Risk factors for more rapid progression of severe liver fibrosis in children with cystic fibrosis‐related liver disease: A multi‐center study validated by liver biopsy

Abstract

AbstractBackground and AimsEarly identification of risk factors for the development of severe fibrosis in children with cystic fibrosis‐related liver disease (CFLD) is crucial as promising therapies emerge.MethodsThis multi‐center cohort study of children with a priori defined CFLD from 1999 to 2016, was designed to evaluate the clinical utility of CF‐specific characteristics and liver biomarkers assessed years prior to liver biopsy‐proven CFLD to predict risk of developing severe fibrosis (F3‐4) over time. Fibrosis was staged by Metavir classification.ResultsThe overall study cohort of 42 patients (F0‐2 (n = 22) and F3‐4 (n = 20)) was 57% male (n = 24) with median age of 7.6 years at baseline visit versus 10.3 years at biopsy. Median FEV1% predicted was lower in F3‐4 participants at baseline versus F0‐2 (59% vs. 85%; p = .002), while baseline FIB‐4, APRI and GGT were higher in F3‐4. Median splits for FIB‐4 (≥.13), APRI (≥.36), GPR (≥.09), GGT (≥25.5), and FEV1% (<64%) were associated with more rapid progression to F3‐4 (p < .01 for all). Using a combination of change/year in FIB‐4, APRI, and GPR to predict F3‐4, the AUROC was .81 (95% CI, .66, .96; p < .0001). For up to 5.8 years prior, thresholds for GPR were met 6.5‐fold more rapidly, and those for APRI and FIB‐4 were met 2.5‐fold more rapidly, in those who progressed to F3‐4 than those that did not.ConclusionsThis study suggests mild–moderate pulmonary dysfunction and higher liver biomarker indices at baseline may be associated with faster progression of CFLD.