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    • HBV VL quantitation has been shown to be affected

    2021-10-15

    HBV VL quantitation has been shown to be affected by genotype/subtype, and varying degrees of positive and negative bias has been seen in previous comparison studies when analyzing across HBV genotypes. In studies comparing RealTime and Cobas for example, negative bias of ∼0.25 log10 was seen for genotypes A and D [21], [23], while a positive bias of ∼0.3 log10 was seen for genotypes B and C [19], [20]. HBeAg status, mutations, even sample volume have also been shown to affect quantitation [22]. Unfortunately a limitation of our study is that HBV genotype/subtype and HBeAg status were not available to permit further evaluation of differences, however a recent study comparing Veris and Cobas showed median differences of between −0.16 to −0.56 logIU/mL for HBV genotypes A – G [24]. Most laboratories do not routinely type HBV patients, unless possible drug resistant mutations are suspected, as treatment is the same regardless of genotype. Further detailed studies of Veris performance are needed nevertheless to clarify bias differences by genotype. Monitoring on treatment is an important part of management of chronic HBV patients and is used to determine efficacy of treatment and occurrence of VB. VB represents possible development of antiviral resistance necessitating a change in treatment after evaluation for other possible causes, such as treatment noncompliance [1], [2]. Detecting VB as early as possible increases the likelihood of achieving and maintaining a VR. Patient monitoring plots track similarly for VLs with Veris versus Cobas, RealTime and artus. Patients 2 and 9 results of VERIS and RealTime comparison may potentially lead to differing decisions, indicating potential VB according to RealTime results. In clinical practice results would be repeated to verify them before making any treatment changes and other clinical factors and laboratory results, such as 1 78 synthesis mutation analysis, would be considered. HBV VL suppression is the only reliable measure of ongoing treatment response in most patients who do not achieve durable serological endpoints [11]. The fully automated, sample to result DxN VERIS system demonstrated comparable performance to other currently marked HBV DNA assays, with varying degrees of negative bias. The QMCD HBV Panel results illustrate the variability in quantitation that can exist between different assays. The negative bias demonstrated in our study should be taken into consideration if switching to HBV VL monitoring with Veris. It is recommended that the same assay be used to monitor patients, or a re-baselining of patients take place to account for any bias differences between assays [18], [23]. Clinicians and laboratories should be aware that HBV DNA levels are influenced by specific assay characteristics and adaptation to clinical practice, along with other clinical markers, should always be undertaken.
    Funding This study was supported and funded by Beckman Coulter, Inc.
    Competing interests
    Ethical approval
    Author contributions
    Acknowledgements
    Introduction Chronic Hepatitis B virus (HBV) infection remains a serious public health problem worldwide, which will lead to the hepatocellular carcinoma (HCC) or decompensated cirrhosis [1,2]. HBV is a small and enveloped DNA virus with an icosahedral core that replicates via reverse transcription [3,4]. To date, three kinds of anti-HBV drugs have been approved for treating chronic HBV: interferons (IFN-α) [3], nucleos(t)ide analogues (such as lamivudine, telbivudine, entecavir, adefovir, and tenofovir disoproxil fumarate) [5] and non-nucleoside drugs [6]. Nevertheless, interferon therapy is limited by some adverse effects (symptoms, anemia, leucopenia); and nucleos(t)ides analogues often cause drug-resistance over a long period treatment [2]. In recently years, as a viable and novel approach for the treatment of chronic HBV infection, non-nucleoside drugs have been paid significant attention that target the nucleocapsid formation, some of which are already into clinical investigation [1]. Heteroaryldihydropyrimidines (HAPs) are discovered as a kind of antiviral molecules that bind at the dimer-dimer interface of the HBV core protein, induce protein assembly, and increase stability [[7], [8], [9], [10], [11], [12]]. Strangely, the binding of HAPs to HBV capsid protein does not alter the morphology of the protein but does enhance the interdimer contact energy [13]. Many active HAPs analogues are shown to share a few common features for the specific substitutions around the HAP core [1]. For example, an often halogen-substituted phenyl group is usually seen at the 4′th of the HAP core with R stereo configuration, an ester substitution is common at the 5′th, and at the 2′th a heterocycle is preferred [1]. Bay41-4109 [14] is able to inhibit HBV replication in vitro owing to its heterocycle (3,5-difluoropyridin-2-yl group) and presents good drug pharmacokinetic properties [15]; GLS4 [16] and NVR-010-001-E2 [12] include morpholine group (GLS4 is now in clinical trial against HBV infection [17]). So far, many novel HAPs derivatives have been developed and synthesized as HBV capsid assembly inhibitors.