Triple CFTR modulator therapy in severe cystic fibrosis-associated liver disease: a case report of an adverse outcome and the role of adherence to follow-up

Abstract

Background. Cystic fibrosis (CF) is a multisystem disease in which liver involvement occurs in 20-40% of patients. The introduction of CFTR modulator therapy has substantially improved the prognosis of patients with CF; however, patients with established cirrhosis have typically been excluded from clinical trials, which limits the evidence base and underscores the need to collect and publish data on the use of these agents in this patient group. Materials and methods. We report a case with an unfavorable outcome in a 19-year-old patient with CF-associated Child-Pugh class B cirrhosis complicated by portal hypertension and a previous episode of esophageal variceal bleeding. Triple CFTR modulator therapy with elexacaftor + tezacaftor + ivacaftor/ivacaftor was initiated as a life-saving measure at a reduced dose in order to stabilize the patient until a decision on liver transplantation could be made. However, following subjective improvement in respiratory status, the patient was lost to specialist follow-up for approximately two years, during which liver function was not monitored and the transplant workup was not advanced; this culminated in decompensation of cirrhosis (Child-Pugh class C), multiorgan failure, and death. Conclusion. This case demonstrates that in severe CF-associated liver disease the safety of highly effective targeted therapy depends not only on the choice of drug and the dosing regimen, but also on the continuity of specialist follow-up, regular assessment of liver function, timely adjustment of treatment and transplant strategy, and the patient's adherence to follow-up.