340 HBV C1 full-genomes analysis from GenBank
    Chuon C, Takahashi K, Matsuo J, Katayama K, Yamamoto C, Ko K, et al.
    Sci Rep, 2019 08 21;9(1):12186.
    PMID: 31434918 DOI: 10.1038/s41598-019-48304-z
    Approximately 75% of hepatocellular carcinomas (HCC) occur in Asia; core promoter mutations are associated with HCC in HBV genotype C, the dominant genotype in Cambodia. We analyzed these mutations in Cambodian residents and compared them with HBV full genomes registered in GenBank. We investigated the characteristics of 26 full-length HBV genomes among 35 residents positive for hepatitis B surface antigen in Siem Reap province, Cambodia. Genotype C1 was dominant (92.3%, 24/26), with one case of B2 and B4 each. Multiple mutations were confirmed in 24 Cambodian C1 isolates, especially double mutation at A1762T/G1764A in 18 isolates (75.0%), and combination mutation at C1653T and/or T1753V and A1762T/G1764A in 14 isolates (58.3%). In phylogenetic analysis, 16 of 24 isolates were located in the cluster with Laos, Thailand, and Malaysia. In 340 GenBank-registered C1 strains, 113 (33.2%) had combination mutation amongst which 16.5%, 34.2%, and 95.2% were found in ASC, chronic hepatitis, and liver cirrhosis (LC)/HCC respectively (P 
    Matched MeSH terms: Hepatitis B/virology*
  14. An Overview of Hepatitis B Virus Surface Antigen Mutant in the Asia Pacific
    Hudu SA, Malik YA, Niazlin MT, Harmal NS, Sekawi Z
    Curr Issues Mol Biol, 2014;16:69-78.
    PMID: 24014801
    Hepatitis B virus infection is a serious health problem worldwide, and more than 350 million people are chronic carriers, constituting a major global threat. Southeast Asia and the Western Pacific have the highest levels of endemicity in the world, with an estimated seroprevalence ranging between 2% and 31%. Mutations in the hepatitis B surface antigen (HBsAg) have been reported in many parts of the world but are most common in Asian infants; such mutants have several clinical effects, such as the development of hepatocellular carcinoma. Diagnostic failures by commercial assays have reduced the diagnostic effectiveness of HBsAg detection. For example the substitution of an amino acid in the major hydrophilic region of the S gene reduces the binding of hepatitis B surface antibodies leading to immune escape. The safety of blood transfusion may be compromised by current screening tests due to escape from being neutralised by antibodies induced by HBsAg mutants, and undetectable levels of viral surface protein. Data on the epidemiology of HBsAg mutation in Asia Pacific are scant; however, this manuscript has reviewed the available information on the epidemiology of HBsAg mutation in Asia Pacific.
    Matched MeSH terms: Hepatitis B/virology
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