Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Department of Hepatitis Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Can J Gastroenterol Hepatol. 2023 Jul 10;2023:6164611. doi: 10.1155/2023/6164611. eCollection 2023.
The rapidly evolving organ failure and high short-run mortality of acute-on-chronic liver failure (ACLF) are inseparable from the role of systemic inflammatory response. S100A8 and S100A9 are associated with the excessive cytokine storm and play a decisive part within the process of inflammation. We aimed to clarify the role of them in predicting prognosis of hepatitis B virus-related ACLF (HBV-ACLF).
S100A8 and S100A9 levels were analyzed in plasma of 187 transplant-free HBV-ACLF patients, 28 healthy controls and 40 chronic hepatitis B (CHB) patients. S100A8 and S100A9 mRNAs were checked in liver samples from 32 HBV-ACLF patients with liver transplantation, 19 patients undergoing surgery for hepatic hemangioma and 10 CHB patients with needle biopsy.
The plasma levels of the S100A8 and S100A9 were higher in HBV-ACLF patients than in CHB patients (S100A8 : < 0.001 and S100A9 : < 0.001) and healthy controls (S100A8 : < 0.001 and S100A9 : < 0.001), and similar results were obtained for mRNA expression. Moreover, both proteins were related to ACLF grade, different types of organ failure, and infection, and they correlated with other prognostic scoring systems. S100A8 and S100A9 can dependently predict 28/90-day mortality (28-day: S100A8: hazard ratio (HR): 1.027; 95% confidence interval (CI): 1.007-1.048; =0.026, S100A9 : HR: 1.009; 95% CI: 1.001-1.017; =0.007, 90-day: S100A8 : HR: 1.023; 95% CI: 1.011-1.035; =0.004, S100A9 : HR: 1.008; 95% CI: 1.004-1.012; and < 0.001). Among all of the scoring systems, the combined scoring model (S100A8 and S100A9 jointly with the Chronic Liver Failure-Consortium Organ Failure score (CLIF-C OFs)) displayed the highest area under the receiver operating curve (0.923 (95% CI, 0.887-0.961)) in the prediction of 90-day mortality.
S100A8 and S100A9 are promising biomarkers for the analysis of risk stratification and prognosis in ACLF patients. In addition, combining them with the CLIF-C OFs may better predict the prognosis of ACLF.
急性肝衰竭（ACLF）的器官衰竭迅速进展和短期高死亡率与全身炎症反应的作用密不可分。S100A8 和 S100A9 与过度细胞因子风暴有关，并在炎症过程中起决定性作用。我们旨在阐明它们在预测乙型肝炎病毒相关 ACLF（HBV-ACLF）预后中的作用。
分析了 187 例无肝移植 HBV-ACLF 患者、28 名健康对照者和 40 名慢性乙型肝炎（CHB）患者的血浆 S100A8 和 S100A9 水平。检查了 32 例接受肝移植的 HBV-ACLF 患者、19 例接受肝血管瘤手术治疗的患者和 10 例接受 CHB 肝活检的患者的肝组织 S100A8 和 S100A9mRNA。
HBV-ACLF 患者的血浆 S100A8 和 S100A9 水平高于 CHB 患者（S100A8：<0.001 和 S100A9：<0.001）和健康对照者（S100A8：<0.001 和 S100A9：<0.001），mRNA 表达也得到了类似的结果。此外，这两种蛋白均与 ACLF 分级、不同类型的器官衰竭和感染有关，且与其他预后评分系统相关。S100A8 和 S100A9 可独立预测 28/90 天死亡率（28 天：S100A8：危险比（HR）：1.027；95%置信区间（CI）：1.007-1.048；=0.026，S100A9：HR：1.009；95%CI：1.001-1.017；=0.007，90 天：S100A8：HR：1.023；95%CI：1.011-1.035；=0.004，S100A9：HR：1.008；95%CI：1.004-1.012；<0.001）。在所有评分系统中，联合评分模型（S100A8 和 S100A9 联合慢性肝衰竭联盟器官衰竭评分（CLIF-C OFs））在预测 90 天死亡率方面显示出最高的受试者工作特征曲线下面积（0.923（95%CI，0.887-0.961））。
S100A8 和 S100A9 是分析 ACLF 患者风险分层和预后的有前途的生物标志物。此外，将其与 CLIF-C OFs 相结合可能更好地预测 ACLF 的预后。
