{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:43:47Z","timestamp":1793447027078,"version":"4.5.0"},"reference-count":58,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","theclinics.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinics in Liver Disease"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1016\/j.cld.2018.12.008","type":"journal-article","created":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T23:49:51Z","timestamp":1550792991000},"page":"263-277","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":54,"title":["Hepatic Manifestations of Cystic Fibrosis"],"prefix":"10.1016","volume":"23","author":[{"given":"Sasan","family":"Sakiani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Kleiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Heller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cld.2018.12.008_bib1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1097\/MCP.0b013e3282f10a16","article-title":"Liver disease in cystic fibrosis","volume":"13","author":"Colombo","year":"2007","journal-title":"Curr Opin Pulm Med"},{"key":"10.1016\/j.cld.2018.12.008_bib2","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1056\/NEJMra043184","article-title":"Mechanisms of disease: cystic fibrosis","volume":"352","author":"Rowe","year":"2005","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.cld.2018.12.008_bib3","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/hep.29217","article-title":"Adult-onset cystic fibrosis liver disease: diagnosis and characterization of an underappreciated entity","volume":"66","author":"Koh","year":"2017","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2018.12.008_bib4","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ccm.2007.02.011","article-title":"Cystic fibrosis: a review of epidemiology and pathobiology","volume":"28","author":"Strausbaugh","year":"2007","journal-title":"Clin Chest Med"},{"key":"10.1016\/j.cld.2018.12.008_bib5","unstructured":"Cystic Fibrosis Foundation: Patient registry 2016 annual data report. Bethesda, Maryland, \u00a92017 Cystic Fibrosis Foundation."},{"key":"10.1016\/j.cld.2018.12.008_bib6","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1097\/MCG.0b013e31819e8bbd","article-title":"Hepatobiliary abnormalities and disease in cystic fibrosis epidemiology and outcomes through adulthood","volume":"43","author":"Bhardwaj","year":"2009","journal-title":"J\u00a0Clin Gastroenterol"},{"key":"10.1016\/j.cld.2018.12.008_bib7","article-title":"Liver disease in cystic fibrosis: illuminating the black box","author":"Colombo","year":"2018","journal-title":"Hepatology"},{"issue":"Suppl 2","key":"10.1016\/j.cld.2018.12.008_bib8","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1016\/j.jcf.2017.07.002","article-title":"Cystic fibrosis-related cirrhosis","volume":"16","author":"Leung","year":"2017","journal-title":"J\u00a0Cyst Fibros"},{"key":"10.1016\/j.cld.2018.12.008_bib9","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/MOG.0000000000000432","article-title":"Liver disease in patients with cystic fibrosis","volume":"34","author":"Kamal","year":"2018","journal-title":"Curr Opin Gastroenterol"},{"key":"10.1016\/j.cld.2018.12.008_bib10","doi-asserted-by":"crossref","first-page":"316","DOI":"10.5603\/ARM.2016.0041","article-title":"Contemporary national trends of cystic fibrosis hospitalizations and co-morbidities in the United States","volume":"84","author":"Chatterjee","year":"2016","journal-title":"Adv Respir Med"},{"key":"10.1016\/j.cld.2018.12.008_bib11","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.jhep.2004.08.006","article-title":"Epidemiology of liver disease in cystic fibrosis: a longitudinal study","volume":"41","author":"Lamireau","year":"2004","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.cld.2018.12.008_bib12","article-title":"Cystic fibrosis liver disease: outcomes and risk factors in a large cohort of French patients","author":"Boelle","year":"2018","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2018.12.008_bib13","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/0016-5085(93)91085-V","article-title":"Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells","volume":"105","author":"Cohn","year":"1993","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2018.12.008_bib14","first-page":"136","article-title":"Liver disease in cystic fibrosis","volume":"9","author":"Kobelska-Dubiel","year":"2014","journal-title":"Prz Gastroenterol"},{"key":"10.1016\/j.cld.2018.12.008_bib15","first-page":"G1236","article-title":"Functional polarity of Na+\/H+ and Cl\u2013\/HCO3\u2013 exchangers in a rat cholangiocyte cell line","volume":"275","author":"Spirli","year":"1998","journal-title":"Am J Physiol"},{"key":"10.1016\/j.cld.2018.12.008_bib16","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1002\/hep.1840360613","article-title":"Liver disease in cystic fibrosis: a prospective study on incidence, risk factors, and outcome","volume":"36","author":"Colombo","year":"2002","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2018.12.008_bib17","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1016\/S1569-1993(11)60006-4","article-title":"Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease","volume":"10","author":"Debray","year":"2011","journal-title":"J\u00a0Cyst Fibros"},{"key":"10.1016\/j.cld.2018.12.008_bib18","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1002\/hep.28817","article-title":"The cystic fibrosis transmembrane conductance regulator controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity","volume":"64","author":"Fiorotto","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2018.12.008_bib19","doi-asserted-by":"crossref","first-page":"e0116967","DOI":"10.1371\/journal.pone.0116967","article-title":"Intestinal lesions are associated with altered intestinal microbiome and are more frequent in children and young adults with cystic fibrosis and cirrhosis","volume":"10","author":"Flass","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.cld.2018.12.008_bib20","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1002\/hep.510300527","article-title":"Natural history of liver disease in cystic fibrosis","volume":"30","author":"Lindblad","year":"1999","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2018.12.008_bib21","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jcf.2011.09.002","article-title":"The prevalence of \"risky behaviour\" in adults with cystic fibrosis","volume":"11","author":"Mc Ewan","year":"2012","journal-title":"J\u00a0Cyst Fibros"},{"key":"10.1016\/j.cld.2018.12.008_bib22","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/j.1440-1843.2010.01771.x","article-title":"Metabolic abnormalities in adults with cystic fibrosis","volume":"15","author":"Georgiopoulou","year":"2010","journal-title":"Respirology"},{"key":"10.1016\/j.cld.2018.12.008_bib23","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1002\/lt.24842","article-title":"Liver transplantation in adult cystic fibrosis: clinical, imaging, and pathological evidence of obliterative portal venopathy","volume":"23","author":"Hillaire","year":"2017","journal-title":"Liver Transpl"},{"key":"10.1016\/j.cld.2018.12.008_bib24","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1016\/j.jcf.2017.03.006","article-title":"Liver disease in cystic fibrosis presents as non-cirrhotic portal hypertension","volume":"16","author":"Witters","year":"2017","journal-title":"J\u00a0Cyst Fibros"},{"key":"10.1016\/j.cld.2018.12.008_bib25","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/S0168-8278(99)80259-1","article-title":"Sclerosing cholangitis in adults with cystic fibrosis: a magnetic resonance cholangiographic prospective study","volume":"30","author":"Durieu","year":"1999","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.cld.2018.12.008_bib26","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.jcf.2018.04.005","article-title":"Primary sclerosing cholangitis is associated with abnormalities in CFTR","volume":"17","author":"Werlin","year":"2018","journal-title":"J\u00a0Cyst Fibros"},{"key":"10.1016\/j.cld.2018.12.008_bib27","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jcf.2016.08.002","article-title":"Prevalence of elevated liver enzymes in children with cystic fibrosis diagnosed by newborn screen","volume":"16","author":"Woodruff","year":"2017","journal-title":"J\u00a0Cyst Fibros"},{"key":"10.1016\/j.cld.2018.12.008_bib28","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1053\/j.gastro.2009.12.052","article-title":"SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease","volume":"138","author":"Schwimmer","year":"2010","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cld.2018.12.008_bib29","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/MPG.0000000000000758","article-title":"Increase of serum gamma-glutamyltransferase associated with development of cirrhotic cystic fibrosis liver disease","volume":"61","author":"Bodewes","year":"2015","journal-title":"J\u00a0Pediatr Gastroenterol Nutr"},{"issue":"2","key":"10.1016\/j.cld.2018.12.008_bib30","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1007\/s00330-018-5650-5","article-title":"The efficacy of MRI in the diagnostic workup of cystic fibrosis-associated liver disease: a clinical observational cohort study","volume":"29","author":"Poetter-Lang","year":"2019","journal-title":"Eur Radiol"},{"key":"10.1016\/j.cld.2018.12.008_bib31","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1002\/hep.28016","article-title":"Aspartate aminotransferase to platelet ratio and fibrosis-4 as biomarkers in biopsy-validated pediatric cystic fibrosis liver disease","volume":"62","author":"Leung","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2018.12.008_bib32","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/liv.12113","article-title":"Utility of transient elastography in the non-invasive evaluation of cystic fibrosis liver disease","volume":"33","author":"Kitson","year":"2013","journal-title":"Liver Int"},{"key":"10.1016\/j.cld.2018.12.008_bib33","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1097\/MPG.0000000000001448","article-title":"Correlation of transient elastography with severity of cystic fibrosis-related liver disease","volume":"64","author":"Aqul","year":"2017","journal-title":"J\u00a0Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.cld.2018.12.008_bib34","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1097\/MPG.0000000000001822","article-title":"Assessment of liver disease progression in cystic fibrosis using transient elastography","volume":"66","author":"Gominon","year":"2018","journal-title":"J\u00a0Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.cld.2018.12.008_bib35","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jcf.2012.11.010","article-title":"Cirrhosis and other liver disease in cystic fibrosis","volume":"12","author":"Flass","year":"2013","journal-title":"J\u00a0Cyst Fibros"},{"key":"10.1016\/j.cld.2018.12.008_bib36","unstructured":"LiverTox: Cystic fibrosis agents - ivacaftor and lumacaftor. https:\/\/livertox.nlm.nih.gov\/IvacaftorLumacaftor.htm. Accessed September, 2018."},{"key":"10.1016\/j.cld.2018.12.008_bib37","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1002\/lt.20465","article-title":"Variceal hemorrhage and cystic fibrosis: outcomes and implications for liver transplantation","volume":"11","author":"Gooding","year":"2005","journal-title":"Liver Transpl"},{"key":"10.1016\/j.cld.2018.12.008_bib38","first-page":"24","article-title":"Assessment of liver disease in cystic fibrosis","volume":"27","author":"Davison","year":"2018","journal-title":"Paediatr Respir Rev"},{"issue":"4","key":"10.1016\/j.cld.2018.12.008_bib39","article-title":"Platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices in people with chronic liver disease or portal vein thrombosis","author":"Colli","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.cld.2018.12.008_bib40","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1097\/MPG.0000000000001453","article-title":"Survey on clinical practice of primary prophylaxis in portal hypertension in children","volume":"64","author":"Jeanniard-Malet","year":"2017","journal-title":"J\u00a0Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.cld.2018.12.008_bib41","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.jhep.2016.06.021","article-title":"Validation of the Baveno VI criteria to identify low risk cirrhotic patients not requiring endoscopic surveillance for varices","volume":"65","author":"Maurice","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.cld.2018.12.008_bib42","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/cld.470","article-title":"Surgical management of noncirrhotic portal hypertension","volume":"5","author":"Marti","year":"2015","journal-title":"Clin Liver Dis"},{"key":"10.1016\/j.cld.2018.12.008_bib43","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/jpc.13921","article-title":"Practical approach to the gastrointestinal manifestations of cystic fibrosis","volume":"54","author":"Bolia","year":"2018","journal-title":"J\u00a0Paediatr Child Health"},{"key":"10.1016\/j.cld.2018.12.008_bib44","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1053\/jhep.2002.36088","article-title":"Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited","volume":"36","author":"Paumgartner","year":"2002","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2018.12.008_bib45","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1365-2036.2012.05177.x","article-title":"Ursodeoxycholic acid therapy in cystic fibrosis liver disease--a retrospective long-term follow-up case-control study","volume":"36","author":"Kappler","year":"2012","journal-title":"Aliment Pharmacol Ther"},{"issue":"9","key":"10.1016\/j.cld.2018.12.008_bib46","article-title":"Ursodeoxycholic acid for cystic fibrosis-related liver disease","author":"Cheng","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.cld.2018.12.008_bib47","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.jcf.2016.07.009","article-title":"Ursodeoxycholic acid treatment is associated with improvement of liver stiffness in cystic fibrosis patients","volume":"15","author":"van der Feen","year":"2016","journal-title":"J\u00a0Cyst Fibros"},{"key":"10.1016\/j.cld.2018.12.008_bib48","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1056\/NEJMoa1105185","article-title":"A\u00a0CFTR potentiator in patients with cystic fibrosis and the G551D mutation","volume":"365","author":"Ramsey","year":"2011","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.cld.2018.12.008_bib49","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/MCP.0000000000000423","article-title":"Effects of new and emerging therapies on gastrointestinal outcomes in cystic fibrosis","volume":"23","author":"Houwen","year":"2017","journal-title":"Curr Opin Pulm Med"},{"key":"10.1016\/j.cld.2018.12.008_bib50","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1002\/hep.29400","article-title":"Src kinase inhibition reduces inflammatory and cytoskeletal changes in DeltaF508 human cholangiocytes and improves cystic fibrosis transmembrane conductance regulator correctors efficacy","volume":"67","author":"Fiorotto","year":"2018","journal-title":"Hepatology"},{"key":"10.1016\/j.cld.2018.12.008_bib51","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1111\/j.1600-6143.2011.03904.x","article-title":"Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis","volume":"12","author":"Dowman","year":"2012","journal-title":"Am J Transplant"},{"key":"10.1016\/j.cld.2018.12.008_bib52","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/hep.29913","article-title":"Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases","volume":"68","author":"Marrero","year":"2018","journal-title":"Hepatology"},{"issue":"Suppl 3","key":"10.1016\/j.cld.2018.12.008_bib53","article-title":"Outcomes of combined liver\/lung transplantation for cystic fibrosis using SRTR analysis","volume":"17","author":"Halldorson","year":"2017","journal-title":"Am J Transplant"},{"key":"10.1016\/j.cld.2018.12.008_bib54","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/j.1399-3046.2010.01460.x","article-title":"Liver and combined lung and liver transplantation for cystic fibrosis: analysis of the UNOS database","volume":"15","author":"Arnon","year":"2011","journal-title":"Pediatr Transplant"},{"key":"10.1016\/j.cld.2018.12.008_bib55","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/lt.23389","article-title":"Pulmonary function in individuals who underwent liver transplantation: from the US cystic fibrosis foundation registry","volume":"18","author":"Miller","year":"2012","journal-title":"Liver Transpl"},{"key":"10.1016\/j.cld.2018.12.008_bib56","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1111\/imj.13126","article-title":"Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience","volume":"46","author":"Sivam","year":"2016","journal-title":"Intern Med J"},{"key":"10.1016\/j.cld.2018.12.008_bib57","unstructured":"OPTN\/UNOS liver review board policy. 2017."},{"key":"10.1016\/j.cld.2018.12.008_bib58","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/lt.22240","article-title":"Liver transplantation in patients with cystic fibrosis: analysis of United Network for Organ Sharing data","volume":"17","author":"Mendizabal","year":"2011","journal-title":"Liver Transpl"}],"container-title":["Clinics in Liver Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1089326118301120?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1089326118301120?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:57:06Z","timestamp":1761069426000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1089326118301120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["S1089326118301120"],"URL":"https:\/\/doi.org\/10.1016\/j.cld.2018.12.008","relation":{},"ISSN":["1089-3261"],"issn-type":[{"value":"1089-3261","type":"print"}],"subject":[],"published":{"date-parts":[[2019,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hepatic Manifestations of Cystic Fibrosis","name":"articletitle","label":"Article Title"},{"value":"Clinics in Liver Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cld.2018.12.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}