Cystic Fibrosis‐related Liver Disease is Associated With Increased Disease Burden and Endocrine Comorbidities

ABSTRACT Background: Cystic fibrosis‐related liver disease (CFLD) is the leading nonpulmonary cause of mortality in cystic fibrosis (CF). We evaluated and compared the burden of disease and nonrespiratory comorbidities of those with severe CFLD and those without (noCFLD). Methods: A retrospective nationwide (Australia) longitudinal review (from 1998 to 2016) of severe CFLD patients compared with noCFLD controls (matched 1 : 1 for age, genotype, pancreatic insufficiency, and center). Results: One hundred sixty‐six patients with severe CFLD and 166 with noCFLD were identified. Forced expiratory volume in 1 second percentage of predicted (FEV1%) was significantly lower in CFLD than noCFLD across all ages (estimate [SE] −6.05% [2.12]; P  = 0.004). Median (IQR) hospitalizations per patient per year were higher in CFLD than noCFLD for: respiratory indications (0.6 [0.2–1.3] vs 0.4 [0.1–0.9]; P  = 0.002); gastrointestinal indications (0.09 [0–0.2] vs 0 [0–0.05]; P  < 0.001); and other indications (0.05 [0–0.2] vs 0 [0–0.1]; P  = 0.03). In the CFLD cohort, there was increased use of nasogastric (12.6% vs 5.4%; OR 2.51 [95% CI 1.06–6.46]; P  = 0.03) and gastrostomy nutritional supplementation (22.9% vs 13.2%; OR 1.93 [95% CI 1.05–3.63]; P  = 0.03). Additionally, the CFLD cohort had a higher frequency of bone diseases, osteopenia (26.5% vs 16.8%; OR 1.77 [95%CI 1.01–3.15]; P  = 0.04) and osteoporosis (16.2% vs 8.4%; OR 2.1 [95% CI 1.01–4.52]; P  = 0.04), as well as CF‐related diabetes (38.5% vs 19.2%; OR 2.61 [95% CI 1.55–4.47]; P  = 0.001). Conclusions: Patients with severe CFLD have greater disease burden, with higher number of hospitalizations (both respiratory and nonrespiratory indications), nutritional interventions, and are at higher risk of CF‐related bone disease and diabetes.