Architect Hepatitis B Surface Antigen Research Articles

Comparison of architect assay and elecsys HBs Ag II assay in the quantification of hepatitis B surface antigen in chronic HBV patients

Background. Hepatitis B virus (HBV) infection is a global health concern, with an estimated 296 million chronic carriers worldwide. Quantification of hepatitis B surface antigen (HBsAg) is a crucial tool in HBV disease management, providing valuable insights into disease progression and treatment efficacy. Objective. To evaluate the comparative performance of the Abbott Architect HBsAg QT and Roche Elecsys HBsAg II assays in quantifying hepatitis B surface antigen (HBsAg) levels in patients with chronic hepatitis B (CHB). Methods. This prospective study enrolled 60 confirmed CHB patients between February 2021 and November 2021. HBsAg levels were measured using both assays and subsequently log-transformed (log10 IU/mL) for statistical analysis. Interclass correlation coefficient (ICC), Pearson correlation coefficient, and Bland-Altman analyses were employed to assess assay concordance and systematic bias. Results. A statistically significant positive correlation was observed between the Elecsys HBsAg II and Architect HBsAg QT assays for both untreated and treatment-receiving CHB patients (ICC values not specified, p <0.001). Notably, Architect consistently yielded higher HBsAg measurements compared to Elecsys. Conclusion. Both the Elecsys HBsAg II and Architect HBsAg QT assays demonstrate robust correlation in quantifying HBsAg levels in CHB patients. However, the Architect assay exhibits a systematic positive bias relative to Elecsys, which should be considered when interpreting results and making clinical decisions. Both tools provide reliable assessments for HBsAg quantification within CHB management strategies, but it is essential to be aware of potential assay-specific differences.

Detection of the Hepatitis B Surface Antigen in Patients with Occult Hepatitis B by Use of an Assay with Enhanced Sensitivity

Patients with occult hepatitis B infection (OBI) have undetectable hepatitis B surface antigen (HBsAg) by conventional assays but detectable hepatitis B virus (HBV) DNA in blood/liver. We evaluated the key performance characteristics of a sensitive HBsAg assay (Architect HBsAg Next qualitative assay, referred to as NEXT) with respect to HBsAg detection. Assay precision, sample carryover, and seroconversion sensitivity of NEXT were evaluated. HBsAg was measured by NEXT in 1,138 individuals, including 1,038 patients who attended liver clinics in a tertiary hospital (200 HBV DNA-positive blood donors whose HBsAg was undetectable by conventional assays, 38 patients receiving immunosuppressive therapy, and 800 chronic hepatitis B patients with HBsAg seroclearance) and 100 HBsAg-negative subjects recruited from a community project. The within-run and within-laboratory coefficients of variation were <6% for the positive sample pools. In 9 seroconversion panels tested, NEXT allowed an earlier HBsAg detection than conventional assays. NEXT detected HBsAg in 10/200 (5%) HBsAg-negative blood donors, 1/20 (5%) and 0/18 HBsAg-negative patients with and without HBV reactivation, respectively, and 59/800 (7.3%) patients with HBsAg seroclearance. HBsAg was detectable by NEXT in 27.8%, 8.2%, 6.9%, 3.8%, and 1.9% samples at <3, 3 to 5, >5 to 8, >8 to 11, and >11 years after HBsAg seroclearance, respectively. Seven out of 100 HBsAg-negative community-identified subjects were tested positive by NEXT. Compared with conventional HBsAg assays, NEXT demonstrated a higher sensitivity and conferred an increment of 5 to 7% detection rate in patients with OBI, thereby helping in identifying HBV carriers and prevention of OBI-associated HBV transmission and reactivation.

Hepatitis B seroconversion revisited: new insights into the natural history of acute hepatitis B virus (HBV) infection from quantitative and highly sensitive assays and novel biomarkers

BackgroundHepatitis B virus (HBV) serum markers during typical acute self-limited infection are usually depicted as a composite of traditional HBV markers. The current study updates and expands our knowledge of acute hepatitis B with quantitative molecular and serological data on longitudinal samples from five plasmapheresis donors with acute HBV.Methods137 longitudinal samples from five plasmapheresis donors with acute HBV were tested, four with self-limited infection and one who developed persistent infection. Testing included quantitative hepatitis B surface antigen (HBsAg), antibodies to HBV antigens, quantitative HBV e antigen (HBeAg), HBV DNA, quantitative HBV core-related antigen (HBcrAg), the highly sensitive ARCHITECT HBsAg NEXT (HBsAgNx) assay, and a quantitative research assay for HBV pregenomic RNA (pg RNA).ResultsPeak levels of HBV DNA and HBsAg differed by several orders of magnitude among the panels (2.2 × 105–2.7 × 109 IU/ml for HBV DNA and 7.9–1.1 × 105 IU/ml for HBsAg). HBsAg levels peaked an average of 2.8 days after the HBV DNA peak. The overall duration of observed HBsAg positivity was increased by the more sensitive HBsAgNx assay compared to the quantitative assay in four panels. Intermittently detectable low-level HBV DNA was observed after HBsAg loss in three panels. Peak HBeAg levels occurred 2–20 days after the DNA peak and ranged from 1.1 to 4.5 × 103 IU/ml. In four panels with resolution of infection, anti-HBs levels indicating immunity (≥ 10 mIU/ml) were detected 19–317 days after the HBV DNA peak. Maximum HBcrAg concentrations ranged from 1 × 105 to > 6.4 × 106 U/ml and correlated with HBeAg values (R2 = 0.9495) and with HBV DNA values (R2 = 0.8828). Peak pgRNA values ranged from 1.6 × 103 to 1.4 × 108 U/ml and correlated with HBV DNA (R2 = 0.9013).ConclusionTraditional and new/novel HBV biomarkers were used to generate molecular and serological profiles for seroconversion panels spanning the early to late phases of acute HBV. Seroconversion profiles were heterogeneous and may be instructive in appreciating the spectrum of acute profiles relative to the typical composite representation.

Potential of ultra-highly sensitive immunoassays for hepatitis B surface and core-related antigens in patients with or without development of hepatocellular carcinoma after hepatitis B surface antigen seroclearance.

Hepatitis B surface antigen (HBsAg) seroclearance indicates a "functional cure" in chronic hepatitis B (CHB) virus infection. However, several cases of hepatocellular carcinoma (HCC) development have been reported after HBsAg seroclearance. We evaluated the potential of HBsAg and hepatitis B core-related antigen (HBcrAg), measured by the ultra-highly sensitive assays, in cases with HCC development after HBsAg seroclearance. We enrolled 17 patients with CHB who achieved HBsAg seroclearance, defined by the conventional assay using Architect HBsAg QT kit (five HCC patients and 12 non-HCC patients). HBsAg and HBcrAg were measured in their stored serum samples using ultra-highly sensitive assays featuring "immunoassay for total antigen including complex via pretreatment (iTACT)" technology. All five patients who developed HCC were positive for HBsAg or HBcrAg by iTACT-HBsAg or iTACT-HBcrAg at all follow-up points. HBcrAg levels in the HCC group, using iTACT-HBcrAg, were significantly higher than those in the non-HCC group at HBsAg seroclearance (3.6 LogU/ml (2.8-4.2) versus 2.6 (<2.1-3.8), p=0.020). The best cutoff value of iTACT-HBcrAg for predicting HCC development was 2.7 LogU/ml by receiver operating characteristic curve analysis. The prevalence of HBcrAg ≥2.7 in the HCC group was significantly higher than that in non-HCC group (100% [5/5] versus 33% [4/12], p=0.029). Residual low viral antigen might predict HCC development even if HBsAg seroclearance was achieved according to a conventional assay. The results suggest that iTACT assays of HBsAg and HBcrAg would be useful for monitoring CHB patients.

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

BackgroundHepatitis 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).MethodsA 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.ResultsThe 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 hook-free algorithm recognized 100% of the underestimated results. Furthermore, similar HBsAg dynamics were demonstrated using the LICA and Architect HBsAg assay.ConclusionsThe hook-free LICA provides a reliable tool for screening for HBV infection and quantifying HBsAg.

Performance of HBsAg point-of-care tests for detection of diagnostic escape-variants in clinical samples

BackgroundHepatitis B viruses (HBV) harboring mutations in the a-determinant of the Hepatitis B surface antigen (HBsAg) are associated with reduced reactivity of HBsAg assays. ObjectivesTo evaluate the sensitivity and specificity of three HBsAg point-of-care tests for the detection of HBsAg of viruses harboring HBsAg mutations. Study designA selection of 50 clinical plasma samples containing HBV with HBsAg mutations was used to evaluate the performance of three HBsAg point-of-care tests (Vikia®, bioMérieux, Marcy-L’Étoile, France. Alere Determine HBsAg™, Iverness Biomedical Innovations, Köln, Germany. Quick Profile™, LumiQuick Diagnostics, California, USA) and compared to the ARCHITECT HBsAg Qualitative® assay (Abbott Laboratories, Sligo, Ireland). ResultsThe sensitivity of the point-of-care tests ranged from 98% to 100%. The only false-negative result occurred using the Quick Profile™ assay with a virus harboring a D144A mutation. ConclusionsThe evaluated point-of-care tests revealed an excellent sensitivity in detecting HBV samples harboring HBsAg mutations.

Clinical significance of serum HBsAg levels, HBsAg/HBV DNA ratio, and association with liver inflammation activity in HBeAg-positive chronic hepatitis B

To study the clinical significance of hepatitis B surface antigen (HBsAg) levels and HBsAg/hepatitis B virus (HBV) DNA ratio in relation to liver inflammation in HBeAg-positive chronic hepatitis B (CHB). One hundred and fifty-three Chinese patients with chronic HBV infection with HBeAg-positive status were enrolled in the study.Quantitative measurements were made for HBsAg levels by immunoassay (Architect HBsAg QT by Abbott Diagnostic) and HBV DNA by real-time fluorescence quantitative PCR.Levels of liver function markers were measured by standard methods.Liver biopsy specimens were obtained from all patients and used to score the histology (liver inflammation) activity index (HAI) and grade (G) the extent of necroinflammation.Statistical correlation analysis was performed to determine the association of HBsAg titre or HBsAg/HBV DNA ratio with the various parameters of liver injury. HBsAg titre and HBsAg/HBV DNA ratio were significantly correlated (r =0.578, P less than 0.0001).A significant positive correlation (r =0.642, P less than 0.0001) was found between HBsAg titre and HBV DNA load, and a significant negative correlation was found between the HAI and HBsAg (r =-0.389, P less than 0.0001) and HBsAg/HBV DNA ratio (r =-0.307, P=0.000l).A significant positive correlation was found between alanine aminotransferase (ALT) level and the HAI (r =0.480, P less than 0.0001).Patients with G less than 2 necroinflammation had significantly higher HBsAg titre and HBsAg/HBV DNA ratio than patients with G more than or equal to 2 necroinflammation (both P less than 0.01) but similar levels ofHBV DNA.Generation of a receiver operating characteristic curve using G more than or equal to 2 as the positive index provided the following area under the curve (AUC) values:HBsAg titre, 0.700; HBsAg/HBV DNA ratio, 0.672; ALT level, 0.713.When the random chance AUC was 0.5, all levels of AUC were statistically significant (Pless than 0.001).HBsAg titre (sensitivity =76.92%) was more sensitive than ALT level (sensitivity =76.92%), and HBsAg/HBV DNA ratio (specificity =81.33%) was more specific than ALT level (specificity =81.33%).Youden's index for comprehensive evaluation using ALT was higher than those for HBsAg titre or HBsAg/HBV DNA ratio.When HBsAg and ALT were considered in parallel, the sensitivity increased to 94.08% and specificity rose to 85.60%. HBsAg titre, HBsAg/HBV DNA ratio and ALT levels can be used as the index for judging the degree of liver inflammation in HBeAg-positive CHB patients.Higher sensitivity and specificity are attained when HBsAg and ALT are used in series or parallel.

Highly Sensitive Detection of Hepatitis B Virus Surface Antigen by Use of a Semiautomated Immune Complex Transfer Chemiluminescence Enzyme Immunoassay

The performance of hepatitis B surface antigen (HBsAg) screening assays is continuously improved to reduce the risk of transfusion-associated hepatitis B. In this study, a semiautomated immune complex transfer chemiluminescence enzyme immunoassay (ICT-CLEIA) for the detection of HBsAg, which is as sensitive as hepatitis B virus (HBV) DNA PCR, was developed; the ICT-CLEIA assay performance was compared with the performance of the Architect HBsAg QT assay and HBV DNA PCR. The specificities in the initial assay and after retesting were 99.50% (1,988/1,998 samples) and 99.95% (1,997/1,998 samples), respectively. The analytical detection limit was determined to be 0.2 mIU/ml using the 2nd International WHO HBsAg standard, and the cutoff value (0.5 mIU/ml) of the ICT-CLEIA assay was 8.0 standard deviations (SD) above the mean of the HBsAg-negative specimens. The ICT-CLEIA assay could detect HBsAg even in the presence of anti-HBs antibodies and demonstrated a 23.6-day-shorter window period using commercially available HBsAg seroconversion panels than the Architect HBsAg QT assay. Furthermore, the monitoring of the viral kinetics by the ICT-CLEIA assay and the HBV DNA PCR produced very similarly shaped curves during both the HBsAg seroconversion and reverse seroconversion periods. Therefore, the ICT-CLEIA assay may be useful not only for an earlier detection of HBV reactivation but also for the monitoring of hepatitis B patients.

Serum hepatitis B surface antigen levels correlate with high serum HBV DNA levels in patients with chronic hepatitis B: A cross-sectional study

Purpose: The hallmark of chronic hepatitis B (CHB) infection is the presence of hepatitis B surface antigen (HBsAg) positivity for at least 6 months. Recently, serum levels of HBsAg have been compared with serum HBV DNA as a surrogate marker to monitor CHB patients. However, data correlating these two markers are scarce. Hence, the present study was done to correlate HBV DNA with HBsAg in CHB patients. Materials and Methods: Consecutive patients of CHB were included. HBV DNA was measured by real-time polymerase chain reaction (PCR). Serum HBsAg was measured by Architect HBsAg. Results: Of the 198 patients enrolled, 166 fulfilled the inclusion criteria (mean age 43 ± 14 years, 87% males) and the median HBV DNA was 1.7 × 103 (range 6.0–1.1 × 108) IU/ml. Median HBsAg was 8.7 × 103 (range 5.0–3.2 × 105) IU/ml. Overall correlation between HBV DNA and HBsAg was weak but significant (Spearman ρ = 0.443, P < 0.01). Correlation in HBe antigen-positive group was better (ρ = 0.402, P < 0.01) in comparison to HBe antigen-negative group (ρ = 0.193 P = 0.05). Good correlation existed in treatment-naïve group (ρ = 0.538, P < 0.01). Correlation was regardless of normal or raised alanine transaminase (ALT). Eighty (48%) patients had high HBV DNA (≥2000 IU/ml). Correlation in high DNA group was significant (P < 0.01). The best cut-off of HBsAg for diagnosing high DNA is 3.36 ×103 IU/ml. Conclusions: Serum HBsAg correlates with HBV DNA in CHB patients, especially in high serum HBV DNA, HBe antigen-positive and treatment-naïve group. HBsAg levels can be used for predicting high serum HBV DNA levels.

Quantitation of HBsAg predicts response to entecavir therapy in HBV genotype C patients

To analysis the factors that predict the response to entecavir therapy in chronic hepatitis patients with hepatitis B virus (HBV) genotype C. Fifty patients [hepatitis B e antigen (HBeAg)-negative:HBeAg-positive = 26:24] with HBV genotype C, who received naïve entecavir therapy for > 2 years, were analyzed. Patients who showed HBV DNA levels ≥ 3.0 log viral copies/mL after 2 years of entecavir therapy were designated as slow-responders, while those that showed < 3.0 log copies/mL were termed rapid-responders. Quantitative hepatitis B surface antigen (HBsAg) levels (qHBsAg) were determined by the Architect HBsAg QT immunoassay. Hepatitis B core-related antigen was detected by enzyme immunoassay. Pre-C and Core promoter mutations were determined using by polymerase chain reaction (PCR). Drug-resistance mutations were detected by the PCR-Invader method. At year 2, HBV DNA levels in all patients in the HBeAg-negative group were < 3.0 log copies/mL. In contrast, in the HBeAg-positive group, 41.7% were slow-responders, while 58.3% were rapid-responders. No entecavir-resistant mutants were detected in the slow-responders. When the pretreatment factors were compared between the slow- and rapid-responders; the median qHBsAg in the slow-responders was 4.57 log IU/mL, compared with 3.63 log IU/mL in the rapid-responders (P < 0.01). When the pretreatment factors predictive of HBV DNA-negative status at year 2 in all 50 patients were analyzed, HBeAg-negative status, low HBV DNA levels, and low qHBsAg levels were significant (P < 0.01). Multivariate analysis revealed that the low qHBsAg level was the most significant predictive factor (P = 0.03). Quantitation of HBsAg could be a useful indicator to predict response to entecavir therapy.

Factors Associated with Serum Hepatitis B Surface Antigen Levels and Its On-Treatment Changes in Patients under Lamivudine Therapy

We aimed to investigate factors associated with serum hepatitis B surface antigen (HBsAg) levels and its kinetics under lamivudine treatment in chronic hepatitis B patients. HBsAg levels were measured with the Architect HBsAg assay (Abbott laboratories, Abbott Park, IL, USA) in genotype B (HBV/B) or C (HBV/C) patients (n=218). Early HBsAg kinetics in 86 hepatitis B e antigen (HBeAg)-positive patients and long-term HBsAg changes in 45 patients with rapid and sustained viral suppression were further analysed. Mean HBsAg levels were higher in male (n=181) than in female (n=37) patients (3.59 versus 3.23 log(10) IU/ml; P=0.036), and higher in 121 HBV/B than in 97 HBV/C patients (3.68 versus 3.34 log(10) IU/ml; P=0.006). In addition to HBV DNA loads (P<0.001), male gender (P=0.012) and HBV/B infection (P=0.035) were independently associated with higher HBsAg levels in antiviral-naive patients. HBsAg increases (0.00-0.87 log(10)) were found in 28/86 patients who obtained viral suppression under 12 weeks of lamivudine therapy. Higher baseline HBsAg levels (P=0.046), HBV/B infection (P=0.007) and faster HBV DNA declines (P=0.006) independently contributed to greater HBsAg decreases under 12 weeks treatment. An apparent dissociation between HBsAg and HBV DNA changes were found in 14/45 patients with rapid and sustained viral suppression, who had low baseline HBsAg levels and predominant HBV/C infection. HBV/B and male gender were associated with higher HBsAg levels in antiviral-naive patients. Higher baseline HBsAg levels and HBV/B infection contributed to greater early HBsAg declines in HBeAg-positive patients, and might correlate with discordance between HBsAg and HBeAg or HBV DNA under long-term lamivudine treatment.

HBsAg blood screening and diagnosis: performance evaluation of the ARCHITECT HBsAg qualitative and ARCHITECT HBsAg qualitative confirmatory assays

A low initial reactive rate for screening assays is important for time- and cost-effective infectious disease testing. Therefore, the new ARCHITECT HBsAg Qualitative screening assay, in conjunction with the new ARCHITECT HBsAg Qualitative Confirmatory assay, was introduced. As the role of hepatitis B surface antigen (HBsAg) as surrogate marker for HBV resolution and the monitoring of drug effectiveness are becoming increasingly important, the established ARCHITECT HBsAg Quantitative assay remains available on the market. Precision, sensitivity, and specificity of the newly developed screening assay were in the range of established HBsAg assays. Seroconversion sensitivity was slightly superior compared to other commercially available assays. An initial reactive rate of 0.2% (without HBsAg-confirmed positive samples of 0.17%) for the ARCHITECT HBsAg Qualitative assay was observed. As the new screening assay is a 1-step assay format, the “high-dose hook effect” was investigated to assess the risk of false-negative results, but even very high positive HBsAg samples obtained signals clearly above the cutoff.

A comparison of two assays for quantification of Hepatitis B surface Antigen in patients with chronic hepatitis B

Background and objectivesSerum Hepatitis B surface Antigen (HBsAg) levels correlate with hepatitis B virus intrahepatic covalently closed circular DNA and may predict response to treatment. Currently, 2 commercial platforms are available for HBsAg quantification in clinical practice, the Architect HBsAg QT and the Elecsys HBsAg. We aimed to directly compare the results of these assays. Study designHBsAg levels were measured in 1427 serum samples from HBeAg-positive chronic hepatitis B patients who participated in a randomized trial of peginterferon alfa-2b±lamivudine. Samples were extracted from our serum bank, thawed, and subsequently analysed for HBsAg levels using both assays. ResultsOf 1427 samples, 242 (17%) were taken before and 1185 during the treatment phase of the study. Distribution of HBV genotypes was 447 (31%) genotype A, 125 (9%) B, 210 (15%) C and 534 (37%) D. Correlation between Architect and Elecsys results was high (r=0.96, p<0.001). By Bland–Altman analysis, agreement between the two assays was close (mean difference between Architect and Elecsys: −0.01logIU/mL, 95% CI: −0.55–0.52logIU/mL), also when analysed separately for HBV genotypes A–D. Additionally, the performance of our recently published stopping rule for HBeAg-positive patients treated with peginterferon was comparable: the negative predictive values were 96% and 98% for Elecsys and Architect, respectively. ConclusionsThere is a high correlation and close agreement between quantitative HBsAg measurements conducted with the Architect and the Elecsys. Clinical prediction rules derived from data from one platform can be applied on the other; both can therefore be used in clinical practice.

Correlation between the Elecsys HBsAg II assay and the Architect assay for the quantification of hepatitis B surface antigen (HBsAg) in the serum

Background Hepatitis B surface antigen (HBsAg) clearance during chronic hepatitis B (CHB) infection is associated with improved long-term clinical outcome, so is considered an important therapeutic goal in CHB. Studies have shown that serum HBsAg quantification during, and at end of, treatment may predict long-term HBsAg loss. Objectives Performance comparison of the qualitative Elecsys HBsAg II assay using a quantitative research protocol and an established quantitative HBsAg assay. Study design A dilution algorithm was developed for the Elecsys HBsAg II assay to allow quantification of HBsAg levels; this was used to measure HBsAg levels in a range of samples including sera from patients infected with different HBV genotypes, HBV mutants, and longitudinal samples from patients undergoing antiviral treatment. Results were compared with those from the quantitative Architect HBsAg assay. Results There was significant overall correlation between Elecsys and Architect assays (correlation coefficient [ r] = 0.97; p < 0.001). HBsAg levels measured with both assays correlated well in all phases of infection ( r = 0.80–0.96), across all genotypes tested (HBV genotype A, r = 0.89; HBV genotype D, r = 0.97), and in samples with lamivudine-resistant mutations ( r = 0.94). Bland–Altman analysis showed only minor discordance between assays in different phases of chronic HBV-infection (3.8–5.1%). This strong correlation was also present for sera with lower HBsAg concentrations. On-treatment HBsAg levels were similar when measured with either assay. Conclusions Using a simple dilution algorithm, the quantitative Elecsys HBsAg II assay reliably determined serum HBsAg levels in a wide range of samples, and showed very high correlation with the Architect HBsAg assay.

Serum HBsAg levels during peginterferon α‐2a treatment with or without thymosin α‐1 in HBeAg‐positive chronic hepatitis B patients

The importance of serum hepatitis B surface antigen (HBsAg) level as a surrogate marker for viral load and a predictor of treatment response remains unclear. The aim of this study was to investigate whether serum HBsAg correlates with serum hepatitis B virus (HBV) DNA during peginterferon (PEG-IFN) α-2a treatment (with or without thymosin α-1) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients and whether it can predict treatment response. Sera from 37 HBeAg-positive chronic hepatitis B patients receiving 48-weeks PEG-IFN α-2a with (n = 20) or without (n = 17) an initial 12-weeks thymosin α-1 were obtained at baseline and at weeks 12, 24, 36, 48 (end of treatment), 56, 72, 84, and 96 (end of follow-up). Taqman HBV DNA tests (Roche) and Architect HBsAg QT (Abbott) were performed. There was a moderate correlation between the HBsAg and HBV DNA levels (r = 0.452, P < 0.001). Median HBsAg levels at baseline and at week 96 were 6,218 IU/ml and 4,038 IU/ml, respectively. The mean HBV DNA and alanine aminotransferase (ALT) levels were 7.48 log(10) IU/ml and 173 IU/L at baseline and 5.37 log(10) IU/ml and 102 IU/L at week 96, respectively. A decrease to <60% of baseline levels of HBsAg at week 12 was identified as an independent predictive factor for HBeAg seroconversion (OR = 45.7, P < 0.05) at week 96. Serum HBsAg levels may be helpful for predicting the response to PEG-IFN therapy in HBeAg-positive chronic hepatitis B patients.

Change in Serum Hepatitis B Surface Antigen Level and Its Clinical Significance in Treatment-naïve, Hepatitis B e Antigen-positive Patients Receiving Entecavir

We investigated changes in hepatitis B surface antigen (HBsAg) level and its correlation with clinical outcomes in treatment-naive chronic hepatitis B (CHB) patients undergoing entecavir therapy. Among 51 hepatitis B e antigen (HBeAg)-positive treatment-naive CHB patients receiving entecavir for more than 1 year, 28 were enrolled. HBsAg levels were measured at baseline, 6 months, and 12 months after treatment using the Architect HBsAg QT assay (Abbott, dynamic; range: 0.05 to 125,000 IU/mL). Serum alanine aminotransferase, HBeAg, anti-HBe, and hepatitis B virus (HBV) DNA (Cobas Taqman: low detection limit 1.84 log10 copies/mL) were measured at baseline and every 3 months. The HBsAg response was defined as an HBsAg level that decreased more than 1 log10 IU/mL from baseline level at 12 months after entecavir treatment. Twenty-eight patients were treated for a median period of 21 months (range: 18 to 24 mo). Serum HBsAg level showed a mean of 4.0, 3.7, and 3.6 log10 IU/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P<0.001). Serum HBV DNA level showed a mean of 8.1, 3.1, and 2.4 log10 copies/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P<0.001). The decline in HBsAg level was significantly correlated with that of the HBV DNA level at 12 months from baseline (γ=0.391, P=0.044). Five patients showed an HBsAg response, and cumulative incidence of HBeAg loss at 1 year after entecavir treatment was 80% versus 30% in patients with an HBsAg response and those without, respectively (P=0.034). Monitoring changes in quantitative HBsAg level could be a useful parameter for assessing the response to entecavir therapy in HBeAg-positive treatment-naive CHB patients.

Peginterferon for chronic hepatitis B: Predicting success with on‐treatment benchmarks

Peginterferon for chronic hepatitis B: Predicting success with on‐treatment benchmarks

Comparison of Nine Different Qualitative HBsAg Assay Kits

Qualitative hepatitis B surface antigen (HBsAg) assay kits are still commonly used in Korea where hepatitis B virus (HBV) infection is endemic. The accurate determination of HBsAg plays a crucial role in the diagnosis and prevention of HBV infection, especially in endemic areas. The aim of this study was to compare the detection sensitivities of 9 qualitative HBsAg assay kits. Seven pooled sera with HBsAg concentration ranging from 0.14 IU/mL to 29.96 IU/mL were prepared. The HBsAg concentration of each pooled serum was determined by a quantitative HBsAg assay, Architect HBsAg (Abbott Laboratories, Ireland). The fully automated immunoassay kits included Elecsys HBsAg (Roche Diagnostics, Germany) and Immulite 2000 HBsAg (DPC, USA) and the rapid tests included 5 immunochromatographic assay (ICA) kits and 2 reverse passive hemagglutination assay (RPHA) kits. Elecsys HBsAg (Roche Diagnostics) showed positive result in pooled serum with HBsAg concentration of 0.14 IU/mL, but Immulite 2000 HBsAg (DPC) showed negative result in the same concentration. Although ICA kits showed variable results among different assay kits, all of them showed negative results in pooled sera with HBsAg concentration of < or = 1.89 IU/mL. Two RPHA kits showed negative results in pooled sera with HBsAg concentration of < or = 7.98 IU/mL. Although ICAs were more sensitive than RPHAs, they had variable sensitivities for HBsAg and were less sensitive than the automated immunoassay kits. Therefore, ICAs and RPHAs should be used with caution in the screening tests for HBsAg and their sensitivities need to be improved.

Comparison of the technical and clinical performance of the Elecsys® HBsAg II assay with the Architect®, AxSym®, and Advia® Centaur HBsAg screening assays

South East Asia has some of the highest prevalence rates of hepatitis B virus (HBV) infection (>or=8%) in the world, and the emergence of hepatitis B surface antigen (HBsAg) mutant strains is a growing problem. Assays with the highest levels of sensitivity, including mutant detection, should be used for routine HBsAg screening. In this large multicenter study, the clinical and technical performance of the fully automated Elecsys HBsAg II assay was compared with the Architect, AxSYM, and Advia Centaur HBsAg assays for HBsAg screening. Nine laboratories (three each from Thailand, Korea, and Singapore) compared the Elecsys HBsAg II assay with their routine HBsAg screening assay against a range of stored and routine clinical samples, including recombinant mutants. The Elecsys HBsAg II assay demonstrated equivalent sensitivity and specificity to the Architect HBsAg assay. However, the Elecsys HBsAg II assay recognized a native mutant sample (L94S, L97V, L98V, T123A) that the Architect HBsAg assay failed to detect. The AxSYM and Advia Centaur HBsAg assays appeared less sensitive for the detection of early HBV infection and also failed to detect some of the recombinant mutant strains. There was almost complete agreement between the Elecsys HBsAg II assay and comparator assays with respect to routine serum samples. The results of this study demonstrate that the Elecsys HBsAg II assay is a highly sensitive and specific screening assay for HBsAg and detects reliably the most important and clinically relevant HBV mutants and genotypes. It is suitable for routine HBsAg screening in Asia.

Multicentre evaluation of the Elecsys® hepatitis B surface antigen II assay for detection of HBsAg in comparison with other commercially available assays

Screening for hepatitis B surface antigen (HBsAg) demands highly sensitive and specific immunoassays with the ability to detect clinically relevant surface gene mutants-the presence of which is an increasing concern and can compromise test results. The objective of the study was to compare the clinical and technical performance of the fully automated Elecsys HBsAg II assay with other widely used HBsAg immunoassays in China. This was a multicentre study in which eight Chinese laboratories compared the Elecsys HBsAg II assay with the Architect HBsAg assay, AxSYM HBsAg assay, or generic microtitre plate (MTP) enzyme-linked immunosorbent assays (manufactured in China) against preselected samples, including recombinant surface gene mutants, and routine clinical samples. Elecsys HBsAg II was the most sensitive assay for detecting positive results in seroconversion samples: up to 14, 11, and 22 days earlier than the Architect, AxSYM, and MTP HBsAg assays, respectively. It also detected all 211 preselected HBsAg-positive specimens and all 13 recombinant HBsAg mutants; the AxSYM and MTP HBsAg assays failed to detect 3 and 10 mutant samples, respectively. Sensitivity was 100% for Elecsys HBsAg II with routine samples, compared with 99.1, 98.9, and 95.2% for the Architect, AxSYM, and MTP HBsAg assays, respectively. In conclusion, it was demonstrated that the Elecsys HBsAg II assay is suitable for routine HBsAg screening in China.