TY - JOUR
T1 - Early HBcrAg and Anti-HBc Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation-A Pooled Analysis of Two Clinical Trials
AU - Dongelmans, Edo J.
AU - Feld, Jordan J.
AU - Boonstra, Andre
AU - Brakenhoff, Sylvia M.
AU - Wong, David
AU - Yim, Colina
AU - Claassen, Mark
AU - Honkoop, Pieter
AU - Hansen, Bettina E.
AU - de Man, Robert A.
AU - Fung, Scott
AU - Berg, Thomas
AU - van Boemmel, Florian
AU - Janssen, Harry L. A.
AU - Sonneveld, Milan J.
N1 - Publisher Copyright:
© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
PY - 2024/12/3
Y1 - 2024/12/3
N2 - Background: Severe flares (ALT ≥ 10×ULN) are a well-recognised adverse outcome after nucleos(t)ide analogue (NA) cessation and may lead to liver failure. Thus, identification of patients at risk for these flares is of major importance. Methods: Data were used from two prospective studies on NA cessation conducted in the Netherlands and Canada. Patients were eligible based on EASL criteria. HBcrAg and anti-HBc levels were measured at end of treatment (EOT) and week 6 (FUW6). Logistic regression was used to study the association with severe flares. Results: Seventy-eight patients were analysed with a mean age of 49 years, 16 (21%) Caucasian and a majority (65%) were treated with Tenofovir. Overall, 22 patients (28%) developed a severe flare, and 29 (37%) patients were retreated. At EOT, higher HBcrAg levels (aOR: 1.97, p = 0.05; ≥ 4log: 47% severe flare vs. < 3log: 19%, p = 0.036), lower anti-HBc (aOR: 0.29, p = 0.036; < 2log: 50% vs. ≥ 3log: 11%, p = 0.029) and higher HBcrAg/anti-HBc-ratio (aOR: 3.17, p = 0.015; ≥ 2: 58% vs. < 1.5: 14%, p < 0.001) were associated with an increased risk of severe flares, adjusted for HBsAg. At FUW6, higher HBcrAg (aOR: 2.91, p = 0.035; ≥ 5log: 83%, < 3log: 4%, p < 0.001), lower anti-HBc (aOR: 0.46, p = 0.29; < 2log: 50% vs. ≥ 3log: 0%, p = 0.003) and higher HBcrAg/anti-HBc-ratio (aOR: 2.19, p = 0.048; ≥ 1.75: 52% vs. < 1.75: 8%, p < 0.001) were associated with an increased risk of severe flares, adjusted for HBV DNA and ALT. Conclusion: Higher HBcrAg, lower anti-HBc and higher HBcrAg/anti-HBc ratio at EOT and during the first weeks of post-treatment follow-up are associated with an increased risk of hepatic flares after NA withdrawal and could therefore potentially be used to select patients eligible for therapy cessation and to identify patients requiring retreatment. Trial Registration: This study was a post hoc and follow-up study of two previously registered clinical trials (NCT01911156 & NTR7001). No new patients were prospectively included.
AB - Background: Severe flares (ALT ≥ 10×ULN) are a well-recognised adverse outcome after nucleos(t)ide analogue (NA) cessation and may lead to liver failure. Thus, identification of patients at risk for these flares is of major importance. Methods: Data were used from two prospective studies on NA cessation conducted in the Netherlands and Canada. Patients were eligible based on EASL criteria. HBcrAg and anti-HBc levels were measured at end of treatment (EOT) and week 6 (FUW6). Logistic regression was used to study the association with severe flares. Results: Seventy-eight patients were analysed with a mean age of 49 years, 16 (21%) Caucasian and a majority (65%) were treated with Tenofovir. Overall, 22 patients (28%) developed a severe flare, and 29 (37%) patients were retreated. At EOT, higher HBcrAg levels (aOR: 1.97, p = 0.05; ≥ 4log: 47% severe flare vs. < 3log: 19%, p = 0.036), lower anti-HBc (aOR: 0.29, p = 0.036; < 2log: 50% vs. ≥ 3log: 11%, p = 0.029) and higher HBcrAg/anti-HBc-ratio (aOR: 3.17, p = 0.015; ≥ 2: 58% vs. < 1.5: 14%, p < 0.001) were associated with an increased risk of severe flares, adjusted for HBsAg. At FUW6, higher HBcrAg (aOR: 2.91, p = 0.035; ≥ 5log: 83%, < 3log: 4%, p < 0.001), lower anti-HBc (aOR: 0.46, p = 0.29; < 2log: 50% vs. ≥ 3log: 0%, p = 0.003) and higher HBcrAg/anti-HBc-ratio (aOR: 2.19, p = 0.048; ≥ 1.75: 52% vs. < 1.75: 8%, p < 0.001) were associated with an increased risk of severe flares, adjusted for HBV DNA and ALT. Conclusion: Higher HBcrAg, lower anti-HBc and higher HBcrAg/anti-HBc ratio at EOT and during the first weeks of post-treatment follow-up are associated with an increased risk of hepatic flares after NA withdrawal and could therefore potentially be used to select patients eligible for therapy cessation and to identify patients requiring retreatment. Trial Registration: This study was a post hoc and follow-up study of two previously registered clinical trials (NCT01911156 & NTR7001). No new patients were prospectively included.
UR - http://www.scopus.com/inward/record.url?scp=85211146674&partnerID=8YFLogxK
U2 - 10.1111/apt.18416
DO - 10.1111/apt.18416
M3 - Article
C2 - 39624922
SN - 0269-2813
VL - 61
SP - 570
EP - 578
JO - Alimentary Pharmacology & Therapeutics
JF - Alimentary Pharmacology & Therapeutics
IS - 3
ER -