(228) Hold the Mayo on the "Trikafta" Special! A single center experience.

Background: Cystic Fibrosis (CF) is an autosomal recessive disease with a negative energy balance in the setting of malnutrition due to malabsorption, decreased intake and increased energy expenditure. These stem from the impairment in function of the cystic fibrosis transmembrane conductance regulator (CFTR) in multiple cell types. CF patients are generally encouraged to eat a high fat, calorie dense diet in order to overcome the negative energy balance. This is thought to be due to decreased lipid absorption. With longer life expectancies and rising obesity rates, there may be an increase in cardiovascular disease among people with CF in the coming years. However, the effects of these diets on overall lipid profiles in the adult CF population is not well characterized. The mechanisms postulated to explain this disturbance are a very carbohydrate rich diet, insulin resistance, liver dysfunction, an increase in pro-inflammatory cytokines and the use of corticosteroids, probably all acting synergistically. Tissues deficient in CFTR have altered levels of fatty acids. Studies have reported increased levels of plasma membrane cholesterol and abnormal intracellular cholesterol trafficking in in-vitro CF cell models. The enhanced liver biosynthesis is unable to maintain normal plasma cholesterol levels. This is likely because of the altered activity of the CFTR gene impairing liver cholesterol secretion. Our study looks at the lipid profiles in adult CF patients, prior to and after initiation of elexacaftor/tezacaftor/ivacaftor (ETI) therapy.

Methods: This is a retrospective, single center study performed at the Keck Medical Center of USC Anton Yelchin CF Clinic between January 2018 to December 2021 and is IRB approved. Subjects were included if they attended the adult CF clinic and had not received a solid organ transplantation. Data collected was via chart review, which included demographic data, family history, comorbidities, medication history, body mass indices (BMI), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride (TG) levels prior to and after initiation of ETI therapy. Continuous variables were analyzed using the Wilcoxon signed rank test.

Results: This study included 21 individuals (48% female, 24% Hispanic) ranging from 23 to 52 years of age, with a mean age of 33.5+ 7.8 years. All included subjects had at least one copy of F508 deletion (43% were homozygous) and 14% of subjects with family history of dyslipidemia. A majority of the subjects were pancreatic insufficient (91%) and 38% were previously diagnosed with CF related diabetes. Prior to ETI, the BMI was 22.3 (20.3, 26.1) kg/m² (median, interquartile range) and total cholesterol was 146 (124.5, 175.5) mg/dL (median, interquartile range). After initiation of ETI, there was a significant change in both BMI and total cholesterol, with a medium increase of 0.61 kg/m² (p - < 0.001) and 11 mg/dL (p - 0.009) respectively. Further analysis of the lipid profile showed a significant increase in LDL, with median increase of 18 mg/dL (p - 0.002), however changes to HDL and TG were not significant, with an increase of 1 mg/dL (p - 0.872) and decrease of 6.5 mg/dL (p - 0.514) respectively.

Conclusions: ETI has significantly increased BMI and total cholesterol in adult CF patients. More studies are needed to better understand the metabolic changes of the ETI with the lipid profiles.

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