Please use this identifier to cite or link to this item: https://dora.health.qld.gov.au/qldresearchjspui/handle/1/4482
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dc.contributor.authorLewindon, P. J.en
dc.contributor.authorLeung, D. H.en
dc.contributor.authorRamm, G. A.en
dc.contributor.authorStaples, H.en
dc.contributor.authorMinard, C. G.en
dc.contributor.authorRamm, L. E.en
dc.date.accessioned2022-11-07T23:53:13Z-
dc.date.available2022-11-07T23:53:13Z-
dc.date.issued2019en
dc.identifier.citation54 , 2019, p. 264en
dc.identifier.otherRISen
dc.identifier.urihttp://dora.health.qld.gov.au/qldresearchjspui/handle/1/4482-
dc.description.abstractIntroduction: Early identification of risk factors for the development of severe fibrosis in children with cystic fibrosis-related liver disease (CFLD) is crucial as promising CFTR modulator therapies emerge. Few liver biopsy validated studies exist. Objectives: To evaluate the clinical utility of biomarker indices, clinical characteristics and laboratory parameters in pediatric CFLD to predict risk of developing severe fibrosis (F3-4). Methods: This was a multicenter cohort study of children with CFLD (≥2: hepatomegaly ±splenomegaly; >6 months elevation of ALT (>1.5x ULN); fibrosis on liver biopsy; abnormal liver ultrasound findings) and liver histology (biopsy or explant) from September 1999 to November 2016. Baseline clinical features, labs, calculated APRI, FIB-4, GGT to platelet ratio (GPR), and anthropometrics were collected a median of 2.1 years prior to biopsy. Liver fibrosis was staged by Metavir classification. A Wilcoxon rank sum test was used to compare differences between fibrosis stage F0-2 (mild) vs F3-4 (severe). Logistic regression was used to evaluate specific variables to predict F3-4 fibrosis and product-limit survival estimates were used to determine how characteristics impacted time to F3-4 fibrosis. Results: The study cohort (n=42) was 57% male with a median age of 7.6 years at baseline and 10.3 years at biopsy. Fibrosis groupings were F0-2 (n=22) and F3-4 (n=20). Median FEV1 % predicted was lower (64%, p=0.029) in F3-4 patients at baseline compared to F0-2 (87.1%). The following markers (median) were higher in F3-4 vs F0-2 at baseline: FIB-4 (0.23 vs 0.11; p=0.03), APRI (0.5 vs 0.28; p=0.004), GGT (59.5 vs 18; p=0.002) and GPR (0.21 vs 0.06; p<0.001). Cutoffs for FEV1 , platelets, FIB-4, APRI and GPR were associated with more rapid progression to F3-4: FEV1 <74% (1.05 years vs 9.62, p=0.003, 95% CI [0.36, 1.52]); platelets <298.52 x103/μL (1.3 years vs 3.8, p=0.015, 95% CI [0.77, &infin]); FIB-4 ≥ 0.55 (0.96 years vs 3.8, p<0.0001, 95% CI [0.15, 1.52]), APRI ≥ 0.78 (0.96 years vs 3.8, p<0.0001, 95% CI [0.15, 1.52]); and GPR ≥ 0.41 (0.96 years vs 4.5, p<0.0001, 95% CI [0.15, 1.52]). Positive Pseudomonas aeruginosa from a respiratory culture ≥2 years of age progressed to F3-4 more rapidly (2.73 years vs 3.78, p=0.04, 95% CI [0.53, 2.73]) than F0-2. The AUROC of change/year of a combination of FIB-4, APRI, platelets, and GPR was 0.81 (p<0.0001). Conclusion: Children with CFLD who develop F3-F4 fibrosis validated by liver biopsy are unique in clinical characteristics and biomarker indices preceding liver biopsy, up to 2 years prior. FEV1 <74% among CFLD dichotomized those who would progress to F3-4, 9-fold more rapidly. These lab and biomarker differences may assist in cohorting patients with CFLD as more likely to develop severe fibrosis, allowing for earlier surveillance and intervention.L6293886432019-09-26 <br />en
dc.language.isoenen
dc.relation.ispartofPediatric Pulmonologyen
dc.titleRisk factors for severe liver fibrosis in children with CFLD in a multicenter study validated by liver biopsyen
dc.typeArticleen
dc.identifier.doi10.1002/ppul.22495en
dc.subject.keywordsliver biopsyen
dc.subject.keywordsliver fibrosisen
dc.subject.keywordsliver histologyen
dc.subject.keywordsmaleen
dc.subject.keywordsmulticenter studyen
dc.subject.keywordsnonhumanen
dc.subject.keywordsPseudomonas aeruginosaen
dc.subject.keywordsrank sum testen
dc.subject.keywordsrisk factoren
dc.subject.keywordsschool childen
dc.subject.keywordsthrombocyteen
dc.subject.keywordsultrasounden
dc.subject.keywordsreceiver operating characteristicen
dc.subject.keywordsbiological markerendogenous compounden
dc.subject.keywordsgamma glutamyltransferaseen
dc.subject.keywordsanthropometryen
dc.subject.keywordschilden
dc.subject.keywordsclinical articleen
dc.subject.keywordsclinical featureen
dc.subject.keywordscohort analysisen
dc.subject.keywordsconference abstracten
dc.subject.keywordscontrolled studyen
dc.subject.keywordscystic fibrosisen
dc.subject.keywordsexplanten
dc.subject.keywordsfemaleen
dc.subject.keywordsforced expiratory volumeen
dc.subject.keywordshepatomegalyen
dc.subject.keywordshistopathologyen
dc.subject.keywordshumanen
dc.subject.keywordshuman cellen
dc.subject.keywordshuman tissueen
dc.relation.urlhttps://www.embase.com/search/results?subaction=viewrecord&id=L629388643&from=exporthttp://dx.doi.org/10.1002/ppul.22495 |en
dc.identifier.risid2021en
dc.description.pages264en
item.grantfulltextnone-
item.openairetypeArticle-
item.fulltextNo Fulltext-
item.languageiso639-1en-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
Appears in Sites:Children's Health Queensland Publications
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