{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:12:19Z","timestamp":1787508739748,"version":"build-2736575974"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p>\n                    Current guidelines recommend restricting acetaminophen (APAP) use in patients with cirrhosis, but evidence to support that recommendation is lacking. Prior studies focused on pharmacokinetics (PK) of APAP in cirrhosis but did not rigorously examine clinical outcomes, sensitive biomarkers of liver damage, or serum APAP\u2010protein adducts, which are a specific marker of toxic bioactivation. Hence, the goal of this pilot study was to test the effects of regularly scheduled APAP dosing in a well\u2010defined compensated cirrhosis group compared to control subjects without cirrhosis, using the abovementioned outcomes. After a 2\u2010week washout, 12 subjects with and 12 subjects without cirrhosis received 650\u00a0mg APAP twice per day (1.3\u00a0g\/day) for 4\u00a0days, followed by 650\u00a0mg on the morning of day 5. Patients were assessed in\u2010person at study initiation (day 1) and on days 3 and 5. APAP\u2010protein adducts and both conventional (alanine aminotransferase) and sensitive (glutamate dehydrogenase [GLDH], full\u2010length keratin 18 [K18], and total high\u2010mobility group box 1 protein) biomarkers of liver injury were measured in serum on the mornings of days 1, 3, and 5, with detailed PK analysis of APAP, metabolites, and APAP\u2010protein adducts throughout day 5. No subject experienced adverse clinical outcomes. GLDH and K18 were significantly different at baseline but did not change in either group during APAP administration. In contrast, clearance of APAP\u2010protein adducts was dramatically delayed in the cirrhosis group. Minor differences for other APAP metabolites were also detected.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Short\u2010term administration of low\u2010dose APAP (650\u00a0mg twice per day, &lt;1\u00a0week) is likely safe in patients with compensated cirrhosis. These data provide a foundation for future studies to test higher doses, longer treatment, and subjects who are decompensated, especially in light of the remarkably delayed adduct clearance in subjects with cirrhosis.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1810","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T02:14:14Z","timestamp":1629944054000},"page":"361-373","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":25,"title":["Short\u2010Term Safety of Repeated Acetaminophen Use in Patients With Compensated Cirrhosis"],"prefix":"10.1097","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0401-0463","authenticated-orcid":false,"given":"Mitchell R.","family":"McGill","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health,Fay W. Boozman College of Public Health,University of Arkansas for Medical Sciences,Little Rock,AR,USA"},{"name":"Department of Pharmacology and Toxicology,College of Medicine,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura P.","family":"James","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,College of Medicine,University of Arkansas for Medical Sciences,Little Rock,AR,USA"},{"name":"Translational Research Institute,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra S.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,College of Medicine,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery H.","family":"Moran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology,College of Medicine,University of Arkansas for Medical Sciences,Little Rock,AR,USA"},{"name":"PinPoint Testing, LLC,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel E.","family":"Mathews","sequence":"additional","affiliation":[{"name":"PinPoint Testing, LLC,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology,College of Medicine,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davis P.","family":"Fleming","sequence":"additional","affiliation":[{"name":"Translational Research Institute,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan E.","family":"Tripod","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,College of Medicine,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel H.","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology,College of Medicine,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kennon\u2010McGill","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health,Fay W. Boozman College of Public Health,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horace J.","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Biostatistics,College of Medicine,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Dranoff","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Internal Medicine,College of Medicine,University of Arkansas for Medical Sciences,Little Rock,AR,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"hep41810-bib-0001-20241114","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S0140-6736(19)31894-X","article-title":"Acute liver 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