- Email: [email protected]
570 NEW PARAMETERS IN THE EVALUATION OF CIRRHOTIC PORTAL HYPERTENSION: HEPATIC AND PORTAL VEINS DOPPLER FLOW PHASICITY
POSTERS the role of endogenous H2 S on chronotropic responsiveness of isolated atria, some tissues were incubated with propargylglycine (PAG, a cystathionine-g-lyase inhibitor) and oxamic acid (AOAA, a cystathionine-b-synthase inhibitor). We also measured the expression of cystathionine-g-lyase and cystathionine-b-synthase in isolated atria using quantitative RT-PCR. Results: 30 min incubation of the atria with PAG and AOAA was associated with a significant desensitization of chronotropic response to adrenergic stimulation in controls rats. This indicates that endogenous H2 S might be involved in modulation of adrenergic signaling in the atrium. Bile duct ligation was associated with impaired chronotropic responsiveness to adrenergic stimulation in comparison with sham-operated rats. In contrast to control group, Incubation of the atria with PAG and AOAA was able to significantly improve the chronotropic responsiveness to catecholamines in cirrhotic rats. There was no significant difference in atrial cystathionine-g-lyase and cystathionine-b-synthase mRNA levels in control and cirrhotic rats. Conclusions: Our data shows that local inhibition of endogenous hydrogen sulfide in atria has opposite effect in cirrhotic versus control rats. Endogenous H2 S might be involved in pathophysiology of cardiac chrontropic dysfunction in experimental cirrhosis. 568 FENOFIBRATE INCREASES BILE ACID GLUCURONIDATION IN HUMANS: A TARGETED METABOLOMIC STUDY J. Trottier1 , P. Caron1 , R.J. Straka2 , O. Barbier1 . 1 Laboratory of Molecular Pharmacology, Laval University, Quebec, QC, Canada; 2 Experimental and Clinical Pharmacology Department, University of Minnesota, Minneapolis, MN, USA E-mail: [email protected] Background: Glucuronidation is an important detoxification mechanism for numerous xeno- and endobiotics, including toxic bile acids. This enzymatic reaction increases the solubility of its substrates, thus favouring their elimination from the human body. Fenofibrate is a triglyceride-lowering agent acting as an activator of the peroxisome proliferator activated receptor alpha. This nuclear receptor was evidenced as a positive regulator of bile acid glucuronidation in vitro. Aim: The present study aimed at evaluating whether fenofibrate interferes with bile acids glucuronidation in a clinical setting with non-cholestatic volunteers. Methods: Participants (150 men and 150 women) from the Genetics of Lipid Lowering Drugs and Diet Network study completed a 3-week intervention with fenofibrate (160 mg daily). Eleven glucuronide (−G) conjugates of the bile acids, cholic (CA-24G), chenodeoxycholic (CDCA-3 and -24G), lithocholic (LCA-3 and 24G), deoxycholic (DCA-3 and 24G), hyocholic (HCA-6 and 24G) and hyodeoxycholic acids (HDCA-6 and 24G) were profiled using liquid chromatography coupled to tandem mass spectrometry in serum samples drawn before and after fenofibrate treatment. Results: While the concentrations of CDCA, LCA and DCA glucuronide conjugates were not statistically affected, CA-24G (+17%), HDCA-6 (+77%) and -24G (+28%), and HCA-6 (+36%) and -24G (+50%) levels were significantly increased in post-fenofibrate sera when compared to pre-treatment samples. Consequently, the total glucuronide concentration (+32%) was also significantly increased by fenofibrate. At baseline, the total of glucuronide conjugated acids was significantly lower in women than in men; however this difference was corrected after fenofibrate treatment. Conclusion: This study demonstrates that fenofibrate increases the circulating level of bile acid glucuronides in humans, an effect which may participate to the beneficial properties of the drug in patients suffering from primary biliary cirrhosis and primary sclerosing cholangitis. These patients sustain strong hepatic accumulation of toxic bile acids, and our results suggest S226
that, by stimulating bile acid glucuronidation, fenofibrate may limit this accumulation. 569 ENDOCANNABINOIDS AND CIRRHOSIS: HAVE WE PICKED THE RIGHT ONE? V. Bevilacqua1 , F. Fanelli2 , B. Benazzi1 , F. Giannone2 , M. Baldassarre2 , M. Mastroroberto1 , M. Domenicali2 , P. Caraceni2 , M. Bernardi2 . 1 Clinical Medicine, 2 Clinical Medicine and Center for Biomedical Applied Research, University of Bologna, Bologna, Italy E-mail: [email protected] Background and Aims: Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most studied endocannabinoids (ECs), but other related molecules have been more recently identified, including N-palmitoyl-ethanolamine (PEA) and Noleoyl-ethanolamine (OEA). In advanced cirrhosis, research has been mostly focused on AEA as it appears to contribute to the pathogenesis of hyperdynamic circulation and cirrhotic cardiomiopathy. However, we have recently shown that circulating OEA and PEA are even more elevated than AEA in cirrhosis although in a small number of patients. Thus, we assessed: 1. whether the circulating levels AEA, OEA, and PEA are elevated in a larger sample of hospitalized cirrhotic patients; and 2. whether these levels correlate with disease severity or clinical features, including the major complications of cirrhosis. Methods: Blood samples of 101 cirrhotic hospitalized patients without HCC exceeding the Milan criteria (Child-Pugh A/B/C:21/58/22) and 101 age- and sex-matched controls were witdrawn at admission to measure AEA, PEA and OEA by LC/MS/MS. Clinical and laboratory data were collected and the patients followed until discharge. Results: Circulating ECs were significantly higher in cirrhotics than healthy controls (AEA: 1.42±0.06 vs 1.07±0.03 pmol/ml; OEA: 10.9±0.5 vs 5.1±0.2 pmol/ml; PEA: 26.1±0.8 vs 16.3±0.4 pmol/ml, all p < 0.0001). No correlation was found between AEA and disease severity. In contrast, Child-Pugh and MELD scores were positively correlated with OEA (p < 0.01) and PEA (p < 0.05). Compared to those in Child-PughA/B, Child-Pugh C patients showed significantly higher OEA and PEA. An inverse relation close to the statistical significance was observed between OEA and PEA and mean arterial pressure. ECs did not differ when patients were divided according the presence of ascites, gastrointestinal bleeding, hepatic encephalopathy, and renal failure. In contrast, compared to noninfected patients (n = 80), those with bacterial infection (n = 21) presented higher OEA (10.2±0.5 vs 13.0±1.4 pmol/ml; p < 0.05) and PEA levels (24.9±0.8 vs 29.9±2.6 pmol/ml; p < 0.05). Conclusions: The EC system is up-regulated in patients with cirrhosis. However, rather than AEA, the more recent discovered OEA and PEA, with no activity at the CB-receptor sites, but capable to activate PPAR-a and TRPV1 receptors, correlate with disease severity and are affected by bacterial infections. These data prompt further investigations to explore the biological and clinical role of these novel compounds in cirrhosis. 570 NEW PARAMETERS IN THE EVALUATION OF CIRRHOTIC PORTAL HYPERTENSION: HEPATIC AND PORTAL VEINS DOPPLER FLOW PHASICITY P. Bizzotto, G. Bombonato, P. Pesce, S. Gaiani, S. Brocco, S. Tonello, M. Bolognesi, C. Merkel, D. Sacerdoti. Medicina Clinica e Sperimentale, Universit` a di Padova, Padova, Italy E-mail: [email protected] Background: Hepatic and portal veins Doppler flow profiles, that are determined by right heart function, are often abnormal in cirrhosis with portal hypertension. The pathophysiology is still not clear.
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POSTERS Aim: To estabilish quantitative parameters for hepatic and portal veins Doppler flow profiles evaluation and to define their alterations in liver cirrhosis. Methods: 22 cirrhotic patients (age 52±12 yr) (Child A: 11; Child B: 5; Child C: 6) and 22 control subjects (age 43±15 yr) were included. Abdominal echo-color-Doppler examination was performed associated with ECG registration. In 7 patients the hepatic venous pressure gradient (HVPG) was evaluated. Hepatic and portal veins A and S waves velocity were identified in relation respectively to P and QRS ECG waves. A/S ratio was calculated. Results: Hepatic veins A wave was reduced in cirrhotic patients (−5.00±15.88 cm/s vs 13.22±3.77 cm/s, p < 0.001), S wave was not different (−35.80±15.81 cm/s vs −31.12±8.92 cm/s). A/S ratio was significantly higher (−0.04±0.4 vs −0.44±0.14, p < 0.0001). Portal vein A and S wave were significantly reduced in cirrhotic patients (A-wave: 17.77±5.13 vs 22.61±7.76 cm/s, p < 0.05), (S-wave: 25.01±6.89 vs 37.98±11.05 cm/s, p < 0.0001). Portal A/S ratio was significantly higher in cirrhotic patients (0.72±0.13 vs 0.60±0.12, p < 0.01). Portal and hepatic A/S ratio were significantly correlated (p < 0.001). Both portal and hepatic A/S ratios were strictly related to HVPG (hepatic vein A/S: R2 = 0.89; p < 0.01; portal vein A/S: R2 = 0.81; p < 0.05). Conclusions: A/S ratio of hepatic and portal veins, an echoDoppler parameter of phasicity, is reduced in cirrhosis with portal hypertension. The correlation between hepatic veins and portal A/S ratio and HVPG suggests that this reduction is due to the elevated portal pressure. These parameters may be used in non invasive estimate of portal pressure. 571 A HIGH PREVALENCE OF HETEROZYGOUS ALPHA-1 ANTITRYPSIN DEFICIENCY IN PATIENTS WITH ADVANCED PARENCHYMAL LIVER DISEASE T. Bugeja1 , W. Gelson1 , A. Massood1 , G. Maguire2 , S.E. Davies3 , W.J.H. Griffiths1 . 1 Hepatology, 2 Biochemistry, 3 Pathology, Addenbrookes Hospital, Cambridge, UK E-mail: [email protected] Background and Aims: The degree to which heterozygous forms of alpha1-antitrypsin (A1AT), principally MZ, cause liver disease is uncertain. 2.8% of Europeans carry the MZ phenotype. If heterozygosity is a relevant co-factor, over-representation in patients with endstage liver disease would be predicted. The aim of this study was to assess the prevalence of a heterozygous A1AT phenotype in the largest cohort of patients with end stage liver disease to date. Methods: We retrospectively analysed 969 patients assessed for liver transplantation in our unit between January 2003 and December 2010. A1AT heterozygotes were identified on the basis of agarose gel serum electrophoresis and/or histology demonstrating A1AT globule deposition consistent with an abnormal phenotype. Results: 95 patients (10%) were found to be A1AT heterozygotes. Frequency was highest in NASH cirrhosis (22.6%), followed by 11.9% of patients with other parenchymal disease, autoimmune disease (11.4%), alcoholic liver disease (10.2%), hepatitis C (7.2%), hepatitis B (3.1%) and biliary disease (1.9%). Compared with the European population, heterozygote frequency was significantly higher in patients with NASH cirrhosis (22.6%, p ≤ 0.0001) and lower in the biliary sub-group (1.9%, p = 0.004). Conclusions: This is the largest study to date to show a significantly increased prevalence of A1AT heterozygotes in a cohort of patients with end stage parenchymal liver disease. This may be due to a disruption of A1AT proteostasis by external stimuli, with net accumulation of misfolded A1AT aggregates and accelerated progression to end stage disease compared to the wild type population.
572 CARDIAC FUNCTION AND DYNAMICS OF QT INTERVAL IN PATIENTS WITH MILD CIRRHOSIS DURING MAXIMAL BETA-ADRENERGIC DRIVE: A DOBUTAMIN STRESS STUDY E.K. Dahl1 , S. Møller2 , F. Bendtsen3 , A. Kjær4 , C.L. Petersen2 , A. Krag3 . 1 Copenhagen University Hospital Gentofte, 2 Centre of Functional Imaging and Research, 3 Gastroenterology, Hvidovre Hospital, 4 Clinical Physiology Nuclear Medicine and PET, Rigshospital, University of Copenhagen, Copenhagen, Denmark E-mail: [email protected] Background and Aims: Presence of cardiac dysfunction including QT interval prolongation in patients with advanced cirrhosis is widely accepted, but in mild cirrhosis data are limited. Since systolic dysfunction may only be detectable during severe cardiac stress, we investigated dynamics of QT-interval, systolic and diastolic function in patients with mild cirrhosis during maximal beta-adrenergic drive. Methods: Nineteen patients with Child A (n = 12) and B cirrhosis (n = 7) and 7 matched controls participated. ECG was recorded at rest and during cardiac stress induced by increasing dosages of dobutamine and atropine. Cardiac volumes, including left ventricular end-diastolic volume (EDV) and diastolic function were assessed by gated-myocardial perfusion imaging (SPECT). Results: Pharmacological responsiveness was similar in cirrhosis and controls and the HR increased by 66±15 vs. 67±8 min−1 . Cardiac work, calculated as the heart rate-blood pressure product, increased equally 115% in cirrhosis and controls, an increase of 10510 vs. 10786 mmHg/min. The QTc interval increased after dobutamin infusion in cirrhosis (0.41±0.02 vs. 0.43±0.02 sec, p = 0.001). Similar dynamics was seen in controls, NS. Peak filling rate was longer in cirrhosis compared to controls (1.8±0.4 vs. 1.4±0.2 EDV/s, p = 0.007), but not time to peak filling (330±103 vs. 259±41 ms, p = 0.10) and peak ejection rate (−2.3±0.5 vs. −2.0±0.4 EDV/s, p = 0.16). E/A ratio was similar (1.4±0.2 vs. 1.3±0.1, p = 0.82). Child B patients had a higher resting cardiac index than Child A patients (4.1±1.2 vs. 3.2±0.5 L/min/m2 , p = 0.03). This was merely due to increased EDV and stroke volume (SV) and not heart rate. SV, EDV and ESV correlated with MELD score (r = 0.62 p < 0.01, r = 0.62, p < 0.01 and r = 0.56, p = 0.01), respectively. The ejection fraction was similar in patients and controls. Conclusions: Cardiac chronotropic and inotropic response to dobutamin was normal in mild cirrhosis. The QTc interval increases during maximal stress, but the adaption in ventricular repolarisation is normal. Patients with cirrhosis had signs of early diastolic dysfunction. This could be due to an early and mild hyperdynamic state related to a higher EDV and SV. 573 HEPATIC ENCEPHALOPATHY IS ASSOCIATED WITH IMPAIRED BRAIN OXYGEN METABOLISM AND BLOOD FLOW, NOT INCREASED AMMONIA UPTAKE G. Dam1,2 , S. Keiding1 , O.L. Munk1 , P. Ott2 , H. Vilstrup2 , L.K. Bak3 , H.S. Waagepetersen3 , A. Schousboe3 , M. Sørensen1 . 1 PET Centre, Aarhus University, 2 Department of Medicine V, Hepatology, Aarhus University Hospital, Aarhus, 3 Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark E-mail: [email protected] Background and Aims: It is unknown whether the reduced oxygen metabolism and cerebral blood flow (CBF) in cirrhotic patients with hepatic encephalopathy (HE) relate to the HE or the liver disease, and whether the impaired brain oxidative metabolism is related to the high blood ammonia. We studied these questions in a paired study.
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that, by stimulating bile acid glucuronidation, fenofibrate may limit this accumulation. 569 ENDOCANNABINOIDS AND CIRRHOSIS: HAVE WE PICKED THE RIGHT ONE? V. Bevilacqua1 , F. Fanelli2 , B. Benazzi1 , F. Giannone2 , M. Baldassarre2 , M. Mastroroberto1 , M. Domenicali2 , P. Caraceni2 , M. Bernardi2 . 1 Clinical Medicine, 2 Clinical Medicine and Center for Biomedical Applied Research, University of Bologna, Bologna, Italy E-mail: [email protected] Background and Aims: Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most studied endocannabinoids (ECs), but other related molecules have been more recently identified, including N-palmitoyl-ethanolamine (PEA) and Noleoyl-ethanolamine (OEA). In advanced cirrhosis, research has been mostly focused on AEA as it appears to contribute to the pathogenesis of hyperdynamic circulation and cirrhotic cardiomiopathy. However, we have recently shown that circulating OEA and PEA are even more elevated than AEA in cirrhosis although in a small number of patients. Thus, we assessed: 1. whether the circulating levels AEA, OEA, and PEA are elevated in a larger sample of hospitalized cirrhotic patients; and 2. whether these levels correlate with disease severity or clinical features, including the major complications of cirrhosis. Methods: Blood samples of 101 cirrhotic hospitalized patients without HCC exceeding the Milan criteria (Child-Pugh A/B/C:21/58/22) and 101 age- and sex-matched controls were witdrawn at admission to measure AEA, PEA and OEA by LC/MS/MS. Clinical and laboratory data were collected and the patients followed until discharge. Results: Circulating ECs were significantly higher in cirrhotics than healthy controls (AEA: 1.42±0.06 vs 1.07±0.03 pmol/ml; OEA: 10.9±0.5 vs 5.1±0.2 pmol/ml; PEA: 26.1±0.8 vs 16.3±0.4 pmol/ml, all p < 0.0001). No correlation was found between AEA and disease severity. In contrast, Child-Pugh and MELD scores were positively correlated with OEA (p < 0.01) and PEA (p < 0.05). Compared to those in Child-PughA/B, Child-Pugh C patients showed significantly higher OEA and PEA. An inverse relation close to the statistical significance was observed between OEA and PEA and mean arterial pressure. ECs did not differ when patients were divided according the presence of ascites, gastrointestinal bleeding, hepatic encephalopathy, and renal failure. In contrast, compared to noninfected patients (n = 80), those with bacterial infection (n = 21) presented higher OEA (10.2±0.5 vs 13.0±1.4 pmol/ml; p < 0.05) and PEA levels (24.9±0.8 vs 29.9±2.6 pmol/ml; p < 0.05). Conclusions: The EC system is up-regulated in patients with cirrhosis. However, rather than AEA, the more recent discovered OEA and PEA, with no activity at the CB-receptor sites, but capable to activate PPAR-a and TRPV1 receptors, correlate with disease severity and are affected by bacterial infections. These data prompt further investigations to explore the biological and clinical role of these novel compounds in cirrhosis. 570 NEW PARAMETERS IN THE EVALUATION OF CIRRHOTIC PORTAL HYPERTENSION: HEPATIC AND PORTAL VEINS DOPPLER FLOW PHASICITY P. Bizzotto, G. Bombonato, P. Pesce, S. Gaiani, S. Brocco, S. Tonello, M. Bolognesi, C. Merkel, D. Sacerdoti. Medicina Clinica e Sperimentale, Universit` a di Padova, Padova, Italy E-mail: [email protected] Background: Hepatic and portal veins Doppler flow profiles, that are determined by right heart function, are often abnormal in cirrhosis with portal hypertension. The pathophysiology is still not clear.
Journal of Hepatology 2012 vol. 56 | S225–S388
POSTERS Aim: To estabilish quantitative parameters for hepatic and portal veins Doppler flow profiles evaluation and to define their alterations in liver cirrhosis. Methods: 22 cirrhotic patients (age 52±12 yr) (Child A: 11; Child B: 5; Child C: 6) and 22 control subjects (age 43±15 yr) were included. Abdominal echo-color-Doppler examination was performed associated with ECG registration. In 7 patients the hepatic venous pressure gradient (HVPG) was evaluated. Hepatic and portal veins A and S waves velocity were identified in relation respectively to P and QRS ECG waves. A/S ratio was calculated. Results: Hepatic veins A wave was reduced in cirrhotic patients (−5.00±15.88 cm/s vs 13.22±3.77 cm/s, p < 0.001), S wave was not different (−35.80±15.81 cm/s vs −31.12±8.92 cm/s). A/S ratio was significantly higher (−0.04±0.4 vs −0.44±0.14, p < 0.0001). Portal vein A and S wave were significantly reduced in cirrhotic patients (A-wave: 17.77±5.13 vs 22.61±7.76 cm/s, p < 0.05), (S-wave: 25.01±6.89 vs 37.98±11.05 cm/s, p < 0.0001). Portal A/S ratio was significantly higher in cirrhotic patients (0.72±0.13 vs 0.60±0.12, p < 0.01). Portal and hepatic A/S ratio were significantly correlated (p < 0.001). Both portal and hepatic A/S ratios were strictly related to HVPG (hepatic vein A/S: R2 = 0.89; p < 0.01; portal vein A/S: R2 = 0.81; p < 0.05). Conclusions: A/S ratio of hepatic and portal veins, an echoDoppler parameter of phasicity, is reduced in cirrhosis with portal hypertension. The correlation between hepatic veins and portal A/S ratio and HVPG suggests that this reduction is due to the elevated portal pressure. These parameters may be used in non invasive estimate of portal pressure. 571 A HIGH PREVALENCE OF HETEROZYGOUS ALPHA-1 ANTITRYPSIN DEFICIENCY IN PATIENTS WITH ADVANCED PARENCHYMAL LIVER DISEASE T. Bugeja1 , W. Gelson1 , A. Massood1 , G. Maguire2 , S.E. Davies3 , W.J.H. Griffiths1 . 1 Hepatology, 2 Biochemistry, 3 Pathology, Addenbrookes Hospital, Cambridge, UK E-mail: [email protected] Background and Aims: The degree to which heterozygous forms of alpha1-antitrypsin (A1AT), principally MZ, cause liver disease is uncertain. 2.8% of Europeans carry the MZ phenotype. If heterozygosity is a relevant co-factor, over-representation in patients with endstage liver disease would be predicted. The aim of this study was to assess the prevalence of a heterozygous A1AT phenotype in the largest cohort of patients with end stage liver disease to date. Methods: We retrospectively analysed 969 patients assessed for liver transplantation in our unit between January 2003 and December 2010. A1AT heterozygotes were identified on the basis of agarose gel serum electrophoresis and/or histology demonstrating A1AT globule deposition consistent with an abnormal phenotype. Results: 95 patients (10%) were found to be A1AT heterozygotes. Frequency was highest in NASH cirrhosis (22.6%), followed by 11.9% of patients with other parenchymal disease, autoimmune disease (11.4%), alcoholic liver disease (10.2%), hepatitis C (7.2%), hepatitis B (3.1%) and biliary disease (1.9%). Compared with the European population, heterozygote frequency was significantly higher in patients with NASH cirrhosis (22.6%, p ≤ 0.0001) and lower in the biliary sub-group (1.9%, p = 0.004). Conclusions: This is the largest study to date to show a significantly increased prevalence of A1AT heterozygotes in a cohort of patients with end stage parenchymal liver disease. This may be due to a disruption of A1AT proteostasis by external stimuli, with net accumulation of misfolded A1AT aggregates and accelerated progression to end stage disease compared to the wild type population.
572 CARDIAC FUNCTION AND DYNAMICS OF QT INTERVAL IN PATIENTS WITH MILD CIRRHOSIS DURING MAXIMAL BETA-ADRENERGIC DRIVE: A DOBUTAMIN STRESS STUDY E.K. Dahl1 , S. Møller2 , F. Bendtsen3 , A. Kjær4 , C.L. Petersen2 , A. Krag3 . 1 Copenhagen University Hospital Gentofte, 2 Centre of Functional Imaging and Research, 3 Gastroenterology, Hvidovre Hospital, 4 Clinical Physiology Nuclear Medicine and PET, Rigshospital, University of Copenhagen, Copenhagen, Denmark E-mail: [email protected] Background and Aims: Presence of cardiac dysfunction including QT interval prolongation in patients with advanced cirrhosis is widely accepted, but in mild cirrhosis data are limited. Since systolic dysfunction may only be detectable during severe cardiac stress, we investigated dynamics of QT-interval, systolic and diastolic function in patients with mild cirrhosis during maximal beta-adrenergic drive. Methods: Nineteen patients with Child A (n = 12) and B cirrhosis (n = 7) and 7 matched controls participated. ECG was recorded at rest and during cardiac stress induced by increasing dosages of dobutamine and atropine. Cardiac volumes, including left ventricular end-diastolic volume (EDV) and diastolic function were assessed by gated-myocardial perfusion imaging (SPECT). Results: Pharmacological responsiveness was similar in cirrhosis and controls and the HR increased by 66±15 vs. 67±8 min−1 . Cardiac work, calculated as the heart rate-blood pressure product, increased equally 115% in cirrhosis and controls, an increase of 10510 vs. 10786 mmHg/min. The QTc interval increased after dobutamin infusion in cirrhosis (0.41±0.02 vs. 0.43±0.02 sec, p = 0.001). Similar dynamics was seen in controls, NS. Peak filling rate was longer in cirrhosis compared to controls (1.8±0.4 vs. 1.4±0.2 EDV/s, p = 0.007), but not time to peak filling (330±103 vs. 259±41 ms, p = 0.10) and peak ejection rate (−2.3±0.5 vs. −2.0±0.4 EDV/s, p = 0.16). E/A ratio was similar (1.4±0.2 vs. 1.3±0.1, p = 0.82). Child B patients had a higher resting cardiac index than Child A patients (4.1±1.2 vs. 3.2±0.5 L/min/m2 , p = 0.03). This was merely due to increased EDV and stroke volume (SV) and not heart rate. SV, EDV and ESV correlated with MELD score (r = 0.62 p < 0.01, r = 0.62, p < 0.01 and r = 0.56, p = 0.01), respectively. The ejection fraction was similar in patients and controls. Conclusions: Cardiac chronotropic and inotropic response to dobutamin was normal in mild cirrhosis. The QTc interval increases during maximal stress, but the adaption in ventricular repolarisation is normal. Patients with cirrhosis had signs of early diastolic dysfunction. This could be due to an early and mild hyperdynamic state related to a higher EDV and SV. 573 HEPATIC ENCEPHALOPATHY IS ASSOCIATED WITH IMPAIRED BRAIN OXYGEN METABOLISM AND BLOOD FLOW, NOT INCREASED AMMONIA UPTAKE G. Dam1,2 , S. Keiding1 , O.L. Munk1 , P. Ott2 , H. Vilstrup2 , L.K. Bak3 , H.S. Waagepetersen3 , A. Schousboe3 , M. Sørensen1 . 1 PET Centre, Aarhus University, 2 Department of Medicine V, Hepatology, Aarhus University Hospital, Aarhus, 3 Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark E-mail: [email protected] Background and Aims: It is unknown whether the reduced oxygen metabolism and cerebral blood flow (CBF) in cirrhotic patients with hepatic encephalopathy (HE) relate to the HE or the liver disease, and whether the impaired brain oxidative metabolism is related to the high blood ammonia. We studied these questions in a paired study.
Journal of Hepatology 2012 vol. 56 | S225–S388
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