Sanem ERYILMAZ POLAT, Mina HIZAL, Beste ÖZSEZEN, Gökçen Dilşa TUĞCU, Ayşe Gül ALIMLI, Güzin CİNEL

Kistik Fibrozisli Çocuklarda Karaciğer Tutulumunun Shear-Wave Elastografi ile Non-invaziv Değerlendirilmesi

Amaç: Kistik fibrozis dünyada beyaz ırkın en sık görülen genetik hastalığıdır. Kistik fibroziste ortalama yaşam beklentisiarttığından komplikasyonlar ve yönetimi daha önem kazanmıştır. Shear-wave elastografi, odaklanmış ultrasonografikullanılarak yumuşak doku üzerinde lokal mekanik kompresyon uygulanmasını ve doku tepkisini gösteren gerinim elde edilmesini içeren yeni, invaziv olmayan bir yöntemdir. Bu çalışmada kistik fibrozisli çocukların abdominal ultrasonografive Shear-wave elastografi ile klinik ve laboratuvar bulgularını prospektif olarak karşılaştırmayı amaçladık. Gereç ve Yöntemler: Bu çalışma, Şubat 2018 ile Mart 2019 tarihleri arasında takip edilen on üç kistik fibrozis hastasında gerçekleştirilenprospektif bir çalışmadır. Kistik fibrozis ile ilişkili karaciğer hastalığının şiddeti uluslararası kriterlere göre kategorize edildi. Hastalarda karınultrasonografisi ile karaciğerin değerlendirilmesi ile aynı seansta elastografi ölçümü yapıldı. Bulgular: Toplam on üç kistik fibrozisli çocuk değerlendirildi. Shear-wave elastografi ile karaciğer sertliği ölçümlerinin median değeri 6.36(IQR 5.40-10.80) kiloPaskal’dı. Kistik fibrozise bağlı karaciğer hastalığı olmayan deneklerde medyan karaciğer sertliği ölçümü 6.30 (IQR 5.26-16.18) kiloPaskal (n=5)’di; Kistik fibrozis ilişkili karaciğer hastalığı olan kişilerde medyan karaciğer sertliği ölçümü 6.46 (IQR 5.43-10.80) kiloPaskal olmuştur. kiloPascal değerleri ile yaş, cinsiyet, AST, ALT, HbA1c değerleri arasında anlamlı bir ilişki bulunmazken, kistik fibrozis ilişkili karaciğer hastalığı ile hemoglobin A1c ve ALT değerleri arasında güçlü bir pozitif korelasyon bulundu (sırasıyla r=0.702, p=0.007; r=0.761, p=0.003). Sonuç: Kistik fibrozis ile ilişkili karaciğer hastalığı, önemli ölçüde değişen bir hastalık yüküne sahiptir, prevalansı artmaktadır ve erken tanınması tedavi ve takip için çok önemlidir. Shear-wave elastografide doku sertliği ölçümlerinde çocuklar için belirlenmiş net bir aralık değerleri olmamakla birlikte klinik ve diğer laboratuvar ve görüntüleme yöntemleri ile takip ve değerlendirme önemlidir.

Anahtar Kelimeler:

Kistik fibrozis, Çocuklar, Karaciğer, Shear-wave elastografi

Non-invasive Evaluation of Liver Involvement of Children with Cystic Fibrosis by Shear-Wave Elastography

Objectives: Hepatobiliary complications commonly occur in cystic fibrosis with increasing prevalence due to longer life expectancies and widespread screening efforts. Shear-wave elastography is a novel noninvasive method that involves application of local mechanical compression on soft tissue using focused ultrasonography and acquiring strain images that show tissue response. We aimed to compare abdominal ultrasonography and Shear-wave elastography and also clinical and laboratory findings of children with cystic fibrosis prospectively. Methods: This study is a prospective study conducted in 13 cystic fibrosis patients followed between February 2018 and March 2019. The severity of cystic fibrosis-related liver disease was categorized according to international criteria. Elastography measurement was performed in the same session with the evaluation of the liver by abdominal ultrasonography in the patients. The liver stiffness measurements were compared with clinical data, biochemistry parameters and ultrasound findings. Results: Measurements were performed in 13 cystic fibrosis children (3 boys, 10 girls). The mean kiloPascal values of liver stiffness measurements with shear-wave elastography were 8.68 (4.1-20.2). The median liver stiffness measurement in subjects without cystic fibrosis-related liver disease was 7.79 kiloPascals (n=5); The median liver stiffness measurement in subjects with cystic fibrosis-related liver disease was 9.23 kiloPascals. Conclusion: Cystic fibrosis-related liver disease has a significantly varying disease burden, its prevalence is increasing, and its early recognition is crucial for treatment and follow-up. Although there are no clear range values determined for children in tissue stiffness measurements in Shear-wave elastography, clinical and other laboratory and imaging methods and follow-up and evaluation are important.

Keywords:

Cystic fibrosis, liver, children, shear-wave elastography,

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Shteinberg M, Haq IJ, Polineni D, Davies JC. Cystic fibrosis. Lancet 2021;397:2195-211.
Toledano MB, Mukherjee SK, Howell J, Westaby D, Khan SA, Bilton D, et al. The emerging burden of liver disease in cystic fibrosis patients: A UK nationwide study. PLoS One 2019;14:e0212779.
Stonebraker JR, Ooi CY, Pace RG, Corvol H, Knowles MR, Durie PR, et al. Features of Severe Liver Disease With Portal Hypertension in Patients With Cystic Fibrosis. Clin Gastroenterol Hepatol 2016;14:1207-15 e3.
Yavuz S, Piskin FC, Oktay C, Tumgor G. Assessment of hepatic involvement by two-dimensional shear wave elastography in paediatric patients with cystic fibrosis. J Paediatr Child Health 2022;58:459-62.
Debray D, Kelly D, Houwen R, Strandvik B, Colombo C. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease. J Cyst Fibros 2011;10 Suppl 2:S29-36.
Flass T, Narkewicz MR. Cirrhosis and other liver disease in cystic fibrosis. J Cyst Fibros 2013;12:116-24.
H E, Cr H, S D, Ea E. 2D Shear Wave Elastography, a promising screening tool for Cystic Fibrosis liver disease, shows a correlation between vitamin D and liver stiffness. J Cyst Fibros 2022;21:873-7.
Aqul A, Jonas MM, Harney S, Raza R, Sawicki GS, Mitchell PD, et al. Correlation of Transient Elastography With Severity of Cystic Fibrosis-related Liver Disease. J Pediatr Gastroenterol Nutr 2017;64:505-11.
Lewindon PJ, Shepherd RW, Walsh MJ, Greer RM, Williamson R, Pereira TN, et al. Importance of hepatic fibrosis in cystic fibrosis and the predictive value of liver biopsy. Hepatology 2011;53:193-201.
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;12:431-9.
Calvopina DA, Noble C, Weis A, Hartel GF, Ramm LE, Balouch F, et al. Supersonic shear-wave elastography and APRI for the detection and staging of liver disease in pediatric cystic fibrosis. J Cyst Fibros 2020;19:449-54.
Schulz M, Kleinjans M, Strnad P, Demir M, Holtmann TM, Tacke F, et al. Shear Wave Elastography and Shear Wave Dispersion Imaging in the Assessment of Liver Disease in Alpha1-Antitrypsin Deficiency. Diagnostics (Basel) 2021;11:629.
Franchi-Abella S, Corno L, Gonzales E, Antoni G, Fabre M, Ducot B, et al. Feasibility and Diagnostic Accuracy of Supersonic Shear-Wave Elastography for the Assessment of Liver Stiffness and Liver Fibrosis in Children: A Pilot Study of 96 Patients. Radiology 2016;278:554-62.
Zhou LY, Jiang H, Shan QY, Chen D, Lin XN, Liu BX, et al. Liver stiffness measurements with supersonic shear wave elastography in the diagnosis of biliary atresia: a comparative study with grey-scale US. Eur Radiol 2017;27:3474-84.
Tutar O, Beser OF, Adaletli I, Tunc N, Gulcu D, Kantarci F, et al. Shear wave elastography in the evaluation of liver fibrosis in children. J Pediatr Gastroenterol Nutr 2014;58:750-5.
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;42:848-54.
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:e0178784.
Lam S, Nettel-Aguirre A, Van Biervliet S, Roeb E, Sadler MD, Friedrich-Rust M, et al. Transient Elastography in the Evaluation of Cystic Fibrosis-Associated Liver Disease: Systematic Review and Meta-analysis. J Can Assoc Gastroenterol 2019;2:71-80.
Kim JR, Suh CH, Yoon HM, Lee JS, Cho YA, Jung AY. The diagnostic performance of shear-wave elastography for liver fibrosis in children and adolescents: A systematic review and diagnostic meta-analysis. Eur Radiol 2018;28:1175-86.
Gominon AL, Frison E, Hiriart JB, Vergniol J, Clouzeau H, Enaud R, et al. Assessment of Liver Disease Progression in Cystic Fibrosis Using Transient Elastography. J Pediatr Gastroenterol Nutr 2018;66:455-60.
Colombo C, Battezzati PM, Crosignani A, Morabito A, Costantini D, Padoan R, et al. Liver disease in cystic fibrosis: A prospective study on incidence, risk factors, and outcome. Hepatology 2002;36:1374-82.
Colombo C, Russo MC, Zazzeron L, Romano G. Liver disease in cystic fibrosis. J Pediatr Gastroenterol Nutr 2006;43 Suppl 1:S49-55.
Perrem L, Stanojevic S, Solomon M, Carpenter S, Ratjen F. Incidence and risk factors of paediatric cystic fibrosis-related diabetes. J Cyst Fibros 2019;18:874-8.
Boelle PY, Debray D, Guillot L, Clement A, Corvol H, French CFMGSI. Cystic Fibrosis Liver Disease: Outcomes and Risk Factors in a Large Cohort of French Patients. Hepatology 2019;69:1648-56.
Rodriguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome--a liver-induced lung vascular disorder. N Engl J Med. 2008;358:2378-87.
Schaible B, Taylor CT, Schaffer K. Hypoxia increases antibiotic resistance in Pseudomonas aeruginosa through altering the composition of multidrug efflux pumps. Antimicrob Agents Chemother 2012;56:2114-8.
Cheng K, Ashby D, Smyth RL. Ursodeoxycholic acid for cystic fibrosis-related liver disease. Cochrane Database Syst Rev 2017;9:CD000222.
Minicucci L, Lorini R, Giannattasio A, Colombo C, Iapichino L, Reali MF, et al. Liver disease as risk factor for cystic fibrosis-related diabetes development. Acta Paediatr 2007;96:736-9.
Marshall BC, Butler SM, Stoddard M, Moran AM, Liou TG, Morgan WJ. Epidemiology of cystic fibrosis-related diabetes. J Pediatr 2005;146:681-7.