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dc.contributor.authorVatsalya, Vatsalya
dc.contributor.authorCave, Matthew C.
dc.contributor.authorKong, Maiying
dc.contributor.authorGobejishvili, Leila
dc.contributor.authorFalkner, K. Cameron
dc.contributor.authorCraycroft, John
dc.contributor.authorMitchell, Mack
dc.contributor.authorSzabo, Gyongyi
dc.contributor.authorMcCullough, Arthur
dc.contributor.authorDasarathy, Srinivasan
dc.contributor.authorRadaeva, Svetlana
dc.contributor.authorBarton, Bruce A.
dc.contributor.authorMcClain, Craig J.
dc.date2022-08-11T08:10:36.000
dc.date.accessioned2022-08-23T17:13:59Z
dc.date.available2022-08-23T17:13:59Z
dc.date.issued2019-12-04
dc.date.submitted2020-01-22
dc.identifier.citation<p>Clin Gastroenterol Hepatol. 2019 Dec 4. pii: S1542-3565(19)31390-4. doi: 10.1016/j.cgh.2019.11.050. [Epub ahead of print] <a href="https://doi.org/10.1016/j.cgh.2019.11.050">Link to article on publisher's site</a></p>
dc.identifier.issn1542-3565 (Linking)
dc.identifier.doi10.1016/j.cgh.2019.11.050
dc.identifier.pmid31811953
dc.identifier.urihttp://hdl.handle.net/20.500.14038/46856
dc.description.abstractBACKGROUND: and Aims: Acute alcoholic hepatitis (AAH) is a major cause of liver-related morbidity and mortality; there are no good blood biomarkers for diagnosis or determining magnitude of cell death. Keratin 18 (KRT18, also called K18), found in epithelial cells, is released from hepatocytes upon death. We investigated whether level of K18 is a better marker of hepatocyte death than standard biomarkers and might be used to identify patients with AAH at risk for death within 90 days. METHODS: We analyzed data from 173 participants in a large trial performed at 4 medical centers. Participants with AAH were classified as severe (n=57, model for end-stage liver disease [MELD] scores above 20) or moderate (n=27, MELD scores from 12 to 19); 38 participants had alcohol use disorder with mild (n=28) or no liver injury (n=10); 34 participants had non-alcoholic steatohepatitis; and 17 participants were healthy (controls). We quantified serum levels of K18 using ELISAs and APOPTOSENSE kits. RESULTS: Serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the ratio of AST:ALT did not correlate with MELD scores. Patients with alcohol use disorder had higher serum levels of ALT than patients with severe AAH. Levels of K18M65 and K18M30 had statistically significant increases as liver disease worsened, as did the degree of necrosis (ratio of K18 M65:M30). The ratio of K18M65:ALT was increased in serum from patients with AAH compared with controls. Serum levels of K18 identified patients who died within 90 days with greater accuracy than commonly used static biomarkers. CONCLUSIONS: There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers (AST, ALT, and the AST:ALT ratio). The ratio of K18M65:M30 might be used as marker of mechanism of hepatocyte death, and the ratio of K18M65:ALT might be used to distinguish patients with AAH from patients with non-alcoholic steatohepatitis. Serum levels of K18 might be used to identify patients with severe AAH at risk for death.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31811953&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1016/j.cgh.2019.11.050
dc.subjectNASH
dc.subjecthepatic
dc.subjectpredictive
dc.subjectprognosis
dc.subjectBiological Factors
dc.subjectDiagnosis
dc.subjectDigestive System Diseases
dc.subjectGastroenterology
dc.subjectHepatology
dc.titleKeratin 18 is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis
dc.typeJournal Article
dc.source.journaltitleClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/qhs_pp/1327
dc.identifier.contextkey16301637
html.description.abstract<p>BACKGROUND: and Aims: Acute alcoholic hepatitis (AAH) is a major cause of liver-related morbidity and mortality; there are no good blood biomarkers for diagnosis or determining magnitude of cell death. Keratin 18 (KRT18, also called K18), found in epithelial cells, is released from hepatocytes upon death. We investigated whether level of K18 is a better marker of hepatocyte death than standard biomarkers and might be used to identify patients with AAH at risk for death within 90 days.</p> <p>METHODS: We analyzed data from 173 participants in a large trial performed at 4 medical centers. Participants with AAH were classified as severe (n=57, model for end-stage liver disease [MELD] scores above 20) or moderate (n=27, MELD scores from 12 to 19); 38 participants had alcohol use disorder with mild (n=28) or no liver injury (n=10); 34 participants had non-alcoholic steatohepatitis; and 17 participants were healthy (controls). We quantified serum levels of K18 using ELISAs and APOPTOSENSE kits.</p> <p>RESULTS: Serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the ratio of AST:ALT did not correlate with MELD scores. Patients with alcohol use disorder had higher serum levels of ALT than patients with severe AAH. Levels of K18M65 and K18M30 had statistically significant increases as liver disease worsened, as did the degree of necrosis (ratio of K18 M65:M30). The ratio of K18M65:ALT was increased in serum from patients with AAH compared with controls. Serum levels of K18 identified patients who died within 90 days with greater accuracy than commonly used static biomarkers.</p> <p>CONCLUSIONS: There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers (AST, ALT, and the AST:ALT ratio). The ratio of K18M65:M30 might be used as marker of mechanism of hepatocyte death, and the ratio of K18M65:ALT might be used to distinguish patients with AAH from patients with non-alcoholic steatohepatitis. Serum levels of K18 might be used to identify patients with severe AAH at risk for death.</p>
dc.identifier.submissionpathqhs_pp/1327
dc.contributor.departmentDepartment of Population and Quantitative Health Sciences
dc.contributor.departmentDepartment of Medicine, Division of Gastroenterology


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