Liver and Bile

Gastroenterology. 2024;166(1):168–77.e8

Sonneveld MJ, Chiu SM, Park JY, Brakenhoff SM, Kaewdech A, Seto WK, Tanaka Y, Carey I, Papatheodoridi M, Colombatto P, van Bömmel F, Janssen HL, Berg T, Zoulim F, Ahn SH, Dalekos GN, Erler NS, Brunetto M, Wedemeyer H, Cornberg M, Yuen MF, Agarwal K, Boonstra A, Buti M, Piratvisuth T, Papatheodoridis G, Chen CH, Maasoumy B; CREATE Study Group

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.

DOI: 10.1053/j.gastro.2023.09.033