{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:48:38Z","timestamp":1791607718090,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cirrhosis induces multi\u2010organ dysfunction, yet the specific physiological determinants underlying reduced cardiorespiratory fitness (CRF) remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To compare patients with cirrhosis to healthy controls to assess and identify their major CRF physiological contributors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty\u2010five patients with cirrhosis and 45 age\u2010 and sex\u2010matched controls underwent incremental cardiopulmonary exercise testing (CPET) on a cycle ergometer. The pulmonary, cardiac, vascular, and muscular components of CRF were measured, including peak oxygen uptake (VO\n                      <jats:sub>2Peak<\/jats:sub>\n                      ), ventilatory efficiency (VE\/VCO\n                      <jats:sub>2<\/jats:sub>\n                      ), oxygen uptake efficiency slope (OUES), and chronotropic response. Non\u2010invasive hemodynamic monitoring (Physioflow) was used to estimate cardiac output and arteriovenous oxygen difference (a\u2010vO\n                      <jats:sub>2<\/jats:sub>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with cirrhosis exhibited markedly reduced CRF compared with controls (VO\n                      <jats:sub>2Peak<\/jats:sub>\n                      : 15.4\u2009\u00b1\u20095.5 vs. 29.3\u2009\u00b1\u20097.5\u2009mL.min\n                      <jats:sup>\u22121<\/jats:sup>\n                      .kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and the decline was proportional to Child\u2010Pugh score. Kinetic parameters (OUES, Lowest VE\/VCO\n                      <jats:sub>2<\/jats:sub>\n                      , Wilkoff index) were also significantly impaired and chronotropic incompetence was highly prevalent (89%). Cardiac output was preserved but a\u2010vO\n                      <jats:sub>2<\/jats:sub>\n                      was lower (10.7\u2009\u00b1\u20093.0 vs. 14.1\u2009\u00b1\u20091.1 mlO\n                      <jats:sub>2<\/jats:sub>\n                      .dL\n                      <jats:sup>\u22121<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), indicating a defective peripheral oxygen extraction in patients with cirrhosis. Multivariate regression analysis (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.79) identified maximal heart rate and muscle performance (5\u2010sit to stand) as independent predictors of VO\n                      <jats:sub>2Peak<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Reduced CRF in cirrhosis appears to primarily result from impaired skeletal muscle oxygen utilization, compounded by chronotropic incompetence. These findings emphasize the value of integrative functional evaluation in cirrhosis management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cph4.70195","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:16:51Z","timestamp":1782278211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduced Cardiorespiratory Fitness and Its Physiological Determinants in Patients With Cirrhosis: Evidence of Cirrhosis\u2010Induced Myopathy"],"prefix":"10.1002","volume":"16","author":[{"given":"Couret","family":"Alexis","sequence":"first","affiliation":[{"name":"Clermont Auvergne University, CRNH, AME2P  Clermont\u2010Ferrand France"},{"name":"Department of Digestive and Hepatobiliary Medicine CHU Clermont\u2010Ferrand  Clermont\u2010Ferrand 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