How to achieve functional cure of HBV: Stopping NUCs, adding interferon or new drug development?

Current treatment of chronic hepatitis B: Clinical aspects and future directions

“…There are still many researches need to be done to better address these issues. The controversy over when antiviral therapy should be discontinued in CHB patients is partly due to the lack of effective methods for evaluating cccDNA in the liver cell nucleus ( Caviglia et al, 2018 ; Martinez et al, 2021 ; Wong et al, 2022 ). In recent years, growing evidence has identified HBcAg and HBV RNA as favorable biomarkers as an alternative in assessing antiviral efficacy, decision-making on NA withdrawal, and predicting the risk of recurrence ( Giersch et al, 2017 ; Wu et al, 2017 ; Xie et al, 2021 ).…”

Moving toward hepatitis B virus functional cure - the impact of on-treatment kinetics of serum viral markers

“…Importantly, the field is currently working towards functional cure of CHB (i.e., HBsAg seroclearance and sustained off-treatment HBV DNA suppression). [1,19] Because HBsAg seroclearance is rare with the current oral NAs, this is unlikely the area where the new virological markers will be applied. Rather, the roles of HBV RNA, HBcrAg and HBsAg levels in predicting the response to novel direct-acting antivirals and immunological treatments in HBV cure programs is one of the hottest research areas in hepatology.…”

“…Functional cure of chronic hepatitis B virus (HBV) infection is currently set as the treatment goal of new HBV therapies, which is serologically defined as clearance of hepatitis B surface antigen (HBsAg), with or without anti-HBs seroconversion, and undetectable serum HBV DNA. [1] A handful of studies showed that patients with chronic hepatitis B (CHB) who achieve functional cure generally have a favorable clinical coursenamely much reduced risk of hepatic events and HCC. [2] Nonetheless, there is still a low yet definite risk of HCC occurrence, especially male patients who achieve functional cure after 50 years old.…”

Letter: the probability to predict HBV‐specific CD8+ cell response derived from HLA‐A2+ may not foresee the functional cure well in Asian off‐therapy cohort—authors' reply

“…Stopping NUC therapy can lead to a functional cure in some Caucasians but rarely in Asian patients. 3 We should clarify that our LRM to predict the development of an HBV-multi-specific CD8+ T-cell response during NUC treatment was developed in a Caucasian cohort from the Mediterranean basin, which has a different source of infection, HBV genotype and haplotype background than Asian patients. These could affect the immune response and, consequently, calculated LRM probabilities.…”