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The most effective anti\u2010fibrotic therapy is treatment of the underlying disease, however when not possible, interventions to reverse or slow fibrosis progression are needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of this study was to study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase\u2010like 2 (<jats:styled-content style=\"fixed-case\">LOXL<\/jats:styled-content>2) enzyme, in subjects with hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>), human immunodeficiency virus (<jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>), or <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> co\u2010infection and advanced liver disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighteen subjects with advanced liver fibrosis received simtuzumab 700 mg intravenously every 2 weeks for 22 weeks. Transjugular liver biopsies were performed during screening and at the end of treatment to measure hepatic venous pressure gradient (<jats:styled-content style=\"fixed-case\">HVPG<\/jats:styled-content>) and to stage fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment was well\u2010tolerated with no discontinuations due to adverse events. No significant changes were seen in <jats:styled-content style=\"fixed-case\">HVPG<\/jats:styled-content> or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre\u2010 and post\u2010treatment liver biopsy and serum samples suggested up\u2010regulation of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b23 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 pathways with treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this open\u2010label, pilot clinical trial, simtuzumab treatment was well\u2010tolerated in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010 and <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010infected subjects with advanced liver disease. Putative modulation of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b23 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 pathways during simtuzumab treatment merits investigation in future trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13177","type":"journal-article","created":{"date-parts":[[2016,5,27]],"date-time":"2016-05-27T14:34:43Z","timestamp":1464359683000},"page":"1783-1792","source":"Crossref","is-referenced-by-count":91,"title":["Simtuzumab treatment of advanced liver fibrosis in <scp>HIV<\/scp> and <scp>HCV<\/scp>\u2010infected adults: results of a 6\u2010month open\u2010label safety trial"],"prefix":"10.1111","volume":"36","author":[{"given":"Eric G.","family":"Meissner","sequence":"first","affiliation":[{"name":"Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases Bethesda MD USA"},{"name":"Division of Infectious Diseases Department of Microbiology and Immunology Medical University of South Carolina Charleston SC USA"},{"name":"Critical Care Medicine Department AIDS Section NIH Clinical Center Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Matthews","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department AIDS Section NIH Clinical Center Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Gharib","sequence":"additional","affiliation":[{"name":"Biomedical and Metabolic Imaging Branch National Institute of Diabetes and Digestive and Kidney Diseases Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford J.","family":"Wood","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences NIH Clinical Center Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Levy","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences NIH Clinical Center Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Sinkus","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Imaging Sciences and Biomedical Engineering Division Kings College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimmo","family":"Virtaneva","sequence":"additional","affiliation":[{"name":"Genomics Unit Research Technology Section Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases Hamilton MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Sturdevant","sequence":"additional","affiliation":[{"name":"Genomics Unit Research Technology Section Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases Hamilton MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Martens","sequence":"additional","affiliation":[{"name":"Genomics Unit Research Technology Section Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases Hamilton MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Porcella","sequence":"additional","affiliation":[{"name":"Genomics Unit Research Technology Section Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases Hamilton MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary D.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Center for Liver Diseases Inova Fairfax Hospital Falls Church VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bittoo","family":"Kanwar","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc. 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