Hepatic steatosis in adults on CFTR modulators is commonly associated with cardiometabolic criteria consistent with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND/AIMS: Hepatic steatosis (HS) is common in Cystic fibrosis (CF). CF transmembrane conductance-regulator (CFTR) modulators have been associated with improved nutritional status. The controlled attenuation parameter (CAP) is a non-invasive method for assessing HS. This study aimed to evaluate HS and to investigate whether its presence is associated with features suggestive of metabolic dysfunction-associated steatotic liver disease (MASLD).

METHODS

We conducted a prospective study (duration 25±2.5 months) including 45 patients receiving elexacaftor/tezacaftor/ivacaftor (treatment duration 32.7 ± 9.9 months). Clinical and laboratory data, as well as non-invasive markers of liver fibrosis, were recorded at enrolment and at final assessment (FA).

RESULTS

From enrolment to FA, body mass index (BMI) increased significantly (p < 0.001), whereas HS either persisted or developed during follow-up. At FA, BMI and waist circumference were associated with HS in univariate analysis; however, in multivariate analysis, only BMI remained independently associated with HS [OR 1.338 (95%CI 1.064-1.682), p = 0.013]. Among 12 (26.6%) patients with CAP≥248 dB/m at FA, all but one fulfilled at least one cardiometabolic criterion for MASLD. Overall, liver stiffness measurement and AST-to-Platelet-Ratio Index decreased at FA compared with enrolment (p = 0.044 and p = 0.027, respectively). This improvement persisted after BMI stratification only in patients with BMI<25 kg/m2 (p = 0.014 and p = 0.029, respectively).

CONCLUSIONS

BMI is independently associated with HS. Weight gain does not necessarily lead to HS, particularly when BMI remains within the normal range. Liver stiffness improves under CFTR modulators. However, in overweight/obese individuals, improvements in liver fibrosis are attenuated, and most patients with steatosis exhibit cardiometabolic features consistent with MASLD.