Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic HBV treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilising cure is achievable and should be defined as sustained
HBsAg loss in addition to undetectable HBV
DNA 6 months post-treatment. The primary endpoint of phase III trials should be functional cure;
HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV
DNA) without
HBsAg loss 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity for the prediction of sustained
HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with
HBeAg-positive or negative
chronic hepatitis, who are treatment-naïve or virally suppressed on nucleos(t)ide analogues. A
hepatitis flare associated with an increase in
bilirubin or international normalised ratio should prompt temporary or permanent cessation of an
investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase III trials for HDV
coinfection should be undetectable serum HDV
RNA 6 months after stopping treatment. On treatment HDV
RNA suppression associated with normalisation of
alanine aminotransferase is considered an intermediate goal. In conclusion, regarding HBV 'functional cure', the primary goal is sustained
HBsAg loss with undetectable HBV
DNA after completion of treatment and the intermediate goal is sustained undetectable HBV
DNA without
HBsAg loss after stopping treatment.