Slide 1: THRIVE-1: Prevalence of Choline Deficiency in Patients Dependent on Parenteral Support
THRIVE-1: A MULTI-CENTER, CROSS-SECTIONAL, OBSERVATIONAL STUDY TO ASSESS THE PREVALENCE OF CHOLINE DEFICIENCY INPATIENTS DEPENDENT ON PARENTERAL SUPPORT Dejan Micic, MD Associate Professor of Medicine Loyola University Medical Center Chicago, Illinois
Slide 2: Disclosures
Disclosures • Takeda Pharmaceuticals, Consultant • Ironwood Pharmaceuticals, Consultant • Takeda Pharmaceuticals, Speaker’s Bureau • Protara Therapeutics, Consultant
Slide 3: Learning Objectives
Learning Objectives Upon completion of this educational activity, the learner will be able to: • Understand the demographics, baseline characteristics, and parenteral support history of patients dependent on parenteral support (PS) • Assess the prevalence of choline deficiency in patients dependent
Slide 4: Background: Choline – A Key Essential Nutrient
Background: Choline – A Key Essential Nutrient • Choline is a quaternary amine that is an essential dietary nutrient in humans recognized by the Institute of Medicine in 19981,2 ￮ Choline plays a critical role in several metabolic processes ￮ Methyl donor in many key metabolic reactions, similar to
Slide 5: Background: Choline Deficiency
Background: Choline Deficiency • Patients with intestinal failure dependent on PS are at high risk of choline deficiency because choline is not routinely added to parenteral nutrition (PN) solutions. • Dependence on PS leads to choline deficiency, which can subsequently lead to the development of he
Slide 6: Background: Choline Deficiency Results in Hepatobiliary Pathophysiology
Background: Choline Deficiency Results in Hepatobiliary Pathophysiology Diminished Choline = Insufficient phosphatidylcholine (PC), resulting in hepatobiliary injury Affected pathways Steatosis Cholestasis 2 1 PC is the most ubiquitous phospholipid in the body PC is the primary lipid of the VLDL
Slide 7: Methods: THRIVE-1, A Multi-center, Cross-sectional, Observational Study
Methods: THRIVE-1 , A Multi-center, Cross-sectional, Observational Study • THRIVE-1 was a multi-center, cross-sectional, observational study to Key Assessments assess the prevalence of choline deficiency and liver injury in • Choline deficiency was patients dependent on PS defined as plasma free cho
Slide 8: Results: Demographics and Baseline Characteristics
Results: Demographics and Baseline Characteristics Characteristics Enrolled Set (N = 78) Age (years) • 78 patients enrolled; 75 completed; 3 Mean (SD) 51.9 (16.6) Age group, n (%) withdrew from the study 12-<18 2 (2.6) 18-65 61 (78.2) • Mean age was 51.9 years (SD: 16.6) >65 15 (19.2) Sex, n (%) Mal
Slide 9: Results: Parenteral Support History
Results: Parenteral Support History Enrolled set Total infusion volume of PS/day or night, N = 78 PS components, mean (SD) (N = 78) Mean: 2614.9 mL (SD: 1151.8) Amino Acids (grams per day per week) 60.7 (33.5) Median: 2350.0 mL (Min: 721, Max: 6433) Amino Acids (grams per kg day per week) 1.0 (0.5)
Slide 10: Results: Approximately 78% of patients were choline deficient
Results: Approximately 78% of patients were choline deficient • Mean plasma free choline concentration: 7.5 nmol/mL (SD: 3.9) Prevalence of choline deficiency • Choline deficiency was present in 78.2% (61/78) of patients • These findings are consistent with the published literature on prevalence of
Slide 11: Results: High prevalence of choline deficiency across subgroups by PS duration and age
Results: High prevalence of choline deficiency across subgroups including by PS duration and age By PS duration n/N (%) By PS duration ≤6 months 2/3 (66.7) >6 months to ≤12 months 5/6 (83.3) 100.0 >12 months to ≤24 months 8/13 (61.5) 100.0 100.0 >24 months to ≤36 months 4/4 (100.0) 90.0 >36 months t
Slide 12: Results: High prevalence across subgroups by intestinal failure subtype
Results: High prevalence of choline deficiency across subgroups of underlying conditions by intestinal failure subtype • Patients had at least one of the following underlying Patients with choline deficiency by Enrolled set conditions based on European Society for Clinical underlying condition (IF c
Slide 13: Results: Liver injury present in approximately 63% of choline deficient patients
Results: Liver injury was present in approximately 63% of choline deficient patients Prevalence of liver injury 100 • Liver injury was defined as any elevated liver 90 tests (> 1.5 x ULN; ALP, AST, ALT, GGT, direct 80 bilirubin, total bilirubin) or steatosis (MRI-PDFF ≥ 70 8%) 60 63.3% 50 40 30 20 1
Slide 14: Summary/Highlights
Summary/Highlights • Choline deficiency is a significant problem in the IF population and has been associated with liver injury. • Significant heterogeneity of liver injury was observed and warrants further investigation. • IV Choline Chloride, an investigational phospholipid substrate replacement t
Slide 15: References List
References List 1. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academies Press. 1998. 2. Zeisel SH. Choline: critical role during fetal development and dietary requirements in adult