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1 Treatments with nucleos(t)ide analogues (NA) or interferon (IFN) alfa result in HBV DNA suppression and slowing of disease progression in patients with chronic hepatitis B (CHB). Hepatitis B virus (HBV) infection remains a major global health problem with approximately 257 million people worldwide chronically infected, resulting in 887 000 deaths per year due to progressive liver disease and hepatocellular carcinoma (HCC). Overall, our data provide new insights that are important for patient stratification considerations for novel therapies aimed at functional cure of HBV. The data also suggest that patients with low HBsAg and/or low HBcrAg are better candidates for immune-based therapies (eg, checkpoint inhibition) regardless of age, supporting the hypothesis for antigen lowering, for example, with RNA interference. Our findings also highlight that HBcrAg might be a better viral marker than HBsAg to discriminate hepatitis B e antigen negative patients with preserved HBV-specific (CD4 +) T cell responses and thus may be considered to stratify patients for novel therapies aimed at HBsAg loss. This data is important for considering young patients for novel immune-based therapies aimed at functional cure of HBV.

The results highlight that age as an indicator of duration of infection is an important factor for the functionality of HBV-specific CD8 + and CD4 + T cells, not only for HBV surface-specific T cells but also for HBV core-specific and pol-specific T cells, which is independent of HBsAg level. How might it impact on clinical practice in the foreseeable future?