Progressive systemic inflammation precedes decompensation in compensated cirrhosis
Background & Aims: Systemic inflammation is a driver of decompensation in cirrhosis with unclear relevance in the compensated stage. We evaluated inflammation and bacterial translocation markers in compensated cirrhosis and their dynamics in relation to the first decompensation. Methods: Thi...
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Elsevier
2025-02-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555924002350 |
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| author | Rubén Sánchez-Aldehuelo Càndid Villanueva Joan Genescà Juan Carlos García-Pagán Elisa Castillo José Luis Calleja Carles Aracil Rafael Bañares Luis Téllez Lorena Paule Rosa María Morillas María Poca Beatriz Peñas Salvador Augustin Juan G. Abraldes Edilmar Alvarado-Tapias Jaume Bosch Agustín Albillos |
| author_facet | Rubén Sánchez-Aldehuelo Càndid Villanueva Joan Genescà Juan Carlos García-Pagán Elisa Castillo José Luis Calleja Carles Aracil Rafael Bañares Luis Téllez Lorena Paule Rosa María Morillas María Poca Beatriz Peñas Salvador Augustin Juan G. Abraldes Edilmar Alvarado-Tapias Jaume Bosch Agustín Albillos |
| author_sort | Rubén Sánchez-Aldehuelo |
| collection | DOAJ |
| description | Background & Aims: Systemic inflammation is a driver of decompensation in cirrhosis with unclear relevance in the compensated stage. We evaluated inflammation and bacterial translocation markers in compensated cirrhosis and their dynamics in relation to the first decompensation. Methods: This study is nested within the PREDESCI trial, which investigated non-selective beta-blockers for preventing decompensation in compensated cirrhosis and clinically significant portal hypertension (CSPH: hepatic venous pressure gradient ≥10 mmHg). Blood biomarkers were measured at baseline and at 1 and 2 years in patients who remained compensated and had available samples (n = 164). Values of patients with CSPH were split at each time point by decompensation development in the next time interval after sampling. We also included 54 patients with cirrhosis and subclinical portal hypertension (PH) and 35 controls. We assessed markers of inflammation (interleukin-6 [IL-6], tumor necrosis factor-alpha, von Willebrand factor [vWF], C-reactive protein), macrophage activation (CD14, CD163), intestinal barrier integrity (fatty acid-binding protein [FABP], haptoglobin), and bacterial translocation (lipopolysaccharide [LPS]). Results: IL-6, CD163, and vWF were higher (p <0.01) at baseline in patients with cirrhosis and CSPH compared to those with subclinical PH and controls. IL-6 increased (p <0.05) at 1 year in patients with CSPH, with a greater rise in those who developed decompensation. CD163 was higher (p <0.01) in patients who decompensated at baseline and 1 and 2 years. FABP was elevated (p <0.01) in patients with CSPH compared to subclinical PH and controls at baseline and 1 year, while haptoglobin was lower (p <0.01). LPS was higher (p <0.01) in patients with CSPH than in those with subclinical PH and controls and increased at 1 year regardless of decompensation development. Conclusions: Inflammation and bacterial products are present in the systemic circulation in patients with compensated cirrhosis and CSPH. Progressive inflammation precedes the first decompensation. Impact and implications: Systemic inflammation drives cirrhosis progression during the decompensated stage, but its role in the compensated stage is unclear. We evaluated biomarkers of systemic inflammation, intestinal barrier integrity and bacterial translocation in patients with compensated cirrhosis and their dynamics in relation to the first decompensation. We demonstrate that low-grade inflammation and bacterial products are present in the systemic circulation in compensated cirrhosis, provided clinically significant portal hypertension has developed. We also show that worsening of systemic inflammation precedes the development of first clinical decompensation. |
| format | Article |
| id | doaj-art-e5867098309040e3aaaf297d6775eeae |
| institution | Kabale University |
| issn | 2589-5559 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | JHEP Reports |
| spelling | doaj-art-e5867098309040e3aaaf297d6775eeae2025-02-07T04:48:07ZengElsevierJHEP Reports2589-55592025-02-0172101231Progressive systemic inflammation precedes decompensation in compensated cirrhosisRubén Sánchez-Aldehuelo0Càndid Villanueva1Joan Genescà2Juan Carlos García-Pagán3Elisa Castillo4José Luis Calleja5Carles Aracil6Rafael Bañares7Luis Téllez8Lorena Paule9Rosa María Morillas10María Poca11Beatriz Peñas12Salvador Augustin13Juan G. Abraldes14Edilmar Alvarado-Tapias15Jaume Bosch16Agustín Albillos17Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramon y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08025 Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Digestive Diseases Area, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Research (VHIR), Vall d’Hebron Barcelona Hospital Campus, Autonomous University of Barcelona, Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Institute of Digestive and Metabolic Diseases, August Pi i Sunyer Institute of Biomedical Research, Hospital Clínic, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Departament de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, SpainDepartment of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramon y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro-Majadahonda, Puerta de Hierro Hospital Research Institute, Universidad Autónoma de Madrid, Madrid, SpainDepartment of Gastroenterology and Hepatology, Institute of Biomedical Research, Arnau de Vilanova University Hospital (IRB Lleida), Lleida, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Gastroenterology and Hepatology Department, Hospital Universitario Gregorio Marañón, Instituto de Investigacion Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, Madrid, SpainDepartment of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramon y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, SpainDepartment of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramon y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Section, Hospital Universitari Germans Trias i Pujol, IGTP, Badalona, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08025 Barcelona, SpainDepartment of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramon y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Digestive Diseases Area, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Research (VHIR), Vall d’Hebron Barcelona Hospital Campus, Autonomous University of Barcelona, Barcelona, SpainLiver Unit, Division of Gastroenterology, University of Alberta, Edmonton, CanadaCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08025 Barcelona, SpainDepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, SwitzerlandDepartment of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramon y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Corresponding author. Address: Department of Gastroenterology and Hepatology, Hospital Universitario Ramon y Cajal, M-607, km. 9.100, 28034 Madrid, Spain.Background & Aims: Systemic inflammation is a driver of decompensation in cirrhosis with unclear relevance in the compensated stage. We evaluated inflammation and bacterial translocation markers in compensated cirrhosis and their dynamics in relation to the first decompensation. Methods: This study is nested within the PREDESCI trial, which investigated non-selective beta-blockers for preventing decompensation in compensated cirrhosis and clinically significant portal hypertension (CSPH: hepatic venous pressure gradient ≥10 mmHg). Blood biomarkers were measured at baseline and at 1 and 2 years in patients who remained compensated and had available samples (n = 164). Values of patients with CSPH were split at each time point by decompensation development in the next time interval after sampling. We also included 54 patients with cirrhosis and subclinical portal hypertension (PH) and 35 controls. We assessed markers of inflammation (interleukin-6 [IL-6], tumor necrosis factor-alpha, von Willebrand factor [vWF], C-reactive protein), macrophage activation (CD14, CD163), intestinal barrier integrity (fatty acid-binding protein [FABP], haptoglobin), and bacterial translocation (lipopolysaccharide [LPS]). Results: IL-6, CD163, and vWF were higher (p <0.01) at baseline in patients with cirrhosis and CSPH compared to those with subclinical PH and controls. IL-6 increased (p <0.05) at 1 year in patients with CSPH, with a greater rise in those who developed decompensation. CD163 was higher (p <0.01) in patients who decompensated at baseline and 1 and 2 years. FABP was elevated (p <0.01) in patients with CSPH compared to subclinical PH and controls at baseline and 1 year, while haptoglobin was lower (p <0.01). LPS was higher (p <0.01) in patients with CSPH than in those with subclinical PH and controls and increased at 1 year regardless of decompensation development. Conclusions: Inflammation and bacterial products are present in the systemic circulation in patients with compensated cirrhosis and CSPH. Progressive inflammation precedes the first decompensation. Impact and implications: Systemic inflammation drives cirrhosis progression during the decompensated stage, but its role in the compensated stage is unclear. We evaluated biomarkers of systemic inflammation, intestinal barrier integrity and bacterial translocation in patients with compensated cirrhosis and their dynamics in relation to the first decompensation. We demonstrate that low-grade inflammation and bacterial products are present in the systemic circulation in compensated cirrhosis, provided clinically significant portal hypertension has developed. We also show that worsening of systemic inflammation precedes the development of first clinical decompensation.http://www.sciencedirect.com/science/article/pii/S2589555924002350cytokinebacterial translocationportal hypertensionchronic advanced liver diseaseimmunity |
| spellingShingle | Rubén Sánchez-Aldehuelo Càndid Villanueva Joan Genescà Juan Carlos García-Pagán Elisa Castillo José Luis Calleja Carles Aracil Rafael Bañares Luis Téllez Lorena Paule Rosa María Morillas María Poca Beatriz Peñas Salvador Augustin Juan G. Abraldes Edilmar Alvarado-Tapias Jaume Bosch Agustín Albillos Progressive systemic inflammation precedes decompensation in compensated cirrhosis JHEP Reports cytokine bacterial translocation portal hypertension chronic advanced liver disease immunity |
| title | Progressive systemic inflammation precedes decompensation in compensated cirrhosis |
| title_full | Progressive systemic inflammation precedes decompensation in compensated cirrhosis |
| title_fullStr | Progressive systemic inflammation precedes decompensation in compensated cirrhosis |
| title_full_unstemmed | Progressive systemic inflammation precedes decompensation in compensated cirrhosis |
| title_short | Progressive systemic inflammation precedes decompensation in compensated cirrhosis |
| title_sort | progressive systemic inflammation precedes decompensation in compensated cirrhosis |
| topic | cytokine bacterial translocation portal hypertension chronic advanced liver disease immunity |
| url | http://www.sciencedirect.com/science/article/pii/S2589555924002350 |
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