{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:29:13Z","timestamp":1793021353950,"version":"4.5.0"},"reference-count":101,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T00:00:00Z","timestamp":1577059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K08DK098623"],"award-info":[{"award-number":["K08DK098623"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R03EB015955\u201001"],"award-info":[{"award-number":["R03EB015955\u201001"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R13DK109671\u201001"],"award-info":[{"award-number":["R13DK109671\u201001"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aspenjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nut in Clin Prac"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parenteral nutrition (PN) has revolutionized the care of patients with intestinal failure by providing nutrition intravenously. Worldwide, PN remains a standard tool of nutrition delivery in neonatal, pediatric, and adult patients. Though the benefits are evident, patients receiving PN can suffer serious cholestasis due to lack of enteral feeding and sometimes have fatal complications from liver injury and gut atrophy, including PN\u2010associated liver disease or intestinal failure\u2013associated liver disease. Recent studies into gut\u2010systemic cross talk via the bile acid\u2013regulated farnesoid X receptor (FXR)\u2013fibroblast growth factor 19 (FGF19) axis, gut microbial control of the TGR5\u2013glucagon\u2010like peptide (GLP) axis, sepsis, and role of prematurity of hepatobiliary receptors are greatly broadening our understanding of PN\u2010associated injury. It has also been shown that the composition of \u03c9\u20106\/\u03c9\u20103 polyunsaturated fatty acids given parenterally as lipid emulsions can variably drive damage to hepatocytes and cell integrity. This manuscript reviews the mechanisms for the multifactorial pathogenesis of liver disease and gut injury with PN and discusses novel ameliorative strategies.<\/jats:p>","DOI":"10.1002\/ncp.10461","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T20:24:25Z","timestamp":1577132665000},"page":"63-71","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Mechanisms of Parenteral Nutrition\u2013Associated Liver and Gut Injury"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0682-656X","authenticated-orcid":false,"given":"Himani","family":"Madnawat","sequence":"first","affiliation":[{"name":"Department of Pediatrics St. Louis University School of Medicine Cardinal Glennon Children's Medical Center  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L.","family":"Welu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Louis University School of Medicine Cardinal Glennon Children's Medical Center  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester J.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Louis University School of Medicine Cardinal Glennon Children's Medical Center  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derian B.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Louis University School of Medicine Cardinal Glennon Children's Medical Center  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Louis University School of Medicine Cardinal Glennon Children's Medical Center  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrashekhara","family":"Manithody","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Louis University School of Medicine Cardinal Glennon Children's Medical Center  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Blomenkamp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Louis University School of Medicine Cardinal Glennon Children's Medical Center  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9420-5722","authenticated-orcid":false,"given":"Ajay K.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Louis University School of Medicine Cardinal Glennon Children's Medical Center  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5049.63637"},{"issue":"10","key":"e_1_2_8_3_1","first-page":"E136","article-title":"Role of the gut(\u2010)liver axis in driving parenteral nutrition\u2010associated injury","volume":"5","author":"Denton C","year":"2018","journal-title":"Children (Basel)"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000586"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jpen.1167"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9090987"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.04.008"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/gov011"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-9007(97)00232-3"},{"issue":"6","key":"e_1_2_8_10_1","first-page":"418","article-title":"Total parenteral nutrition\u2010related liver disease","volume":"38","author":"Sokol RJ","year":"1997","journal-title":"Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2004.10.008"},{"issue":"11","key":"e_1_2_8_12_1","first-page":"953","article-title":"Total parenteral nutrition in neonates","volume":"43","author":"Chaudhari S","year":"2006","journal-title":"Indian Pediatr"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2005.03.019"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(00)00043-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00280.2011"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198363"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2006.01731.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.03.019"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.20.15482"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0648"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700330-JLR200"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.107"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2007-0113"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.64.3.342"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1093\/ajcp\/77.3.378a","article-title":"Total parenteral alimentation and cholestasis","volume":"77","author":"Finegold MJ","year":"1982","journal-title":"Am J Clin Pathol"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(75)80486-0"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpgasthep0796"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1536-4801.1983.tb08510.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(79)80604-6"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198603000-00003"},{"issue":"5","key":"e_1_2_8_31_1","first-page":"G665","article-title":"Taurocholate transport and Na+\u2010K+\u2010ATPase activity in fetal and neonatal rat liver plasma membrane vesicles","volume":"251","author":"Suchy FJ","year":"1986","journal-title":"Am J Physiol"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.054"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2013-6331"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3736"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607105029004248"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1927348"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.09.007"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2016.09.002"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2016.12.005"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.6.1467"},{"key":"e_1_2_8_41_1","article-title":"Newly identified mechanisms of total parenteral nutrition related liver injury","volume":"2014","author":"Jain AK","year":"2014","journal-title":"Advances in Hepatology"},{"issue":"6","key":"e_1_2_8_42_1","first-page":"459","article-title":"Growth and nitrogen utilization in rats on continuous and intermittent parenteral nutrition with and without fat (intralipid 20%)","volume":"147","author":"Roos KA","year":"1981","journal-title":"Acta Chir Scand"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199608)168:2<476::AID-JCP26>3.0.CO;2-#"},{"issue":"5","key":"e_1_2_8_44_1","first-page":"G1100","article-title":"GH elevates serum IGF\u2010I levels but does not alter mucosal atrophy in parenterally fed rats","volume":"272","author":"Peterson CA","year":"1997","journal-title":"Am J Physiol"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surge.2012.03.003"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201746"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-199507000-00006"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607116688437"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1017\/ice.2017.167"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R500013-JLR200"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/jam.13158"},{"issue":"1","key":"e_1_2_8_52_1","first-page":"s15","article-title":"The role of the gut microbiota in bile acid metabolism","volume":"16","author":"Ramirez\u2010Perez O","year":"2017","journal-title":"Ann Hepatol"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2015.09.001"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000000057"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1079"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00118-10"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.112.162388"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.10.5832-5839.2004"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2009.01.022"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-269480"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-200115040-00012"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-198706000-00010"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-007-9289-1"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1680"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v111.pm8698199"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4804(85)90049-6"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.113.004770"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12624-9"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1159\/000073797"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2004.01038.x"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9040388"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181852201"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00047.2006"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2017.09.017"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11050966"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.111.155259"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04374.x"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11040799"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.2000.00965.x"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-004-1331-2"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.01.063"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)91079-W"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3181256492"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(89)90186-0"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920012803762693"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2018.1461827"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2012-301885.132"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607110363614"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2014.118"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607106030006526"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.5223\/pghn.2016.19.1.44"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06572.x"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e328341235a"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.05.042"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpgasthep0521"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.2298\/SARH1404184S"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-985070"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1241865"},{"key":"e_1_2_8_99_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607112450301"},{"key":"e_1_2_8_100_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607104028003163"},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607111424412"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2018-000946"}],"container-title":["Nutrition in Clinical Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fncp.10461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aspenjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ncp.10461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:16:50Z","timestamp":1760955410000},"score":1,"resource":{"primary":{"URL":"https:\/\/aspenjournals.onlinelibrary.wiley.com\/doi\/10.1002\/ncp.10461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,23]]},"references-count":101,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1002\/ncp.10461"],"URL":"https:\/\/doi.org\/10.1002\/ncp.10461","archive":["Portico"],"relation":{},"ISSN":["0884-5336","1941-2452"],"issn-type":[{"value":"0884-5336","type":"print"},{"value":"1941-2452","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,23]]},"assertion":[{"value":"2019-12-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}