New strategies for clinical cure and Institute of hepatitis B: viral suppression combined with immune modulation and its road map

Chronic hepatitis B virus (HBV) infection remains a major global health issue. At present, nucleos(t)ide analogues (NAs) and interferon (IFN) or pegylated interferon (PEG-IFN) are used as the antiviral therapy. NA therapy is generally safe and well tolerated, but it has a high virological recurrence rate after drug withdrawal and a long course of treatment which may require lifelong medication. PEG-IFN therapy has the advantages of relatively shorter course of treatment, longer response, and lower rate of resistance; however, only some patients can achieve sustained response to IFN, and IFN has a high rate of adverse events, which limits the wide application of IFN in clinical practice. Since HBV covalently closed circular DNA and the integrated HBV genome stably exist in the nuclei of infected hepatocytes, it is difficult to achieve the elimination (complete cure) of HBV. The ideal endpoint of antiviral therapy for chronic hepatitis B recommended by most guidelines is the sustained disappearance of HBsAg, with or without HBsAb seroconversion (functional cure). Theoretically, a combination of antiviral agents with different anti-HBV mechanisms, including the drugs for viral suppression and immune modulation, is a promising strategy for the treatment of chronic hepatitis B. Latest studies have demonstrated that compared with NA alone, NA given concurrently or sequentially with PEG-IFN has certain advantages in virologic and serological response. Our articles published in Journal of Hepatology in 2015 and Journal of Infectious Diseases in December 2017 introduce the research advances in treatment strategies for chronic hepatitis B and put forward our thoughts on clinical cure of chronic hepatitis B and related clinical routes, with reference to research findings in China and foreign countries. This article provides some updated information