HBV Lifecycle and New Biomarkers 20 Aug 2021 10:20 10:32

HBV Lifecycle and New Biomarkers 20 Aug 2021 10:20 10:32

(12mins)
Lim Seng-Gee Speaker
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Biomarkers are indicators of biologic or pathogenic process or pharmacologic responses, while surrogate endpoints are early and accurate predictors of clinical endpoints, while clinical endpoints are measurements of how a patient feels, functions or survives. HBV biomarkers (qHBsAg, HBV RNA & HBcrAg) are best used in evaluating HBV related events rather than liver events and best used as prognostic markers rather than diagnostic markers. The best utility of such biomarkers is in prediction of HBsAg loss, HBV flares and response to HBV therapy. The lifecycle of HBV provides insights into how these biomarkers may function. The replicative pathway is the part of the lifecycle that allow viral replication and utlises HBV polymerase, while the secretory pathway is that which leads to production of viral transcripts and proteins such as HBeAg and HBsAg as secreted products. This pathway is also divided into two interrelated pathways, one where precore/pregenomic gene leads to production of HBV RNA and subsequently to products related to HBcrAg (HBeAg, HBcAg and p22cr) while the HBsAg pathway produces HBsAg RNA and HBsAg subviral particles (1000x in excess of infected virus). We can understand the responses to antiviral therapy since nucleoside analogues rapidly reduces HBV DNA (replicative pathway) but takes longer to reduce transcription and translation (HBV RNA and HBcrAg). There is poor correlation of HBsAg with NA and peginterferon therapy compared to HBV DNA, HBV RNA and HBcrAg. QHBsAg levels are good predictors of HBsAg during pegIFN therapy (AUROC 0.77-0.91) and better than HBcrAg & HBV RNA. The best predictors of HBeAg seroconversion are HBV RNA & qHBeAg at week 12 of pegIFN therapy (AUROC 0.77 & 0.75 respectively). The best predictors of relapse after stopping therapy post seroconversion are combined HBV RNA & HBcrAg (AUROC 0.7-0.85), and in HBeAg neg CHB the predictors are not fully validated. Stopping rules for pegIFN rely on treatment qHBsAg>20,000 IU/ml. In conclusion, HBV biomarkers are useful as predictors in management of CHB

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