Cystic fibrosis (CF) is the most common autosomal recessive metabolic disease with a current incidence of 1:3300–4800 in Germany and an annual increase of approximately 300 newborns. Hepatic involvement in CF, called cystic fibrosis liver disease (CFLD), has the third highest mortality rate in CF. Over a third of patients develop liver involvement in form of advanced fibrosis and cirrhosis in their first decade of life. Therefore, an early diagnosis of CFLD is crucial for improving the prognosis and quality of life. Transient elastography (TE) to measure liver stiffness (LS) is a noninvasive and accurate method for the diagnosis of hepatic fibrosis and cirrhosis (especially severe fibrosis F3 and F4). However, the assessment of significant fibrosis (F = 2) by TE shows a high variability of diagnostic accuracy. Since 2009, several longitudinal studies were conducted and TE serves as diagnostic tool, either alone or in combination with several other biomarkers such as matrix metalloproteinases and their inhibitors. These are elevated in patients with CFLD and, in combination with TE, can be used for the detection of CFLD and portal hypertension. Determination of TIMP-4 and Endoglin together with TE increased the sensitivity for the noninvasive diagnosis of CFLD. In comparative studies, TE performed superior to conventional fibrosis scores in detecting progressive CFLD. An annual increase of liver stiffness >0.38 kPa may be suggestive of progressing disease before the manifestation of severe fibrosis.
Cystic fibrosis Transient elastography TE Liver fibrosis Cystic fibrosis liver disease CFLD MMPs TIMP Endoglin
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Sakiani S, Kleiner DE, Heller T, Koh C. Hepatic manifestations of cystic fibrosis. Clin Liver Dis. 2019;23(2):263–77.CrossRefGoogle Scholar
Rath T, Menendez KM, Kügler M, Hage L, Wenzel C, Schulz R, et al. TIMP-1/-2 and transient elastography allow non invasive diagnosis of cystic fibrosis associated liver disease. Dig Liver Dis. 2012;44(9):780–7.CrossRefGoogle Scholar
Menten R, Leonard A, Clapuyt P, Vincke P, Nicolae A-C, Lebecque P. Transient elastography in patients with cystic fibrosis. Pediatr Radiol. 2010;40(7):1231–5.CrossRefGoogle Scholar
Karlas T, Neuschulz M, Oltmanns A, Guttler A, Petroff D, Wirtz H, et al. Non-invasive evaluation of cystic fibrosis related liver disease in adults with ARFI, transient elastography and different fibrosis scores. PLoS One. 2012;7(7):e42139.CrossRefGoogle Scholar
Kitson MT, Kemp WW, Iser DM, Paul E, Wilson JW, Roberts SK. Utility of transient elastography in the non-invasive evaluation of cystic fibrosis liver disease. Liver Int. 2013;33(5):698–705.CrossRefGoogle Scholar
Sadler MD, Crotty P, Fatovich L, Wilson S, Rabin HR, Myers RP. Noninvasive methods, including transient elastography, for the detection of liver disease in adults with cystic fibrosis. Can J Gastroenterol Hepatol. 2015;29(3):139–44.CrossRefGoogle Scholar
Van Biervliet S, Verdievel H, Vande Velde S, De Bruyne R, De Looze D, Verhelst X, et al. Longitudinal transient elastography measurements used in follow-up for patients with cystic fibrosis. Ultrasound Med Biol. 2016;42(4):848–54.CrossRefGoogle Scholar
Rath T, Hage L, Kügler M, Menendez Menendez K, Zachoval R, Naehrlich L, et al. Serum proteome profiling identifies novel and powerful markers of cystic fibrosis liver disease. PLoS One. 2013;8(3):e58955.CrossRefGoogle Scholar
Klotter V, Gunchick C, Siemers E, Rath T, Hudel H, Naehrlich L, et al. Assessment of pathologic increase in liver stiffness enables earlier diagnosis of CFLD: results from a prospective longitudinal cohort study. PLoS One. 2017;12(6):e0178784-e.CrossRefGoogle Scholar
Gominon A-L, Frison E, Hiriart J-B, Vergniol J, Clouzeau H, Enaud R, et al. Assessment of liver disease progression in cystic fibrosis using transient elastography. J Pediatr Gastroenterol Nutr. 2018;66(3):455–60.CrossRefGoogle Scholar
Friedrich-Rust M, Schlueter N, Smaczny C, Eickmeier O, Rosewich M, Feifel K, et al. Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis. J Cyst Fibros. 2013;12(5):431–9.CrossRefGoogle Scholar
Kloth C, Fabricius D, Wendlik I, Schmidt SA, Pfahler M, Lormes E, et al. Diagnostic accuracy of MRI with MRCP and B-Mode-sonography with elastography of the pancreas in patients with cystic fibrosis: a point-to-point comparison. BMC Res Notes. 2019;12(1):150.CrossRefGoogle Scholar
Bader RM, Jonas MM, Mitchell PD, Wiggins S, Lee CK. Controlled attenuation parameter: a measure of hepatic steatosis in patients with cystic fibrosis. J Cyst Fibros. 2019;18(2):280–5.CrossRefGoogle Scholar