Molecular characterization of hepatitis B virus surface antigen mutants in Singapore patients with hepatocellular carcinoma and hepatitis B virus carriers negative for HBsAg but positive for anti‐HBs and anti‐HBc

Oon, Chong Jin; Chen, Wei Ning; Goh, Kee Tai; Mesenas, Steven; Ng, Han Seong; Chiang, G. S. C.; Tan, C.H.C.; S, Koh; Teng, Siaw Wei; Toh, Ivy; Moh, Mei Chung; Goo, Kian Sim; Tan, Kaeling; Leong, Ai Lin; Tan, Gek San

doi:10.1046/j.1440-1746.17.s4.16.x

Cited by 23 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Only a few studies have addressed the questions of the rate of HBV mutations in tumor tissues (Pontisso et al, 1984;Raimondo et al, 1988;Clementi et al, 1993). However, our group and others have shown that mutations in basal core promoter, PreC/C, envelope and X sequences can be identified in HCC tissues (Minami et al, 1996;Fan et al, 2000Fan et al, , 2001Tu et al, 2001;Oon et al, 2002;Iavarone et al, 2003;Kao et al, 2003;Kuang et al, 2004). We have observed that in the Core gene, most of the non-synonymous mutations (i.e.…”

Section: The Role Of Hepatitis B Virus In Liver Cell Carcinogenesismentioning

confidence: 79%

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

et al. 2006

View full text Add to dashboard Cite

As discussed in detail in other chapters of this review, chronic hepatitis B (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other, being much higher in the southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated with the cirrhosis. This heterogeneity is probably a reflection of different environmental and genetic factors. This review will summarize the current knowledge on the mechanisms involved in HBVrelated liver carcinogenesis. It will show in particular how viruses can be viewed as tools to discover and dissect new cellular pathways involved in cancer development and emphasize the potential synergistic effects between HBV and hepatitis C virus, as well as between viral infections and other environmental factors, such as alcohol.

show abstract

Section: The Role Of Hepatitis B Virus In Liver Cell Carcinogenesismentioning

confidence: 79%

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

et al. 2006

View full text Add to dashboard Cite

show abstract

“…HBsAg escape mutations, such as G130D, T131N, M133T, and G145R, were found in patients who were positive for anti-HBs but negative for HBsAg (9,30). Oon et al (32) reported that HBV carriers, including HCC patients who were negative for HBsAg but positive for anti-HBc and anti-HBs, had the T126S, Q129D, M133L, T140I, and G145R mutations within the S region. Wu et al (31) reported that amino acid residues at positions 122 and 145 of HBsAg had a major effect on antigenicity and immunogenicity.…”

Section: Discussionmentioning

confidence: 99%

Application of a Newly Developed High-Sensitivity HBsAg Chemiluminescent Enzyme Immunoassay for Hepatitis B Patients with HBsAg Seroclearance

et al. 2013

View full text Add to dashboard Cite

We modified and automated a highly sensitive chemiluminescent enzyme immunoassay (CLEIA) for surface antigen (HBsAg) detection using a combination of monoclonal antibodies, each for a specific epitope of HBsAg, and by improving an earlier conjugation technique. Of 471 hepatitis B virus (HBV) carriers seen in our hospital between 2009 and 2012, 26 were HBsAg seronegative as determined by the Abbott Architect assay. The Lumipulse HBsAg-HQ assay was used to recheck those 26 patients who demonstrated seroclearance by the Abbott Architect assay. The performance of the Lumipulse HBsAg-HQ assay was compared with that of a quantitative HBsAg detection system (Abbott Architect) and the Roche Cobas TaqMan HBV DNA assay (CTM) (lower limit of detection, 2.1 log copies/ml) using blood serum samples from patients who were determined to be HBsAg seronegative by the Abbott Architect assay. Ten patients had spontaneous HBsAg loss. Of 8 patients treated with nucleotide analogues (NAs), two were HBsAg seronegative after stopping lamivudine therapy and 6 were HBsAg seronegative during entecavir therapy. Eight acute hepatitis B (AH) patients became HBsAg seronegative. Of the 26 patients, 16 were HBsAg positive by the Lumipulse HBsAg-HQ assay but negative by the Abbott Architect assay. The differences between the two assays in terms of detectable HBsAg persisted over the long term in the spontaneous loss group (median, 10 months), the NA-treated group (2.5 months), and the AH group (0.5 months). In 9 patients, the Lumipulse HBsAg-HQ assay detected HBsAg when HBV DNA was negative by the CTM assay. HBsAg was also detected by the Lumipulse HBsAg-HQ assay in 4 patients with an anti-HBs concentration of >10 mIU/ml, 3 of whom had no HBsAg escape mutations. The automatic, highly sensitive HBsAg CLEIA Lumipulse HBsAg-HQ is a convenient and precise assay for HBV monitoring.T oday, Ͼ400 million people worldwide are hepatitis B virus (HBV) carriers (1). We have monitored HBV markers, such as HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HB core-related antigen (HBcrAg), in chronic hepatitis B patients. The measurement of HBV DNA levels by a PCR-based method is the state-of-the-art technique for monitoring HBV replication in clinical practice (2). However, it is suboptimal for chronic hepatitis B patients who are medicated with nucleotide analogues (NAs), as those, in many cases, can decrease HBV DNA to below the limit of detection.HBsAg is a secreted envelope protein that is continuously shed into the blood as long as HBV infection persists, irrespective of viral replication. Recent advances in HBsAg quantification (qHBsAg) have opened up new perspectives in the study of HBV; qHBsAg levels are correlated with intrahepatic covalently closed circular (ccc) DNA, which is used as a template for viral transcription and maintains the chronic HBV infection state (3-5). Additionally, a correlation between qHBsAg and HBV DNA has been suggested, with the possibility of a role for qHBsAg as a surrogate marker for viral r...

show abstract

“…Such mutants have also been reported in association with escape from vaccineinduced immunity [Oon et al, 1995;Carman, 1997;Ho et al, 1998;Chong-Jin et al, 1999;He et al, 2001;Lee et al, 2001;Seddigh-Tonekaboni et al, 2001] and with failures of therapy with specific immunoglobulin in newborns from carrier women and in liver-transplant recipients [Harrison et al, 1994;Oon et al, 1996Oon et al, , 2002Brind et al, 1997;Carman, 1997;Ngui et al, 1997;Protzer-Knolle et al, 1998;Santantonio et al, 1999;Roznovsky et al, 2000;Liu et al, 2002]. The amino-acid substitution Gly145Arg has been reported most frequently [Francois et al, 2001], and is known to be stable [Zuckerman and Zuckerman, 1999].…”

Section: Introductionmentioning

confidence: 96%

“…Vaccine-induced immunity may also act as a selection factor that might lead to the emergence of particular mutants in the population. 'a' determinant mutants have been sought in selected patients Oon et al, 2002;Alhababi et al, 2003;Wagner et al, 2004], but few attempts have been made to estimate the prevalence of these mutants among unselected chronic carriers [Liu et al, 2002;Hsu et al, 2004;Song et al, 2005]. Such studies have been recommended recently [Gerlich, 2004].…”

Section: Introductionmentioning

confidence: 99%

Frequency of hepatitis B virus ‘a’ determinant variants in unselected Spanish chronic carriers

Avellón

Echevarría

2005

Journal of Medical Virology

101

125

View full text Add to dashboard Cite

The prevalence in the population of hepatitis B virus (HBV) surface antigen (HBsAg) variants that may impair diagnosis, or allow the virus to escape vaccine‐induced immunity or passive immunoglobulin therapy is unknown. A genome fragment encoding HBsAg amino acids 112–212 was amplified and sequenced from the sera of 272 unselected DNA‐positive, HBV‐chronic carriers from Spain. The genotype and the HBsAg subtype were predicted from the sequences. Analysis of amino‐acid positions 112–157 revealed single or multiple substitutions in 39% of the carriers studied. Mutations were not detected for residues 121, 135, 137, 139, 140, 141, 142, 146, 147, 148, 149, 151, 152, 153, 155, 156, and 157. Substitutions reported previously to be in association with failures of diagnostic tests or with vaccine or immunoglobulin therapy escape were found in 12.5%, 6.6%, and 9.2% of carriers, respectively. Met133Thr (2.2%); Gln129His, Met133Ile, Phe/Tyr134Asn (1.8%); Phe/Tyr134Leu, Gly145Ala (1.5%), and Pro120Thr (1.1%) were the most frequent. Other substitutions, including Gly145Arg (0.4%), were found at a frequency of less than 1%. Samples containing HBV mutants were tested with three commercial assays for HBsAg screening. Almost all the mutants reacted to the upper cut‐off values of the assays, but six samples with weak reactivity with one or more of the methods were also found. Thus, HBV mutants with a potential impact on clinical and public health issues are moderately frequent among chronic carriers from Spain, although their influence on the performance of diagnostic tests seems to be slight. J. Med. Virol. 78:24–36, 2006. © 2005 Wiley‐Liss, inc.

show abstract

Molecular characterization of hepatitis B virus surface antigen mutants in Singapore patients with hepatocellular carcinoma and hepatitis B virus carriers negative for HBsAg but positive for anti‐HBs and anti‐HBc

Cited by 23 publications

References 32 publications

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

Application of a Newly Developed High-Sensitivity HBsAg Chemiluminescent Enzyme Immunoassay for Hepatitis B Patients with HBsAg Seroclearance

Frequency of hepatitis B virus ‘a’ determinant variants in unselected Spanish chronic carriers

Contact Info

Product

Resources

About