Evolution of hepatobiliary involvement in cystic fibrosis children on CFTR modulators

Abstract

Background: There are great changes in cystic fibrosis (CF) disease following introduction of modulator treatments. We aimed to focus on the evolution of hepatobiliary involvement following lumacaftor-ivacaftor (LI) and elexacaftor-tezacaftor-ivacaftor (ETI) initiation.

Methods: A retrospective monocentric observational study included 62 CF children treated with CFTR modulators. Data were collected at initiation and after one year of treatment. The primary objective was to describe the evolution of hepatobiliary involvement under CFTR modulator treatment.

Results: We identified hepatobiliary involvement before treatment in 37 patients (59.7 %). Fifteen had persistently (during >6 months) elevated liver enzymes (mostly ALT); 17 had abnormal ultrasound including 3 with nodular liver and 3 with pathological elastography; 5 had isolated splenomegaly. Biliary involvement was found in 19 patients. The evolution of hepatic parameters in the overall population was not significant (p > 0.05). However, we observed a trend towards improvement in laboratory values under treatment. There was only one inaugural diagnosis of nodular liver under LI and none under ETI. All patients had preserved liver function (PT>50 %).

Conclusions: We did not find a significant improvement or worsening of hepatobiliary involvement under CFTR modulators. We hypothesize that it could be stabilized with these treatments, but this will need confirmation through further studies with longer follow-up and larger cohorts. The other hypothesis proposed is that biological monitoring may not be an accurate assessment of the hepatobiliary response to modulators. This study supports the safety of CFTR modulator use.

Keywords: Cftr modulator; Elexacaftor-tezacaftor-ivacaftor; Lumacaftor-ivacaftor; children; cystic fibrosis related liver disease.