Validation of liver elastography in patients with primary sclerosing cholangitis and healthy individuals. Normal values and correlation to fibrosis parameters.
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Liver elastography applies ultrasound-based measurements of liver stiffness (LS), used as a quantification of liver fibrosis. Correlation between liver stiffness measurements (LSM) and histological stages of liver fibrosis was already established; however, technological and methodological differences between ultrasound equipment and biological differences related to age or liver disease etiology, may influence the interpretation of LSM. Correct assessment of disease relies on a precise definition of normality, but reference values and inter-system differences were lacking for several elastography systems. Data were particularly scarce for children and patients with primary sclerosing cholangitis (PSC). In this rare and complicated liver disease, non-invasive surveillance of fibrosis development is recommended as part of follow-up. Thus, we aimed to establish reference values for LSM in children and adults using several elastography systems and to compare principally different methods such as transient elastography (TE), point shear wave elastography (pSWE), and two-dimensional shear wave elastography (2D-SWE) in a head-to-head setup. We furthermore investigated, for the first time, the feasibility of pSWE and 2D-SWE in PSC patients. In studies II and III, we included 343 healthy individuals aged 4-70 years. Applying two or three elastography systems head-to-head in every participant, we defined age-specific reference values for each system. Reference values were determined for different age groups: 4-7 years, 8-11 years, 12–14 years, 15–17 years, and 20–70 years. We found a gender difference in subjects 12–70 years, with no similar difference in young children. LSM was higher in adolescents and adults compared to younger children. Correlation between different observers was good. In studies I and IV, a cohort of adult PSC patients was followed, collecting clinical data and performing LSM and blood tests. Paper I describes pSWE in PSC for the first time, comparing assessments of both liver lobes and concluding that left liver LSM is unreliable; hence, subsequent measurements forming Paper IV were applied in the right liver lobe only. All PSC patients were examined by pSWE at every visit. For Paper IV, all patients were examined head-to-head by both pSWE, 2D-SWE, and TE: all three systems were feasible in PSC patients, and all were highly correlated with other indications of liver fibrosis (B-mode findings, liver biochemistry, fibrosis scores, and prognostic scores). In conclusion, the results demonstrate that elastography systems representing three principally different methods are feasible and perform well in healthy subjects and PSC patients. We have established reference values for healthy children and adults, with head-to-head inter-system comparisons and descriptions of interobserver differences. Ultrasound elastography of the liver should be adopted broadly in the medical environment; in screening, diagnostics, and clinical patient follow-up of both children and adults.
Består avPaper I: Mjelle AB, Mulabecirovic A, Hausken T, Havre RF, Gilja OH, Vesterhus M. Ultrasound and point shear wave elastography in livers of patients with primary sclerosing cholangitis. Ultrasound Med Biol. 2016 Sep; 42(9):2146-55. The article is available in the thesis file. The article is also available at: http://dx.doi.org/10.1016/j.ultrasmedbio.2016.04.016
Paper II: Mjelle AB, Mulabecirovic A, Havre RF, Rosendahl K, Juliusson PB, Olafsdottir E, Gilja OH, Vesterhus M. Normal liver stiffness values in children: A comparison between three different elastography methods. J Pediatr Gastroenterol Nutr. 2019 May;68(5):706-712. The article is available at: https://hdl.handle.net/1956/19864
Paper III: Mulabecirovic A, Mjelle AB, Gilja OH, Vesterhus M, Havre RF. Liver elasticity in healthy individuals by two novel shear-wave elastography systems – Comparison by age, gender, BMI and number of measurements. PloS One. 2018 Sep 14;13(9):e0203486. The article is available in the thesis file. The article is also available at: https://doi.org/10.1371/journal.pone.0203486
Paper IV: Mjelle AB, Fossdal G, Gilja OH, Vesterhus M. Liver elastography in primary sclerosing cholangitis patients using three different scanner systems. Ultrasound Med Biol. 2020 Aug;46(8):1854-1864. The article is available in the thesis file. The article is also available at: https://doi.org/10.1016/j.ultrasmedbio.2020.03.025