Circulating Receptor-Interacting Protein Kinase 3 Are Increased in HBV Patients With Acute-on-Chronic Liver Failure and Are Associated With Clinical Outcome

Frontiers in Physiology

Kehui Liu¹  Hui Wang²  Liwen Chen²  Qing Xie²  Yezhou Ding²  Xiaogang Xiang²  Zhujun Cao²  Lei Yan²  Shisan Bao³  Chuanwu Zhu⁴  Xinghua Shen⁴ 

[1] Department of Infectious Diseases, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Discipline of Pathology, School of Medical Sciences and Bosch Institute, Charles Perkin Centre, University of Sydney, Sydney, NSW, Australia;Intensive Care Unit, The Affiliated Infectious Diseases Hospital of Soochow University, Jiangsu, China;

关键词: HBV;    acute-on-chronic liver failure;    cell death;    RIPK3;    necroptosis;   

DOI  :  10.3389/fphys.2020.00526

来源: DOAJ

【 摘 要 】

Background and AimsNecroptosis is a newly identified type of cell death with programmed pathways. The current study was performed to investigate necroptosis by measuring its key regulators; receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) in patients with Hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF).MethodsHBV-related ACLF (HBV-ACLF) patients (n = 90), non-ACLF patients without cirrhosis (N = 70), patients with cirrhosis (N = 40), and healthy controls (HCs; n = 70) were enrolled in the study. All patients were subject to serum RIPK3 measurement. Hepatic RIPK3 and MLKL were also determined in the livers of 18 patients and five donors, using immunohistochemistry.ResultsSerum RIPK3 was significantly elevated in HBV-ACLF patients compared to that of non-ACLF patients and the HCs. Serum RIPK3 in ACLF patients at recruitment was significantly higher in non-survivors than those in survivors at the 90-day follow-up. The predictive accuracy of serum RIPK3 at the 90-day outcome was relatively good with an area under the receiver operating curve (AUROC) of 0.72 (p < 0.001), similar to that of the model of end-staged liver disease (MELD) score (0.76, p < 0.001). The combined use of RIPK3 and MELD score further increased the AUROC to 0.80. The hepatic RIPK3 and MLKL measured by immunohistochemistry, significantly increased in the patients with HBV-ACLF than in the patients without ACLF and the HCs.ConclusionCirculating RIPK3 was significantly increased in patients with HBV-ACLF and was associated with a clinical outcome. The improved combined objective scores could offer additional prognostic value in ACLF patients, for physicians with more accurate expectations.

【 授权许可】

Unknown