The impact of liver disease on mortality in cystic fibrosis - a systematic review protocol

Abstract

Background Cystic fibrosis (CF) is a multiorgan disease affecting the lungs pancreas and gastrointestinal tract. Pulmonary complications are the most common clinical manifestation of the disease. Recent advances in the treatment of pulmonary complications have resulted in substantial improvement in life expectancy. Less than 10% of persons with CF (PWCF) develop liver disease (CFLD). There is conflicting evidence as to the impact of liver disease on mortality in CF, with evidence suggesting that CFLD contributes to increased mortality in CF, while other studies suggest that the impact on mortality is limited. Understanding the contribution of liver disease to mortality in CF is essential if further improvements in life expectancy are to be achieved. Objective: To document the impact of liver disease on life expectancy for PWCF. Methods: This systematic review will be conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P 2015). PubMed, Medline and Embase will be searched for English language publications between 1949 and 2020 reporting liver related and all-cause mortality in CF. Observational studies that use an unambiguous definition of liver disease in well-defined CF populations will be included. Studies with and without a comparator will be evaluated. Clinical trials of ursodeoxycholic acid will be excluded as well as organ transplantation outcome studies. The ROBINS-1 risk of bias tool for non-randomised studies will be used to evaluate the quality of the studies. We will provide a narrative synthesis of our findings using tabular formats to highlight any impact of liver disease on mortality in CF. Conclusion: It is anticipated that this review will bring clarity to the question of whether CFLD shortens life expectancy in PWCF and stimulate new approaches to the management of CFLD. Registration: This protocol has been submitted for registration on PROSPERO and is awaiting review.