Detection of in vivo hepatitis B virus surface antigen mutations—A comparison of four routine screening assays

Abstract

An important requirement for a state-of-the-art hepatitis B surface antigen (HBsAg) screening assay is reliable detection of mutated HBsAg. Currently, there is a striking shortage of data regarding the detection rates of in vivo HBsAg mutations for these clinically important assays. Therefore, we compared the detection rates of four commercial HBsAg screening assays using a global cohort of 1553 patients from four continents with known HBV genotypes. These samples, which represent the broadest spectrum of known and novel HBsAg major hydrophilic region (MHR) mutations to date, were analyzed for the presence of HBsAg using the Roche Elecsys HBsAg II Qualitative, Siemens ADVIA Centaur XP HBsAg II, Abbott Architect HBsAg Qualitative II and DiaSorin Liaison HBsAg Qualitative assays, respectively. Of the 1553 samples, 1391 samples could be sequenced; of these, 1013 (72.8%) carried at least one of the 345 currently known amino acid substitutions (distinct HBsAg mutation) in the HBsAg MHR. All 1553 patient samples were positive for HBsAg using the Elecsys HBsAg II Qual assay, with a sensitivity (95% confidence interval) of 99.94% (99.64%-100%), followed by the Abbott Architect 99.81% (99.44%-99.96%), Siemens ADVIA 99.81% (99.44%-99.96%) and DiaSorin Liaison 99.36% (98.82%-99.69%) assays, respectively. Our results indicate that the Elecsys HBsAg II Qual assay exhibits the highest sensitivity among the commercial HBsAg screening assays, and demonstrate that its capacity to detect HBV infection is not compromised by HBsAg MHR mutants.

Serological and Molecular Detection of Hepatitis B virus among patients referred to Kurdistan Center for Hepatology and Gastroenterology in Sulaimani City/Kurdistan Region of Iraq

“…The current study showed that not all HBsAg seropositive patients were positive for HBV DNA detection by RT-PCR, which was agreed with observations reported by a study done in Nairobi (Kenya) in 2017 by Mathai et al [27]. They reported that the seropositive results of HBsAg and HBV DNA detection are totally different, and none of ELISA and RT-PCR cannot be alternative for each other [28]. Unlike conclusions of the current study, other researchers found that HBsAg detection and quantification by ELISA is more sensitive and gives more accurate results in detection of HBV infection, and they found that ELISA can be considered as an acceptable or adequate method in the diagnosis of HBV infection and HBsAg detection [29].…”

Detection of hepatitis B virus infection in German blood donors 2008–2015

“…One HBsAg‐negative donation at a viral load of 9200 IU/ml that was expected to be HBsAg positive was due to HBsAg mutations that inhibited HBsAg detection and/or secretion. Interestingly, the identified HBsAg escape double mutation (Q129R and F134L) which has not been reported previously should be detectable as single mutations in the HBsAg tests used . HBsAg negatives due to HBsAg mutations can still occur at higher viral loads (>10 3 ‐10 4 IU/ml), as already reported .…”

“…Despite the relatively large MP size of mostly 96, the effective LoD per ID was 208 IU/ml in 2008–2009, and 89 IU/ml as of 2010. The three HBsAg tests used since 2011 are comparably sensitive and are considered robust against the HBV genotypes as well as HBsAg mutants and do reflect the current status. Less sensitive HBsAg test versions were replaced in 2009 and 2011.…”

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

“…The performance of the LICA for measuring various genotypes and HBsAg mutations was also assessed. The sensitivity of many commercial assays might be subject to HBsAg mutations (36)(37)(38). However, our results showed that the LICA was resistant to these mutations.…”