RAPID COMMUNICATION

Improvement of Hepatic Steatosis in Cystic Fibrosis With Ivacaftor Therapy 

Don Hayes Jr, yPatrick S. Warren, Karen S. McCoy, and Shahid I. Sheikh

ABSTRACT Treatment of liver disease, including hepatic steatosis, in patients with cystic fibrosis (CF) is limited. With the development of ivacaftor, which corrects the gating defect of the CF transmembrane regulator channel, there is a potential new therapy available for this subgroup of the CF patient population. We present an adolescent with CF who had significant improvement in hepatic steatosis with ivacaftor treatment while hypothesizing on a mechanism of why it occurred. Key Words: cystic fibrosis, G551D, hepatic steatosis, ivacaftor

(JPGN 2015;60: 578–579)

T

he spectrum of hepatobiliary disorders in cystic fibrosis (CF) includes specific alterations from the underlying genetic defect and lesions of iatrogenic origin or that reflect the effects of a disease process occurring outside the liver (1). In general, CFrelated liver disease is presently classified among genetic cholangiopathies and results from lack or dysfunction of the cystic fibrosis transmembrane regulator (CFTR) at the apical membrane of bile duct cells (1). Although hepatic steatosis is a common liver complication in CF, it does necessarily progress to fibrotic liver disease (2), which is the accepted consensus of the majority of experts caring for patients. With increasing life expectancy, liver complications of CF are being recognized more frequently as a result of an older-age distribution (3). Liver disease has been found to be an independent risk factor for mortality in CF (4). There have been significant advancements in the treatment of CF, which has assisted in extending the life expectancy into adulthood. One innovation was the development of ivacaftor therapy, which corrects the gating defect of the CFTR channel (5). The genetic mutation with the most research completed using ivacaftor is G551D. We present a case of an adolescent patient with CF who had significant improvement in hepatic steatosis with ivacaftor. A 17-year-old girl with CF (DF508/G551D genotype) had 2 previous liver biopsies with mild fatty metamorphosis of the parenchyma in 1997 with progression to macrovesicular steatosis and mild portal inflammation and fibrosis in 2006. Noncontrast computed tomography (CT) of the abdomen before the biopsy in 2006 demonstrated an abnormal appearance of the hepatic

Received December 3, 2014; accepted February 10, 2015. From the Department of Pediatrics, and the yDepartment of Radiology, Ohio State University College of Medicine, Columbus. Address correspondence and reprint requests to Don Hayes Jr, MD, MS, Ohio State University, Nationwide Children’s Hospital, 700 Children’s Dr, Columbus, OH 43205 (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2015 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000765

parenchyma with uniformly diminished radiodensity consistent with steatosis with an average radiodensity of the liver measuring only 14 Hounsfield units (HU), with reference splenic radiodensity measuring 50 HU (Fig. 1A). Moreover, alanine aminotransferase and aspartate aminotransferase levels were 81 U/L (normal

Improvement of hepatic steatosis in cystic fibrosis with ivacaftor therapy.

Treatment of liver disease, including hepatic steatosis, in patients with cystic fibrosis (CF) is limited. With the development of ivacaftor, which co...
220KB Sizes 0 Downloads 12 Views