Predictors of hepatic flares after nucleos(t)ide analogue cessation – Results of a global cohort study (RETRACT-B study)

作者：Edo J. Dongelmans, Grishma Hirode, Bettina E. Hansen, Chien‐Hung Chen, Tung‐Hung Su, Wai‐Kay Seto, Arno Furquim d’Almeida, Stijn Van Hees, Μargarita Papatheodoridi, Sabela Lens, Grace Lai‐Hung Wong, Sylvia M. Brakenhoff, Rong‐Nan Chien, Jordan J. Feld, Henry Lik‐Yuen Chan, Xavier Forns, George Papatheodoridis, Thomas Vanwolleghem, Man‐Fung Yuen, Yao‐Chun Hsu, Jia‐Horng Kao, Markus Cornberg, Milan J. Sonneveld, Wen‐Juei Jeng, Harry L.A. Janssen · 发表于：Journal of Hepatology · 年份：2024 · DOI：10.1016/j.jhep.2024.08.015 · 被引用次数：38 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、Liver Disease and Transplantation

Background and Aims Flares after nucleos(t)ide analogue (NA) cessation are common and potentially harmful. Predictors of flares are required for risk stratification and to guide off-treatment follow-up. Method This multicenter cohort study included virally suppressed patients with chronic hepatitis B (CHB) who were hepatitis B e antigen negative at NA cessation. Hepatic flares were defined based on an ALT-levels of ≥5-, 10- or 20 x upper limit of normal (ULN). Multivariable Cox regression analyses were performed censoring at retreatment, HBsAg-loss and loss-to-follow-up. A sub-analysis was performed including HBV DNA levels Results Of the 1552 included patients, 350 developed a flare (ALT≥5xULN), of whom 70% within the first year. One-year cumulative incidences for ALT flares ≥5x, ≥10x, ≥20xULN were 18.6%, 10.2% and 3.4%, respectively. Severity of flares decreased over time, but severe flares still occurred after one year. Thirteen patients decompensated after a flare, of whom 3 died. Flares seemed not associated with increased rates of HBsAg loss (adjusted Hazard Ratio [aHR] 1.42, P=0.28). Multivariable-analyses showed that older age (aHR:1.02,P=0.001), male sex (aHR:1.57,P=0.003), HBsAg levels at NA withdrawal (100-1,000 IU/mL; aHR:1.99,P<0.001; >1,000 IU/mL; aHR:2.65,P<0.001) and Tenofovir (TDF) vs. Entecavir therapy (aHR:2.99,P<0.001) were predictive for flares (≥5xULN). Early HBV DNA levels >5log 10 IU/mL were associated with the highest risk of flares (aHR:2.36,P<0.001)...