Journal of pediatric gastroenterology and nutrition · 2025
Impact of elexacaftor/tezacaftor/ivacaftor on biomarkers of cystic fibrosis hepatobiliary involvement in the PUSH study.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Ye Wen, Magee John C, Huang Suiyuan, Leung Daniel H, Bozic Molly, Stoll Janis, C Ling Simon, Paranjape Shruti M, Karnsakul Wikrom, Jay Freeman A, Schwarzenberg Sarah Jane, Palermo Joseph, Alonso Estella, Green Nicole, Masand Prakash, Karmazyn Boaz, Harned Roger, Navarro Oscar M, Siegel Marilyn J, Towbin Alex, Alazraki Adina, Otto Randolph K, Nicholas Jennifer L, Narkewicz Michael R
Аннотация
OBJECTIVES: The impact of elexacaftor/tezacaftor/ivacaftor (ETI) on cystic fibrosis (CF) hepatobiliary involvement (CFHBI) is uncertain. The goal of this study was to investigate the changes in key liver parameters in PUSH study participants who started ETI compared to those who did not (noETI).
METHODS: PUSH was a prospective observational study of persons with CF (pwCF) (3-12 yo at PUSH entry). Linear mixed effect model (LMEM) with one knot tested if ETI changed the slope of trajectories of clinical parameters by comparing ETI to noETI. Index time (IT) for ETI was ETI start and time of ETI availability for noETI. Time zero in the LMEM was index time.
RESULTS: One hundred forty-seven participants (104 ETI, 43 noETI). At IT, the groups were similar, for age, and liver parameters. Mean duration of ETI use was 22 months. The annual rate of change over time after IT in ETI compared to noETI was significantly improved for FEV1% pre (+3.4/yr p = 0.02) and wt z score (+0.06/yr, p = 0.006). There was improvement for ETI vs noETI for GGT (-15%/yr, p = 0.01) and ALT (-12%/yr, p = 0.02). Participants with CFHBI on ETI demonstrated similar trends and also had improvements in GGT and GGT to platelet ratio (GPR), but there were no differences in liver stiffness or US classification changes.
CONCLUSIONS: GGT and GPR improve in pwCF and CFHBI who received ETI compared to noETI. There were no changes in other liver parameters. This suggests an early signal for positive impact on CFHBI, but no early improvement in fibrosis.
METHODS: PUSH was a prospective observational study of persons with CF (pwCF) (3-12 yo at PUSH entry). Linear mixed effect model (LMEM) with one knot tested if ETI changed the slope of trajectories of clinical parameters by comparing ETI to noETI. Index time (IT) for ETI was ETI start and time of ETI availability for noETI. Time zero in the LMEM was index time.
RESULTS: One hundred forty-seven participants (104 ETI, 43 noETI). At IT, the groups were similar, for age, and liver parameters. Mean duration of ETI use was 22 months. The annual rate of change over time after IT in ETI compared to noETI was significantly improved for FEV1% pre (+3.4/yr p = 0.02) and wt z score (+0.06/yr, p = 0.006). There was improvement for ETI vs noETI for GGT (-15%/yr, p = 0.01) and ALT (-12%/yr, p = 0.02). Participants with CFHBI on ETI demonstrated similar trends and also had improvements in GGT and GGT to platelet ratio (GPR), but there were no differences in liver stiffness or US classification changes.
CONCLUSIONS: GGT and GPR improve in pwCF and CFHBI who received ETI compared to noETI. There were no changes in other liver parameters. This suggests an early signal for positive impact on CFHBI, but no early improvement in fibrosis.