Cracking the host functional network involved in hepatitis B virus cccDNA biology

Hepatitis B virus (HBV) causes chronic infection in at least 250 million people worldwide, resulting in approximately 850 000 deaths annually. Chronic carriers are at risk of developing severe liver disease including decompensated cirrhosis and hepatocellular carcinoma (HCC). HBV infection can be prevented with a highly effective prophylactic vaccine. Viraemia can be suppressed with nucleos/tide analogues targeting the HBV polymerase, but standard-of-care therapy rarely leads to a cure leaving patients requiring lifelong therapy to prevent relapse of viral replication. Furthermore, even on treatment patients remain at a residual risk of developing HCC. Development of treatments resulting in a functional cure has been hampered by our incomplete understanding of HBV persistence and the difficulty of targeting pharmacologically essential steps in the viral replicative cycle.1