早期HBcrAg和抗-HBc水平可识别核苷（酸）类似物停药后严重病情复发的高危患者——两项临床试验的汇总分析
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.
作者信息
Dongelmans Edo J, Feld Jordan J, Boonstra André, Brakenhoff Sylvia M, Wong David, Yim Colina, Claassen Mark, Honkoop Pieter, Hansen Bettina E, de Man Robert A, Fung Scott, Berg Thomas, van Bömmel Florian, Janssen Harry L A, Sonneveld Milan J
机构信息
Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
出版信息
Aliment Pharmacol Ther. 2025 Feb;61(3):570-578. doi: 10.1111/apt.18416. Epub 2024 Dec 3.
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.
背景
严重肝炎发作（ALT≥10×ULN）是核苷（酸）类似物（NA）停药后公认的不良后果，可能导致肝衰竭。因此，识别有这些肝炎发作风险的患者至关重要。
方法
使用了在荷兰和加拿大进行的两项关于NA停药的前瞻性研究的数据。患者根据欧洲肝脏研究学会（EASL）标准符合入选条件。在治疗结束时（EOT）和第6周（随访第6周，FUW6）测量HBcrAg和抗-HBc水平。采用逻辑回归研究与严重肝炎发作的关联。
结果
分析了78例患者，平均年龄49岁，16例（21%）为白种人，大多数（65%）接受替诺福韦治疗。总体而言，22例患者（28%）发生严重肝炎发作，29例（37%）患者重新接受治疗。在EOT时，较高的HBcrAg水平（调整后的比值比[aOR]：1.97，p = 0.05；≥4log：严重肝炎发作率47% vs. <3log：19%，p = 0.036）、较低的抗-HBc水平（aOR：0.29，p = 0.036；<2log：50% vs. ≥3log：11%，p = 0.029）以及较高的HBcrAg/抗-HBc比值（aOR：3.17，p = 0.015；≥2：58% vs. <1.5：14%，p <0.001）与严重肝炎发作风险增加相关，校正了HBsAg。在FUW6时，较高的HBcrAg水平（aOR：2.91，p = 0.035；≥5log：83%，<3log：4%，p <0.001）、较低的抗-HBc水平（aOR：0.46，p = 0.29；<2log：50% vs. ≥3log：0%，p = 0.003）以及较高的HBcrAg/抗-HBc比值（aOR：2.19，p = 0.048；≥1.75：52% vs. <1.75：8%，p <0.001）与严重肝炎发作风险增加相关，校正了HBV DNA和ALT。
结论
在EOT时以及治疗后随访的最初几周内，较高的HBcrAg、较低的抗-HBc和较高的HBcrAg/抗-HBc比值与NA停药后肝炎发作风险增加相关，因此有可能用于选择适合停药的患者以及识别需要重新治疗的患者。
试验注册
本研究是对两项先前注册的临床试验（NCT0191 / 1156和NTR7001）的事后分析和随访研究。没有前瞻性纳入新患者。
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