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Chronic hepatitis B virus (HBV) infection leads to liver damage that increases the risk of hepatocellular carcinoma and liver cirrhosis. Individuals with chronic HBV infection are often either treated with interferon alpha or nucleoside reverse transcriptase inhibitors (NTRL). While these NTRLs inhibit de novo DNA synthesis, they do not represent a functional cure for chronic HBV infection and so must be taken indefinitely. The resulting life-long treatment leads to an increased risk of selection for treatment resistant strains of HBV. Consequently, there is increased interest in a novel treatment modality, capsid protein allosteric modulators (CPAMs), that blocks a crucial step in the viral life cycle. I’ll discuss recent work that identifies HBV serum RNA as an informative biomarker of CPAM treatment efficacy, evaluates CPAMs as a potential functional cure for HBV infection, and illustrates the role of mechanistic modelling in trial design using an age structured, multi-scale mathematical model.
