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

y BACKGROUND Functional cure of chronic hepatitis B virus (HBV) infection, which is currently set as the treatment goal of new HBV ther-apies, is serologically defined as the clearance of hepatitis B surface antigen (HBsAg), with or without anti-HBs serocon-version, and undetectable serum HBV DNA.1 A handful of studies have shown that patients with chronic hepatitis B (CHB) who achieve functional cure generally have a favorable clinical course - namely much reduced risk of hepatic events and hepatocellular carcinoma (HCC).(2) Nonetheless, there is still a low yet definite risk of HCC occurrence, especially in male patients who achieve functional cure after 50 years of age.(3) While the current antiviral treatment with oral nucleos (t)ide analogues (NAs) are potent and safe, they generally lead to very low rates of functional cure; hence, novel HBV therapeutic regimens are eagerly wanted for improving the functional cure rate.4,5Before achieving functional cure, the holy grail of treat-ment goals, favourable HBsAg response (FHR) is a reasonable intermediate step towards HBV cure. FHR was defined as HB-sAg seroclearance or HBsAg =100 IU/mL at the end of follow-up (EOFU). Such a low HBsAg cutoff is often adopted for stop-ping NA therapy in hepatitis B e antigen (HBeAg)-negative patients, as their relapse rate would be low.(6) End-of-treat-ment HBsAg <100 IU/mL is also one of the few virologic pre-dictors of functional cure.1 Several studies have investigated the functional cure rate after stopping NA in HBeAg-negative patients, with variable rates of success ranging from 2.7- 16.7%/year in Caucasian patients and 0-3.8%/year among Asian patients; the most consistent predictor of functional cure is a low HBsAg level at the time of NA withdrawal.1