Longitudinal Transient Elastography measurements (Fibroscan) used in follow-up for patients with Cystic Fibrosis. Stephanie Van Biervliet, Hugo Verdievel,

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Longitudinal Transient Elastography measurements (Fibroscan) used in follow-up for patients with Cystic Fibrosis. Stephanie Van Biervliet, Hugo Verdievel, Saskia Vande Velde, Ruth De Bruyne, Myriam Van Winckel, Danny De Looze, Xavier Verhelst, Anja Geerts, Frans De Baets, Hans Van Vlierberghe

Background & Objectives Cystic fibrosis related liver disease (CFLD) is diagnosed using a combination of criteria (1). Transient elastography (TE), an ultrasonografic method to evaluate liver stiffness, differentiates cystic fibrosis patients with and without liver disease (CFnoLD) (2) and identifies patients with an increased risk for developing varices as result of portal hypertension (3). Aim: Use of TE measurements for detection of evolving CFLD 1. Debray D, et al Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease. J Cyst Fibros 2011; 10: S29-S36 2. Menten R, et al. Transient elsatography in patients with cystic fibrosis. pediatr radiol 2010; 40: 1231-5 3. Malbrunot-Wagner AC, et al. Transient elsatography and portal hypertension in pediatric patients with cystic fibrosis. J Cyst Fibros 2011; 10: 338-42 4.Kitson MT, et al. Utility of transient elastography in the non-invasive evaluation of cystic fibrosis liver disease. Liver international 2013; 698-705

Methods Retrospective study (2007-2013) including all patients with TE measurements, performed by the same operator & correlating the measurement to the presence or development of CFLD based on the medical files. Ethical approval (n° EC UZG 2014/0581) is obtained.

Results TOTAL group Normal liver CFLD Significance p- value N° patients (n° patients with consecutive TE) 150 (118) 130 (99) 20 (19) N° TE measurements (interval between measurements Yrs) 433 (1 year (1-2)) 359 74 Age (Years) 17 (9 – 24) 17 (8,75 – 24,2) 18 (9 – 23,2) n.s. Pancreatic function 129 PI / 21 PS 109 PI / 21 PS 20 PI / 0 PS Ultrasound score 3 (3-3) 7 (6-8) 0.0001 SGPT (X ULN) 0.6 (0.4-0.8) 0.5 (0.4-0.7) 0.7 (0.4-1.2) GGT (X ULN) 0.5 (0.3-0.8) 0.4 (0.3-0.6) 1.1 (0.7-2.4) Bilirubin 0.1 (0.1-0.2) 0.2 (0.1-0.2) N scans/ patient 3 (2-4) TE result (kPa) 4.8 (3.8 – 5.9) 4.6 (3.7 – 5,3) 14 (8.7 – 32.2)

Results 150 CF (median age 17(9-24) years), 20 (14%) CFLD at the first TE measurement TE result predicts the presence of CFLD with an AROC of 0.969 (CI 0.947-0.99). A cut off > 6.8 (4) has a PPV of 91,7% and a NPV of 90.1%

Results Intra-individual differences : 0.05 (-1 – 1.2) in CFnoLD 0.55 (- 1.68 –1.53) in CFLD 5 (3%) developed CFLD during follow-up. Patients with developing CFLD had progressively increasing TE measurements.

Conclusion TE measurements above the cut off of 6.8 kPa accurately predict CFLD(4). TE results progressively increase in CF patients developing CFLD. A prospective study is needed to evaluate whether TE will be able to detect CFLD before it becomes clinically apparent.