Novel Therapy for Functional Cure of Chronic Hepatitis B Virus Infection

Abstract

Functional cure is the currently preferable and optimal treatment endpoint, which refers to sustained seroclearance of HBsAg with or without seroconversion of antibody to HBsAg. Functional cure is associated with improved clinical outcomes. The unsatisfactorily low rate of functional cure achieved by currently approved therapies [i.e. nucleos(t)ide reverse transcriptase inhibitor (NRTI) or pegylated interferon] triggers the on-going search for new treatment approaches. Cessation of long-term NRTI aiming at subsequent functional cure has led to heterogeneous results in patients with different baseline characteristics. Meticulous patient selection is required with efforts to identify patients with favorable factors including Caucasian ethnicity and low HBsAg level. For novel agents, reduction of viral burden and enhancement/ restoration of host immunity are equally important. Most agents currently in clinical phase of development demonstrated favorable results in suppression of viral proteins and genomic materials, and some agents will enter phase 3 clinical trials for further evaluation. Safety data is of paramount importance. The future treatment regime will likely entail a combination of NRTI, virus-directing agent, and immunity-boosting agent. The best cocktail therapy is still unknown, and will need to be revealed by well-designed randomized controlled trials.