Liver and Bile
Gastroenterology. 2024;166(1):168–77.e8
HBV DNA and HBsAg levels at 24 weeks off-treatment predict clinical relapse and HBsAg loss in HBeAg-negative patients who discontinued antiviral therapy
Background and aims: Patients who discontinue nucleo(s)tide analogue therapy are at risk of viral rebound and severe hepatitis flares, necessitating intensive off-treatment follow-up.
Methods: The authors studied the association between hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels at off-treatment follow-up week 24 (FU W24), with subsequent clinical relapse, and HBsAg loss in a multicenter cohort of hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B who discontinued nucleo(s)tide analogue therapy.
Results: They studied 475 patients, 82% Asian, and 55% treated with entecavir. Patients with higher HBV DNA levels at FU W24 had a higher risk of clinical relapse (hazard ratio [HR] = 1.576; p < 0.001) and a lower chance of HBsAg loss (HR = 0.454; p < 0.001). Similarly, patients with higher HBsAg levels at FU W24 had a higher risk of clinical relapse (HR = 1.579; p < 0.001) and a lower chance of HBsAg loss (HR = 0.263; p < 0.001). A combination of both HBsAg < 100 IU/ml and HBV DNA < 100 IU/ml at FU W24 identified patients with excellent outcomes (9.9% clinical relapse and 58% HBsAg loss at 216 weeks of follow-up). Conversely, relapse rates were high and HBsAg loss rates negligible among patients with both HBsAg > 100 IU/ml and HBV DNA > 100 IU/ml (p < 0.001).
Conclusions: Among hepatitis B e antigen-negative patients with chronic hepatitis B who discontinued antiviral therapy and who did not experience clinical relapse before follow-up week 24 (FU W24), serum levels of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) at FU W24 can be used to predict subsequent clinical relapse and HBsAg clearance. A combination of HBsAg < 100 IU/ml with HBV DNA < 100 IU/ml identifies patients with a low risk of relapse and excellent chances of HBsAg loss and could potentially be used as an early surrogate end point for studies aiming at finite therapy in HBV.