{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:33:29Z","timestamp":1792035209636,"version":"4.4.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Interleukin\u201022 has beneficial effects on inflammation and impaired hepatic regeneration that characterize alcohol\u2010associated hepatitis (AH). F\u2010652 is a recombinant fusion protein of human interleukin\u201022 and immunoglobulin G2 fragment crystallizable. This study aims to assess the safety and efficacy signals of F\u2010652 in patients with moderate and severe AH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>A phase\u20102 dose\u2010escalating study was carried out. F\u2010652 (10\u00a0\u03bcg\/kg, 30\u00a0\u03bcg\/kg, or 45\u00a0\u03bcg\/kg) administered on days 1 and 7 was tested in 3 patients each with moderate (Model for End\u2010Stage Liver Disease [MELD] scores: 11\u201020) and severe AH (MELD scores: 21\u201028). Safety was defined by absence of serious adverse events and efficacy was assessed by Lille score, changes in MELD score, and serum bilirubin and aminotransferases at days 28 and 42. Three independent propensity\u2010matched comparator patient cohorts were used. Plasma extracellular vesicles and multiplex serum cytokines were measured to assess inflammation and hepatic regeneration. Eighteen patients (9 moderate and 9 severe AH) were enrolled, 66% were male, and the mean age was 48\u00a0years. The half\u2010life of F\u2010652 following the first dose was 61\u201085\u00a0hours. There were no serious adverse events leading to discontinuation. The MELD score and serum aminotransferases decreased significantly at days 28 and 42 from baseline (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.05). Day\u20107 Lille score was 0.45 or less in 83% patients as compared with 6%, 12%, and 56% among the comparator cohorts. Extracellular vesicle counts decreased significantly at day 28 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.013). Cytokine inflammatory markers were down\u2010regulated, and regeneration markers were up\u2010regulated at days 28 and 42.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>F\u2010652 is safe in doses up to 45\u00a0\u03bcg\/kg and associated with a high rate of improvement as determined by Lille and MELD scores, reductions in markers of inflammation and increases in markers of hepatic regeneration. This study supports the need for randomized placebo\u2010controlled trials to test the efficacy of F\u2010652 in AH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31046","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T15:43:29Z","timestamp":1574869409000},"page":"441-453","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":179,"title":["An Open\u2010Label, Dose\u2010Escalation Study to Assess the Safety and Efficacy of IL\u201022 Agonist F\u2010652 in Patients With Alcohol\u2010associated Hepatitis"],"prefix":"10.1097","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8561-396X","authenticated-orcid":false,"given":"Juan P.","family":"Arab","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"},{"name":"Department of Gastroenterology, School of Medicine,Pontifical Catholic University of 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