peer-reviewedAbstracts of the 38th European Cystic Fibrosis ConferenceObjectives
Ivacaftor is effective in the treatment of patients with CF and the G551D gating mutation. We present faecal analysis results of the CORK cohort, a single-centre, adult (n = 20), prospective, longitudinal study of G551D clinical responders (median follow-up 12 months), examining the gut microbiota, exocrine pancreatic function and intestinal inflammation on a 3 monthly basis after commencing treatment

Deane, Jennifer

Eustace, J. A.

Fouhy, Fiona

Hill, C. J.

McCarthy, M.

Murphy, D. M.

O'Callaghan, G. P.

O'Sullivan, Orla

Plant, B. J.

Rea, Mary

Ronan, N. J.

Ross, R Paul

Shanahan, F.

STANTON, CATHERINE

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Oral Presentations Workshop 16. GI and liver abnormalities S29WS16.1 Clinical Outcomes of Real-World Kalydeco (CORK) study −Investigating the impact of CFTR potentiation on the intestinalmicrobiota, exocrine pancreatic function and intestinalinflammation prospectively over 12 monthsJ. Deane1,2,3, N.J. Ronan2,4, G.P. O’Callaghan2,4,5, F. Fouhy1, M.C. Rea1,5,O. O’Sullivan1,5, C.J. Hill3,5, F. Shanahan5,6, R.P. Ross3, M. McCarthy4,D.M. Murphy2,4, J.A. Eustace2, C. Stanton1,5, B.J. Plant2,4,5. 1Teagasc FoodResearch Centre, Moorepark, Fermoy, Ireland; 2HRB Clinical Research Facility,University College Cork, Cork, Ireland; 3School of Microbiology, University CollegeCork, Cork, Ireland; 4Cork Adult Cystic Fibrosis Centre, University College Cork,Cork University Hospital, Cork, Ireland; 5Alimentary Pharmabiotic Centre, UniversityCollege Cork, National University of Ireland, Cork, Ireland; 6Department of Medicine,University College Cork, National University of Ireland, Cork, IrelandObjectives: Ivacaftor is effective in the treatment of patients with CF and the G551Dgating mutation. We present faecal analysis results of the CORK cohort, a single-centre,adult (n = 20), prospective, longitudinal study of G551D clinical responders (medianfollow-up 12 months), examining the gut microbiota, exocrine pancreatic function andintestinal inflammation on a 3 monthly basis after commencing treatment.Methods: Stool samples pre- and 3 monthly post commencement of ivacaftor in 20adult patients underwent metagenomic profiling of faecal microbiota. Faecal elastase-1(FE-1), faecal calprotectin (FC) and faecal lactoferrin (FL) were measured usingcommercially available ELISA kits.Results: Ivacaftor did not significantly alter gut microbial diversity, as measured bychao1 (p = 0.886). At phylum, family and genus levels significant increases wereobserved in Bacteroidetes (p = 0.044), Bacteroidaceae (p = 0.021) and Bacteroides(p = 0.021). Significant decreases were observed in Microbacteriaceae (p = 0.003) andEubacteriaceae (p = 0.014). A significant positive correlation was seen between FEV1and gut microbiota diversity following treatment (r = 0.4, p = 0.002). No significantdifference was measured in levels of FE-1 (p = 0.267), FC (p = 0.406) or FL (p = 0.779).Conclusion: Ivacaftor therapy has a normalisation effect on the gut microbiota,directing the microbiota towards a non-CF profile. Despite this elevated intestinal in-flammation was sustained. Lack of exocrine pancreatic recovery may reflect establishedexocrine pancreatic dysfunction in an adult cohort. On-going longitudinal prospectivedata may demonstrate further improvements in the gut health of this cohort.WS16.2 The prevalence of gastroesophageal reflux disease in infantswith cystic fibrosis diagnosed by newborn screening and therelationship with lung infectionR. Thursfield1, R. Ravindran2, A. Bush2,3, J.C. Davies2,3, S.B. Carr4. 1Alder HeyChildren’s Hospital, Liverpool, United Kingdom; 2Royal Brompton & HarefieldNHS Foundation Trust, London, United Kingdom; 3Imperial College London,London, United Kingdom; 4Royal Brompton & Harefield NHS Foundation Trust,Paediatric Respiratory, London, United KingdomGastro-oesophageal reflux disease (GORD) has been implicated in the respiratorysymptoms of CF. Studies in small populations suggest GORD may be present inup to 40% of these infants.Aim: To describe the prevalence of GORD in a large cohort of infants with CFdiagnosed by NBS. The secondary aim was to look for an association with bacterialinfection.Methods: Our NBS surveillance programme includes a 24 hr dual probe pH studyand BAL for microbiology. Results were collected on infants over a 6 year period.GORD was diagnosed using ESPGHAN criteria: corrected reflux index (RI) >12%,reflux episodes >72, length of longest reflux episode >41 minutes. An associationbetween GORD and positive bacterial samples was explored.Results: Infants: n = 117, median age: 4.1 months (range 1.8−9.7 mo), 57 males(48%), 15 pancreatic insufficient (13%). 103 had valid pH studies (88%). RI >12%n= 44 (43%), reflux episodes >72 n = 55 (53%), reflux episodes >41min n = 2.Positive bacteria at BAL = 29%. Including: PA= 3, SA= 8, HI = 5, coliforms = 7,other = 8 (some with mixed growths). There was no statistical difference in bacteriabetween those with and without GORD. There was a significant difference inwt z score −0.98 vs −0.2 p< 0.02. A scatter plot showed no significant reductionin RI with age.Discussion: This large study confirms the high prevalence of GORD in infants withCF when using RI alone (43%), the true prevalence may be higher, 53% showed anabnormally high number of reflux episodes. No association with bacterial infectionwas found.In conclusion: GORD appears more prevalent than thought in infants with CF andthe significantly lower weight in this group needs further exploration.WS16.3 Consecutive transient elastography measurements to detectcystic fibrosis liver diseaseS. Van Biervliet1, R. De Bruyne1, S. Vande Velde1, M. Van Winckel1,H. Verdievel2, D. De Looze2, F. De Baets3, H. Van Vlierberghe2. 1GhentUniversity Hospital, Pediatric Gastroenterology and Nutrition, Ghent, Belgium;2Ghent University Hospital, Gastroenterology, Ghent, Belgium; 3Ghent UniversityHospital, Pediatric Pneumology, Ghent, BelgiumBackground: Cystic fibrosis (CF) related liver disease (CFLD) is diagnosed usinga combination of criteria. Transient elastography (TE) (ultrasonographic methodevaluating liver stiffness) differentiates CF patients with and without liver disease(CFnoLD) and identifies patients with an increased risk for portal hypertension.Aim: Detect evolving CFLD using TE measurements.Method: Retrospective study (2007–2013) including all patients with TE measure-ments, performed by the same operator. Measurement was correlated to the presenceor development of CFLD based on the medical files.Results: 150 CF patients [median age 17 (9−24) years] were included, 118 withrepeated TE: 20 (14%) had CFLD at the first TE measurement, 4 (3%) developedCFLD during follow-up. The median TE value in CFLD was 14 (8.7–32.2)compared to 5.3 (4.9−5.7) in CFnoLD (P = 0.0001). The intra-individual differencesbetween 2 consecutive measurements [median interval between measurements1 yr (1−2)] was 0.05 (−1, 1.2) in CFnoLD and 0.55 (−1.68, 1.53) in the CFLDpatients. The area under the receiver operating curve for TE predicting CFLDwas 0.985. TE measurements above 6.55 kPa predicted CFLD with a sensitiv-ity of 94.7% and a specificity of 90.8% according to the AUROC. In CF <14 years aTE measurement above 6.55 kPa had a positive predictive value of 83%, decreasingto 60% for the total group and a negative predictive value of 100%. Patients withdeveloping CFLD had progressively increasing TE measurements.Conclusion: TE measurements progressively increased in CF patients developingCFLD. A prospective study is needed to evaluate whether TE will be able to detectCFLD before it becomes clinically apparent.WS16.4 Non invasive liver elastography (LSM) and computedtomography (CT) for evaluation of liver disease in 57cystic fibrosis adult patientsS. Hillaire1, N. Regnard2, D. Cazals-Hatem3, S. De Miranda4, A. Roux4,A. Guth2, F. Mellot2, D. Grenet4. 1Hôpital Foch, Department Medicine, CysticFibrosis Center, Suresnes, France; 2Hôpital Foch, Department of Radiology,Suresnes, France; 3Hôpital Beaujon, Université Paris 7, Department of Pathology,Clichy, France; 4Hôpital Foch, Pneumology, Cystic Fibrosis Center, Suresnes,FranceObjectives: Portal hypertension (PHT) is the main complication of cystic fibrosisliver disease (CFLD) but severe liver dysfunction occurred only in 0.5% of thepatients. The early diagnosis of CFLD is elusive and a gold standard for diagnosisof liver disease is lacking. The aim of this study was to evaluate liver stiffnessmeasurement (LSM) and CT with IV injected contrast medium in CF adult patients.Median LSM in 241 CF patients was 5.9 kPa.Methods: 57 CF patients (28F, 33 yrs −18; 51) had LSM and CT done for lungtransplant assessement or after lung transplantation.Results: LSM was obtained in 53 patients (92%). PHT was evident on CT in 25patients (portosystemic collaterals 12, splenomegaly 19, proeminent portal vein 25).PHT was present in 60% of the patients when LSM was >5.9 and in 12%when LSM was <5.9. None of the patients had variceal bleeding but 20/25 hadscreening for esophagal varices and 5 preventive variceal ligation (LSM 41.6,range 20−64). Nine patients had transient and easy to treat ascitis after lungtransplantation. Only one patient (with good respiratory function) had refractoryascitis (LSM 64). Three patients received a combined lung and liver transplantation(LSM: 29/39/73 kPa). Explanted liver analysis disclosed absence of cirrhosis butobliterative portal venopathy.Conclusion: CFLD with PHT could be present in patient with low LSM. Decom-pensation of PHT is unfrequent even in adults with end stage pulmonary diseaseor after lung transplantation. Portal venopathy without cirrhosis could explainPHT. The mechanism remains obscure but could explain the rare occurence ofhepatocellular deficiency in CFLD.

WS16.1 Clinical Outcomes of Real-World Kalydeco (CORK) study – Investigating the impact of CFTR potentiation on the intestinal microbiota, exocrine pancreatic function and intestinal inflammation prospectively over 12 months

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WS16.1 Clinical Outcomes of Real-World Kalydeco (CORK) study – Investigating the impact of CFTR potentiation on the intestinal microbiota, exocrine pancreatic function and intestinal inflammation prospectively over 12 months

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