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Guidelines for CFLD are outdated and are early in the process of being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.