Zhao Ruihong, Wu Wei, Zhou Zhibo, Zheng Xiaoqing, Sun Wenjie, Shi Yemin, Yu Haiying, Wang Fang, Zhao Hong, Sun Shanshan, Jin Linfeng, Sheng Jifang, Shi Yu
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Infectious Diseases, Shulan Hospital, Hangzhou, China.
Hepatol Res. 2019 Jan;49(1):42-50. doi: 10.1111/hepr.13251. Epub 2018 Oct 18.
Flare-ups of chronic hepatitis B can sometimes be severe and even progress to acute-on-chronic liver failure (ACLF), with high short-term mortality. A timely estimation of the risk of death should be initiated early. The aim of the present study was to determine whether novel biomarkers add prognostic information beyond current clinical scoring systems.
Patients with hepatitis B-associated ACLF were prospectively enrolled from five hospitals in China between August 2017 and March 2018. Their plasma was screened for soluble CD163 (sCD163), neutrophil gelatinase-associated lipocalin (NGAL), and copeptin. The association between these biomarkers and mortality was analyzed. The performance of the Model for End-stage Liver Disease, Asian-Pacific Association for the Study of the Liver-ACLF Research Consortium score, and the Chronic Liver Failure Consortium ACLF score, with or without biomarkers, were compared.
One hundred fifty one patients were enrolled. Advanced ACLF patients had significantly higher levels than early ACLF individuals of plasma biomarkers sCD163 (P = 0.001), NGAL (P = 0.006), and copeptin (P = 0.049). Thirty-four deaths occurred during the 28-day follow-up period (22.5%). Both sCD163 and NGAL showed a strong independent association with 28-day mortality, whereas copeptin did not. Scoring systems incorporating sCD163 and NGAL had better discrimination and calibration, as measured by area under the receiver operating characteristic curves, the Akaike information criteria, integrated discrimination improvement, and net reclassification improvement.
Soluble CD163 and NGAL are independently associated with short-term mortality in hepatitis B-associated ACLF. Use of a combination of sCD163 and NGAL improves prognostication.
慢性乙型肝炎的病情发作有时会很严重，甚至进展为慢加急性肝衰竭（ACLF），短期死亡率很高。应尽早开始对死亡风险进行及时评估。本研究的目的是确定新型生物标志物是否能在现有临床评分系统之外增加预后信息。
2017年8月至2018年3月期间，在中国的五家医院前瞻性招募了乙型肝炎相关ACLF患者。对他们的血浆进行可溶性CD163（sCD163）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和 copeptin 的筛查。分析这些生物标志物与死亡率之间的关联。比较了终末期肝病模型、亚太肝脏研究协会 - ACLF 研究联盟评分以及慢性肝衰竭联盟ACLF评分在有或没有生物标志物情况下的表现。
共纳入151例患者。晚期ACLF患者血浆生物标志物sCD163（P = 0.001）、NGAL（P = 0.006）和copeptin（P = 0.049）的水平显著高于早期ACLF患者。在28天的随访期内发生了34例死亡（22.5%）。sCD163和NGAL均与28天死亡率呈现出强烈的独立关联，而copeptin则没有。通过受试者工作特征曲线下面积、赤池信息准则、综合判别改善和净重新分类改善来衡量，纳入sCD163和NGAL的评分系统具有更好的区分度和校准度。
可溶性CD163和NGAL与乙型肝炎相关ACLF的短期死亡率独立相关。联合使用sCD163和NGAL可改善预后。
