FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3117369512> ?p ?o ?g. }

• W3117369512 endingPage "1265" @default.
• W3117369512 startingPage "1264" @default.
• W3117369512 abstract "With great interest we read the recent paper by Arroyo and coworkers in Journal of Hepatology, in which they propose that systemic inflammation plays a central role in the transition from compensated to decompensated cirrhosis, and the development of acute decompensation and acute-on-chronic liver failure (ACLF)[1]Arroyo V. Angeli P. Moreau R. Jalan R. Claria J. Trebicka J. et al.The systemic inflammation hypothesis: towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis.J Hepatol. 2021; 74: 670-685Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar We fully concur with the authors that this intriguing hypothesis will create new research perspectives, and would like to propose one such research theme, not directly addressed by the authors. It has been well established that inflammatory responses are accompanied by activation of coagulation, and vice versa.[2]Foley J.H. Conway E.M. Cross talk pathways between coagulation and inflammation.Circ Res. 2016; 118: 1392-1408Crossref PubMed Scopus (190) Google Scholar Thus, if inflammatory responses drive clinical deterioration in patients with liver disease, there is likely exaggeration of coagulation activation in decompensating patients. We propose a number of potential consequences of an inflammation-induced activation of coagulation in patients with decompensating disease. First, intrahepatic activation of hemostasis with deposition of platelets and fibrin has been demonstrated in animal models of liver disease.[3]Kopec A.K. Joshi N. Luyendyk J.P. Role of hemostatic factors in hepatic injury and disease: animal models de-liver.J Thromb Haemost. 2016; 14: 1337-1349Crossref PubMed Scopus (18) Google Scholar This intrahepatic activation of coagulation was demonstrated to propagate disease progression by 1) inducing local ischemia, 2) activation of hepatic cells by coagulation proteases, 3) effects of fibrin on modulating cellular inflammatory responses.[3]Kopec A.K. Joshi N. Luyendyk J.P. Role of hemostatic factors in hepatic injury and disease: animal models de-liver.J Thromb Haemost. 2016; 14: 1337-1349Crossref PubMed Scopus (18) Google Scholar,[4]Luyendyk J.P. Schoenecker J.G. Flick M.J. The multifaceted role of fibrinogen in tissue injury and inflammation.Blood. 2019; 133: 511-520Crossref PubMed Scopus (80) Google Scholar We propose that inflammation-induced aggravation of coagulation will worsen intrahepatic deposition of fibrin and platelets and in this way hasten the progression of liver injury. Second, systemic inflammation will likely lead to systemic activation of hemostasis, which may result in fibrin deposition in extrahepatic tissues, leading to failure of other organs as is seen in patients with ACLF. Disseminated intravascular coagulation (DIC) may lead to multiple organ failure by a thrombotic mechanism.[5]Levi M. Sivapalaratnam S. Disseminated intravascular coagulation: an update on pathogenesis and diagnosis.Expert Rev Hematol. 2018; 11: 663-672Crossref PubMed Scopus (29) Google Scholar It has long been debated whether patients with cirrhosis develop DIC, but the systemic inflammation hypothesis would suggest that (low-grade) DIC will develop in the decompensating patient, consistent with the concept that inflammation-mediated activation of coagulation could contribute to multiple organ failure in ACLF. In patients without underlying liver disease, inflammation is thought to result in upregulation of coagulation, impairment of natural anticoagulant mechanisms, and downregulation of fibrinolysis.[2]Foley J.H. Conway E.M. Cross talk pathways between coagulation and inflammation.Circ Res. 2016; 118: 1392-1408Crossref PubMed Scopus (190) Google Scholar In patients with compensated liver disease, these changes are already apparent, and inflammation-affiliated mechanisms are likely to aggravate these changes, potentially to a more thrombotic phenotype. This prothrombotic state could promote intraorgan microthrombosis that may contribute to multiple organ failure.[6]Jackson S.P. Darbousset R. Schoenwaelder S.M. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms.Blood. 2019; 133: 906-918Crossref PubMed Scopus (175) Google Scholar In addition, the thrombotic state could precipitate macrovascular events such as venous thrombosis and portal vein thrombosis. Third, local or systemic activation of coagulation would lead to consumption of coagulation factors. In this way, systemic inflammation may contribute to the further decline in hepatocyte-derived coagulation proteins by consumption, perhaps in addition to the decrease in coagulation factor synthesis. In this way, systemic inflammation may form the basis of the progressing hemostatic changes in decompensating patients.[7]Fisher C. Patel V.C. Stoy S.H. Singanayagam A. Adelmeijer J. Wendon J. et al.Balanced haemostasis with both hypo- and hyper-coagulable features in critically ill patients with acute-on-chronic-liver failure.J Crit Care. 2018; 43: 54-60Crossref PubMed Scopus (44) Google Scholar Forth, although downregulation of fibrinolysis is a hallmark of systemic inflammation in patients without underlying liver disease, the picture is more complicated in decompensating patients with cirrhosis.[8]Blasi A. Patel V.C. Adelmeijer J. Azarian S. Hernandez Tejero M. Calvo A. et al.Mixed fibrinolytic phenotypes in decompensated cirrhosis and acute-on-chronic liver failure with hypofibrinolysis in those with complications and poor survival.Hepatology. 2020; 71: 1381-1390Crossref PubMed Scopus (25) Google Scholar Mixed fibrinolytic patterns are observed in patients with acute decompensation and ACLF, with upregulation of fibrinolysis in acutely decompensating patients and downregulation of fibrinolysis in particular in those patients with sepsis. In acutely ill patients without underlying liver disease, the fibrinolytic system was uniformly downregulated.[9]Lisman T. Arefaine B. Adelmeijer J. Zamalloa A. Corcoran E. Smith J.G. et al.Global hemostatic status in patients with acute-on-chronic liver failure and septics without underlying liver disease.J Thromb Haemost. 2020; (in press. Available from:)https://pubmed.ncbi.nlm.nih.gov/33006808/Google Scholar There may indeed be divergent effects of liver injury and systemic inflammation on the fibrinolytic system, with additional study required as to whether the inflammatory response overrules the profibrinolytic effects of liver injury. Fifth, systemic inflammation with concomitant activation of coagulation will activate additional processes that may propagate injury to the liver and other organs. Such processes include the generation of neutrophil extracellular traps that may be formed in response to activation of hemostasis, and activation of complement that is also known to communicate with the coagulation system.[2]Foley J.H. Conway E.M. Cross talk pathways between coagulation and inflammation.Circ Res. 2016; 118: 1392-1408Crossref PubMed Scopus (190) Google Scholar,[10]von Meijenfeldt F.A. Jenne C.N. Netting liver disease: neutrophil extracellular traps in the initiation and exacerbation of liver pathology.Semin Thromb Hemost. 2020; 46: 724-734Crossref PubMed Scopus (2) Google Scholar Both of these processes have established roles in organ injury and their connection to the systemic inflammation hypothesis should not be overlooked. Overall, we propose that reciprocal connections between the hemostatic system and systemic inflammatory response may contribute to hepatic and extrahepatic injury and clinical deterioration in patients through enhancement of micro- or macrovascular thromboses. It will be of considerable interest to investigate whether anti-inflammatory or antithrombotic strategies (or a combination thereof) will halt clinical deterioration. Indeed, anticoagulant therapy reduced the risk of portal vein thrombosis and decompensation in a small randomized controlled trial,[11]Villa E. Cammà C. Marietta M. Luongo M. Critelli R. Colopi S. et al.Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis.Gastroenterology. 2012; 143: 1253-1260Abstract Full Text Full Text PDF PubMed Scopus (439) Google Scholar although these data require validation before this concept can be clinically applied. As a final remark, we suggest a need for precise definitions of systemic inflammation in this context. Classifying elevated circulating markers of inflammation as a true measure of systemic inflammation is challenging, as this could also be a readout of massive hepatic inflammation. This will be critical as we seek to understand whether a switch from hepatic to systemic inflammation is a cause or consequence of extrahepatic organ injury. It is also possible that the proportion of patients with genuine systemic inflammation in studies like PREDICT is unintentionally overestimated. This is because many inflammatory markers measured are cleared by the liver,[12]Andus T. Bauer J. Gerok W. Effects of cytokines on the liver.Hepatology. 1991; 13: 364-375Crossref PubMed Scopus (379) Google Scholar creating a scenario in which hepatic dysfunction indirectly elevates inflammatory biomarkers. The authors received no financial support to produce this manuscript. TL and JPL jointly wrote the manuscript. The authors have no conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details. The following is/are the supplementary data to this article: Download .pdf (.15 MB) Help with pdf files Multimedia component 1 The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosisJournal of HepatologyVol. 74Issue 3PreviewAcute decompensation (AD) of cirrhosis is defined by the development of ascites, hepatic encephalopathy and/or variceal bleeding. Ascites is traditionally attributed to splanchnic arterial vasodilation and left ventricular dysfunction, hepatic encephalopathy to hyperammonaemia, and variceal haemorrhage to portal hypertension. Recent large-scale European observational studies have shown that systemic inflammation is a hallmark of AD. Here we present a working hypothesis, the systemic inflammation hypothesis, suggesting that systemic inflammation through an impairment of the functions of one or more of the major organ systems may be a common theme and act synergistically with the traditional mechanisms involved in the development of AD. Full-Text PDF Open AccessReply to: “Systemic inflammation and disorders of hemostasis in the AD-ACLF syndrome”Journal of HepatologyVol. 74Issue 5PreviewWe are grateful to Drs. Lisman and Luyendyk for their interest in our hypothesis proposing systemic inflammation as the common mechanism of the major complications of cirrhosis.1 The core of the hypothesis consists of a variety of systemic disorders induced by systemic inflammation (immunopathology, systemic metabolic dysregulation and immunosuppression) which, operating in synergy with organ-specific mechanisms (hyperammonemia, sinusoidal portal hypertension and cardiocirculatory dysfunction), form a complex pathophysiological network that explains the systemic nature of the acute decompensation-acute-on-chronic liver failure (AD-ACLF) syndrome. Full-Text PDF" @default.
• W3117369512 created "2021-01-05" @default.
• W3117369512 creator A5040736302 @default.
• W3117369512 creator A5074302578 @default.
• W3117369512 date "2021-05-01" @default.
• W3117369512 modified "2023-09-27" @default.
• W3117369512 title "Systemic inflammation and disorders of hemostasis in the AD-ACLF syndrome" @default.
• W3117369512 cites W1972689256 @default.
• W3117369512 cites W1993340951 @default.
• W3117369512 cites W2328891881 @default.
• W3117369512 cites W2342473733 @default.
• W3117369512 cites W2747912680 @default.
• W3117369512 cites W2884786019 @default.
• W3117369512 cites W2903302497 @default.
• W3117369512 cites W2911093128 @default.
• W3117369512 cites W2971304637 @default.
• W3117369512 cites W3084158847 @default.
• W3117369512 cites W3111137164 @default.
• W3117369512 doi "https://doi.org/10.1016/j.jhep.2020.12.017" @default.
• W3117369512 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33347950" @default.
• W3117369512 hasPublicationYear "2021" @default.
• W3117369512 type Work @default.
• W3117369512 sameAs 3117369512 @default.
• W3117369512 citedByCount "5" @default.
• W3117369512 countsByYear W31173695122021 @default.
• W3117369512 countsByYear W31173695122022 @default.
• W3117369512 countsByYear W31173695122023 @default.
• W3117369512 crossrefType "journal-article" @default.
• W3117369512 hasAuthorship W3117369512A5040736302 @default.
• W3117369512 hasAuthorship W3117369512A5074302578 @default.
• W3117369512 hasBestOaLocation W31173695121 @default.
• W3117369512 hasConcept C126322002 @default.
• W3117369512 hasConcept C203014093 @default.
• W3117369512 hasConcept C2776252253 @default.
• W3117369512 hasConcept C2776914184 @default.
• W3117369512 hasConcept C2778589496 @default.
• W3117369512 hasConcept C71924100 @default.
• W3117369512 hasConceptScore W3117369512C126322002 @default.
• W3117369512 hasConceptScore W3117369512C203014093 @default.
• W3117369512 hasConceptScore W3117369512C2776252253 @default.
• W3117369512 hasConceptScore W3117369512C2776914184 @default.
• W3117369512 hasConceptScore W3117369512C2778589496 @default.
• W3117369512 hasConceptScore W3117369512C71924100 @default.
• W3117369512 hasIssue "5" @default.
• W3117369512 hasLocation W31173695121 @default.
• W3117369512 hasLocation W31173695122 @default.
• W3117369512 hasLocation W31173695123 @default.
• W3117369512 hasOpenAccess W3117369512 @default.
• W3117369512 hasPrimaryLocation W31173695121 @default.
• W3117369512 hasRelatedWork W1770615850 @default.
• W3117369512 hasRelatedWork W2066382330 @default.
• W3117369512 hasRelatedWork W2068516100 @default.
• W3117369512 hasRelatedWork W2089799535 @default.
• W3117369512 hasRelatedWork W2163381552 @default.
• W3117369512 hasRelatedWork W2373393772 @default.
• W3117369512 hasRelatedWork W2375557308 @default.
• W3117369512 hasRelatedWork W2387503964 @default.
• W3117369512 hasRelatedWork W3008678378 @default.
• W3117369512 hasRelatedWork W4297982189 @default.
• W3117369512 hasVolume "74" @default.
• W3117369512 isParatext "false" @default.
• W3117369512 isRetracted "false" @default.
• W3117369512 magId "3117369512" @default.
• W3117369512 workType "article" @default.