使用HBsAg和HBcrAg水平预测核苷（酸）类似物停药后的持续应答：一项多中心研究（CREATE）
Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE).
作者信息
Sonneveld Milan J, Park Jun Yong, Kaewdech Apichat, Seto Wai-Kay, Tanaka Yasuhito, Carey Ivana, Papatheodoridi Margarita, van Bömmel Florian, Berg Thomas, Zoulim Fabien, Ahn Sang Hoon, Dalekos George N, Erler Nicole S, Höner Zu Siederdissen Christoph, Wedemeyer Heiner, Cornberg Markus, Yuen Man-Fung, Agarwal Kosh, Boonstra Andre, Buti Maria, Piratvisuth Teerha, Papatheodoridis George, Maasoumy Benjamin
机构信息
Department of Gastroenterology and Hepatology, Rotterdam, the Netherlands.
Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
出版信息
Clin Gastroenterol Hepatol. 2022 Apr;20(4):e784-e793. doi: 10.1016/j.cgh.2020.12.005. Epub 2020 Dec 10.
BACKGROUND & AIMS: Predictors of successful nucleo(s)tide analogue (NA) therapy withdrawal remain elusive. We studied the relationship between end-of-treatment levels of hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg) and outcome after therapy cessation.
METHODS
Patients who discontinued NA therapy in centers in Asia and Europe were enrolled. HBcrAg and HBsAg were measured at treatment cessation, and associations with off-treatment outcomes were explored. The SCALE-B (Surface antigen, Core-related antigen, Age, ALT, and tenofovir for HBV) score was calculated as previously reported. End points included sustained virologic response (VR; hepatitis B virus DNA level <2000 IU/mL), HBsAg loss, and alanine aminotransferase (ALT) flares (>3× upper limit of normal). Re-treated patients were considered nonresponders.
RESULTS
We analyzed 572 patients, 457 (80%) were Asian and 95 (17%) were hepatitis B e antigen positive at the start of NA therapy. The median treatment duration was 295 weeks. VR was observed in 267 (47%), HBsAg loss was observed in 24 (4.2%), and ALT flare was observed in 92 (16%). VR (67% vs 42%) and HBsAg loss (15% vs 1.5%) was observed more frequently in non-Asian patients when compared to Asian patients (P < .001). Lower HBcrAg levels were associated with higher rates of VR (odds ratio [OR], 0.701; P < .001) and HBsAg loss (OR, 0.476; P < .001), and lower rates of ALT flares (OR, 1.288; P = .005). Similar results were observed with HBsAg (VR: OR, 0.812; P = .011; HBsAg loss: OR, 0.380; P < .001; and ALT flare: OR, 1.833; P < .001). Lower SCALE-B scores were associated with higher rates of VR, HBsAg loss, and lower rates of ALT flares in both Asian and non-Asian patients (P < .001).
CONCLUSIONS
In this multicenter study, off-treatment outcomes after NA cessation varied with ethnicity. Lower levels of HBcrAg and HBsAg were associated with favorable outcomes. A risk score comprising both factors can be used for risk stratification.
背景与目的
核苷酸类似物（NA）治疗停药成功的预测因素仍不明确。我们研究了乙型肝炎核心相关抗原（HBcrAg）和乙型肝炎表面抗原（HBsAg）的治疗结束水平与停药后结局之间的关系。
方法
纳入在亚洲和欧洲各中心停用NA治疗的患者。在停药时检测HBcrAg和HBsAg，并探讨其与停药后结局的相关性。如先前报道计算SCALE - B（表面抗原、核心相关抗原、年龄、丙氨酸氨基转移酶和用于治疗HBV的替诺福韦）评分。终点包括持续病毒学应答（VR；乙型肝炎病毒DNA水平<2000 IU/mL）、HBsAg消失和丙氨酸氨基转移酶（ALT） flare（>3倍正常上限）。再次治疗的患者被视为无应答者。
结果
我们分析了572例患者，457例（80%）为亚洲人，95例（17%）在NA治疗开始时为乙型肝炎e抗原阳性。中位治疗持续时间为295周。267例（47%）观察到VR，24例（4.2%）观察到HBsAg消失，92例（16%）观察到ALT flare。与亚洲患者相比，非亚洲患者更频繁观察到VR（67%对42%）和HBsAg消失（15%对1.5%）（P <.001）。较低的HBcrAg水平与较高的VR发生率（优势比[OR]，0.701；P <.001）和HBsAg消失率（OR，0.476；P <.001）以及较低的ALT flare发生率（OR，1.288；P =.005）相关。HBsAg也观察到类似结果（VR：OR，0.812；P =.011；HBsAg消失：OR，0.380；P <.001；ALT flare：OR，1.833；P <.001）。在亚洲和非亚洲患者中，较低的SCALE - B评分与较高的VR发生率、HBsAg消失率以及较低的ALT flare发生率相关（P <.001）。
结论
在这项多中心研究中，NA停药后的停药后结局因种族而异。较低水平的HBcrAg和HBsAg与良好结局相关。包含这两个因素的风险评分可用于风险分层。
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