Date Published: April 4, 2019
Publisher: Public Library of Science
Author(s): M. B. Toledano, S. K. Mukherjee, J. Howell, D. Westaby, S. A. Khan, D. Bilton, N. J. Simmonds, Pavel Strnad.
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.
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.
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.
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.
Cystic fibrosis (CF) is the most common autosomal recessive disorder in Europe, affecting 1 in 2500 live births in the UK annually. It is one of the commonest life-shortening genetic diseases in the Western world: however, prognosis has improved markedly with modern multidisciplinary care: median predicted survival in the UK is currently 47.0 years. This is primarily due to improved management of respiratory and nutritional complications of CF. As a result of this, other non-pulmonary complications are becoming increasingly important[3,4]. Hepatic complications (encompassing cirrhosis, portal hypertension with variceal bleeding and ultimately liver transplantation) are an increasingly important cause of morbidity and mortality[5,6].
This is the first UK nationwide study of CFLD and one of the largest multi-centre studies of its kind in Europe[5,7,9,12,14,15,17–19]. We have demonstrated that CFLD prevalence in the UK is slowly increasing and is associated with higher mortality compared to CF patients without liver disease. Our data suggest cirrhosis can be diagnosed in adulthood and also confirmed reports that male sex, P.aeruginosa and CF related diabetes are significant independent risk factors for cirrhosis in CF patients. Our data also suggest a possible survival benefit for ursodeoxycholic acid in CFLD.