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

Background Cystic fibrosis (CF) is a multiorgan disease affecting the lungs pancreas and gastrointestinal tract. Pulmonary complications are the most common 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 about 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 (1949-2020). Studies reporting the outcome for CFLD will be included where the definition of CFLD is outlined clearly in a CF population. Studies with and without a comparator will be evaluated. Clinical trials of ursodeoxycholic acid will be excluded as well as organ transplantation outcome studies. We will examine all-cause and specific causes of mortality.We will include transplantation in our estimates of all-cause mortality. The Axis Risk of Bias Tool for Observational Studies will be used to evaluate the quality of 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.