The American Journal of GASTROENTEROLOGY VOLUME 106 | JANUARY 2011 www.amjgastro.com ORIGINAL CONTRIBUTIONS nature publishing group 104 LIVER INTRODUCTION Cystic fibrosis (CF) is a multiorgan disease caused by mutations in the CFTR gene ( cystic fibrosis transmembrane conductance regula- tor) (1). Pulmonary disease remains the main cause of morbidity and mortality in CF. However, other complications such as cystic fibrosis liver disease (CFLD) are now important clinical problems (2). CFLD is an unusual form of liver disease characterized by nonuniform portal tract abnormalities, termed focal biliary cir- rhosis (3,4). e localization of damage to intrahepatic bile ducts leading to portal tract fibrosis with preserved hepatic architecture is characteristic of CFLD. e clinical significance of this abnor- mality, in contrast to many other types of cirrhosis, is that portal hypertension and its sequelae such as variceal hemorrhage can be prominent features of the disorder without significant hepatocel- lular failure (3,4). e subtle nature of CFLD makes early detec- tion difficult, and there are no clinical or laboratory tests that are confirmatory until portal hypertension is well established. Although 70% of postmortem specimens have evidence of focal biliary cirrhosis, < 10% of patients with CF will develop clinically significant liver disease (5–7). Although there is general agreement that CFLD should be diagnosed only when there is clinically mani- fest liver disease (or evidence of multilobular cirrhosis and portal hypertension), many previous studies have used less-stringent crite- ria (8,9). is has contributed to uncertainty among clinicians and investigators regarding the benign nature or otherwise of the out- come in CFLD (5,7,10,11). Early studies suggested that patients with Outcome in Cystic Fibrosis Liver Disease Marion Rowland, MB, PhD 1,2 , Charles G. Gallagher, MB, FRCPI, FRCPC, FCCP 3 , Risteard Ó’Laoide, MRCPI, FFRRCSI, FRCR 4 , Gerard Canny, MD, FRCPC, FAAP, FCCP 5 , Annemarie Broderick, MB, BCh, BAO, MedSc, MRCPI 6 , Roisin Hayes, MRCPI, FRCR, FFRRCSI 7 , Peter Greally, MD, FRCPI, FRCPCH 8 , Dubhfeassa Slattery, MB, PhD, FRCPI 9 , Leslie Daly, PhD, MFPHM, FFPH 7 , Peter Durie, MD, FRCPC 10 and Billy Bourke, MD, MRCPI 6 OBJECTIVES: Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD. METHODS: This is a 7-year follow-up of 42 children with CFLD and their age- and sex-matched controls. Participants were reviewed clinically, biochemically, and radiologically at follow-up. RESULTS: Overall, 85% (72 of 84) of the original cohort were included, 36 CFLD participants and 36 CF controls. There was no significant difference in the number of deaths/transplants between groups (7 of 36 (19.4%) CFLD participants, 3 of 36 (8.3%) CF controls). There was a tendency for participants with CFLD to die younger than their respective CF controls. There was no difference in height, weight, body mass index, or pulmonary function between the groups. Nutritional param- eters (sum skinfold thickness 31.6 vs. 42.3, P = 0.03; mean upper arm fat area 15.08 vs. 10.59, P = 0.001; Shwachman score 43.7 vs. 32.1, P = 0.001) were worse among CFLD participants than among CF controls. Cystic fibrosis-related diabetes was more common in CFLD participants (11 of 27 (40.7%) vs. 5 of 33 (15.2%), P = 0.02). Eight children (22.2%) with evidence of CFLD at baseline had no clinical evidence of liver disease as adults. CONCLUSIONS: Patients with CFLD have a more severe CF phenotype than do CF patients without liver disease. However, a subgroup of children with CFLD will not manifest clinically significant liver disease as adults. Am J Gastroenterol 2011; 106:104–109; doi:10.1038/ajg.2010.316; published online 24 August 2010 1 The Children’s Research Centre, Dublin, Ireland; 2 UCD School of Medicine and Medical Science, Dublin, Ireland; 3 Department of Respiratory Medicine, National Referral Centre for Adult Cystic Fibrosis, St Vincent’s University Hospital, Elm Park, Dublin, Ireland; 4 Department of Radiology, St Vincent’s University Hospital, Elm Park, Dublin, Ireland; 5 Cystic Fibrosis Unit, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland; 6 Department of Gastroenterology, Our Lady’s Children’s Hospital, Dublin, Ireland; 7 Department of Radiology, Our Lady’s Children’s Hospital, Dublin, Ireland; 8 Cystic Fibrosis Unit, National Children’s Hospital, Dublin, Ireland; 9 Cystic Fibrosis Unit, Children’s University Hospital, Dublin, Ireland; 10 Division of Gastroenterology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada. Correspondence: Marion Rowland, MB, PhD, UCD School of Medicine and Medical Science, The Catherine McAuley Research and Education Centre, Nelson Street, Dublin 7, Ireland. E-mail: marion.rowland@ucd.ie Received 29 March 2010; accepted 14 July 2010