Enhancing functional cure in patients with chronic hepatitis B infection

With the existing treatment by either nucleos(t)ide reversetranscriptase inhibitor (NRTI) or pegylated interferon, we can achieve on-treatment viral suppression for virtually all patients with chronic hepatitis B infection. However, even if HBV DNA is suppressed with current antiviral therapy, liver-related complications still arise. Disappointingly, only few percent of patients can achieve functional cure even on long-term therapy. Functional cure is the currently preferable and optimal treatment endpoint,which refers to sustained seroclearance of HBsAg with or withoutseroconversion of antibody to HBsAg. Functional cure is associated withimproved clinical outcomes. The unsatisfactorily low rate of functional cureachieved by currently approved therapies triggers the on-goingsearch for new treatment approaches. Cessation of long-term NRTI aiming atsubsequent functional cure has led to heterogeneous results in patients withdifferent baseline characteristics. Meticulous patient selection is required withefforts to identify patients with favorable factors including Caucasian ethnicityand low HBsAg level. For novel agents, reduction of viral burden andenhancement/ restoration of host immunity are equally important. Most agents currently in clinical phase of development demonstrated favorable results insuppression of viral proteins and genomic materials, and some agents willenter phase 3 clinical trials for further evaluation. Safety data is of paramountimportance. The future treatment regime will likely entail a combination ofNRTI, virus-directing agent, and immunity-boosting agent. The best cocktailtherapy is still unknown, and will need to be revealed by well-designed randomized controlled trials.