Cystic fibrosis related liver disease and endocrine considerations

Jordan S Sherwood; Jagdeesh Ullal; Katherine Kutney; Kara S Hughan

doi:10.1016/j.jcte.2021.100283

Cystic fibrosis related liver disease and endocrine considerations

J Clin Transl Endocrinol. 2021 Dec 13:27:100283. doi: 10.1016/j.jcte.2021.100283. eCollection 2022 Mar.

Authors

Jordan S Sherwood¹, Jagdeesh Ullal², Katherine Kutney³, Kara S Hughan⁴

Affiliations

¹ Department of Pediatrics, Diabetes Research Center, Division of Pediatric Endocrinology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, United States.
² Department of Medicine, UPMC Center for Diabetes and Endocrinology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States.
³ Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, United States.
⁴ Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States.

Abstract

Cystic fibrosis-liver disease (CFLD) is one of the most common non-pulmonary complications in the CF population, is associated with significant morbidity and represents the third leading cause of mortality in those with CF. CFLD encompasses a broad spectrum of hepatobiliary manifestations ranging from mild transaminitis, biliary disease, hepatic steatosis, focal biliary cirrhosis and multilobular biliary cirrhosis. The diagnosis of CFLD and prediction of disease progression remains a clinical challenge. The identification of novel CFLD biomarkers as well as the role of newer imaging techniques such as elastography to allow for early detection and intervention are active areas of research focus. Biliary cirrhosis with portal hypertension represents the most severe spectrum of CFLD, almost exclusively develops in the pediatric population, and is associated with a decline in pulmonary function, poor nutritional status, and greater risk of hospitalization. Furthermore, those with CFLD are at increased risk for vitamin deficiencies and endocrinopathies including CF-related diabetes, CF-related bone disease and hypogonadism, which can have further implications on disease outcomes and management. Effective treatment for CFLD remains limited and current interventions focus on optimization of nutritional status, identification and treatment of comorbid conditions, as well as early detection and management of CFLD specific sequelae such as portal hypertension or variceal bleeding. The extent to which highly effective modulator therapies may prevent the development or modify the progression of CFLD remains an active area of research. In this review, we discuss the challenges with defining and evaluating CFLD and the endocrine considerations and current management of CFLD.

Keywords: APRI, aspartate aminotransferase to platelet ratio; BMI, body mass index; CFBD, CF bone disease; CFLD, Cystic fibrosis-liver disease; CFRD, CF related diabetes; CFTR, cystic fibrosis transmembrane conductance regulator; Cirrhosis; Cystic fibrosis liver disease; Cystic fibrosis-related diabetes; FFA, free fatty acids; Fib-4, Fibrosis-4; GH, growth hormone; IGF-1, insulin-like growth factor-1; Insulin resistance; UDCA, ursodeoxycholic acid; ULN, upper limit of normal.