Plasma S100A8 and S100A9 Are Strong Prognostic Factors for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

Yao Zhang; Xueyun Zhang; Jiajia Han; Yifei Guo; Jingjing He; Feifei Yang; Richeng Mao; Yuxian Huang; Jiming Zhang

doi:10.1155/2023/6164611

Plasma S100A8 and S100A9 Are Strong Prognostic Factors for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

Can J Gastroenterol Hepatol. 2023 Jul 10:2023:6164611. doi: 10.1155/2023/6164611. eCollection 2023.

Authors

Yao Zhang¹, Xueyun Zhang¹, Jiajia Han¹, Yifei Guo¹, Jingjing He¹, Feifei Yang¹, Richeng Mao¹, Yuxian Huang^{1

2}, Jiming Zhang^{1

3}

Affiliations

¹ 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.
² Department of Hepatitis Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
³ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Abstract

Objectives: 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).

Methods: 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.

Results: The plasma levels of the S100A8 and S100A9 were higher in HBV-ACLF patients than in CHB patients (S100A8 : P < 0.001 and S100A9 : P < 0.001) and healthy controls (S100A8 : P < 0.001 and S100A9 : P < 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; P=0.026, S100A9 : HR: 1.009; 95% CI: 1.001-1.017; P=0.007, 90-day: S100A8 : HR: 1.023; 95% CI: 1.011-1.035; P=0.004, S100A9 : HR: 1.008; 95% CI: 1.004-1.012; and P < 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.

Conclusions: 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.

MeSH terms

Acute-On-Chronic Liver Failure* / virology
Biomarkers
Hepatitis B virus / genetics
Hepatitis B, Chronic* / complications
Humans
Organ Dysfunction Scores
Prognosis
ROC Curve
Retrospective Studies

Substances

Biomarkers
S100A8 protein, human
S100A9 protein, human