Analysis of the prognostic efficacy of syndecan-1 for patients with ACLF and its functional role in liver regeneration
Abstract Background Acute‐on‐chronic liver failure (ACLF) is a syndrome characterized by systemic inflammation with a high short-term mortality rate. Syndecan-1 (SDC-1) can independently predict the 90-day mortality of patients with septic shock. However, the role of SDC-1 in ACLF remains unknown. M...
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2025-02-01
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| Online Access: | https://doi.org/10.1186/s12916-025-03931-4 |
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| author | Yingli He Xiaoli Zhang Yichen Yao Juan Li Shan Fu Yali Feng Tianzhi Ni Ruojing Wang Qiao Zhang Yushan Liu Zhijun Liu Jinfeng Liu Yuan Yang Yingren Zhao Yalei Zhao |
| author_facet | Yingli He Xiaoli Zhang Yichen Yao Juan Li Shan Fu Yali Feng Tianzhi Ni Ruojing Wang Qiao Zhang Yushan Liu Zhijun Liu Jinfeng Liu Yuan Yang Yingren Zhao Yalei Zhao |
| author_sort | Yingli He |
| collection | DOAJ |
| description | Abstract Background Acute‐on‐chronic liver failure (ACLF) is a syndrome characterized by systemic inflammation with a high short-term mortality rate. Syndecan-1 (SDC-1) can independently predict the 90-day mortality of patients with septic shock. However, the role of SDC-1 in ACLF remains unknown. Methods In this study, serum SDC-1 levels were examined in 2 cohorts, which included 174 ACLF patients. And a mouse ACLF model induced by tetrachloride, lipopolysaccharide, and D-galactosamine was established, to evaluate the effects of sulodexide and heparan sulfate (side chains of SDC-1) on ACLF in vivo. Results Baseline serum SDC-1 levels in 101 ACLF patients (847.72, 499.79–1511.37 ng/ml) were significantly higher than in healthy controls (33.58, 27.08–43.34 ng/ml) (P < 0.0001). The baseline SDC-1 levels of patients who died or accepted a liver transplantation within 90 days were markedly higher than those of patients who survived (P < 0.05). A novel prognostic model (UIAS) based on upper gastrointestinal bleeding, INR, age, and SDC-1 was developed. The AUROC of the UIAS score for 28-day deterioration in ACLF patients was 0.884, indicating an obviously greater predictive performance for the outcomes of ACLF than those of the Child‐Pugh (AUROC = 0.646), MELD (AUROC = 0.713), and COSSH‐ACLF II scores (AUROC = 0.713). Moreover, we found that heparan sulfate and sulodexide could increase the expression of SDC-1 and attenuate liver injury, by promoting liver regeneration and inhibiting cell apoptosis through the activation of JAK1/STAT3 signalling. Conclusions Collectively, our findings suggest that SDC-1 represents a potential prognostic and therapeutic target for ACLF and should be further investigated. |
| format | Article |
| id | doaj-art-c8ddb5e1255b493fb41ce6c977a712b0 |
| institution | OA Journals |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj-art-c8ddb5e1255b493fb41ce6c977a712b02025-08-20T02:15:06ZengBMCBMC Medicine1741-70152025-02-0123111710.1186/s12916-025-03931-4Analysis of the prognostic efficacy of syndecan-1 for patients with ACLF and its functional role in liver regenerationYingli He0Xiaoli Zhang1Yichen Yao2Juan Li3Shan Fu4Yali Feng5Tianzhi Ni6Ruojing Wang7Qiao Zhang8Yushan Liu9Zhijun Liu10Jinfeng Liu11Yuan Yang12Yingren Zhao13Yalei Zhao14Department of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeNanfang Hospital, Southern Medical UniversityDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeDepartment of Infectious Diseases, the First Affiliated Hospital of Xi’an Jiaotong University Medical CollegeAbstract Background Acute‐on‐chronic liver failure (ACLF) is a syndrome characterized by systemic inflammation with a high short-term mortality rate. Syndecan-1 (SDC-1) can independently predict the 90-day mortality of patients with septic shock. However, the role of SDC-1 in ACLF remains unknown. Methods In this study, serum SDC-1 levels were examined in 2 cohorts, which included 174 ACLF patients. And a mouse ACLF model induced by tetrachloride, lipopolysaccharide, and D-galactosamine was established, to evaluate the effects of sulodexide and heparan sulfate (side chains of SDC-1) on ACLF in vivo. Results Baseline serum SDC-1 levels in 101 ACLF patients (847.72, 499.79–1511.37 ng/ml) were significantly higher than in healthy controls (33.58, 27.08–43.34 ng/ml) (P < 0.0001). The baseline SDC-1 levels of patients who died or accepted a liver transplantation within 90 days were markedly higher than those of patients who survived (P < 0.05). A novel prognostic model (UIAS) based on upper gastrointestinal bleeding, INR, age, and SDC-1 was developed. The AUROC of the UIAS score for 28-day deterioration in ACLF patients was 0.884, indicating an obviously greater predictive performance for the outcomes of ACLF than those of the Child‐Pugh (AUROC = 0.646), MELD (AUROC = 0.713), and COSSH‐ACLF II scores (AUROC = 0.713). Moreover, we found that heparan sulfate and sulodexide could increase the expression of SDC-1 and attenuate liver injury, by promoting liver regeneration and inhibiting cell apoptosis through the activation of JAK1/STAT3 signalling. Conclusions Collectively, our findings suggest that SDC-1 represents a potential prognostic and therapeutic target for ACLF and should be further investigated.https://doi.org/10.1186/s12916-025-03931-4Acute‐on‐chronic liver failureSyndecan-1Heparan sulfateSulodexideLiver regenerationCell apoptosis |
| spellingShingle | Yingli He Xiaoli Zhang Yichen Yao Juan Li Shan Fu Yali Feng Tianzhi Ni Ruojing Wang Qiao Zhang Yushan Liu Zhijun Liu Jinfeng Liu Yuan Yang Yingren Zhao Yalei Zhao Analysis of the prognostic efficacy of syndecan-1 for patients with ACLF and its functional role in liver regeneration BMC Medicine Acute‐on‐chronic liver failure Syndecan-1 Heparan sulfate Sulodexide Liver regeneration Cell apoptosis |
| title | Analysis of the prognostic efficacy of syndecan-1 for patients with ACLF and its functional role in liver regeneration |
| title_full | Analysis of the prognostic efficacy of syndecan-1 for patients with ACLF and its functional role in liver regeneration |
| title_fullStr | Analysis of the prognostic efficacy of syndecan-1 for patients with ACLF and its functional role in liver regeneration |
| title_full_unstemmed | Analysis of the prognostic efficacy of syndecan-1 for patients with ACLF and its functional role in liver regeneration |
| title_short | Analysis of the prognostic efficacy of syndecan-1 for patients with ACLF and its functional role in liver regeneration |
| title_sort | analysis of the prognostic efficacy of syndecan 1 for patients with aclf and its functional role in liver regeneration |
| topic | Acute‐on‐chronic liver failure Syndecan-1 Heparan sulfate Sulodexide Liver regeneration Cell apoptosis |
| url | https://doi.org/10.1186/s12916-025-03931-4 |
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