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  1. Efficacy and Safety of Hepatitis B Virus Vaccination Following Hepatitis B Immunoglobulin Withdrawal After Liver Transplantation
    Jo HS, Khan JF, Han JH, Yu YD, Kim DS
    Transplant Proc, 2021 Dec;53(10):3016-3021.
    PMID: 34740450 DOI: 10.1016/j.transproceed.2021.09.038
    BACKGROUND: Hepatitis B immunoglobulin (HBIG) and oral nucleoside/nucleotide analogs have been the mainstay of hepatitis B virus (HBV) prophylaxis after liver transplantation. However, long-term HBIG administration could have disadvantages, such as an increase in medical costs and the development of mutant HBV strains. This study aimed to investigate the safety and efficacy of HBV vaccination after the withdrawal of HBIG after liver transplantation.

    METHODS: This prospective open-label single-arm observational clinical trial enrolled 41 patients who underwent liver transplantation between 2010 and 2016 because of a condition related to chronic HBV infection. At the time of enrollment, all patients had taken entecavir and discontinued HBIG administration. When hepatitis B surface antibody titer was undetectable after the withdrawal of HBIG, a recombinant HBV vaccine was injected intramuscularly at month 0, 1, and 6.

    RESULTS: After excluding 5 patients who dropped out and 2 patients who had a persistent hepatitis B surface antibody titer, 9 (26.5%) of 34 patients had a positive vaccination response. The median hepatitis B surface antibody titer at seroconversion was 86 (12-1000) IU/L, and those at the end of follow-up were 216 (30-1000) IU/L. No patients experienced HBV recurrence during the study period. Sex (female, odds ratio 32.91 [1.83-592.54], P = .018) and the dosing interval of HBIG before withdrawal (≥90 days, 16.21 [1.21-217.31], P = .035) were independent contributing factors for positive response to the vaccination.

    CONCLUSION: HBV vaccination still deserves consideration as active immunoprophylaxis after liver transplantation because it could provide added immunity to nucleoside/nucleotide analogs monotherapy with excellent cost-effectiveness.

    Matched MeSH terms: Hepatitis B virus/genetics
  2. Hepatitis B virus DNA methylation and its potential role in chronic hepatitis B
    Low WF, Ngeow YF, Chook JB, Tee KK, Ong SK, Peh SC, et al.
    Expert Rev Mol Med, 2022 Nov 16;25:e11.
    PMID: 36380484 DOI: 10.1017/erm.2022.38
    Hepatitis B virus (HBV) infection led to 66% liver deaths world-wide in year 2015. Thirty-seven per cent of these deaths were the result of chronic hepatitis B (CHB)-associated hepatocellular carcinoma (HCC). Although early diagnosis of HCC improves survival, early detection is rare. Methylation of HBV DNA including covalently closed circular DNA (cccDNA) is more often encountered in HCC cases than those in CHB and cirrhosis. Three typical CpG islands within the HBV genome are the common sites for methylation. The HBV cccDNA methylation affects the viral replication and protein expression in the course of infection and may associate with the disease pathogenesis and HCC development. We review the current findings in HBV DNA methylation that provide insights into its role in HCC diagnosis.
    Matched MeSH terms: Hepatitis B virus/genetics
  3. Fulltext Comparison of PCR-based genotyping methods for hepatitis B virus
    Lim CK, Tan JT, Ravichandran A, Chan YC, Ton SH
    Malays J Pathol, 2007 Dec;29(2):79-90.
    PMID: 19108399 MyJurnal
    Hepatitis B virus (HBV) is classified into eight genotypes (A to H). In this study, three genotyping methods were compared for their sensitivity and accuracy, namely PCR-RFLP on the S region, PCR-RFLP on the pre-S region and nested PCR with type specific primers. Sixty HBV samples from infected sera were genotyped. The nested PCR with type specific primers was found to be the most sensitive and produced substantial numbers of co-infections by genotypes B and C. The sensitivities for both PCR-RFLP methods were lower and did not reveal co-infections. Generally, the three methods produced consistent genotyping results in samples infected by single genotypes but for co-infections by genotypes B and C, the two PCR-RFLP methods yielded only single genotypic results. For the cases of single genotypic infections, genotypes ascertained by sequencing were in concordance across all three methods. However, when co-infections occurred, PCR analysis on clones revealed only single genotypic infections.
    Matched MeSH terms: Hepatitis B virus/genetics*
  4. 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 virus/genetics*
  5. Quantitation of hepatitis B virus DNA in serum of patients with hepatoma
    Lie-Injo LE, Lopez CG, Latu J, Lim ML, Balasegaram M
    Cytobios, 1987;50(201):101-6.
    PMID: 3036422
    Hepatitis B virus (HBV) DNA in the serum of 31 patients with histologically confirmed primary hepatocellular carcinoma (PHC) from Malaysia and Indonesia was quantitated by densitometric scanning of autoradiograms obtained by Southern blot DNA hybridization, after electrophoresis using a 32P DNA cloned into plasmid pBR325 as a probe. This quantitation after electrophoresis is more informative than the usual spot hybridization technique. Five of the 31 sera were positive for HBV DNA. Levels ranged between 1.36 pq and 143.18 pq per ml of serum, and the levels of HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe in the serum were serologically determined. All five sera positive for HBV DNA were also positive for HBsAg. Three of the five positive for HBV DNA were positive for HBeAg and negative for anti-HBe. Two of the sera positive for HBV DNA were negative for HBeAg but positive for anti-HBe. All sera negative for HBV DNA were also negative for HBeAg. Many sera which were negative for HBV DNA and HBeAg were positive for HBsAg. Of the 31 sera from PHC patients, 23 had at least one HBV marker positive (74.2%).
    Matched MeSH terms: Hepatitis B virus/genetics*
  6. 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 virus/genetics*
  7. 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 virus/genetics*
  8. Antigenicity and immunogenicity of the immunodominant region of hepatitis B surface antigen displayed on bacteriophage T7
    Tan GH, Yusoff K, Seow HF, Tan WS
    J Med Virol, 2005 Dec;77(4):475-80.
    PMID: 16254965
    The immunodominant region of hepatitis B virus (HBV) located in the viral small surface antigen (S-HBsAg) elicits virus-neutralizing and protective antibodies. In order to develop an easy and inexpensive method to produce this region without the need for extensive purification, amino acid residues 111-156 of S-HBsAg were fused to the C-terminal end of the 10B capsid protein of T7 phage. Western blotting and ELISA confirmed the expression of the recombinant protein on the surface of the phage particles. The recombinant phage exhibited the antigenic and immunogenic characteristics of HBsAg, illustrating its potential as an immunological reagent and vaccine.
    Matched MeSH terms: Hepatitis B virus/genetics
  9. Genotyping of hepatitis B virus in Malaysia based on the nucleotide sequence of preS and S genes
    Ong HT, Duraisamy G, Kee Peng N, Wen Siang T, Seow HF
    Microbes Infect., 2005 Mar;7(3):494-500.
    PMID: 15792534
    Hepatitis B virus (HBV) has been classified into eight genotypes, designated A-H. These genotypes are known to have distinct geographic distributions. The clinical importance of genotype-related differences in the pathogenicity of HBV has been revealed recently. In Malaysia, the current distribution of HBV remains unclear. The aim of this study was to determine the genotypes and subtypes of HBV by using PCR, followed by DNA sequencing, as well as to analyse the mutations in the immunodominant region of preS and S proteins. The S gene sequence was determined from HBV DNA of four apparently healthy blood donors' sera and three sera from asymptomatic chronic hepatitis B carriers. Of this batch of sera, the preS gene sequence was obtained from HBV DNA from three out of the four blood donors and two out of the three chronic carriers. Due to insufficient sera, we had to resort to using sera from another blood donor to make up for the sixth DNA sequence of the preS gene. Based on the comparative analysis of the preS sequences with the reported sequences in the GenBank database, HBV DNA from two normal carriers was classified as genotype C. Genotype B was assigned to HBV from one blood donor and two hepatitis B chronic carriers, whereas HBV of one chronic carrier was of genotype D. Based on the S gene sequences, HBV from three blood donors was of genotype C, that of one blood donor and one chronic carrier was of genotype B, and the remaining, of genotype D. In the five cases where both preS and S gene sequences were determined, the genotypes assigned based on either the preS or S gene sequences were in concordance. The nature of the deduced amino acid (aa) sequences at positions 125, 127, 134, 143, 159, 161 and 168 of the S gene enabled the classification of these sequences into subtypes, namely, adrq+, adw2 and ayw2. The clustering of our DNA sequences into genotype groups corresponded to their respective subtype, that is, adw2 in genotype B, adrq in genotype C and ayw in genotype D. Analysis of the point mutations revealed that five of the sequences contained aa substitutions at immunodominant epitopes involved in B or/and T cell recognition. In conclusion, despite the low numbers of samples studied, due to budget constraints, these data are still worthwhile reporting, as it is important for the control of HBV infections. In addition, the genotype and mutational data obtained in this study may be useful for designing new treatment regimes for HBV patients.
    Matched MeSH terms: Hepatitis B virus/genetics*
  10. Chronic hepatitis B virus infection in Asian countries
    Merican I, Guan R, Amarapuka D, Alexander MJ, Chutaputti A, Chien RN, et al.
    J Gastroenterol Hepatol, 2000 Dec;15(12):1356-61.
    PMID: 11197043
    Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC.
    Matched MeSH terms: Hepatitis B virus/genetics
  11. Serum hepatitis B virus DNA: relationship with the e-antigen and anti-e status in chronic carriers
    Yap SF, Wong NW, Goh KL
    Malays J Pathol, 1994 Jun;16(1):57-62.
    PMID: 16329577
    The relationship between serum Hepatitis B virus DNA (HBV-DNA) and the Hepatitis B e-antigen/ anti-Hepatitis Be (HBeAg/anti-HBe) serological status in Malaysians was studied. 212 cases of asymptomatic HBV carriers were recruited for this study. 92 cases were positive for the HBeAg at the point of recruitment. 85 (92.4%) of these patients tested positive for HBV-DNA, of whom 55 (64.7%) had levels over 100pg/ml of serum. Three of the remaining 7 HBeAg positive cases who were negative for HBV-DNA subsequently seroconverted. The other 4 cases remained negative for HBV-DNA for periods of 6-12 months. Out of 113 cases who were anti-HBe positive, 12 (10.6%) gave a positive HBV-DNA result. 2 of these 12 patients were recent seroconverters; the remaining cases had transiently increased viral replicative activity which later subsided. 7 out of the 212 carriers were in the e-window period; all 7 tested negative for HBV-DNA. Our data confirm a high frequency of HBV-DNA in HBeAg positive carriers and a negative correlation between HBV-DNA and anti-HBe. An atypical profile of anti-HBe associated with HBV-DNA was observed in 10.6% of the carriers. An inverse relationship between serum HBV-DNA levels and age was also observed.
    Matched MeSH terms: Hepatitis B virus/genetics
  12. Display of hepatitis B virus PreS1 peptide on bacteriophage T7 and its potential in gene delivery into HepG2 cells
    Tang KH, Yusoff K, Tan WS
    J Virol Methods, 2009 Aug;159(2):194-9.
    PMID: 19490973 DOI: 10.1016/j.jviromet.2009.03.015
    Hepatitis B is a major public health problem worldwide which may lead to chronic liver diseases, cirrhosis and hepatocellular carcinoma. An interaction between hepatitis B virus (HBV) envelope protein, particularly the PreS1 region, and a specific cell surface receptor is believed to be the initial step of HBV infection through attachment to hepatocytes. In order to develop a gene delivery system, bacteriophage T7 was modified genetically to display polypeptides of the PreS1 region. A recombinant T7 phage displaying amino acids 60-108 of the PreS1 region (PreS1(60-108)) was demonstrated to be most effective in transfecting HepG2 cells in a dose- and time-dependant manner. The phage genome was recovered from the cell lysate and confirmed by PCR whereas the infectious form of the internalized phage was measured by a plaque-forming assay. The internalized phage exhibited the appearance of green fluorescent dots when examined by immunofluorescence microscopy. Surface modification, particularly by displaying the PreS1(60-108) enhanced phage uptake, resulting in more efficient in vitro gene transfer. The ability of the recombinant phage to transfect HepG2 cells demonstrates the potential of the phage display system as a gene therapy for liver cancer.
    Matched MeSH terms: Hepatitis B virus/genetics*
  13. Recombinant hepatitis B virus core particles: association, dissociation and encapsidation of green fluorescent protein
    Lee KW, Tan WS
    J Virol Methods, 2008 Aug;151(2):172-180.
    PMID: 18584885 DOI: 10.1016/j.jviromet.2008.05.025
    The recombinant hepatitis B virus (HBV) core antigen (HBcAg) expressed in Escherichia coli self-assembles into icosahedral capsids of about 35 nm which can be exploited as gene or drug delivery vehicles. The association and dissociation properties of the C-terminally truncated HBcAg with urea and guanidine hydrochloride (GdnHCl) were studied. Transmission electron microscopy (TEM) revealed that the dissociated HBcAg was able to re-associate into particles when the applied denaturing agents were physically removed. In order to evaluate the potential of the particles in capturing molecules, purified green fluorescent protein (GFP) was applied to the dissociated HBcAg for encapsidation. The HBcAg particles harbouring the GFP molecules were purified using sucrose density gradient ultracentrifugation and analysed using native agarose gel electrophoresis and TEM. A method for the encapsidation of GFP in HBcAg particles which has the potential to capture drugs or nucleic acids was established.
    Matched MeSH terms: Hepatitis B virus/genetics*
  14. Hepatitis B: review of development from the discovery of the "Australia Antigen" to end of the twentieth Century
    Yap SF
    Malays J Pathol, 2004 Jun;26(1):1-12.
    PMID: 16190102
    "Parenteral" or "serum" hepatitis is known to have afflicted man for centuries. However, it was not until the mid-1960s that the causative agent of this infection, the hepatitis B virus, was discovered. Since then, the biology and the replication strategy of the virus, and the clinical features and the epidemiology of the hepatitis B infection have been determined. Knowledge about the virus and the infection it causes led to the development of firstly, a plasma-derived vaccine and later a recombinant vaccine for the prevention of the infection. Integration of the hepatitis B vaccine into newborn vaccination programmes on a worldwide basis represents a major step in the effort to eliminate this infectious disease and its complications. Laboratory tests are available for the diagnosis and monitoring of the disease. Therapies have been developed to halt the progress of the chronic infection in affected individuals. While these developments have resulted in a decrease of the frequency of infection in many countries, particularly those that have implemented universal immunization of newborns, the chronic infection remains a significant global problem. Worldwide, over 300 million individuals are infected and each year, an estimated 1 million persons die from chronic complications of the disease including hepatocellular carcinoma and hepatic failure. The therapies currently available result in elimination of the virus in only a relatively small proportion of subjects and carry with it serious side effects. Geopolitical, economic and other factors hinder the vision of elimination of the infection through immunization programmes. Nevertheless, work continues to clarify further the underlying pathological mechanism of the infection, the host and viral factors that promote elimination or persistence of the virus in the human host. It is hoped that such investigations will reveal viral targets for the design of newer and potentially more effective drugs to treat the infection.
    Matched MeSH terms: Hepatitis B virus/genetics
  15. Interpretation and application of virological testing including resistance in chronic hepatitis B
    Locarnini S
    Med J Malaysia, 2005 Jul;60 Suppl B:41-51.
    PMID: 16108173
    Matched MeSH terms: Hepatitis B virus/genetics
  16. 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 virus/genetics
  17. 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 virus/genetics*
  18. Nucleotide sequence of precore region of hepatitis B virus DNA in HBsAg-positive carriers in Malaysia
    Ton SH, Iskandar K, Noriah R, Thanaletchimy N
    Scand. J. Infect. Dis., 1996;28(6):543-8.
    PMID: 9060053
    As most published studies on precore mutants have been carried out on isolates from patients with liver diseases, and it is unclear whether HBsAg carriers with viraemia in the absence of HBeAg are also generally infected by such mutants, it was decided to sequence the precore region in some HBV-DNA isolated from HBsAg-positive carriers. Precore sequences of HBV-DNA from 43 HBsAg carriers in Malaysia were studied. Three HBV subtypes were identified according to the nucleotide sequence of the precore region. Most of the carriers were found to be infected by the subtype adr. Mutations were detected in the precore regions. The most common conserved mutation was a silent mutation involving conversion from T to C (CCT to CCC) at position 1858 at codon 15 (proline). It was found that 4/43 (9.3%) had a mutation at the penultimate codon where TGG was changed to TAG. All 4 isolates with the TAG mutation had nt T at position 1858. Of the 4 carriers who were infected by these mutant viruses, 2 were coinfected with the wild type, 1 was infected only by a variant with the mutation at position 1896, while another was infected by a variant with mutations at positions 1896 and 1899. Three of the 4 were anti-HBe positive while 1 was HBeAg positive. Alanine aminotransaminase activities in all 4 carriers were normal. This study therefore demonstrated that variants with stop codons at the penultimate codon could be found in asymptomatic carriers in Malaysia.
    Matched MeSH terms: Hepatitis B virus/genetics*
  19. Infectiousness of HBsAg carriers in Malaysia
    Ton SH, Yeoh KS, Lim WC, Noriah R, Cheong SK, Thanaletchimy N
    J Trop Med Hyg, 1995 Aug;98(4):277-80.
    PMID: 7636926
    HBV-DNA were analysed in 330 HBsAg-positive carriers in Malaysia by dot-blot hybridization and polymerase chain reaction. Seventy-three (22.12%) were positive for the virus. Of these, 65 (89%) were males and 8 (11%) were females. Statistically, there was no significant difference (P = 0.13). No significant decline in HBV-DNA with age in the Malay and Chinese males was observed (P = 0.2). Prevalence of HBV-DNA was higher in the Chinese carriers than in the Malay carriers for most age groups in both sexes. Sixty-one HBV-DNA-positive carriers were also positive for HBeAg. However, three individuals were positive only for anti-HBe, one was positive for both HBeAg and anti-HBe, and eight were negative for both HBeAg and anti-HBe. Fifty-seven were positive for HBeAg but negative for HBV-DNA. No relation was observed between raised alanine aminotransaminase and aspartate aminotransaminase levels and the presence of HBV-DNA (P = 0.4).
    Matched MeSH terms: Hepatitis B virus/genetics
  20. Fulltext Phage display creates innovative applications to combat hepatitis B virus
    Tan WS, Ho KL
    World J Gastroenterol, 2014 Sep 7;20(33):11650-70.
    PMID: 25206271 DOI: 10.3748/wjg.v20.i33.11650
    Hepatitis B virus (HBV) has killed countless lives in human history. The invention of HBV vaccines in the 20(th) century has reduced significantly the rate of the viral infection. However, currently there is no effective treatment for chronic HBV carriers. Newly emerging vaccine escape mutants and drug resistant strains have complicated the viral eradication program. The entire world is now facing a new threat of HBV and human immunodeficiency virus co-infection. Could phage display provide solutions to these life-threatening problems? This article reviews critically and comprehensively the innovative and potential applications of phage display in the development of vaccines, therapeutic agents, diagnostic reagents, as well as gene and drug delivery systems to combat HBV. The application of phage display in epitope mapping of HBV antigens is also discussed in detail. Although this review mainly focuses on HBV, the innovative applications of phage display could also be extended to other infectious diseases.
    Matched MeSH terms: Hepatitis B virus/genetics
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