{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:43:46Z","timestamp":1784097826369,"version":"3.55.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2013,8,7]],"date-time":"2013-08-07T00:00:00Z","timestamp":1375833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>The prevalence of relative adrenal insufficiency (RAI) in critically ill cirrhosis patients with severe sepsis is over 60% and associated features include poor liver function, renal failure, refractory shock, and high mortality. RAI may also develop in noncritically ill cirrhosis patients but its relationship to the clinical course has not yet been assessed. The current study was performed in 143 noncritically ill cirrhosis patients admitted for acute decompensation. Within 24 hours after hospitalization adrenal function, plasma renin activity, plasma noradrenaline and vasopressin concentration, and serum levels of nitric oxide, interleukin-6 and tumor necrosis factor alpha were determined. RAI was defined as a serum total cortisol increase &lt;9 \u03bcg\/dL after 250 \u03bcg of intravenous corticotropin from basal values &lt;35 \u03bcg\/dL. Patients were followed for 3 months. RAI was detected in 26% of patients (n = 37). At baseline, patients with RAI presented with lower mean arterial pressure (76 \u00b1 12 versus 83 \u00b1 14 mmHg,<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.009) and serum sodium (131 \u00b1 7 versus 135 \u00b1 5 mEq\/L,<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.007) and higher blood urea nitrogen (32 \u00b1 24 versus 24 \u00b1 15 mg\/dl,<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.06), plasma renin activity (7.1 \u00b1 9.9 versus 3.4 \u00b1 5.6 ng\/mL*h,<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.03), and noradrenaline concentration (544 \u00b1 334 versus 402 \u00b1 316 pg\/mL,<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.02). During follow-up, patients with RAI exhibited a higher probability of infection (41% versus 21%,<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.008), severe sepsis (27% versus 9%,<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.003), type-1 hepatorenal syndrome (HRS) (16% versus 3%,<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.002), and death (22% versus 7%,<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.01).<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      <jats:bold>RAI is frequent in noncritically ill patients with acute decompensation of cirrhosis. As compared with those with normal adrenal function, patients with RAI have greater impairment of circulatory and renal function, higher probability of severe sepsis and type-1 HRS, and higher short-term mortality. (Hepatology 2013;58:1757\u20131765)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.26535","type":"journal-article","created":{"date-parts":[[2013,5,31]],"date-time":"2013-05-31T11:16:03Z","timestamp":1369998963000},"page":"1757-1765","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":126,"title":["Relative adrenal insufficiency in decompensated cirrhosis: Relationship to short-term risk of severe sepsis, hepatorenal syndrome, and death"],"prefix":"10.1097","volume":"58","author":[{"given":"Juan","family":"Acevedo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Prado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anibal","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pavesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Roca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wladimiro","family":"Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pere","family":"Gin\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Arroyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-25-20241201","first-page":"823838","article-title":"and Muller B. 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Recommendations for the diagnosis and management of corticosteroid insufficiency in critical ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.","volume":"36","author":"Marik","year":"2008","journal-title":"Crit Care Med"},{"key":"R8-25-20241201","doi-asserted-by":"crossref","first-page":"7177","DOI":"10.1034\/j.1600-0676.2003.00813.x","article-title":"The effects of supraphysiological doses of corticosteroids in hypotensive liver failure.","volume":"23","author":"Harry","year":"2003","journal-title":"Liver Int"},{"key":"R9-25-20241201","doi-asserted-by":"crossref","first-page":"12541259","DOI":"10.1097\/01.CCM.0000164541.12106.57","article-title":"; Hepatic Cortisol Research and Adrenal Pathophysiology Study Group. 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