Current antiviral therapies, such as pegylated interferon alpha and nucleos(t)ide analogs effectively improve the patient's quality of life. However, they are limited to control the infection but cannot cure infected hepatocytes. Complete HBV cure is hampered due to the lack of therapies that can directly affect the viral minichromosome, covalently closed circular DNA. Efforts currently in the pipeline for early clinical trials aim to achieve a functional cure, defined by the loss of Hepatitis B surface antigen and undetectable HBV DNA levels in serum. However, achieving a complete HBV cure requires therapies that can directly affect the cccDNA pool, either for its degradation, lethal mutations or functional silencing. In this review we discuss cutting-edge technologies that could lead to non-cytolytic direct cccDNA targeting, curing infected hepatocytes.
Maria Guadalupe Martinez, Anders Boyd, Emmanuel Combe, Barbara Testoni, Fabien Zoulim