Hepatitis B virus (HBV) is a global health problem with over 250 million people affected worldwide. Nucleos(t)ide analogues remain the standard of care and suppress production of progeny virions
however, they have limited effect on the viral transcriptome and long-term treatment is associated with off-target toxicities. Promising results are emerging from clinical trials and several drug classes have been evaluated, including capsid assembly modulators and RNA interfering agents. Whilst peripheral biomarkers are used to monitor responses and define treatment endpoints, they fail to reflect the full reservoir of infected hepatocytes. Given these limitations, consideration should be given to the merits of sampling liver tissue, especially in the context of clinical trials. In this review article, we will discuss methods for profiling HBV in liver tissue and their value to the HBV cure programme.