SPP1 as a risk factor for patients with acute on chronic liver failure undergoing liver transplantation

Yeping Yu; Xinyi Mao; Jieying Wang; Mo Chen; Fang Wang; Xiaoni Kong; Hualian Hang

doi:10.1016/j.intimp.2023.110355

SPP1 as a risk factor for patients with acute on chronic liver failure undergoing liver transplantation

Int Immunopharmacol. 2023 Jul:120:110355. doi: 10.1016/j.intimp.2023.110355. Epub 2023 May 29.

Authors

Yeping Yu¹, Xinyi Mao², Jieying Wang³, Mo Chen², Fang Wang⁴, Xiaoni Kong⁴, Hualian Hang⁵

Affiliations

¹ Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
² Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Clinical Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
⁵ Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: hanghualian@shsmu.edu.cn.

PMID: 37257271
DOI: 10.1016/j.intimp.2023.110355

Abstract

Background: Acute on chronic liver failure (ACLF) is characterized by systemic inflammation and significant mortality, calling for accurate assessment due to the diverse prognosis of liver transplantation (LT).

Methods: 8 patients with ACLF and 4 normal controls (NC) underwent peripheral blood mononuclear cells (PBMCs) transcriptomics, whereas 9 patients with ACLF and 3 NC had hepatic CD45⁺ T cells transcriptomics. Thecandidateindicatorfoundinthetranscriptomicswas confirmedbya retrospective cohort (n = 137) and one prospective cohort (n = 68).

Results: Transcriptomics revealed significant differentially expression genes (DEGs) and bioprocesses related to the PBMCs and hepatic CD45⁺ T cells. Secreted phosphoprotein 1 (SPP1) was identified as a potential indicator for ACLF patients receiving LT, which was supported by evidence from the cross-sectional cohorts. As the condition of ACLF got worse, so did SPP1 levels, which were associated with liver failure and coagulation failure. SPP1 levels prior to LT were considerably greater in non-survivors of ACLF within 90 days than that in survivors. In the derivation cohort and validation cohort, ACLF patients with elevated SPP1 levels had significantly shorter cumulative survival durations than those with low SPP1 levels, P = 0.02 and P < 0.001, respectively. The SPP1-MELD and SPP1-chronic liver failure consortium (CLIF-C) ACLF scores had comparatively larger areas under the receiver operating characteristic curves (AUCs) than MELD (P = 0.0388) and CLIF-C ACLF (P = 0.045).

Conclusions: The circulating SPP1 showed promise as a predictor for ACLF patients receiving LT, which demonstrated the need for tracking the clinical outcome of LT.

Keywords: Acute on chronic liver failure; Indicator; Liver transplantation; SPP1.

MeSH terms

Acute-On-Chronic Liver Failure* / complications
Acute-On-Chronic Liver Failure* / surgery
Cross-Sectional Studies
End Stage Liver Disease* / complications
End Stage Liver Disease* / surgery
Humans
Leukocytes, Mononuclear
Liver Cirrhosis
Liver Transplantation* / adverse effects
Osteopontin
Prognosis
Prospective Studies
Retrospective Studies
Risk Factors

Substances

Osteopontin
SPP1 protein, human