{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:49:07Z","timestamp":1782859747734,"version":"3.54.5"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institutes of Health (NIAAA at NIH)","award":["K23AA029198-01"],"award-info":[{"award-number":["K23AA029198-01"]}]},{"name":"the National Institutes of Health (NIAAA at NIH)","award":["R15CA170091-01A1"],"award-info":[{"award-number":["R15CA170091-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: Fibrosis in early-stage alcohol-associated liver disease (ALD) is commonly under-diagnosed in routine clinical practice. This study characterized the liver-injury and cell death response in alcohol use disorder (AUD) patients with ALD who also exhibited fibrosis and assessed the efficacy of standard of care (SOC) treatment in the improvement in liver injury. (2) Methods: Forty-eight heavy-drinking AUD patients aged 21\u201365 yrs. without clinical manifestations of liver injury were grouped by Fibrosis-4 (FIB-4) score, as negative (Gr.1 &lt; 1.45, n = 21) or positive (Gr.2 \u2265 1.45, n = 27). Patients received 2-weeks (2 w) inpatient SOC. Data on demographics, drinking patterns, liver-injury, immune markers, and liver cell death (K18s) markers were analyzed at baseline (BL) and after 2 w SOC. (3) Results: Lifetime drinking (LTDH, yrs.) and acute heavy drinking (Heavy Drinking Days Past 90 Days [HDD90]) markers were significantly higher in Gr.2 vs. Gr.1. BL ALT, AST, AST:ALT and K18M65 were considerably higher in Gr.2. Dysregulated gut dysfunction and elevated immune activity were evident in Gr.2 characterized by TNF-\u03b1, IL-8 and LPS levels. After SOC, Gr.2 showed improvement in AST, ALT, AST\/ALT ratio; and in the K18M65, K18M30 and K18M65\/M30 ratio vs. Gr.1. The true positivity of BL IL-8 response to predict the improvement in K18M65 to normal levels among Gr.2 patients against those who did not have improvement after 2 w SOC was very high (AUROC = 0.830, p = 0.042). (4) Conclusions: Gut dysfunction, elevated cytokine response and necrotic liver cell death were elevated in AUD patients with early-stage ALD. K18 showed promise as a predictive theragnostic factor to differentiate among the AUD patients with early-stage ALD and baseline fibrosis who had improvement in liver injury against those who did not, by the levels of baseline IL-8.<\/jats:p>","DOI":"10.3390\/ijms23105852","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T22:57:22Z","timestamp":1653346642000},"page":"5852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Theragnostic Efficacy of K18 Response in Alcohol Use Disorder with Clinically Significant Fibrosis Using Gut-Liver Axis"],"prefix":"10.3390","volume":"23","author":[{"given":"Manasa","family":"Sagaram","sequence":"first","affiliation":[{"name":"Internal Medicine Residency Program, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranganathan","family":"Parthasarathy","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally L.","family":"Condon","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"Closson","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiying","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40202, USA"},{"name":"Alcohol Research Center, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie L.","family":"Schwandt","sequence":"additional","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta L.","family":"Jophlin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenke","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh J.","family":"Barve","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Robley Rex VA Medical Center, Louisville, KY 40206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6764-6891","authenticated-orcid":false,"given":"Vatsalya","family":"Vatsalya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Alcohol Research Center, University of Louisville, Louisville, KY 40202, USA"},{"name":"National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA"},{"name":"Robley Rex VA Medical Center, Louisville, KY 40206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1053\/j.gastro.2011.09.002","article-title":"Alcoholic liver disease: Pathogenesis and new therapeutic targets","volume":"141","author":"Gao","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.3748\/wjg.v16.i11.1321","article-title":"Alcoholic liver disease and the gut-liver axis","volume":"16","author":"Szabo","year":"2010","journal-title":"World J. 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