{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:11:20Z","timestamp":1789985480488,"version":"4.0.1"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2018,11,15]],"date-time":"2018-11-15T00:00:00Z","timestamp":1542240000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,11,15]],"date-time":"2018-11-15T00:00:00Z","timestamp":1542240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Cystic fibrosis (CF)\u2010associated liver disease (CFLD) is a hepatobiliary complication of CF. Current diagnostic modalities rely on nonspecific assessments, whereas liver biopsy is the gold standard to assess severity of fibrosis. MicroRNAs (miRNAs) regulate liver disease pathogenesis and are proposed as diagnostic biomarkers. We investigated the combined use of serum miRNAs and aspartate aminotransferase (AST) to platelet ratio (APRI) to diagnose and assess CFLD severity. This was a cross\u2010sectional cohort study of the circulatory miRNA signature of 124 children grouped by clinical, biochemical, and imaging assessments as follows: CFLD (n\u00a0=\u00a044), CF patients with no evidence of liver disease (CFnoLD; n\u00a0=\u00a040), and healthy controls (n\u00a0=\u00a040). Serum miRNAs were analyzed using miRNA sequencing (miRNA\u2010Seq). Selected differentially expressed serum miRNA candidates were further validated by qRT\u2010PCR and statistical analysis performed to evaluate utility to predict CFLD and fibrosis severity validated by liver biopsy, alone or in combination with APRI. Serum miR\u2010122\u20105p, miR\u2010365a\u20103p, and miR\u201034a\u20105p levels were elevated in CFLD compared to CFnoLD, whereas miR\u2010142\u20103p and let\u20107g\u20105p were down\u2010regulated in CFLD compared to CFnoLD. Logistic regression analysis combining miR\u2010365a\u20103p, miR\u2010142\u20103p, and let\u20107g\u20105p with APRI showed 21 times greater odds of accurately predicting liver disease in CF with an area under the receiver operating characteristics curve (AUROC)\u00a0=\u00a00.91 (sensitivity\u00a0=\u00a083%, specificity\u00a0=\u00a092%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.0001). Expression levels of serum miR\u201018a\u20105p were correlated with increasing hepatic fibrosis (HF) stage in CFLD (r<jats:sub>s<\/jats:sub>\u00a0=\u00a00.56; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.0001), showing good diagnostic accuracy for distinguishing severe (F3\u2010F4) from mild\/moderate fibrosis (F0\u2010F2). A unit increase of miR\u201018a\u20105p showed a 7\u2010fold increased odds of having severe fibrosis with an AUROC\u00a0=\u00a00.82 (sensitivity\u00a0=\u00a093%, specificity\u00a0=\u00a073%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.004), indicating its potential to predict fibrosis severity. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> We identified a distinct circulatory miRNA profile in pediatric CFLD with potential to accurately discriminate liver disease and fibrosis severity in children with CF.<\/jats:p>","DOI":"10.1002\/hep.30156","type":"journal-article","created":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T02:25:21Z","timestamp":1531794321000},"page":"2301-2316","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":23,"title":["MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis"],"prefix":"10.1097","volume":"68","author":[{"given":"Diego A.","family":"Calvopina","sequence":"first","affiliation":[{"name":"Hepatic Fibrosis Group,QIMR Berghofer Medical Research Institute,Herston,QLD,Australia"},{"name":"Faculty of Medicine,The University of Queensland,Brisbane,QLD,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Chatfield","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Statistics Unit,QIMR Berghofer Medical Research Institute,Herston,QLD,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Weis","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group,QIMR Berghofer Medical Research Institute,Herston,QLD,Australia"},{"name":"Faculty of Medicine,The University of Queensland,Brisbane,QLD,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda A.","family":"Coleman","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group,QIMR Berghofer Medical Research Institute,Herston,QLD,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel A.","family":"Fernandez\u2010Rojo","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group,QIMR Berghofer Medical Research Institute,Herston,QLD,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlton","family":"Noble","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Lady Cilento Children\u2019s Hospital,South Brisbane,QLD,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise E.","family":"Ramm","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group,QIMR Berghofer Medical Research Institute,Herston,QLD,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Baylor College of Medicine,Houston,TX"},{"name":"Division of Pediatric Gastroenterology, Hepatology, Nutrition,Texas Children\u2019s Liver Center,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Lewindon","sequence":"additional","affiliation":[{"name":"Faculty of Medicine,The University of Queensland,Brisbane,QLD,Australia"},{"name":"Department of Gastroenterology and Hepatology,Lady Cilento Children\u2019s Hospital,South Brisbane,QLD,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-6201","authenticated-orcid":false,"given":"Grant A.","family":"Ramm","sequence":"additional","affiliation":[{"name":"Hepatic Fibrosis Group,QIMR Berghofer Medical Research Institute,Herston,QLD,Australia"},{"name":"Faculty of Medicine,The University of 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