Περίληψη:
Background & Aims: Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients. However, predictors of HBsAg loss after NUC withdrawal remain ill-defined. Methods: We studied predictors of HBsAg loss in a global cohort of HBeAg-negative patients with undetectable HBV DNA who discontinued long-term NUC therapy. Patients requiring retreatment after treatment cessation were considered non-responders. Results: We enrolled 1,216 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 (<2log 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% CI 1.490–4.174, p = 0.001). Conclusions: The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (<100 IU/ml) and/or undetectable HBcrAg levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for treatment withdrawal. Lay summary: A subset of patients may achieve clearance of hepatitis B surface antigen (HBsAg) – so-called functional cure – after withdrawal of nucleo(s)tide analogue therapy. In this multicentre study of 1,216 patients who discontinued antiviral therapy, we identified non-Asian ethnicity, HBV genotype C, and low hepatitis B surface antigen and hepatitis B core-related antigen levels as factors associated with an increased chance of HBsAg loss. © 2022 The Author(s)
Συγγραφείς:
Sonneveld, M.J.
Chiu, S.-M.
Park, J.Y.
Brakenhoff, S.M.
Kaewdech, A.
Seto, W.-K.
Tanaka, Y.
Carey, I.
Papatheodoridi, M.
van Bömmel, F.
Berg, T.
Zoulim, F.
Ahn, S.H.
Dalekos, G.N.
Erler, N.S.
Höner zu Siederdissen, C.
Wedemeyer, H.
Cornberg, M.
Yuen, M.-F.
Agarwal, K.
Boonstra, A.
Buti, M.
Piratvisuth, T.
Papatheodoridis, G.
Chen, C.-H.
Maasoumy, B.
CREATE study group
