The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study

M B Toledano, S K Mukherjee, J Howell, D Westaby, S A Khan, D Bilton, N J Simmonds, M B Toledano, S K Mukherjee, J Howell, D Westaby, S A Khan, D Bilton, N J Simmonds

Abstract

Objective: Cystic fibrosis associated liver disease (CFLD) is the third largest cause of mortality in CF. Our aim was to define the burden of CFLD in the UK using national registry data and identify risk factors for progressive disease.

Methods: A longitudinal population-based cohort study was conducted. Cases were defined as all patients with CFLD identified from the UK CF Registry, 2008-2013 (n = 3417). Denominator data were derived from the entire UK CF Registry. The burden of CFLD was characterised. Regression analysis was undertaken to identify risk factors for cirrhosis and progression.

Results: Prevalence of CFLD increased from 203.4 to 228.3 per 1000 patients during 2008-2013. Mortality in CF patients with CFLD was more than double those without; cirrhotic patients had higher all-cause mortality (HR 1.54, 95% CI 1.09 to 2.18, p = 0.015). Median recorded age of cirrhosis diagnosis was 19 (range 5-53) years. Male sex, Pseudomonas airway infection and CF related diabetes were independent risk factors for cirrhosis. Ursodeoxycholic acid use was associated with prolonged survival in patients without cirrhosis.

Conclusions: This study highlights an important changing disease burden of CFLD. The prevalence is slowly increasing and, importantly, the disease is not just being diagnosed in childhood. Although the role of ursodeoxycholic acid remains controversial, this study identified a positive association with survival.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Cumulative frequency of progression to…
Fig 1. Cumulative frequency of progression to cirrhosis in patients with CFLD, by age (years).
117 CFLD patients developed progressive disease and liver cirrhosis during the study, at a median age of 19 years (IQR 16 to 27 years).
Fig 2. Survival in CFLD patients with…
Fig 2. Survival in CFLD patients with and without cirrhosis and with and without ursodeoxycholic acid therapy.
A. Survival was significantly shorter in patients with cirrhosis compared to those without cirrhosis (HR 1.54, 95% CI 1.09 to 2.18, p = 0.015). B. Survival was significantly longer in patients on ursodeoxycholic acid (HR 0.70, 95% CI 0.52–0.96, p = 0.026).

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