Liver and Bile

J Hepatol. 2022;76(5):1042–50

Sonneveld MJ, Chiu SM, Park JY, Brakenhoff SM, Kaewdech A, Seto WK, Tanaka Y, Carey I, Papatheodoridi M, van Bömmel F, Berg T, Zoulim F, Ahn SH, Dalekos GN, Erler NS, Höner Zu Siederdissen C, Wedemeyer H, Cornberg M, Yuen MF, Agarwal K, Boonstra A, Buti M, Piratvisuth T, Papatheodoridis G, Chen CH, Maasoumy B; CREATE study group

Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels

Background and aims: Nucleo(s)tide analogue (NA) withdrawal may result in hepatitis B surface antigen (HBsAg) clearance in a subset of patients. However, predictors of HBsAg loss after NA withdrawal remain ill-defined.
Methods: The authors studied predictors of HBsAg loss in a global cohort of hepatitis B e antigen (HBeAg)-negative patients with undetectable hepatitis B virus (HBV) DNA who discontinued long-term NA therapy. Patients requiring retreatment after treatment cessation were considered non-responders.
Results: They enrolled 1216 patients (991 with genotype data); 98 (8.1%) achieved HBsAg loss. The probability of HBsAg loss was higher in non-Asian patients (adjusted hazard ratio [aHR] = 8.26, p < 0.001), and in patients with lower HBsAg (aHR = 0.243, p < 0.001) and HBV core-related antigen (HBcrAg) (aHR = 0.718, p = 0.001) levels. Combining HBsAg (< 10, 10–100 or > 100 IU/ml) and HBcrAg (< 2 log vs. ≥ 2 log) levels improved prediction of HBsAg loss, with extremely low rates observed in patients with HBsAg > 100 IU/ml with detectable HBcrAg. HBsAg loss rates also varied with HBV genotype; the highest rates were observed for genotypes A and D, and none of the patients with HBV genotype E experienced HBsAg loss (p < 0.001 for the overall comparison across genotypes; p < 0.001 for genotypes A/D vs. genotypes B/C). HBV genotype C was independently associated with a higher probability of HBsAg loss when compared to genotype B among Asian patients (aHR = 2.494; 95% confidence interval: 1.490-4.174, p = 0.001).

Conclusions: The probability of hepatitis B surface antigen (HBsAg) loss after nucleo(s)tide analogue cessation varies according to patient ethnicity, hepatitis B virus (HBV) genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (< 100 IU/ml) and/or undetectable hepatitis core-related antigen levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for treatment withdrawal.

M.J. Sonneveld, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands,

DOI: DOI: 10.1016/j.jhep.2022.01.007

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