{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:58:41Z","timestamp":1790841521010,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["Liver International"],"published-print":{"date-parts":[[2026,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Aims<\/jats:title>\n Regenerative capacity and inflammatory responses are key determinants of outcome in acute liver failure (ALF). However, their prognostic significance in non\u2010acetaminophen drug\u2010induced liver injury with acute liver injury or ALF (non\u2010APAP\u2010DILI\u2010ALI\/ALF) remains poorly defined. We aimed to identify biomarkers of regeneration and inflammation associated with clinical outcomes in this population.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We evaluated clinical laboratory parameters and circulating biomarkers in 79 patients with non\u2010APAP\u2010DILI\u2010ALI\/ALF (20 with ALI, 59 with ALF) and 19 healthy donors. We used multivariable logistic regression to identify independent predictors of 21\u2010day transplant\u2010free survival among these patients. These predictors were used to create a composite model that was compared with the Model for End\u2010Stage Liver Disease (MELD) score.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Markers reflecting hepatic synthetic dysfunction (TBIL, INR, MELD) were strongly associated with the outcomes, whereas aminotransferases were not. HGF levels were markedly elevated in non\u2010APAP\u2010DILI\u2010ALI\/ALF patients versus healthy donors (5070\u2009\u00b1\u20094001 vs. 276\u2009\u00b1\u2009581\u2009pg\/mL;\n p<\/jats:italic>\n \u2009<\u20090.001), increased with injury severity, and were highest in patients who died or underwent transplantation (6421\u2009\u00b1\u20094359 vs. 4102\u2009\u00b1\u20093456\u2009pg\/mL;\n p<\/jats:italic>\n \u2009=\u20090.009). Among inflammatory mediators, only interleukin\u20106 showed a modest association with outcome. We developed an H\u2010Score based on the three variables independently associated with survival on multivariable analysis: HGF (odds ratio, 1.0002;\n p<\/jats:italic>\n \u2009=\u20090.048), TBIL and INR. The H\u2010Score outperformed MELD overall (area under the curve, 0.819 vs. 0.713) and in ALF only patients (0.811 vs. 0.643;\n p<\/jats:italic>\n \u2009=\u20090.040).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n HGF provides independent prognostic value beyond standard measures in non\u2010APAP\u2010DILI\u2010ALF. The H\u2010Score may improve risk stratification over the MELD score and warrants validation in a prospective cohort.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.70895","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:23:01Z","timestamp":1790839381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Hepatocyte Growth Factor Predicts Outcomes in Non\u2010Acetaminophen Drug\u2010Induced Acute Liver Failure"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-3430","authenticated-orcid":false,"given":"Tao","family":"Wang","sequence":"first","affiliation":[{"name":"Office of Pharmaceutical Quality Research Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia M.","family":"Bacot","sequence":"additional","affiliation":[{"name":"Office of Pharmaceutical Quality Research Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamai","family":"Patterson","sequence":"additional","affiliation":[{"name":"Office of Pharmaceutical Quality Research Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devira","family":"Friedman","sequence":"additional","affiliation":[{"name":"Office of Pharmaceutical Quality Research Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Taylor","sequence":"additional","affiliation":[{"name":"Office of Pharmaceutical Quality Research Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixiao","family":"Hong","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics and Biostatistics National Center for Toxicological Research, U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics and Biostatistics National Center for Toxicological Research, U.S. Food and Drug Administration Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5535-7996","authenticated-orcid":false,"given":"Mark I.","family":"Avigan","sequence":"additional","affiliation":[{"name":"Office of Surveillance and Epidemiology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5371-1020","authenticated-orcid":false,"given":"Paul","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Hepatology and Nutrition Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4019-372X","authenticated-orcid":false,"given":"Jody A.","family":"Rule","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Texas Southwestern Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2783-5441","authenticated-orcid":false,"given":"William M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Texas Southwestern Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-9779","authenticated-orcid":false,"given":"Jorge","family":"Rakela","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald M.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Office of Pharmaceutical Quality Research Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6453-2351","authenticated-orcid":false,"given":"Minjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics and Biostatistics National Center for Toxicological Research, U.S. Food and Drug Administration Jefferson Arkansas 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D.","year":"1994","journal-title":"Journal of Hepatology"},{"issue":"43","key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"17081","DOI":"10.1073\/pnas.0704126104","article-title":"The EGF Receptor Is Required for Efficient Liver Regeneration","volume":"104","author":"Natarajan A.","year":"2007","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"e_1_2_12_26_1","doi-asserted-by":"crossref","first-page":"13739","DOI":"10.1038\/s41598-021-92888-4","article-title":"Influence of Cytokines, Circulating Markers and Growth Factors on Liver Regeneration and Post\u2010Hepatectomy Liver Failure: A Systematic Review and Meta\u2010Analysis","volume":"11","author":"Murtha\u2010Lemekhova A.","year":"2021","journal-title":"Scientific Reports"},{"issue":"5","key":"e_1_2_12_27_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhepr.2025.101338","article-title":"Serum Proteomics of Adults With Acute Liver Failure Provides Mechanistic Insights and Attractive Prognostic Biomarkers","volume":"7","author":"Remih K.","year":"2025","journal-title":"JHEP Reports"},{"issue":"5","key":"e_1_2_12_28_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jhep.2008.08.009","article-title":"The Importance of Immune Dysfunction in Determining Outcome in Acute Liver Failure","volume":"49","author":"Antoniades C. G.","year":"2008","journal-title":"Journal of Hepatology"},{"issue":"10","key":"e_1_2_12_29_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0206389","article-title":"Cytokine Profiles in Acute Liver Injury\u2010Results From the US Drug\u2010Induced Liver Injury Network (DILIN) and the Acute Liver Failure Study Group","volume":"13","author":"Bonkovsky H. L.","year":"2018","journal-title":"PLoS One"},{"issue":"3","key":"e_1_2_12_30_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0167-4889(02)00326-9","article-title":"The Role of Cytokines in Liver Failure and Regeneration: Potential New Molecular Therapies","volume":"1592","author":"Galun E.","year":"2002","journal-title":"Biochimica et Biophysica Acta, Molecular Cell Research"},{"key":"e_1_2_12_31_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/1479-5876-9-55","article-title":"Safety and Pharmacokinetics of Recombinant Human Hepatocyte Growth Factor (Rh\u2010HGF) in Patients With Fulminant Hepatitis: A Phase I\/II Clinical Trial, Following Preclinical Studies to Ensure Safety","volume":"9","author":"Ido A.","year":"2011","journal-title":"Journal of Translational Medicine"},{"issue":"6","key":"e_1_2_12_32_1","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/hep.23937","article-title":"Drug\u2010Induced Acute Liver Failure: Results of a U.S. Multicenter, Prospective Study","volume":"52","author":"Reuben A.","year":"2010","journal-title":"Hepatology"},{"issue":"4","key":"e_1_2_12_33_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/cld.219","article-title":"Acute Liver Failure: Peritransplant Management and Outcomes","volume":"2","author":"Fix O. 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