Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis
Abstract 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 wi...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01551-6 |
| _version_ | 1797752840206155776 |
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| author | Katharina Staufer Heidemarie Huber Jasmin Zessner-Spitzenberg Rudolf Stauber Armin Finkenstedt Heike Bantel Thomas S. Weiss Markus Huber Patrick Starlinger Thomas Gruenberger Thomas Reiberger Susanne Sebens Gail McIntyre Ray Tabibiazar Amato Giaccia Heinz Zoller Michael Trauner Wolfgang Mikulits |
| author_facet | Katharina Staufer Heidemarie Huber Jasmin Zessner-Spitzenberg Rudolf Stauber Armin Finkenstedt Heike Bantel Thomas S. Weiss Markus Huber Patrick Starlinger Thomas Gruenberger Thomas Reiberger Susanne Sebens Gail McIntyre Ray Tabibiazar Amato Giaccia Heinz Zoller Michael Trauner Wolfgang Mikulits |
| author_sort | Katharina Staufer |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T17:10:18Z |
| format | Article |
| id | doaj.art-6ec11fb752674d009f3b4dccfb87f223 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-12T17:10:18Z |
| publishDate | 2023-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-6ec11fb752674d009f3b4dccfb87f2232023-08-06T11:06:58ZengNature Publishing GroupCell Death Discovery2058-77162023-08-01911810.1038/s41420-023-01551-6Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosisKatharina Staufer0Heidemarie Huber1Jasmin Zessner-Spitzenberg2Rudolf Stauber3Armin Finkenstedt4Heike Bantel5Thomas S. Weiss6Markus Huber7Patrick Starlinger8Thomas Gruenberger9Thomas Reiberger10Susanne Sebens11Gail McIntyre12Ray Tabibiazar13Amato Giaccia14Heinz Zoller15Michael Trauner16Wolfgang Mikulits17Department of General Surgery, Division of Transplantation, Medical University of ViennaCenter for Cancer Research, Comprehensive Cancer Center Vienna, Medical University of ViennaCenter for Cancer Research, Comprehensive Cancer Center Vienna, Medical University of ViennaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of GrazDepartment of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of InnsbruckDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical SchoolCenter for Liver Cell Research, Children’s University Hospital (KUNO), University of Regensburg HospitalDepartment of Anesthesiology and Pain Therapy, Inselspital, University Hospital BernDepartment of Surgery, Division of General Surgery, Medical University of ViennaClinicum Favoriten, HPB Center, Vienna Health Network and Sigmund Freud Private UniversityDepartment of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of ViennaInstitute for Experimental Cancer Research, Kiel University and University Hospital Schleswig-Holstein (UKSH) Campus KielAravive BiologicsAravive BiologicsAravive BiologicsDepartment of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of InnsbruckDepartment of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of ViennaCenter for Cancer Research, Comprehensive Cancer Center Vienna, Medical University of ViennaAbstract 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.https://doi.org/10.1038/s41420-023-01551-6 |
| spellingShingle | Katharina Staufer Heidemarie Huber Jasmin Zessner-Spitzenberg Rudolf Stauber Armin Finkenstedt Heike Bantel Thomas S. Weiss Markus Huber Patrick Starlinger Thomas Gruenberger Thomas Reiberger Susanne Sebens Gail McIntyre Ray Tabibiazar Amato Giaccia Heinz Zoller Michael Trauner Wolfgang Mikulits Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis Cell Death Discovery |
| 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 |
| url | https://doi.org/10.1038/s41420-023-01551-6 |
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