{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:31:50Z","timestamp":1790641910835,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>\n                    Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute\u2010on\u2010chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan\/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known. The serum levels of Trp, key KP metabolites (kynurenine and kynurenic and quinolinic acids), and cytokines (SI markers) were measured at enrollment in 40 healthy subjects, 39 patients with compensated cirrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients during the 28\u2010day follow\u2010up. Urine KP metabolites were measured in 50 patients with ACLF. Serum KP activity was normal in compensated cirrhosis, increased in AD and further increased in ACLF, in parallel with SI; it was remarkably higher in ACLF with kidney failure than in ACLF without kidney failure in the absence of differences in urine KP activity and fractional excretion of KP metabolites. The short\u2010term course of AD and ACLF (worsening, improvement, stable) correlated closely with follow\u2010up changes in serum KP activity. Among patients with AD at enrollment, those with the highest baseline KP activity developed ACLF during follow\u2010up. Among patients who had ACLF at enrollment, those with immune suppression and the highest KP activity, both at baseline, developed nosocomial infections during follow\u2010up. Finally, higher baseline KP activity independently predicted mortality in patients with AD and ACLF.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Features of KP activation appear in patients with AD, culminate in patients with ACLF, and may be involved in the pathogenesis of ACLF, clinical course, and mortality.\n                  <\/jats:p>","DOI":"10.1002\/hep.30363","type":"journal-article","created":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T14:43:06Z","timestamp":1544107386000},"page":"1686-1701","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":119,"title":["Orchestration of Tryptophan\u2010Kynurenine Pathway, Acute Decompensation, and Acute\u2010on\u2010Chronic Liver Failure in Cirrhosis"],"prefix":"10.1097","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4333-7749","authenticated-orcid":false,"given":"Joan","family":"Cl\u00e0ria","sequence":"first","affiliation":[{"name":"European Foundation for the Study of Chronic Liver Failure Consortium and Grifols Chair,Barcelona,Spain"},{"name":"Hospital Cl\u00ednic,IDIBAPS and CIBERehd,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Moreau","sequence":"additional","affiliation":[{"name":"European Foundation for the Study of Chronic Liver Failure Consortium and Grifols Chair,Barcelona,Spain"},{"name":"Inserm, Centre de Recherche sur l\u2019Inflammation, Universit\u00e9 Paris Diderot\u2010Paris, D\u00e9partement Hospitalo\u2010Universitaire UNITY; Service d\u2019H\u00e9patologie, H\u00f4pital Beaujon, Assistance Publique\u2010H\u00f4pitaux de Paris; Laboratoire d\u2019Excellence Inflamex,ComUE Sorbonne Paris Cit\u00e9,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Fenaille","sequence":"additional","affiliation":[{"name":"CEA, INRA,Universit\u00e9 Paris Saclay,Laboratoire d\u2019Etude du M\u00e9tabolisme des M\u00e9dicaments, MetaboHUB\u2010Paris,Gif\u2010Sur\u2010Yvette,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Amor\u00f3s","sequence":"additional","affiliation":[{"name":"European Foundation for the Study of Chronic Liver Failure Consortium and Grifols Chair,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Junot","sequence":"additional","affiliation":[{"name":"CEA, INRA,Universit\u00e9 Paris Saclay,Laboratoire d\u2019Etude du M\u00e9tabolisme des M\u00e9dicaments, MetaboHUB\u2010Paris,Gif\u2010Sur\u2010Yvette,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Gronbaek","sequence":"additional","affiliation":[{"name":"Department of Hepatology & Gastroenterology,Aarhus University Hospital,Aarhus,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minneke J.","family":"Coenraad","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Leiden University Medical Center,Leiden,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Pruvost","sequence":"additional","affiliation":[{"name":"CEA,INRA Universit\u00e9 Paris Saclay, Service de Pharmacologie et Immunoanalyse, Plateforme SMArt\u2010MS,Gif\u2010sur\u2010Yvette,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Ghettas","sequence":"additional","affiliation":[{"name":"CEA,INRA Universit\u00e9 Paris Saclay, Service de Pharmacologie et Immunoanalyse, Plateforme SMArt\u2010MS,Gif\u2010sur\u2010Yvette,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeline","family":"Chu\u2010Van","sequence":"additional","affiliation":[{"name":"CEA, INRA,Universit\u00e9 Paris Saclay,Laboratoire d\u2019Etude du M\u00e9tabolisme des M\u00e9dicaments, MetaboHUB\u2010Paris,Gif\u2010Sur\u2010Yvette,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"L\u00f3pez\u2010Vicario","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednic,IDIBAPS and CIBERehd,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Oettl","sequence":"additional","affiliation":[{"name":"Medical University of Graz,Graz,Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Caraceni","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences,University of Bologna,Bologna,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Alessandria","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,San Giovanni Battista Hospital,Torino,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-3881","authenticated-orcid":false,"given":"Jonel","family":"Trebicka","sequence":"additional","affiliation":[{"name":"European Foundation for the Study of Chronic Liver Failure Consortium and Grifols Chair,Barcelona,Spain"},{"name":"Department of Internal Medicine I,University of Bonn,Bonn,Germany"},{"name":"J.W. 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