What Should Be Done to Re-evaluate Cessation of Nucleos(t)ide Analog Therapy for Chronic Hepatitis B Infection?

Anti-viral therapy with nucleos(t)ide analogs(NUCs)for chronic hepatitis B(CHB)is generally considered to be a long-term treatment.Relevant guidelines issued by Asian Pacific Association for the Study of the Liver,European Association for the Study of the Liver,and American Association for the Study of Liver Diseases have recently proposed requirements and standards for cessation of NUCs,but it remains unclear which proportion of CHB patients on long-term or prolonged treatment of NUCs will relapse after NUCs cessation.Recently,paradoxical increase in loss of hepatitis B surface antigen(HBsAg)with or without the development of anti-hepatitis B surface antibody has been observed in NUCs’treated CHB patients with cessation of therapy.Hence,it is of great clinical relevance to identify CHB who might have been over-treated with NUCs and might even benefit HBsAg loss or seroconversion with cessation of therapy.To address these issues,our review comprehensively analyzed the data from recent clinical trials in which the antiviral efficacy in the long-term or prolonged treatment of NUCs and/or interferon-a for CHB patients were evaluated.Furthermore,the relevant problems and deficiencies existing in the study design of previous clinical studies were also described.To solve the unmet issues in the field,a prospective study with a large-enough sample size would be required to understand the related virologic and immunological markers that can accurately predict the outcome and prognosis of the CHB patients who stop the NUCs treatment.With the rapid advancement of antiviral drug development for CHB patients,the future ideal regimens should include multiple targets for antiviral drug therapy combined with efficient immune-modulatory therapy,which will help more CHB patients to obtain functional cure with NUCs cessation.