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Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis
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 chroni...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10397215/ https://www.ncbi.nlm.nih.gov/pubmed/37532736 http://dx.doi.org/10.1038/s41420-023-01551-6 |
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author | 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 |
author_facet | 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 |
author_sort | Staufer, Katharina |
collection | PubMed |
description | 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. [Image: see text] |
format | Online Article Text |
id | pubmed-10397215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103972152023-08-04 Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis 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 Cell Death Discov Article 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. [Image: see text] Nature Publishing Group UK 2023-08-02 /pmc/articles/PMC10397215/ /pubmed/37532736 http://dx.doi.org/10.1038/s41420-023-01551-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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 Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis |
title | Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis |
title_full | Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis |
title_fullStr | Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis |
title_full_unstemmed | Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis |
title_short | Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis |
title_sort | gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10397215/ https://www.ncbi.nlm.nih.gov/pubmed/37532736 http://dx.doi.org/10.1038/s41420-023-01551-6 |
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