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INTRODUCTION: CONCLUSIONS: METHODS:

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1 INTRODUCTION: CONCLUSIONS: METHODS:
Assessment of Hepatic Mitochondrial Beta Oxidation Using the Non-Invasive 13C Octanoate Breath Test: A Novel Tool for Assessment of Liver Function Before and After Bariatric Surgery 1Gadi Lalazar, 2Andrei Keidar, 1Tomer Adar, 1Meir Mizrahi, 1Ehud Zigmond, 1Nilla Hemed, 1Yaron Ilan 1Liver Unit, Department of Internal Medicine, 2Department of Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Disclosure: This study was supported in part by Exalenz Bioscience, Yaron Ilan – Exalenz Bioscience Medical Director INTRODUCTION: RESULTS: CONCLUSIONS: Liver complications associated with restrictive or malabsorptive gastric surgery, including hepatic failure, are observed with increasing frequency. It is therefore important to develop tools to enable an accurate assessment of liver reserve both before and after surgery. Increased lipid peroxidation and impairment in mitochondrial β-oxidation are important factors in the pathogenesis of NAFLD and NASH. Octanoate is metabolized via the beta-oxidation pathway, and may therefore aid in assessing mitochondrial function. The point of care non-invasive BreathID® continuous online 13C octanoate breath test (OBT, Exalenz Bioscience) has been used to assess mitochondrial liver function in patients with NAFLD. Aim: To assess the ability of the OBT to detect changes in mitochondrial function in patients undergoing bariatric surgery. The point of care continuous online OBT provides a rapid, non-invasive assessment of hepatic beta-oxidation in patients undergoing bariatric surgery. OBT identified the expected post surgery improvement in beta oxidation. OBT values correlated with insulin resistance, but did not correlate with change in BMI, making the test an ideal measure of changes in mitochondrial function irrespective of body weight before and after surgery. The data suggests that the OBT may enable accurate assessment of hepatic mitochondrial function before surgery and monitor changes following surgery. Patient Data Before Surgery After Surgery p Value Number 16 (12 F, 4 M) NA Age [yr] 41.1 ± 11.3 Weight [kg] 119.6 ± 22.1 84.8 ± 18.9 0.001 BMI [kg/cm^2] 44.1 ± 7.9 30.2 ± 5.0 Waist Circ. [cm] 137.0 ± 9.5 91.5 ± 16.8 ALT [U/l] 34 ± 17.6 20.8 ± 6.0 0.005 PDR45 [%/h] 14.2 ± 8.2 19.7 ± 4.7 0.013 CPDR10 [%] 0.7 ± 0.6 1.6 ± 1.0 0.091 Average ± SD; NA – not applicable * * p = 0.01 Spearman Correlation of Clinical Parameters and Breath Test Scores before intervention Post surgery the average weight and BMI dropped by 30 and 50% respectively. None of the patients suffered clinical liver-decompensation. Octanoate metabolism as measured by PDR45 and CPDR10 increased following surgery. METHODS: PDR15 PDR30 PDR45 PDR60 CPDR10 CPDR30 CRPDR60 Age .019 -.031 -.080 -.274 .141 .028 .009 BMI -.394 -.453 -.432 -.126 -.465 -.488 -.553* HbA1C .828** .837** .410 .762* .862** ALT -.339 -.333 -.528* -.201 -.147 -.296 AST -.202 -.385 -.383 -.566* -.330 -.256 -.358 * p < 0.05; ** p < 0.01 16 Patients (4 male, 12 Female), aged (avg. 41, SD 11) with morbid obesity (BMI 44±8), who were scheduled to undergo bariatric surgery performed OBT before and after the surgery. OBT was performed after an 8 hour fast and ingestion of 75mg 13C-Octanoate diluted in water. Average follow up time was 6 months (range 1-12). Patients were followed for: Clinical outcome and liver related complications. OBT scores [including the PDR 45 (% of 13C dose recovered/hour at 45 minutes), CPDR10 (cumulative PDR at 10 minutes) before and after surgery. PDR45 N Min Max Mean SD Before 16 1.753 25.373 14.18 8.19 After 11 12.564 26.199 19.69 4.69 p=0.013 CPDR10 .08 2.4 .71 .62 .07 2.957 1.56 .96 p=0.091 OBT values correlated with ALT, AST, HDL and HbA1C (p < 0.05), but not BMI before or after surgery.


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