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752 EFFECT OF TIPS ON SOLUBLE CD163 IN PATIENTS WITH LIVER CIRRHOSIS
S276
Poster Session − Saturday, April 25
751 THE ARTERIAL PRESSURE PROFILE IN PATIENTS WITH CIRRHOSIS. FOURIER ANALYSIS IN RELATION TO PRESSURE LEVEL, STROKE VOLUME, AND SEVERITY OF DISEASE J. Henriksen1 , S. Fuglsang1 , F. Bendtsen2 . 1 Department of Clinical Physiology & Nuclear Medicine, Hvidvore University Hospital, 2 Department of Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark E-mail: [email protected] Patients with advanced cirrhosis have cardiac dysfunction and altered mechanical properties of large and small arteries. This study was undertaken in order to analyse the arterial pressure curve in relation to arterial mean pressure level, stroke volume, and severity of disease. Forty-one patients with cirrhosis (Child-Turcotte classes A/B/C = 13/15/13) were studied during a haemodynamic investigation of portal hypertension. Fifteen patients without liver disease served as controls. Stroke volume was significantly increased in the patients with cirrhosis compared to the controls (94 vs 78 ml, p < 0.001). Mean arterial blood pressure was significantly reduced in the patients with cirrhosis (91 vs 98 mmHg, p < 0.001). The initial rise in pulse pressure (dP/dt) was inversely related to the Child-Turcotte score (p < 0.05). Fourier analysis revealed that the harmonic coefficients were significantly lower in the patients with cirrhosis than in the controls (−15 to −24%, p < 0.002), except for the fourth harmonic, which was significantly increased (+19 to 81%, p < 0.05 to 0.01). No substantial effect of the size of stroke volume could be detected in the harmonic pattern. However, in contrast to controls, who showed a highly significant effect of the level of arterial pressure on their harmonic coefficients (p < 0.001), patients with cirrhosis did not show pressure dependence in their harmonics. In conclusion, the different pattern of Fourier harmonics in cirrhosis compared to controls indicates that the arterial pulsation in cirrhosis is qualitatively changed, with a reduction in the low frequency components and a specific increase in medium frequency components. This suggests altered properties in the arterial wall and abnormal pulse reflections in patients with cirrhosis, which may reduce cardiac afterload and protect against manifest cardiac failure.
Conclusion: The results are consistent with the notion of Kupffer-cell being activated in portal hypertension in cirrhosis. Furthermore, not being alleviated by the reduction portal hypertension, this activation most likely plays a primary pathogenic role. 753 THE GALACTOSE ELIMINATION CAPACITY AND MORTALITY IN 781 DANISH PATIENTS WITH NEWLYDIAGNOSED LIVER CIRRHOSIS: A COHORT STUDY P. Jepsen1 , H. Vilstrup2 , P. Ott2 , S. Keiding2 , P.K. Andersen3 , N. Tygstrup4 . 1 Department of Clinical Epidemiology, 2 Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, 3 Department of Biostatistics, Institute of Public Health, University of Copenhagen, 4 The Liver Unit, Rigshospitalet, Copenhagen, Denmark E-mail: [email protected] Introduction: We hypothesized that the function of the liver is important for survival of patients with chronic liver disease. The galactose elimination capacity (GEC) is a physiological measure of the total metabolic capacity of the liver. Thus, we examined whether GEC was associated with mortality among newly-diagnosed cirrhosis patients. Patients and Methods: Combining data from a GEC database with data from healthcare registries we identified cirrhosis patients with a GEC test at the time of cirrhosis diagnosis after August 1st 1992. They were followed until death or December 31st 2005. We divided the patients into 10 equalsized groups according to GEC and calculated the mortality after 30 days, 1 year, and 5 years for each group. Cox regression was used to adjust for age, gender and comorbidity. We repeated the analyses for the group of cirrhosis patients with comorbidity. Results: We included 781 patients, 454 (58%) of whom died during 2,617 years of follow-up. GEC was markedly associated with short- and longterm mortality, most strongly so among the 75% of patients with a GEC below the normal range. The GEC-mortality association was unaffected by confounding, and it was also found among patients with comorbidity.
752 EFFECT OF TIPS ON SOLUBLE CD163 IN PATIENTS WITH LIVER CIRRHOSIS P. Holland-Fischer1 , T.D. Sandahl2 , H. Grønbæk2 , H. Vilstrup2 , S. Moestrup3,4 , O. Riggio5 , L. Ridola5 , N.K. Aagaard2 , H. Møller3 . 1 Department of Medicine V (Gastroenterology and Hepatology), 2 Deparment of Medicine V (Gastroenterology and Hepatology), 3 Department of Clinical Biochemistry, Aarhus University Hospital, 4 Institute for Medical Biochemistry, University of Aarhus, Aarhus, Denmark; 5 Department of Clinical Medicine, University of Rome “La Sapienza”, Rome, Italy E-mail: [email protected] Introduction: Kupffer cells undergo inflammatory activation during the development of portal hypertension in experimental cirrhosis which may play a pathogenic role or be an epi-phenomenon. Our objective was to study serum soluble CD163 (sCD163), a marker of macrophage activation, before and after reduction of portal hypertension by insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) in cirrhosis patients. Methods: Thirty-six Patients were examined before, and 1-, 4- and 52 weeks after TIPS. We measured pre- and after portal venous pressure gradients (PVPG), sCD163, and markers of liver function. Eleven healthy volunteers matched for age and body mass index served as control group. Results: Soluble CD163 before TIPS was markedly increased (median 5.22 mg l−1 vs.1.45 mg l−1 , p < 0.001) compared to controls and was directly related to PVPG (r2 = 0.24, p < 0.001). TIPS, effectively reducing PVPG, did not change sCD163 during follow-up (p = 0.36). Pre-TIPS sCD163 was inversely related to galactose elimination capacity (r2 = 0.31, p < 0.001) and albumin (r2 = 0.37, p < 0.001), and directly related to MELD score (r2 = 0.34, p = 0.017). There was no relation to ALT, INR, or CRP.
Association between GEC and mortality. Conclusions: GEC was associated with both short- and long-term mortality for newly-diagnosed cirrhosis patients. The association was strongest among cirrhosis patients with GEC below 1.75 mmol/min.
Poster Session − Saturday, April 25
751 THE ARTERIAL PRESSURE PROFILE IN PATIENTS WITH CIRRHOSIS. FOURIER ANALYSIS IN RELATION TO PRESSURE LEVEL, STROKE VOLUME, AND SEVERITY OF DISEASE J. Henriksen1 , S. Fuglsang1 , F. Bendtsen2 . 1 Department of Clinical Physiology & Nuclear Medicine, Hvidvore University Hospital, 2 Department of Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark E-mail: [email protected] Patients with advanced cirrhosis have cardiac dysfunction and altered mechanical properties of large and small arteries. This study was undertaken in order to analyse the arterial pressure curve in relation to arterial mean pressure level, stroke volume, and severity of disease. Forty-one patients with cirrhosis (Child-Turcotte classes A/B/C = 13/15/13) were studied during a haemodynamic investigation of portal hypertension. Fifteen patients without liver disease served as controls. Stroke volume was significantly increased in the patients with cirrhosis compared to the controls (94 vs 78 ml, p < 0.001). Mean arterial blood pressure was significantly reduced in the patients with cirrhosis (91 vs 98 mmHg, p < 0.001). The initial rise in pulse pressure (dP/dt) was inversely related to the Child-Turcotte score (p < 0.05). Fourier analysis revealed that the harmonic coefficients were significantly lower in the patients with cirrhosis than in the controls (−15 to −24%, p < 0.002), except for the fourth harmonic, which was significantly increased (+19 to 81%, p < 0.05 to 0.01). No substantial effect of the size of stroke volume could be detected in the harmonic pattern. However, in contrast to controls, who showed a highly significant effect of the level of arterial pressure on their harmonic coefficients (p < 0.001), patients with cirrhosis did not show pressure dependence in their harmonics. In conclusion, the different pattern of Fourier harmonics in cirrhosis compared to controls indicates that the arterial pulsation in cirrhosis is qualitatively changed, with a reduction in the low frequency components and a specific increase in medium frequency components. This suggests altered properties in the arterial wall and abnormal pulse reflections in patients with cirrhosis, which may reduce cardiac afterload and protect against manifest cardiac failure.
Conclusion: The results are consistent with the notion of Kupffer-cell being activated in portal hypertension in cirrhosis. Furthermore, not being alleviated by the reduction portal hypertension, this activation most likely plays a primary pathogenic role. 753 THE GALACTOSE ELIMINATION CAPACITY AND MORTALITY IN 781 DANISH PATIENTS WITH NEWLYDIAGNOSED LIVER CIRRHOSIS: A COHORT STUDY P. Jepsen1 , H. Vilstrup2 , P. Ott2 , S. Keiding2 , P.K. Andersen3 , N. Tygstrup4 . 1 Department of Clinical Epidemiology, 2 Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, 3 Department of Biostatistics, Institute of Public Health, University of Copenhagen, 4 The Liver Unit, Rigshospitalet, Copenhagen, Denmark E-mail: [email protected] Introduction: We hypothesized that the function of the liver is important for survival of patients with chronic liver disease. The galactose elimination capacity (GEC) is a physiological measure of the total metabolic capacity of the liver. Thus, we examined whether GEC was associated with mortality among newly-diagnosed cirrhosis patients. Patients and Methods: Combining data from a GEC database with data from healthcare registries we identified cirrhosis patients with a GEC test at the time of cirrhosis diagnosis after August 1st 1992. They were followed until death or December 31st 2005. We divided the patients into 10 equalsized groups according to GEC and calculated the mortality after 30 days, 1 year, and 5 years for each group. Cox regression was used to adjust for age, gender and comorbidity. We repeated the analyses for the group of cirrhosis patients with comorbidity. Results: We included 781 patients, 454 (58%) of whom died during 2,617 years of follow-up. GEC was markedly associated with short- and longterm mortality, most strongly so among the 75% of patients with a GEC below the normal range. The GEC-mortality association was unaffected by confounding, and it was also found among patients with comorbidity.
752 EFFECT OF TIPS ON SOLUBLE CD163 IN PATIENTS WITH LIVER CIRRHOSIS P. Holland-Fischer1 , T.D. Sandahl2 , H. Grønbæk2 , H. Vilstrup2 , S. Moestrup3,4 , O. Riggio5 , L. Ridola5 , N.K. Aagaard2 , H. Møller3 . 1 Department of Medicine V (Gastroenterology and Hepatology), 2 Deparment of Medicine V (Gastroenterology and Hepatology), 3 Department of Clinical Biochemistry, Aarhus University Hospital, 4 Institute for Medical Biochemistry, University of Aarhus, Aarhus, Denmark; 5 Department of Clinical Medicine, University of Rome “La Sapienza”, Rome, Italy E-mail: [email protected] Introduction: Kupffer cells undergo inflammatory activation during the development of portal hypertension in experimental cirrhosis which may play a pathogenic role or be an epi-phenomenon. Our objective was to study serum soluble CD163 (sCD163), a marker of macrophage activation, before and after reduction of portal hypertension by insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) in cirrhosis patients. Methods: Thirty-six Patients were examined before, and 1-, 4- and 52 weeks after TIPS. We measured pre- and after portal venous pressure gradients (PVPG), sCD163, and markers of liver function. Eleven healthy volunteers matched for age and body mass index served as control group. Results: Soluble CD163 before TIPS was markedly increased (median 5.22 mg l−1 vs.1.45 mg l−1 , p < 0.001) compared to controls and was directly related to PVPG (r2 = 0.24, p < 0.001). TIPS, effectively reducing PVPG, did not change sCD163 during follow-up (p = 0.36). Pre-TIPS sCD163 was inversely related to galactose elimination capacity (r2 = 0.31, p < 0.001) and albumin (r2 = 0.37, p < 0.001), and directly related to MELD score (r2 = 0.34, p = 0.017). There was no relation to ALT, INR, or CRP.
Association between GEC and mortality. Conclusions: GEC was associated with both short- and long-term mortality for newly-diagnosed cirrhosis patients. The association was strongest among cirrhosis patients with GEC below 1.75 mmol/min.