Abstract
BACKGROUND: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD). METHODS: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD. RESULTS: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of nod versus nl. htg had a sensitivity of 82% and specificity of 75% for subsequent nod. negative predictive value of a nl us for subsequent nod was 96%. multivariate logistic prediction model that included baseline us, age, and log(gpr) improved the c-index to 0.90 compared to only baseline us (c-index 0.78). based on survival analysis, 50% of htg develop nod after 8 years. conclusions: research us finding of htg identifies children with cf with a 30-50% risk for acfld. a score based on us pattern, age and gpr may refine the identification of individuals at high risk for acfld. clinical trial registration: prospective study of ultrasound to predict hepatic cirrhosis in cf: nct 01,144,507 (observational study, no consort checklist).>
