Bikunin: A Promising Prognostic Biomarker for Acute-on-Chronic Liver Failure in Patients with Viral Hepatitis B

Abstract

Purpose

To screen out potential prognostic biomarkers for HBV-related acute-on-chronic liver failure (HBV-ACLF).

Patients and Methods

Peripheral blood samples of HBV-ACLF patients (n=56) and normal controls (n=15) from the Affiliated Hospital of Southwest Medical University from January 2021 to April 2022 were collected, 5 normal patients and 10 patients with ACLF were randomly selected for Data independent acquisition (DIA) mass spectrometry analysis, and the potential core proteins were screened out via bioinformatics. All samples were validated by Enzyme linked immunosorbent assays (ELISA) technology, and the survival curve was constructed based on the patient’s 90-day survival time.

Results

A total of 247 differentially expressed proteins (DEPs) were screened, of which 148 were upregulated and 99 were down-regulated. The DEPs were mainly enriched in high-density lipoprotein particle remodeling, coagulation, and hemostasis and participated in signaling pathways such as cholesterol metabolism, coagulation cascades, and PPAR signaling pathway. Finally, bikunin was selected for further study and validated via the ELISA, compared with the normal group, bikunin was poorly expressed in the HBV-ACLF group, the difference was statistically significant (P < 0.0001), the area under the curve (AUC) for Receiver operating characteristic (ROC) analysis was 0.917. Furthermore, compared with the non-survival group, bikunin was highly expressed in the HBV-ACLF survival group, the difference was statistically significant (P=0.0015), and the survival curve showed a positive correlation with patient survival (P=0.0063).

Conclusion

The level of plasma bikunin in HBV-ACLF is down-regulated, which is positively correlated with the survival of the patients with HBV-ACLF, and is expected to become a new prognostic biomarker.

Keywords:

• HBV-ACLF
• AMBP
• bikunin
• DIA

Data Sharing Statement

The DIA data are available at the China National GeneBank DateBase Sequence Archive (CNSA) with the accession number CNP0002611. The clinical raw data of this article will be made available by the corresponding author.

Ethics Approval and Consent to Participate

The study protocol and informed consent were approved by the Clinical Experiment Ethics Committee of Affiliated Hospital of Southwest Medical University (No: KY2021014). The clinical trial registration No. was ChiCTR2100042896. Written informed consents were obtained from all study participants. This study was conducted in accordance with all the guidelines and principles described in the Declaration of Helsinki.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by the Strategic Cooperation Project of Suining First People’s Hospital – Southwest Medical University (2020SNXNYD02); Department of Science and Technology of Sichuan Province (2022NSFSC1522).