Increased aminotransferases do not necessarily mean hepatotoxicity of CFTR modulator therapy

Abstract

Aim of the study The presence of macroenzymes may mimic treatment related hepatotoxicity. Material and methods We present a female subject who developed high alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activity during cystic fibrosis transmembrane regulator (CFTR) modulator therapy. Results The differential work-up did not show any underlying liver disease. CFTR modulators were stopped with subsequent normalization and immediate rise of ALT/AST after modulators were restarted, which was interpreted as the presentation of CFTR modulator hepatotoxicity. Before permanent CFTR modulators’ discontinuation the patient’s blood was tested for the presence of macroALT/macroAST and the result was positive. The patient is continuing a CFTR modulator treatment that is being supervised using standard laboratory tests and a test detecting the presence of macroenzymes. At three subsequent measurements the tests showed the presence of macroenzymes. Conclusions Our patient shows that increased ALT/AST during CFTR modulator therapy may be related to the induction of macroenzymes and not necessarily to hepatotoxicity. Patients with high ALT/AST activity should be considered for testing for the presence of macroenzymes.

Macroenzymes as a reason for aminotransferases flare in cystic fibrosis patients on CFTR modulators therapy – Report of three cases

“…Macroenzymes have not yet been considered as a possible cause for liver function tests abnormality. Until now, the only case of CF patients with ALT/AST flare and presence of macroenzymes during CFTR therapy described in the literature [ 27 ] is our patient no 1 who is included into this report as well. The detection of macroenzymes in this patients triggered us to look for the same explanation for liver function abnormalities in other patients experiencing ALT/AST flare during CFTR modulators treatment.…”