{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:04:43Z","timestamp":1768208683173,"version":"3.49.0"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["19K17502"],"award-info":[{"award-number":["19K17502"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Acute decompensation (AD) of liver cirrhosis (LC) and subsequent acute-on-chronic liver failure (ACLF) are fatal and impair quality of life. Insufficient knowledge of the highly heterogeneous natural history of LC, including decompensation, re-compensation, and possible recurrent decompensation, hinders the development and application of novel therapeutics. Approximately 10%-50% of AD\/ACLF is reported to be precipitated by any indeterminate (unidentifiable, cryptogenic, or unknown) acute insults; however, its clinical characteristics are unclear.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a single-center observational study of 2165 consecutively admitted patients with LC from January 2012 to December 2019. A total of 466 episodes of AD\/ACLF in 285 patients, including their 285 first indexed AD\/ACLF, were extracted for analysis. Stratified analyses of different acute precipitants, classified as indeterminate (AD\/ACLF<jats:sub>IND<\/jats:sub>), bacterial infection (AD\/ACLF<jats:sub>BAC<\/jats:sub>), gastrointestinal bleeding, active alcoholism, and miscellaneous, were performed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>AD\/ACLF<jats:sub>IND<\/jats:sub> was the leading acute precipitant (28%), followed by AD\/ACLF<jats:sub>BAC<\/jats:sub> (23%). AD\/ACLF<jats:sub>IND<\/jats:sub> showed better survival outcomes than AD\/ACLF<jats:sub>BAC<\/jats:sub> (<jats:italic>P<\/jats:italic> = 0.03); however, hyperbilirubinemia, hyponatremia, or leukocytosis significantly and uniquely characterized subgroups of AD\/ACLF<jats:sub>IND<\/jats:sub> with comparable or even worse survival outcomes than those of AD\/ACLF<jats:sub>BAC<\/jats:sub>. Patients with subsequent AD\/ACLF significantly tended to suffer from AD\/ACLF with any organ failure in AD\/ACLF<jats:sub>IND<\/jats:sub> but not in AD\/ACLF<jats:sub>BAC<\/jats:sub> (<jats:italic>P<\/jats:italic> = 0.004, for trend). In competing risk analysis, patients with AD\/ACLF<jats:sub>IND<\/jats:sub> were significantly more vulnerable to suffer from recurrent episodes of AD\/ACLF within 180 days, compared to those triggered by other precipitants (<jats:italic>P<\/jats:italic> = 0.04).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>AD\/ACLF<jats:sub>IND<\/jats:sub>, the leading acute precipitant, also plays a role in subsequent AD\/ACLF. An abruptly exacerbating, remitting, and relapsing nature of systemic inflammation underlying AD\/ACLF may also be useful for risk estimation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0250062","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T18:14:13Z","timestamp":1618337653000},"page":"e0250062","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Vulnerability to recurrent episodes of acute decompensation\/acute-on-chronic liver failure characterizes those triggered by indeterminate precipitants in patients with liver 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