Frequency of hepatitis B surface antigen variants (HBsAg) in hepatitis B virus genotype B and C infected East- and Southeast Asian patients: Detection by the Elecsys ® HBsAg II assay

Kim, Hyun Sook; Chen, Xinyue; Xu, Min; Yan, Cunling; Liu, Yali; Deng, Huiyan; Hoàng, Bùi Hữu; Thúy, Phạm Thị Thu; Wang, Terry; Yi, Yan; Zeng, Zhen; Gencay, Mikael; Westergaard, Gastón; Pabinger, Stephan; Kriegner, Albert; Nauck, Markus; Seffner, Anja; Gohl, Peter; Hübner, Kirsten; Kaminski, Wolfgang E.

doi:10.1016/j.jcv.2018.04.005

Cited by 9 publications

(9 citation statements)

References 27 publications

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“…Most epidemiological data of HBV surface and polymerase mutants have been based on studies performed in Asia or in Europe, in patients infected with genotypes B and C or A and D, respectively, with a paucity of information regarding infections with other genotypes. [13][14][15][16] Particularly, information about genotype F, characteristic of Native American populations of Alaska, South and Central America and likely originated in Amerindian populations, was scarcely addressed. [17][18][19] Additionally, there is no information about VEM, DFM and ARM prevalence in Argentina.…”

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confidence: 99%

Molecular epidemiology of hepatitis B virus mutants associated with vaccine escape, drug resistance and diagnosis failure

Lello

Ridruejo

Martínez

et al. 2019

Journal of Viral Hepatitis

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Summary The massive implementation of the vaccine and antiviral agents against hepatitis B virus (HBV), targeting the envelope and viral polymerase genes, induces a selection pressure that might lead to the emergence of variants that impair the effectiveness of the vaccine, diagnostic methods and antiviral therapy. The aim of this study was to evaluate the prevalence of HBV vaccine escape mutants (VEMs), diagnostic failure mutants (DFMs) and treatment resistance mutants (ARMs) among individuals from Buenos Aires, Argentina. HBV surface antigen and polymerase sequences obtained from serum samples of 530 HBV‐infected individuals were analysed. Samples belonged to genotypes A (28.1%), D (13.6%) and F (58.3%). VEMs, DMFs and ARMs were present in 40 (7.5%), 57 (10.7%) and 27 (5.1%) samples within the studied population. Additionally, eight nonpreviously reported VEMs and nine DFMs were identified. VEMs and DFMs were biased by genotype, being higher in genotype D (33.3% and 33.3%) compared to genotype A (6% and 17.4%) and genotype F (2.3% and 2.3%) (P > 0.001). On the contrary, there was no association between the presence of ARMs and HBV genotype (P = 0.324). VEMs, DFMs and ARMs create public health concerns. The current study provided valuable information about mutants in surface antigen and polymerase in HBV‐infected patients from Argentina where HBV‐F is the most prevalent genotype. Consequently, it constitutes an important reference for Latin American clinicians in order to optimize the management of HBV‐infected patients.

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confidence: 99%

Molecular epidemiology of hepatitis B virus mutants associated with vaccine escape, drug resistance and diagnosis failure

Lello

Ridruejo

Martínez

et al. 2019

Journal of Viral Hepatitis

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“…Second, samples harboring HBsAg mutants were all detected by the LICA. Most of these mutations are commonly found in Asia and other areas around the world (39,40). Third, the LICA gave quantitative results comparable to those of the Architect assay.…”

Section: Discussionmentioning

confidence: 67%

A hook-effect-free homogeneous light-initiated chemiluminescence assay: is it reliable for screening and the quantification of the hepatitis B surface antigen?

et al. 2020

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Background: Hepatitis B virus (HBV) infection remains a threat to global public health. As a hallmark of HBV infection, hepatitis B surface antigen (HBsAg) has been used to screen for HBV infection for decades, and quantitative assays are also being clinically rejuvenated to predict the disease outcome and monitor the antiviral response. Herein, we developed and evaluated a hook-effect-free homogeneous quantitative HBsAg assay based on the light-initiated chemiluminescence immunoassay (LICA).Methods: A hook-effect-free LICA algorithm was established by measuring the relative light units (RLUs) of two time points during the immunoreaction. The precision was assessed using low-and high-level controls. Consecutive clinical serum samples were tested using the LICA and Abbott Architect assay; samples producing inconsistent results were retested using supplementary assays including the HBsAg neutralization, HBV DNA, and Roche Elecsys HBsAg assays for further confirmation. The consistency, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. For the quantitative results, the correlation was analyzed. The coverage of different genotypes and mutations by the LICA was evaluated. Moreover, serial on-treatment and follow-up samples from chronic hepatitis B patients were also measured using the two assays.Results: The LICA had better within-run and within-laboratory precisions than the Architect assay. In total, 5,176 clinical samples were tested. The two assays showed a consistency of 99.63%. The LICA showed greater specificity (99.95% vs. 99.77%) and PPV (99.75% vs. 98.77%) than the Architect assay, whereas the Architect assay showed greater sensitivity (100.00% vs. 99.01%) and NPV (100.00% vs. 99.82%). The two assays displayed an excellent correlation independent of genotypes and mutations. The LICA hookfree algorithm recognized 100% of the underestimated results. Furthermore, similar HBsAg dynamics were demonstrated using the LICA and Architect HBsAg assay. Conclusions:The hook-free LICA provides a reliable tool for screening for HBV infection and quantifying HBsAg.

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“…(2015) [ 30 ], Kim et al . (2018) [ 20 ], Hazawa et al . (2018) [ 31 ], but amino acid change which had been described at amino acid 125 had not been detected in our study.…”

Section: Discussionmentioning

confidence: 99%

“…In a multicenter study on 660 patients from China, Korea and Vietnam, Kim et al . (2018) [ 20 ] had reported 237 amino acid mutations in the MHR on the S region. There was not any report on mutations and their association with HCC on the PreS/S gene in Vietnamese patients.…”

Section: Introductionmentioning

confidence: 99%

Mutations in the HBV PreS/S gene related to hepatocellular carcinoma in Vietnamese chronic HBV-infected patients

et al. 2022

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Background Chronic hepatitis B virus (CHB) infection is a major health problem and leading cause of hepatocellular carcinoma (HCC) worldwide. Several point and deletion mutations on the PreS/S gene have been intensively considered associated with HCC. This study aimed to describe the characteristics of HBV PreS/S mutations in Vietnamese CHB-infected patients and their association with HCC. Methods This cross-sectional study was conducted from 02/2020 to 03/2021, recruited Vietnamese CHB-infected patients with HBV-DNA >3 log10-copies/mL and successful PreS/S gene sequencing. Mutations were detected by direct Sanger sequencing. Results 247 CHB-infected patients were recruited, characterized by 68.8% males, 54.7% HBV genotype B, 57.5% HBeAg positive, 23.1% fibrosis score ≥F3 and 19.8% HCC. 61.8% amino acid replacements were detected throughout the PreS1/PreS2/S genes. The most common point-mutations included N/H51Y/T/S/Q/P (30.4%), V68T/S/I (44.9%), T/N87S/T/P (46.2%) on PreS1 gene; T125S/N/P (30.8%), I150T (42.5%) on PreS2 gene; S53L (37.7%), A184V/G (39.3%), S210K/N/R/S (39.3%) on S gene. The rates of case(s) with any point-mutation on the Major Hydrophylic Region (MHR) and the "a" determinant region were 63.6% and 39.7%, respectively. Most of S point-mutations were presented with low rates such as T47A/E/V/K (9.3%), P120S/T (8.5%), G145R (2%). On multivariable analysis, males (OR = 4.51, 95%CI 1.78–11.4, p = 0.001), age≥40 (OR = 5.5, 95%CI 2.06–14.68, p = 0.001), W4P/R/Y on PreS1 (OR = 11.56, 95%CI 1.99–67.05, p = 0.006) and 4 S point-mutations as: T47A/E/V/K (OR = 3.67, 95%CI 1.19–11.29, p = 0.023), P120S/T (OR = 3.38, 95%CI 1.09–10.49, p = 0.035), S174N (OR = 29.73, 95%CI 2.12–417.07, p = 0.012), P203R (OR = 8.45, 95%CI 1.43–50.06, p = 0.019) were associated with HCC. Conclusions We detected 61% amino acid changes on PreS/S regions in Vietnamese CHB patients. One point-mutation at amino acid 4 on PreS1 gene and 4 point-mutations at amino acids 47, 120, 174, and 203 on S gene were associated with HCC. Further investigations are recommended to further clarify the relationship and interaction between mutations in HBV genome and HCC progression.

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Frequency of hepatitis B surface antigen variants (HBsAg) in hepatitis B virus genotype B and C infected East- and Southeast Asian patients: Detection by the Elecsys ® HBsAg II assay

Cited by 9 publications

References 27 publications

Molecular epidemiology of hepatitis B virus mutants associated with vaccine escape, drug resistance and diagnosis failure

Molecular epidemiology of hepatitis B virus mutants associated with vaccine escape, drug resistance and diagnosis failure

A hook-effect-free homogeneous light-initiated chemiluminescence assay: is it reliable for screening and the quantification of the hepatitis B surface antigen?

Mutations in the HBV PreS/S gene related to hepatocellular carcinoma in Vietnamese chronic HBV-infected patients

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