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We aimed to define gut microbiome and plasma multi\u2010omics signatures associated with severity and 90\u2010day outcomes in ALF\u2010A, compared to drug\u2010induced ALF (ALF\u2010D) as non\u2010viral ALF group. ALF patients (aged 26\u2009\u00b1\u20099\u2009years; 50.7% male, 49.3% female) with IgM HAV positive (ALF\u2010A,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200933), ALF\u2010D (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200938) were recruited along with acute viral hepatitis (AVH\u2010A,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200927) and healthy subjects (HC,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920). Stool bacteria profiling was done at D0; plasma cytokines, metabolites and barrier markers were analysed at D0, 3, 5, 7. Correlations with clinical severity parameters were assessed. Associations with 90\u2010day mortality were assessed using severity\u2010adjusted association analyses. ALF\u2010A patients were more severe at the time of admission than ALF\u2010D. In ALF\u2013A, 90\u2010day mortality was 33% versus 18.4% with increased severity scores like KCH 21% versus 10.5%, SOFA score 7.97\u2009\u00b1\u20092.89 versus 5.87\u2009\u00b1\u20092.32, SIRS 60.6% versus 18.4%, mechanical ventilation 39% versus 21%. At D0, ALF\u2010A was enriched for lactate\/ammonia\/bile salt hydrolase\/histamine\u2010producing pathobionts like\n                    <jats:italic>Enterococcus, Ruminococcus gnavus, Flavonifractor, Thomasclavelia<\/jats:italic>\n                    correlating positively with severity (|r|\u2009&gt;\u20090.4,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) showing higher baseline abundance in ALF\u2010A non\u2010survivors (NS). At D0 in ALF\u2010A, histamine accumulation, reduced tryptophan, butyrate metabolism inversely correlated with severity and worsened in ALF\u2010A_NS by D7. Pro\u2010inflammatory cytokines, IFABP2 were elevated at Day 0 in ALF\u2010A, correlated positively with severity, and remained increased through Day 7 in ALF\u2010A_NS. In contrast, ALF\u2010D_NS retained commensals, showed increased fatty acid, bile acid biosynthesis with low levels of pro\u2010inflammatory cytokines. In ALF\u2010A, gut and plasma integrated multi\u2010omics features were associated with disease severity, 90\u2010day outcomes and identified candidate biomarkers for future validation.\n                  <\/jats:p>","DOI":"10.1002\/jmv.71150","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:30:22Z","timestamp":1789039822000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Admission Gut and Plasma\u2010Derived Signatures Associated With Severity and 90\u2010day Outcome in Hepatitis A\u2013Related and Drug\u2010Induced Acute Liver Failure"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5278-1676","authenticated-orcid":false,"given":"Anoushka","family":"Saxena","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences New Delhi 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