Colombo Carla, Ramm Grant A, Lindblad Anders, Corti Fabiola, Porcaro Luigi, Alghisi Federico, Asherova Irina, Evans Helen, Kashirskaya Nataliya, Kondratyeva Elena, Lewindon Peter J, de Monestrol Isabelle, Oliver Mark, Ooi Chee Y, Padoan Rita, Shankar Sahana, Alicandro Gianfranco
IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy.
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
J Cyst Fibros. 2023 Mar;22(2):263-265. doi: 10.1016/j.jcf.2023.01.012. Epub 2023 Feb 2.
Cystic-fibrosis-related liver disease (CFLD) is a variable phenotype of CF. The severe CFLD variant with cirrhosis or portal hypertension has a poor prognosis and life expectancy. CFTR modulator therapies are now available for people with CF and eligibility for such treatment is based on their CFTR genotype. We evaluated the genetic eligibility for elexacaftor, tezacaftor, ivacaftor (ETI), and ivacaftor (IVA) monotherapy in a previously reported CF cohort of 1591 people with CF of whom 171 with severe CFLD. Based on their CFTR mutations, 13% (N=184/1420) of subjects without CFLD and 11% (N=19/171) of those with severe CFLD are not eligible for either ETI or IVA therapy. The non-eligible patients without CFLD or with severe CFLD can currently not take advantage of the potential benefits of these new treatments. Although this study cannot provide any data regarding the effect of ETI or IVA on the progression of severe CFLD, the consequences for ineligibility of patients with extreme liver phenotype may be even more significant because of their poorer disease risk profile.
囊性纤维化相关肝病（CFLD）是囊性纤维化（CF）的一种可变表型。伴有肝硬化或门静脉高压的严重CFLD变异型预后不良，预期寿命较短。CFTR调节剂疗法目前可用于CF患者，此类治疗的 eligibility 基于其CFTR基因型。我们在先前报道的1591例CF患者队列中评估了依列卡福、替扎卡福、依伐卡托（ETI）和依伐卡托（IVA）单药治疗的基因 eligibility，其中171例患有严重CFLD。根据其CFTR突变，13%（N = 184/1420）的无CFLD受试者和11%（N = 19/171）的严重CFLD受试者不符合ETI或IVA治疗条件。目前，无CFLD或患有严重CFLD的不符合条件患者无法从这些新治疗的潜在益处中获益。尽管本研究无法提供任何关于ETI或IVA对严重CFLD进展影响的数据，但由于极端肝脏表型患者的疾病风险状况较差，不符合条件对他们的影响可能更为显著。 （注：原文中“eligibility”未翻译，因为在医学语境中可能有特定含义，需结合上下文准确理解，这里直接保留英文以便读者结合原文理解。）
