Staufer, Katharina; Huber, Heidemarie; Zessner-Spitzenberg, Jasmin; Stauber, Rudolf; Finkenstedt, Armin; Bantel, Heike; Weiss, Thomas S; Huber, Markus; Starlinger, Patrick; Gruenberger, Thomas; Reiberger, Thomas; Sebens, Susanne; McIntyre, Gail; Tabibiazar, Ray; Giaccia, Amato; Zoller, Heinz; Trauner, Michael; Mikulits, Wolfgang (2023). Gas6 in chronic liver disease-a novel blood-based biomarker for liver fibrosis. Cell death discovery, 9(1), p. 282. Nature 10.1038/s41420-023-01551-6
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The expression of the receptor tyrosine kinase Axl and its cleavage product soluble Axl (sAxl) is increased in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this multicenter study, we evaluated the diagnostic value of Gas6, the high-affinity ligand of Axl, in patients with chronic liver disease. Levels of sAxl and Gas6, and their albumin (alb) ratios were analyzed in serum samples of patients with biopsy-proven liver fibrosis, end-stage liver disease, HCC, and healthy controls, and were compared to Fibrosis-4 (FIB-4), enhanced liver fibrosis (ELF™) test, Child-Pugh score (CPS), model of end-stage liver disease (MELD) score, hepatic venous pressure gradient, and α-fetoprotein, respectively. A total of 1111 patients (median age 57.8 y, 67.3% male) was analyzed. Gas6/alb showed high diagnostic accuracy for the detection of significant (≥F2: AUC 0.805) to advanced fibrosis (≥F3: AUC 0.818), and was superior to Fib-4 for the detection of cirrhosis (F4: AUC 0.897 vs. 0.878). In addition, Gas6/alb was highly predictive of liver disease severity (Odds ratios for CPS B/C, MELD ≥ 15, and clinically significant portal hypertension (CSPH) were 16.534, 10.258, and 12.115), and was associated with transplant-free survival (Hazard ratio 1.031). Although Gas6 and Gas6/alb showed high diagnostic accuracy for the detection of HCC in comparison to chronic liver disease patients without cirrhosis (AUC 0.852, 0.868), they failed to discriminate between HCC in cirrhosis versus cirrhosis only. In conclusion, Gas6/alb shows a high accuracy to detect significant to advanced fibrosis and cirrhosis, and predicts severity of liver disease including CSPH.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy > Partial clinic Insel 04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy |
UniBE Contributor: |
Huber, Markus |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2058-7716 |
Publisher: |
Nature |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
03 Aug 2023 10:47 |
Last Modified: |
20 Aug 2023 02:37 |
Publisher DOI: |
10.1038/s41420-023-01551-6 |
PubMed ID: |
37532736 |
BORIS DOI: |
10.48350/185198 |
URI: |
https://boris.unibe.ch/id/eprint/185198 |
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