Background/Introduction
Cystic fibrosis (CF) related liver disease (CFLD) manifests as a wide spectrum of hepatobiliary disease. The most common is focal biliary cirrhosis which results from biliary obstruction and progressive peri-portal fibrosis. The estimated prevalence of CFLD is approximately 10% with progression to liver failure requiring transplant in about 3% of individuals with CF. 1,2,3
Approved in October 2019, elexacaftor/tezacaftor/ivacaftor (Trikafta, elx/tez/iva) is the newest CF transmembrane conductance regulator (CFTR ) modulator for patients who are 12 years and older who have at least one F508del mutation or a mutation in the CFTR gene that is responsive based on in vitro data.4 Elx/tez/iva is superior to other modulator therapies with the clinical benefits of profound improvements in the percentage of predicted forced expiratory volume in one second (ppFEV1), normalized sweat chloride concentration (which is a surrogate for CFTR function), better respiratory-related quality of life, rapid weight gain and less pulmonary exacerbation.5,6
There is warning and precaution regarding elevated bilirubin and LFTs with elx/tez/iva and individuals with CFLD require more frequent monitoring.4 A dose reduction is required if the benefit exceed the risk for use in patients with moderate hepatic impairment and use should be avoided in severe impairment based on the Child-Pugh classifications.4 There are additional concerns of drug-drug interactions with P-glycoprotein (PGP) substrates as elx/tez/iva is an inhibitor and will lead to increased serum concentrations of PGP substrates.4 Several immunosuppressants commonly utilized in solid organ transplant are substrates of PGP and have a narrow therapeutic index.
Guidelines for CFLD are outdated and are early in the process of being revised. Currently, there are no recommendations provided forCFTR modulator use in this patient population.2,3 There are no published data regarding the use of elx/tez/iva in patients after liver transplant and limited data exists for ivacaftor and tezacaftor in this patient population. This case series describes the use of elx/tez/iva in patients with CF post-liver transplant.