Cystic fibrosis liver disease in the post-modulator era

Abstract

Purpose of review Highly effective modulators of cystic fibrosis transmembrane conductance regulator (CFTR) function have had dramatic impact on pulmonary and nutritional outcomes in persons with cystic fibrosis (pwCF). The impact on liver disease in pwCF was not the focus of the registration trials. The purpose of this review is to assess the current literature on the impact of HEMT on liver disease, progression, regression, and safety. Recent findings Short-term studies of HEMT in pwCF have shown that there is no significant impact on the frequency of liver enzyme abnormalities. There is no evidence for significant improvement in liver enzymes over time on HEMT therapy. There is conflicting data on improvement in liver fibrosis determined by fibrosis indices (APRI and GPR) or elastography. One study showed improvement, and another showed worsening in younger (<20 years old) pwCF. There are reports of resolution or improvement in hepatic steatosis. There are rare reports of severe acute hepatitis and one report of hepatic decompensation leading to liver transplantation due to drug-induced liver disease. Summary HEMT have not been shown to have a significant impact on improving liver disease or preventing fibrosis with short-term therapy. Longer studies are needed to assess the impact of HEMT on liver disease in pwCF.

Clinical and genetic risk factors for cystic fibrosis‐related liver disease in Egyptian CF children: A single‐center experience

“…36 In short term evaluations of their effect on CFLD, they have not been shown to have a significant improvment in liver disease or in preventing fibrosis. 37 Their use in liver disease should be evaluated, especially in patients with advanced cirrhosis. 38 None of the modulators are available in Egypt yet.…”

“…Their effect on CFLD is not defined in randomized studies, and there are some reports of hepatotoxicity 36 . In short term evaluations of their effect on CFLD, they have not been shown to have a significant improvment in liver disease or in preventing fibrosis 37 . Their use in liver disease should be evaluated, especially in patients with advanced cirrhosis 38 .…”