Cystic Fibrosis (CF) is the commonest fatal inherited disorder in Caucasians and the incidence in Ireland is the second highest in the world. Cystic Fibrosis Liver Disease (CFLD) is now a significant cause of morbidity and mortality in this population but its pathogenesis is poorly understood. In a case-control study we found that patients with CFLD were shorter, lighter and had worse pulmonary function than matched controls. After 10 years follow-up of this cohort liver disease was an independent risk factor for mortality and females had a worse outcome. We also found that diabetes was more common in CFLD.
We have therefore established a long-term prospective study of CFLD which to date has enrolled 605 participants (96% of the target pediatric population) to describe the natural history of CFLD and to determine the risk factors for disease onset, and disease progression. We are now seeking funding to continue the prospective study of this national cohort. We also want to address questions arising from our findings to date: (i) characterise the relationship between the onset of CFLD and Cystic Fibrosis Related Diabetes (CFRD) (ii) determine if diabetes in CFLD is predominantly insulin resistant (Type 2 Diabetes), similar to diabetes in other liver diseases, (iii) determine if there is a synergistic relationship between CFLD and CFRD. We also propose to evaluate Transient Elastography (TE) to diagnose and monitor disease progression in CFLD. If TE proves to be useful in CFLD it will greatly enhance the capacity of this long-term study to identify risk factors for liver disease including the contribution of impaired glucose metabolism to CFLD and advance our understanding of the pathogenesis of CFLD. It will also advance our collaboration in identifying modifier genes for CFLD and CFRD.