Longitudinal follow-up of shear-wave elastography for predicting advanced CF liver disease in children

Abstract

Objectives: Early identification of hepatobiliary manifestations of Cystic Fibrosis (CF) and prediction of development of advanced CF-liver disease (aCFLD) is essential for treatment optimisation and assessment for interventions. We evaluated the utility of shear-wave elastography (SWE) for identifying and predicting aCFLD and compared this tool with other available non-invasive markers of liver fibrosis. Methods: Children referred to the CF-Liver Clinic at the Queensland Children's Hospital underwent regular clinical reviews including liver ultrasound, blood tests and serial liver–stiffness measurements (LSM) by SWE between August 2015 - March 2022 and were followed up until October 2024. Liver fibrosis indices – GGT-to-platelet ratio (GPR), AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) were calculated. aCFLD was defined as having one or more of the following: nodular liver, advanced fibrosis (F4), multilobular cirrhosis and portal hypertension. Serial LSM readings were defined as “increasing” if there was a rise of >0.5 kPa/year. Results: A total of 138 pwCF had 386 LSM readings. At baseline, 9 had evidence of aCFLD. By the end of follow up, 27 (19.5%) had developed aCFLD. SWE had the highest AUROC [0.84 vs. 0.80 (GPR) vs. 0.82 (APRI) vs. 0.65 (FIB-4)] in predicting aCFLD. Initial LSM values were significantly higher in those who had or subsequently developed aCFLD 13.3 (8.1) vs. 7.2 (3.3) in patients who did not (p = 0.001). A cut–off of >9.25 kPa predicted aCFLD with a sensitivity of 81.5% and specificity of 74.6%. Increasing LSM values (seen in 39/97 children) were associated with a higher risk of having aCFLD (14/22 vs. 25/75, p = 0.01). Conclusion: LSMs by SWE are superior to ultrasound and other non-invasive indices for the identification and prediction of aCFLD in pwCF. A value of >9.25 kPa and/or the finding of increasing serial LSMs identify patients progressing to aCFLD before ultrasound imaging by at least 12 months.