Lumacaftor/ivacaftor therapy is associated with reduced hepatic steatosis in cystic fibrosis patients

• 作者: Beth Kaminski Chris A Flask Katherine Kutney Kimberly McBennett MaryAnn O’Riordan Rose Gubitosi-Klug Shannon B Donnola Thomas J Sferra
• 来源期刊: 世界肝病学杂志:英文版(电子版)
• 学科: 工学
• 关键词: CYSTIC FIBROSIS LIVER disease Non-alcoholic fatty LIVER disease CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR Lumacaftor/ivacaftor CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR modulator Diabetes mellitus
• 年，卷（期）: 2019,（12）
• 页码范围: 761-772
• 页数: 12页
• 分类号: TV6

摘要

BACKGROUND Hepatic steatosis is a common form of cystic fibrosis associated liver disease(CFLD)seen in an estimated 15%-60%of patients with cystic fibrosis(CF).The pathophysiology and health implications of hepatic steatosis in cystic fibrosis remain largely unknown.In the general population,hepatic steatosis is strongly associated with insulin resistance and type 2 diabetes.Cystic fibrosis related diabetes(CFRD)impacts 40%-50%of CF adults and is characterized by both insulin insufficiency and insulin resistance.We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than cystic fibrosis patients without diabetes.AIM To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF.METHODS Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study.Only pancreatic insufficient patients with CFRD or normal glucose tolerance(NGT)were included.Patients with established CFLD,end stage lung disease,or persistently elevated liver enzymes were excluded.Mean magnetic resonance imaging(MRI)proton density fat fraction(PDFF)was obtained for all participants.Clinical characteristics[age,sex,body mass index,percent predicted forced expiratory volume at 1 s(FEV1),lumacaftor/ivacaftor use]and blood chemistries were assessed for possible association with hepatic steatosis.Hepatic steatosis was defined as a mean MRI PDFF>5%.Patients were grouped by diabetes status(CFRD,NGT)and cystic fibrosis transmembrane conductance regulator(CFTR)modulator use(lumacaftor/ivacaftor,no lumacaftor/ivacaftor)to determine between group differences.Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher’s exact test.RESULTS Twenty subjects were included in the final analysis.The median age was 22.3 years(11.3-39.0)and median FEV1 was 77%(33%-105%).Twelve subjects had CFRD and 8 had NGT.Nine subjects were receiving lumacaftor/iva