J Clin Virol. 2014 Aug;60(4):341-6. doi: 10.1016/j.jcv.2014.05.013.

Quantification of hepatitis B surface antigen with the novel DiaSorin LIAISON XL Murex HBsAg Quant: correlation with the ARCHITECT quantitative assays

Burdino E1, Ruggiero T1, Proietti A1, Milia MG1, Olivero A2, Caviglia GP2, Marietti M2, Rizzetto M2, Smedile A2, Ghisetti V3.
  • 1Laboratory of Microbiology and Virology, Amedeo di Savoia Hospital, Torino, Italy.
  • 2Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Torino, Torino, Italy.
  • 3Laboratory of Microbiology and Virology, Amedeo di Savoia Hospital, Torino, Italy. Electronic address: valeria.ghisetti@gmail.com.

 

ABSTRACT:

BACKGROUND: Recent technologic innovations allow for quantitative assessment of hepatitis B surface antigen (HBsAg) levels in serum; this has been used to monitor the course of chronic HBV hepatitis (CHB) and predict treatment response. LIAISON-XL Murex HBsAg Quant assay (DiaSorin, Saluggia, I) is the newest immunoassay CE approved to quantify HBsAg.

STUDY DESIGN: Sequential serum samples (n=152) from 14 HBe-negative patients with CHB, the majority of them infected by HBV genotype D undergoing antiviral treatment, were retrospectively tested with  LIAISON-XL and ARCHITECT-QT HBsAg as reference test (Abbott Diagnostics, IL, US). The 2nd WHO Standard 00/588 for HBsAg was used for evaluating assay performance.

RESULTS: LIAISON-XL and ARCHITECT-QT correlated by r=0.95, p<0.0001; by Bland-Altman analysis agreement of mean difference was 0.21 ± 0.15 log 10 IU/mL, 95% CI: -0.07 to 0.5). Performance of LIAISON-XL against the 2nd WHO Standard was r=0.998, p<0.0001 (95% CI: 0.993-0.999) with results nearer to the expected WHO values compared to ARCHITECT-QT. Median baseline HBsAg level was similar with the two methods before antiviral treatment, throughout fluctuations of HBsAg level in treatment non-responders and during the decrease of HBsAg titer in treatment responders. Correlation between HBsAg levels and HBV DNA was statistically significant for both the two immunoassays (LIAISON-XL: r=0.4988, 95% CI: 0.3452-0.6264, p<0.0001; ARCHITECT-QT: r=0.480, 95% CI: 0.3233-0.6111, p<0.0001).

CONCLUSIONS: Correlation between HBsAg measurement with LIAISON-XL and ARCHITECT-QT was high. LIAISON-XL accurately quantified HBsAg in clinical samples at baseline or during antiviral therapy; it can be applied for HBsAg quantification in clinical practice and decision making in CHB.  Copyright © 2014 Elsevier B.V.

KEYWORDS: ARCHITECT-QT; HBsAg quantitative; LIAISON-XL

PMID: 24930708

 

SUPPLEMENT:

There is renewed interest in measuring serum levels of HBsAg as a surrogate marker to monitor the natural history of chronic HBV infection and predict the efficacy of antiviral therapy (1,2). Therefore, the quantitative measurement of HBsAg is becoming an important tool in the clinical assessment and management of CHB. The clinical relevance of HBsAg level stems from the apparent correlation with intrahepatic cccDNA levels and influences treatment response (3). The HBsAg decline may portend an immunological response independently from HBV-DNA suppression; monitoring HBsAg levels provides additional information over the measure of HBV-DNA alone and may be used to establish stopping rules for the antiviral treatment of CHB. In particular, in PEG-IFN treated patients, differences in HBsAg decline are now used to predict the success of therapy and stopping rules based on the level of HBsAg have been proposed to optimize patient management (4,5). A new pipeline of immunoassay for the quantification of HBsAg has been recently developed. At present, three diagnostics assays are available for HBsAg quantification: the ARCHITECT HBsAg QT (6), the Elecsys HBsAg II Quant (Roche Diagnostics, Indianapolis, IN, USA) (7) and the LIAISON-XL Murex HBsAg Quant, the latter approved for CE marketing in 2011 (8). ARCHITECT-QT has been the first assay to appear on the market for HBsAg quantification and is the most cited in published studies. Consensus studies have showed a good correlation between HBsAg measurements with ARCHITECT-QT and Elecsys. LIAISON-XL is a new fully integrated chemiluminescence immunoassay for the detection of HBsAg in the setting of blood transfusion; it is also useful to quantify HBsAg level for clinical purposes using onboard dilution. The assay is standardized against the 2nd World Health Organization (WHO) International Standard (analytical sensitivity: 0.03 IU/mL, dynamic range from 0.03 to 150 IU/mL). The design of LIAISON-XL is based on a panel of 7 murine monoclonal antibodies (Mabs) capable of binding the unfolded antigen in the presence of a high concentration of detergents. These Mabs are directed towards the classical “a” loop region as well as to highly conserved domains derived from both the internal hydrophilic loop and the transmembrane regions. This new design makes LIAISON-XL highly sensitive and tolerant to HBsAg variants as recently proved (8).

The importance of this study

We show that LIAISON-XL provides comparable results to the reference ARCHITECT-QT test with a close agreement and a mean quantitation difference of 0.21 log10 IU/mL and 98% of samples within ± 0.5 log IU/mL. LIAISON-XL values were slightly lower than ARCHITECT-QT, and closer to the WHO 2nd International standard than those of ARCHITECT-QT at all the reference standard concentrations (Figure 1). In our study, the quantitation of HBsAg levels in routine clinical samples by LIASON-XL appeared overall to be accurate, with low variability and little discrepancy compared with ARCHITEC-QT. Therefore, threshold or prediction rules established for the ARCHITEC-QT platform may be transferred on the LIAISON-XL, without losing predictive accuracy. The kinetics of HBsAg with LIAISON-XL was similar to ARCHITECT-QT in patients undergoing antiviral treatment, confirming that LIAISON-XL can be used for HBsAg quantification in clinical practice for the management of patients with CHB (Figure 2 and 3). A major advantage of LIAISON-XL is its validation for HBsAg screening in the setting of blood transfusion while ARCHITECT-QT is meant only for the quantitative measurement of HBsAg level in clinical settings, due to a higher sensitivity of its qualitative HBsAg test counterpart, whose analytical sensitivity ranges from 0.017 to 0.022 IU/mL against the WHO 2nd International Standard.

In conclusion, our study shows that LIAISON-XL is a reliable test for HBsAg quantitation providing results that are standardized on the WHO 2nd International Standard. On-board dilution has the advantage of lowering labor costs, turn-around-time and laboratory errors, improving accuracy and precision. LIAISON-XL is therefore suitable for routine clinical use and can be applied for HBsAg quantification in the clinical practice and decision making for patients with chronic hepatitis B.

 

References:

1. Moucari R, Marcellin P. Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B. Liver Int 2011;31 Suppl 1:122–8.
2. Brunetto MR, Oliveri F, Colombatto P, Moriconi F, Ciccorossi P, Coco B, et al. Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. Gastroenterology 2010;139:483–90.
3. Sung JJY, Wong M-L, Bowden S, Liew C-T, Hui AY, Wong VWS, et al. Intrahepatic Hepatitis B Virus Covalently Closed Circular DNA Can Be a Predictor of Sustained Response to Therapy. Gastroenterology 2005;128:1890–7.
4. Sonneveld MJ, Rijckborst V, Boucher CAB, Hansen BE, Janssen HLA. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline. Hepatology 2010;52:1251–7.
5. Rijckborst V, Hansen BE, Ferenci P, Brunetto MR, Tabak F, Cakaloglu Y, et al. Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a. J Hepatol 2012;56:1006–11.
6. Deguchi M, Yamashita N, Kagita M, Asari S, Iwatani Y, Tsuchida T, et al. Quantitation of hepatitis B surface antigen by an automated chemiluminescent microparticle immunoassay. J Virol Methods 2004;115:217–22.
7. Wursthorn K, Jaroszewicz J, Zacher BJ, Darnedde M, Raupach R, Mederacke I, et al. Correlation between the Elecsys HBsAg II assay and the Architect assay for the quantification of hepatitis B surface antigen (HBsAg) in the serum. J Clin Virol 2011;50:292–6.
8. Krawczyk A, Hintze C, Ackermann J, Goitowski B, Trippler M, Grüner N, et al. Clinical performance of the novel DiaSorin LIAISON XL murex: HBsAg Quant, HCV-Ab, HIV-Ab/Ag assays. J Clin Virol 2014; 59:44-9.

 

Acknowledgements: Reagents for HBsAg quantitative testing with LIAISON XL and ARCHITECT-QT were kindly provided by DiaSorin (Saluggia, I).

Contact:

Valeria Ghisetti, MD
Laboratory of Microbiology and Virology
Amedeo di Savoia Hospital
Department of Infectious Diseases
Corso Svizzera 164
10149 Torino
Italy
Email: valeria.ghisetti@gmail.com

Ghisetti-world-biomedical-frontiers_FIG1Fig 1. Performance of the LIAISON-XL and the ARCHITECT-QT assays against the 2nd WHO standard. Values for LIAISON-XL: r=0.998, p
Ghisetti-world-biomedical-frontiers_FIG2Fig 2. HBsAg kinetics with the two immunoassays LIAISON-XL and ARCHITECT-QT in a HBe-negative patient with CHB due to HBV genotype D, who underwent antiviral therapy with Lamivudine from August, 2001 to October, 2004, then followed by Adefovir add-on. After more than 12 years of antiviral therapy, in September, 2013 HBsAg levels tested 230 and 523 IU/mL with LIAISON-XL and the ARCHITECT-QT, respectively.
Ghisetti-world-biomedical-frontiers_FIG3
Fig 3. HBsAg kinetics with the two immunoassays LIAISON-XL and ARCHITECT-QT in a HBe-negative patient with CHB due to HBV genotype A, who underwent antiviral therapy with Pegylated-Interferon from November, 2011. After one year of antiviral therapy, in December, 2012 HBsAg levels tested 84 and 503 IU/mL with LIAISON-XL and the ARCHITECT-QT, respectively.

 

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