{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:37:39Z","timestamp":1791823059685,"version":"4.3.4"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T00:00:00Z","timestamp":1553472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T00:00:00Z","timestamp":1553472000000},"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":[[2019,9]]},"abstract":"<jats:p>\n                    Severe alcoholic hepatitis (SAH) is often a progressive disease with high mortality and limited steroid responsiveness. Management options of steroid nonresponsive SAH (day 7 Lille score &gt; 0.45) are limited. We assessed the efficacy and safety of granulocyte colony\u2010stimulating factor (G\u2010CSF) in steroid nonresponders. A randomized, double\u2010blind, single\u2010center trial (NCT01820208) was conducted between March 2013 and June 2016 in patients with histologically proven SAH, nonresponsive to 40 mg\/day of prednisolone were randomized to G\u2010CSF (12 doses, 300 \u03bcg each in 28 days) or placebo. Responders were continued with prednisolone. Of the 430 patients with SAH, 132 received steroid therapy. Of these, 33 (25%) were nonresponders and were randomized to G\u2010CSF or placebo (14 in each group after exclusions). The baseline characteristics of both groups were comparable. The 28\u2010day mortality was comparable between the groups (21.4%, G\u2010CSF; 28.6%, placebo;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.69). At 90 days, in the G\u2010CSF but not in the placebo group, the Model for End\u2010Stage Liver Disease reduced from 24.6 \u00b1 3.9 to 19.4 \u00b1 3.7 (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.002) and Maddrey\u2019s discriminant function from 74.8 \u00b1 22.8 to 57.4 \u00b1 31 (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.26). Infections were less common (28% versus 71%;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.001) with lower 90\u2010day mortality (35.7% versus 71.4%;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.04) in the G\u2010CSF than in the placebo group. On Cox regression analysis, receiving G\u2010CSF (hazard ratio, 0.37; SD, 0.14\u20100.98;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.04), and high baseline serum creatinine (hazard ratio, 4.12; SD, 1.7\u201010.3;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.002) predicted day\u201090 outcomes in steroid nonresponsive SAH. Patients tolerated G\u2010CSF without any major adverse events.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Approximately one\u2010quarter of patients with SAH do not respond to corticosteroid therapy. Administration of G\u2010CSF is safe and helps to reduce the disease severity and 90\u2010day mortality in these patients.\n                  <\/jats:p>","DOI":"10.1002\/hep.30516","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T11:30:32Z","timestamp":1548070232000},"page":"802-811","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":92,"title":["Efficacy of Granulocyte Colony\u2010stimulating Factor in the Management of Steroid\u2010Nonresponsive Severe Alcoholic Hepatitis: A Double\u2010Blind Randomized Controlled Trial"],"prefix":"10.1097","volume":"70","author":[{"given":"Saggere Muralikrishna","family":"Shasthry","sequence":"first","affiliation":[{"name":"Department of Hepatology,Institute of Liver & Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3448-8334","authenticated-orcid":false,"given":"Manoj Kumar","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver & Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varsha","family":"Shasthry","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver & Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurva","family":"Pande","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver & Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv Kumar","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver & Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,3,25]]},"reference":[{"key":"hep30516-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1002\/hep.21607","article-title":"The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids","volume":"45","year":"2007","journal-title":"Hepatology"},{"key":"hep30516-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1056\/NEJMoa1412278","article-title":"Prednisolone or pentoxifylline for alcoholic hepatitis","volume":"372","year":"2015","journal-title":"N Engl J Med"},{"key":"hep30516-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1002\/lt.20765","article-title":"Consensus conference: Indications for Liver Transplantation, January 19 and 20, 2005, Lyon\u2010Palais Des Congr\u00e8s: text of recommendations (long version)","volume":"12","year":"2006","journal-title":"Liver Transpl"},{"key":"hep30516-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1056\/NEJMoa1105703","article-title":"Early liver transplantation for severe alcoholic hepatitis","volume":"365","year":"2011","journal-title":"N Engl J Med"},{"key":"hep30516-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1002\/hep.25614","article-title":"Liver progenitor cell markers correlate with liver damage and predict short\u2010term mortality in patients with alcoholic hepatitis","volume":"55","year":"2012","journal-title":"Hepatology"},{"key":"hep30516-bib-0006-20241017","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1053\/j.gastro.2011.11.027","article-title":"Granulocyte\u2010colony stimulating factor (G\u2010 CSF) therapy mobilizes CD34 cells and improves survival in patients with acute on chronic liver failure","volume":"142","year":"2012","journal-title":"Gastroenterology"},{"key":"hep30516-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1038\/ajg.2014.154","article-title":"Granulocyte colony\u2010stimulating factor in severe alcoholic hepatitis: a randomized pilot study","volume":"109","year":"2014","journal-title":"Am J Gastroenterol"},{"key":"hep30516-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1038\/ajg.2014.250","article-title":"G\u2010CSF therapy for severe alcoholic hepatitis: targeting liver regeneration or neutrophil function?","volume":"109","year":"2014","journal-title":"Am J Gastroenterol"},{"key":"hep30516-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1053\/j.gastro.2016.02.042","article-title":"Standard definitions and common data elements for clinical trials in patients with alcoholic hepatitis: recommendation from the NIAAA Alcoholic Hepatitis Consortia","volume":"150","year":"2016","journal-title":"Gastroenterology"},{"key":"hep30516-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s00428-018-2330-4","article-title":"Histological activity score on baseline liver biopsy can predict non\u2010response to steroids in patients with severe alcoholic hepatitis","volume":"472","year":"2018","journal-title":"Virchows Arch"},{"key":"hep30516-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1056\/NEJMra0805786","article-title":"Alcoholic hepatitis","volume":"360","year":"2009","journal-title":"N Engl J Med"},{"key":"hep30516-bib-0012-20241017","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1097\/00003246-199206000-00025","article-title":"Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis","volume":"20","year":"1992","journal-title":"Crit Care Med"},{"key":"hep30516-bib-0013-20241017","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.jhep.2010.06.004","article-title":"Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension","volume":"53","year":"2010","journal-title":"J Hepatol"},{"key":"hep30516-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/lt.500030613","article-title":"Minimal criteria for placement of adults on the liver transplant waiting list: a report of a national conference organized by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases","volume":"3","year":"1997","journal-title":"Liver Transpl Surg"},{"key":"hep30516-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1016\/S0140-6736(06)68904-6","article-title":"Recommendations for alcohol\u2010related liver disease","volume":"367","year":"2006","journal-title":"Lancet"},{"key":"hep30516-bib-0016-20241017","first-page":"90","article-title":"Effects of granulocyte colony\u2010stimulating factor on patients with liver failure: a meta\u2010analysis","volume":"4","year":"2016","journal-title":"J Clin Transl Hepatol"},{"key":"hep30516-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.exphem.2004.09.005","article-title":"G\u2010CSF\u2010primed hematopoietic stem cells or G\u2010CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs","volume":"33","year":"2005","journal-title":"Exp Hematol"},{"key":"hep30516-bib-0018-20241017","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/hep.22317","article-title":"Granulocyte\u2010colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial","volume":"48","year":"2008","journal-title":"Hepatology"},{"key":"hep30516-bib-0019-20241017","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S2468-1253(17)30326-6","article-title":"Granulocyte colony\u2010stimulating factor and autologous CD133\u2010positive stem\u2010cell therapy in liver cirrhosis (REALISTIC): an open\u2010label, randomized, controlled phase 2 trial","volume":"3","year":"2018","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"hep30516-bib-0020-20241017","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1053\/j.gastro.2015.02.054","article-title":"Combination of granulocyte colony\u2010stimulating factor and erythropoietin improves outcomes of patients with decompensated cirrhosis","volume":"148","year":"2015","journal-title":"Gastroenterology"},{"key":"hep30516-bib-0021-20241017","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/hep4.1176","article-title":"Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome","volume":"2","year":"2018","journal-title":"Hepatol Commun"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.30516","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.30516","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.30516","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.30516","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T20:08:36Z","timestamp":1729195716000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.30516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,25]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.30516","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734895548.793570533","asserted-by":"object"}]},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,25]]},"assertion":[{"value":"2018-04-17","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-15","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}