Challenges and strategies of antiviral therapy for chronic hepatitis B-how to achieve the maximization of clinical cure?

Hepatitis B virus infection is still a major public health issue in the world, and antiviral therapy is the key therapeutic regimen to delay disease progression and improve outcome in patients with chronic hepatitis B ( CHB) . Various international guidelines recommend nucleos ( t) ide analogues ( NAs) and long-acting interferon as the first-line antiviral therapy. However, long-term administration of NAs has the disadvantages of long course of treatment, low HBeAg seroconversion rate, extremely low HBsAg clearance or seroconversion rate, low safety, and drug resistance. Therefore, it is an important issue to increase the seroconversion rates of HBeAg and HBsAg in treatment-experienced patients and realize clinical cure in the treatment of CHB. In recent years, many global randomized clinical trials including OSST, Switch, and ARES have shown that a combination of NAs and PEG-IFN or sequential therapy with NAs and PEG-IFN can increase the seroconversion rates of HBeAg and HBsAg in CHB patients and realize clinical cure, which provides a new direction for NAs in the treatment of CHB patients.