Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease
Background: Liver disease is often characterized by the activation of coagulation and inflammation. Experimental studies suggest that the interaction between neutrophils and platelets with local activation of coagulation could contribute to liver injury progression, but there have been limited studi...
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Elsevier
2025-01-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037924003613 |
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| author | Fien A. von Meijenfeldt Ton Lisman Alessandra Pacheco Yoh Zen William Bernal |
| author_facet | Fien A. von Meijenfeldt Ton Lisman Alessandra Pacheco Yoh Zen William Bernal |
| author_sort | Fien A. von Meijenfeldt |
| collection | DOAJ |
| description | Background: Liver disease is often characterized by the activation of coagulation and inflammation. Experimental studies suggest that the interaction between neutrophils and platelets with local activation of coagulation could contribute to liver injury progression, but there have been limited studies in humans. Objectives: We studied the hemostatic components and neutrophil extracellular traps (NETs) in liver biopsies from patients with different inflammatory liver diseases. Methods: Liver biopsies from patients with inflammatory liver disease (alcoholic steatohepatitis [ASH], autoimmune hepatitis, primary sclerosing cholangitis, metabolic-associated steatohepatitis, and allograft ischemia-reperfusion injury (IRI), each n = 20) were stained for fibrin(ogen), platelets, and NETs. The correlation of NET formation with deposition of hemostatic components and laboratory measures of disease severity was investigated. Results: In 75% of the liver biopsies, no fibrin(ogen) was detectable, and only 20% of the biopsies showed minimal deposition. Overall, 50% of liver biopsies stained positive for NETs. Platelet deposition and NET formation were highest in IRI, where it correlated with histologic severity of injury (r = .61 [95% CI, .22-.84]; P < .01) and ASH. Platelet deposition was associated with NET formation (r = .44 [95% CI, .27-.59]; P < .001) and colocalized in the biopsies. NET formation, but not fibrin and platelet deposition, was moderately associated with the model of end-stage liver disease score (r = .29 [95% CI, .07-.49]; P < .01). Conclusion: In contrast to experimental studies, we demonstrated minimal intrahepatic fibrin(ogen) deposition in different types of human inflammatory liver disease. Histologic evidence for intrahepatic NETs was common and most pronounced in acute ASH and IRI and was associated with platelet deposition and disease severity. |
| format | Article |
| id | doaj-art-e324ac3daf5646bb8b1a253a0fda531f |
| institution | Kabale University |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-e324ac3daf5646bb8b1a253a0fda531f2025-01-31T05:12:10ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-0191102666Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver diseaseFien A. von Meijenfeldt0Ton Lisman1Alessandra Pacheco2Yoh Zen3William Bernal4Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, Groningen, the NetherlandsSurgical Research Laboratory, Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands; Correspondence Ton Lisman, Department of Surgery, University Medical Center Groningen, BA33, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.Institute of Liver Studies, King’s College Hospital, London, United KingdomInstitute of Liver Studies, King’s College Hospital, London, United KingdomInstitute of Liver Studies, King’s College Hospital, London, United Kingdom; Liver Intensive Care Unit, Institute of Liver Studies, King’s College Hospital, London, United KingdomBackground: Liver disease is often characterized by the activation of coagulation and inflammation. Experimental studies suggest that the interaction between neutrophils and platelets with local activation of coagulation could contribute to liver injury progression, but there have been limited studies in humans. Objectives: We studied the hemostatic components and neutrophil extracellular traps (NETs) in liver biopsies from patients with different inflammatory liver diseases. Methods: Liver biopsies from patients with inflammatory liver disease (alcoholic steatohepatitis [ASH], autoimmune hepatitis, primary sclerosing cholangitis, metabolic-associated steatohepatitis, and allograft ischemia-reperfusion injury (IRI), each n = 20) were stained for fibrin(ogen), platelets, and NETs. The correlation of NET formation with deposition of hemostatic components and laboratory measures of disease severity was investigated. Results: In 75% of the liver biopsies, no fibrin(ogen) was detectable, and only 20% of the biopsies showed minimal deposition. Overall, 50% of liver biopsies stained positive for NETs. Platelet deposition and NET formation were highest in IRI, where it correlated with histologic severity of injury (r = .61 [95% CI, .22-.84]; P < .01) and ASH. Platelet deposition was associated with NET formation (r = .44 [95% CI, .27-.59]; P < .001) and colocalized in the biopsies. NET formation, but not fibrin and platelet deposition, was moderately associated with the model of end-stage liver disease score (r = .29 [95% CI, .07-.49]; P < .01). Conclusion: In contrast to experimental studies, we demonstrated minimal intrahepatic fibrin(ogen) deposition in different types of human inflammatory liver disease. Histologic evidence for intrahepatic NETs was common and most pronounced in acute ASH and IRI and was associated with platelet deposition and disease severity.http://www.sciencedirect.com/science/article/pii/S2475037924003613cirrhosiscoagulationliver injuryplateletsthrombosis |
| spellingShingle | Fien A. von Meijenfeldt Ton Lisman Alessandra Pacheco Yoh Zen William Bernal Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease Research and Practice in Thrombosis and Haemostasis cirrhosis coagulation liver injury platelets thrombosis |
| title | Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease |
| title_full | Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease |
| title_fullStr | Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease |
| title_full_unstemmed | Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease |
| title_short | Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease |
| title_sort | histologic evidence of neutrophil extracellular traps and fibrin ogen deposition in liver biopsies from patients with inflammatory liver disease |
| topic | cirrhosis coagulation liver injury platelets thrombosis |
| url | http://www.sciencedirect.com/science/article/pii/S2475037924003613 |
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