Published online Dec 27, 2019. doi: 10.4254/wjh.v11.i12.761
Peer-review started: September 4, 2019
First decision: October 14, 2019
Revised: October 28, 2019
Accepted: November 25, 2019
Article in press: November 25, 2019
Published online: December 27, 2019
Hepatic steatosis is a common form of cystic fibrosis associated liver disease (CFLD). The journal has published previous manuscripts regarding CFLD.
Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators are a revolutionary therapy which target the underlying cause of CF for the first time. Currently, very little is known about the impact of CFTR modulator therapy on hepatic disease in CF, despite liver failure being the third leading cause of death in CF patients.
The objectives of this study were therefore to determine whether CF related diabetes (CFRD) is associated with hepatic steatosis and to identify predictors of hepatic steatosis in CF.
Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by diabetes status and CFTR modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher’s exact test.
Twelve subjects (60%) had CFRD and 8 subjects (40%) had normal glucose tolerance (NGT). The median hepatic fat fraction for all subjects was 3.0% with a range from 0.0%-21.0%. Six subjects (30%) had hepatic steatosis, defined as PDFF > 5%. Hepatic fat fraction was significantly lower in the 9 subjects receiving CFTR modulator therapy (2.0%, 0.0%-6.4%) than in the 11 subjects not receiving CFTR modulators (4.1%, 2.7%-21.0%), P = 0.002. The median hepatic fat fraction was not statistically different between subjects with CFRD (median, range) (2.2%, 0.0-14.5%) and NGT (4.9%, 2.4-21.0%), P = 0.06.
In the enclosed manuscript, we demonstrate that lumacaftor/ivacaftor therapy is associated with reduced hepatic fat in CF patients. While hepatic steatosis has historically been considered a benign finding in CF, the spreading epidemic of liver failure from non-alcoholic steatohepatitis makes this doubtful.
It suggests a previously unrecognized effect of CFTR modulators of CFLD. CFTR modulator status should be included in future studies of hepatic steatosis or CFLD.