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566 PROTON NMR SERUM METABOLOMIC FINGERPRINT OF ACUTE ON CHRONIC LIVER FAILURE (AOCLF) IN ICU CIRRHOTIC PATIENTS
POSTERS
Poster Session – Friday, April 20, 2012
02a. CIRRHOSIS AND ITS COMPLICATIONS: PATHOPHYSIOLOGY
566 PROTON NMR SERUM METABOLOMIC FINGERPRINT OF ACUTE ON CHRONIC LIVER FAILURE (AOCLF) IN ICU CIRRHOTIC PATIENTS R. Amathieu1,2 , M.N. Triba2 , P. Nahon3 , N. Bouchemal2 , W. Kamoun1 , H. Haouache1 , J.-C. Trinchet3 , G. Dhonneur4 , L. Le Moyec5 . 1 Anesth´esie-R´eanimation, Hˆ opital Jean Verdier, AP-HP, Bondy, 2 Laboratoire CSPBAT, UMR 7244, Equipe Spectroscopie Biomol´ecules et Milieux Biologiques, Universit´e Paris 13, Bobigny, 3 H´epatologie, Hˆ opital Jean Verdier, AP-HP, Bondy, 4 Anesth´esie-R´eanimation, Hˆ opital Henri Mondor, AP-HP, Universit´e Paris 12, Creteil, 5 INSERM U902, UBIAE, Universit´e d’Evry, Evry, France E-mail: [email protected] Background and Aims: Accurate definition of AoCLF is lacking and this term is often used to describe different clinical entities by physicians. Metabolomic investigates metabolic perturbation in a biologic system and allows the identification of biomarkers, metabolic profile or prognostic factors. The present study was performed to assess the interest of 1H NMR spectroscopy as a diagnostic tool for AoCLF. Methods: Ninety-two cirrhotic outpatients with different levels of chronic liver failure (CLF group) and 19 cirrhotic patients (AoCLF group) referred in the ICU for management of acute event responsible of AoCLF were prospectively included. Blood samples were drawn the day of admission and stored at −80°C until analysis. Proton spectra were acquired at 500 MHZ on a Varian Unity Inova spectrometer. Orthogonal Projection of Latent-Structure (OPLS) analysis was run to discriminate CLF and AoCLF groups. Results were visualized by score plot (Figure 1) and metabolites related to AoCLF identified using the loading plot (Figure 2). Demographic, biological data, Child and Meld scores were recorded the day of admission and compared with traditional statistical analysis.
Figure 1.
Figure 2. 1: HDL, 2: Isobutyrate, 3: Lactate, 4: Glutamine, 5: Creatinine, 6: Glucose.
Results: If age and gender did not differ between CLF and AoCLF group: the Child and Meld scores were higher in AoCLF group than CLF group ([9.7±0.4 vs 7.0±0.2 and 23.8±2.2 vs 13.6±0.6 (p < 0.001)] as well as serum creatinine levels (147.7±23.5 vs 85.0±3.8 (p < 0001)). Acute event for AoCLF group were gastrointestinal bleeding (n = 8) and severe sepsis (n = 11). Groups were discriminated in OPLS analysis. The explained variance (R2) of the model was 0.78 and the predictability (Q2) was 0.68. Main metabolites related to AoCLF were lactate, isobutyrate, glucose, glutamine, phenylalanine, and creatinine. High-density lipids (HDL) were higher in CLF group compared with AoCLF group. Conclusion: A serum metabolite fingerprint of AoCLF obtained with proton NMR could be identified. Serum metabolomic profiling may help to refine clinical evaluation of cirrhotic patients admitted for hepatic decompensation or liver function worsening and also provides new insights into metabolic process involved in the acute impairment of hepatic functions. 567 THE ROLE OF ENDOGENOUS HYDROGEN SULFIDE IN THE PATHOGENESIS OF CIRRHOTIC CARDIOMYOPATHY IN RATS M. Babaei Karamshahlou, S. Hajizadeh, A.R. Mani. Physiology, Tarbiat Modares University, Tehran, Iran E-mail: [email protected] Background and Aims: Hydrogen sulfide (H2 S), a novel endogenous gaseous bioactive substance, has recently been implicated in the regulation of cardiovascular functions. Endogenous H2 S is produced by cystathionine-g-lyase and cystathionine-b-synthase in a variety of tissues. Previous studies have shown that the synthesis of endogenous H2 S is partially impaired in cirrhosis. Acceleration of the heart rate in response to catecholamines is also impaired in cirrhosis. The present study is aimed to examine the role of endogenous H2 S in the pathogenesis of cirrhotic cardiomyopathy in rats. Methods: Cirrhosis was induced by surgical ligation of the bile duct in male Wistar rats. Four weeks after bile duct ligation or sham surgery the atria were isolated and spontaneously beating rate and chronotropic responsiveness to adrenergic stimulation was assessed using standard organ bath. In order to investigate
Journal of Hepatology 2012 vol. 56 | S225–S388 © 2012 All rights reserved.
Poster Session – Friday, April 20, 2012
02a. CIRRHOSIS AND ITS COMPLICATIONS: PATHOPHYSIOLOGY
566 PROTON NMR SERUM METABOLOMIC FINGERPRINT OF ACUTE ON CHRONIC LIVER FAILURE (AOCLF) IN ICU CIRRHOTIC PATIENTS R. Amathieu1,2 , M.N. Triba2 , P. Nahon3 , N. Bouchemal2 , W. Kamoun1 , H. Haouache1 , J.-C. Trinchet3 , G. Dhonneur4 , L. Le Moyec5 . 1 Anesth´esie-R´eanimation, Hˆ opital Jean Verdier, AP-HP, Bondy, 2 Laboratoire CSPBAT, UMR 7244, Equipe Spectroscopie Biomol´ecules et Milieux Biologiques, Universit´e Paris 13, Bobigny, 3 H´epatologie, Hˆ opital Jean Verdier, AP-HP, Bondy, 4 Anesth´esie-R´eanimation, Hˆ opital Henri Mondor, AP-HP, Universit´e Paris 12, Creteil, 5 INSERM U902, UBIAE, Universit´e d’Evry, Evry, France E-mail: [email protected] Background and Aims: Accurate definition of AoCLF is lacking and this term is often used to describe different clinical entities by physicians. Metabolomic investigates metabolic perturbation in a biologic system and allows the identification of biomarkers, metabolic profile or prognostic factors. The present study was performed to assess the interest of 1H NMR spectroscopy as a diagnostic tool for AoCLF. Methods: Ninety-two cirrhotic outpatients with different levels of chronic liver failure (CLF group) and 19 cirrhotic patients (AoCLF group) referred in the ICU for management of acute event responsible of AoCLF were prospectively included. Blood samples were drawn the day of admission and stored at −80°C until analysis. Proton spectra were acquired at 500 MHZ on a Varian Unity Inova spectrometer. Orthogonal Projection of Latent-Structure (OPLS) analysis was run to discriminate CLF and AoCLF groups. Results were visualized by score plot (Figure 1) and metabolites related to AoCLF identified using the loading plot (Figure 2). Demographic, biological data, Child and Meld scores were recorded the day of admission and compared with traditional statistical analysis.
Figure 1.
Figure 2. 1: HDL, 2: Isobutyrate, 3: Lactate, 4: Glutamine, 5: Creatinine, 6: Glucose.
Results: If age and gender did not differ between CLF and AoCLF group: the Child and Meld scores were higher in AoCLF group than CLF group ([9.7±0.4 vs 7.0±0.2 and 23.8±2.2 vs 13.6±0.6 (p < 0.001)] as well as serum creatinine levels (147.7±23.5 vs 85.0±3.8 (p < 0001)). Acute event for AoCLF group were gastrointestinal bleeding (n = 8) and severe sepsis (n = 11). Groups were discriminated in OPLS analysis. The explained variance (R2) of the model was 0.78 and the predictability (Q2) was 0.68. Main metabolites related to AoCLF were lactate, isobutyrate, glucose, glutamine, phenylalanine, and creatinine. High-density lipids (HDL) were higher in CLF group compared with AoCLF group. Conclusion: A serum metabolite fingerprint of AoCLF obtained with proton NMR could be identified. Serum metabolomic profiling may help to refine clinical evaluation of cirrhotic patients admitted for hepatic decompensation or liver function worsening and also provides new insights into metabolic process involved in the acute impairment of hepatic functions. 567 THE ROLE OF ENDOGENOUS HYDROGEN SULFIDE IN THE PATHOGENESIS OF CIRRHOTIC CARDIOMYOPATHY IN RATS M. Babaei Karamshahlou, S. Hajizadeh, A.R. Mani. Physiology, Tarbiat Modares University, Tehran, Iran E-mail: [email protected] Background and Aims: Hydrogen sulfide (H2 S), a novel endogenous gaseous bioactive substance, has recently been implicated in the regulation of cardiovascular functions. Endogenous H2 S is produced by cystathionine-g-lyase and cystathionine-b-synthase in a variety of tissues. Previous studies have shown that the synthesis of endogenous H2 S is partially impaired in cirrhosis. Acceleration of the heart rate in response to catecholamines is also impaired in cirrhosis. The present study is aimed to examine the role of endogenous H2 S in the pathogenesis of cirrhotic cardiomyopathy in rats. Methods: Cirrhosis was induced by surgical ligation of the bile duct in male Wistar rats. Four weeks after bile duct ligation or sham surgery the atria were isolated and spontaneously beating rate and chronotropic responsiveness to adrenergic stimulation was assessed using standard organ bath. In order to investigate
Journal of Hepatology 2012 vol. 56 | S225–S388 © 2012 All rights reserved.