Life expectancy for people with Cystic Fibrosis (PWCF) has improved dramatically over the last 2 decades. This improved survival has not been observed in those with CF liver disease (CFLD). In the Irish Longitudinal Study of CFLD (ILSCFLD), we found that those with CFLD had a mortality rate difference of 6.6 versus those with no liver disease. We propose to use data collected as part of the ILSCFLD to address 2 inter-related questions regarding this poorly understood disease. The first is about prediction of risk. Currently no useful validated prediction tool for CFLD exists. We will develop a predictor model using the data collected on > 800 children over the last 15 years as part of the ILSCFLD. This tool would help identify those at risk of CFLD who may benefit from early management and thus potentially avoiding complications. We will then validate this tool in a cohort of PWCF in the UK. The second question addresses the influence of CF Transmembrane Conductance Regulator (CFTR) modulators on (i) the development of liver disease and (ii) on those who have already established CFLD. Again, using the dataset collected over the last 15 years prior to and during the emergence of the CFTR modulators, we will examine changes in prevalence of liver disease, and outcomes of those with CFLD who have been started on these agents. In summary, this project will better define the risk of developing CFLD and identify if CFTR modulators prevent CFLD or affect outcomes in established liver disease.