- Email: [email protected]
522 EXPERIMENT STUDY OF TIMP-1 SIRNA ON LIVER FIBROSIS IN RATS
POSTERS or vehicle. The endpoints of the study were changes in body weight over 4 weeks, the Fisher index (a ratio of BCAAs and AAAs, determined by HPLC, ACQ method, Waters), ammonia (GDH enzymatic method, CobasIntegra, Roche) and nitric oxide levels (ELISAKitR & DSystem, Minneapolis, MI) in plasma. IGF-1 levels in serum were also measured by RIA (Kitmouse/ratIGF-I DSL-2900, Diagnostic, USA). Results: IGF-1 levels were halved in PCS rats that received vehicle versus sham rats (1254±649vs557±437 ng/ml;p < 0.05), correlated with hyperammonemia (r = −0.55, p±0.05), with the Fisher coefficient (r = 0.59, p±0.05) and with weight loss (r = 0.61, p < 0.05). IGF-1 treatment prevented weight loss in rats with PCS, such that sham rats increased weight 81±39g, PCS rats without IGF-1 treatment lost 19±54g, and PCS-treated rats gained 10±64g; (ANOVA, p = 0.001). Instead, no effect was noted of IGF-1 treatment on plasma ammonia levels, the Fisher index, or nitric oxide levels. Conclusions: IGF-1 replacement therapy in rats subjected to PCS prevents weight loss, although does not improve plasma ammonia levels or BCAA/AAAs ratio. Thus, IGF-1 maintains its anabolic effect, but does not improve hepatic encephalopathy in a rodent model of PCS. Acknowledgements: PI070425 & CIBER CB06/04/0047 del ISCIII. 520 FTY720, A FUNCTIONAL S1P1 RECEPTOR ANTAGONIST, ABBREVIATES LIVER FIBROSIS THROUGH INHIBITING THE MIGRATION OF BONE MARROW MESENCHYMAL STEM CELLS TO DAMAGED LIVER Y. Kong, N. Tang, H. Wang, S. Wang, J. Wen, L. Li. Stem Cell Research Centre, Peking University, Beijing, China E-mail: [email protected] Background and Aims: Myofibroblasts of bone marrow mesenchymal stem cells (BMSCs) origin have recently been identified in fibrotic liver. Recently, S1P, a bioactive molecule has been found to play an important role in liver fibrogenesis by inducing BMSCs migration. Here we investigated the mechanism underlying S1P-induced migration of BMSCs and found a new efficient drug for the treatment of liver fibrosis. Methods: ICR mice were lethally irradiated and received BM transplants from enhanced green fluorescent protein transgenic mice. 4 weeks later, mice received 2 weeks of Carbon tetrachloride treatment in the absence or presence of FTY720 administration. The liver tissue was examined by immunofluorescent staining to identify number of BM-derived myofibroblasts. Several other indicators for measuring liver fibrosis were detected in this CCl4 treated mice. Results: After chronic CCl4 intoxication, we observed significantly fewer BM-originated myofibroblasts in FTY720 treated mice. a-sma area was decreased by 85% compared to control. Similarly, mRNA and protein levels were reduced by 55% or 88% in FTY720 therapeutic mice. The expression of collagen and fibrosis area showed a marked reduction of hepatic fibrosis. Moreover, as an important indication of liver function, serum ALT levels were also recovered to near normal level in FTY720 treated mice. Conclusions: FTY720, a novel drug which is now being explored in Phase III studies for several disease, may be a new strategy for the treatment of liver fibrosis.
521 THE VASOPRESSIN-2-RECEPTOR ANTAGONIST SATAVAPTAN IMPROVES PORTAL HYPERTENSION IN THE NON-ASCITIC THIOACETAMIDE CIRRHOTIC RAT WITHIN A NARROW SAFE AND EFFECTIVE DOSE-RANGE W. Laleman1 , J. Trebicka2 , L. Van Landeghem1 , I. Vander Elst1 , T. Sauerbruch2 , D. Cassiman1 , F. Nevens1 . 1 Hepatology, University Hospital Gasthuisberg, Leuven, Belgium; 2 Internal Medicine I, University of Bonn, Bonn, Germany E-mail: [email protected] Background and Aims: The highly selective vasopressin-V2receptor-antagonist satavaptan is effective in the management of ascites (HypoCAT-trial), but encountered safety concerns upon validation (SPARE-1-trial). This indicates a narrow safe and effective dose-range in controlling water balance and suggests heterogeneous effects on splanchnic and systemic hemodynamics in cirrhosis. We aimed to elucidate the effect and safety of multiple doses of satavaptan on the portal hypertensive syndrome in nonascitic cirrhotic rats. Methods: A dose-finding study was performed in a ratmodel of TAA-cirrhosis with free access to water. Satavaptan (0.01–0.05–0.1–1 mg/kg, n = 6/group) or vehicle was injected intraperitoneally 6 hrs prior to portal (PP) and mean arterial pressure (MAP) measurements. Aquaretic effects, liver and renal function were evaluated. In the most effective and safe dose, hemodynamic assesment was performed by systemic microspheres (n = 17), plasma-volume-calculation and in-situ-liver perfusion. Results: Hemodynamic and lethal effects of 0.01–0.05–0.1–1 mg/kg are shown in table 1. The dose of 0.1 mg/kg was considered most valuable. Further hemodynamic characterization with 0.1 mg/kg showed a decrease in PP (9.9±0.8 mmHg vs 15±1.0 mmHg for TAA alone, P < 0.001) without affecting MAP, cardiac output or systemic vascular resistance. The decrease in PP was associated with a decrease in hepatic vascular resistance (1.6±0.3 vs 2.9±0.5 mmHg*min*100g/ml, P = 0.02), also confirmed by in-situliver perfusion, and a decrease in plasma-volume (P = 0.008) and an increase in portal tributary flow (P = 0.01), mesenteric shunting (P = 0.03) and hepatic artery flow (P = 0.04). Satavaptan further increased renal blood flow (P = 0.02) which correlated with urine excretion and inversely with urine osmolality. No liver or renal impairment was observed. Conclusion: Satavaptan improves portal pressure without incapacitating systemic hemodynamics by a potential intrahepatic effect. However, the effective and safe dose for these effects is narrow-ranged, which might explain largely the adverse events encountered in clinical trials. These findings warrant further studies using vaptans for ascites and portal hypertension. Dose-effects after 6 hrs of satavaptan Body weight decrease (g) Urine volume (mL) Portal pressure reduction (%) MAP reduction (%) Mortality (%)
0.01 mg/kg
0.05 mg/kg
0.1 mg/kg
1 mg/kg
5.7±2.3 2.2±0.2 −3.8
5.7±3.4 6.8±1.4 −10.4
5.8±6.3 16.2±4.9 −36.9
49.5±1.2 41.5±0.6 +23.5
12 0
10 0
−3 0
−24 83
522 EXPERIMENT STUDY OF TIMP-1 SIRNA ON LIVER FIBROSIS IN RATS Q. Lang, N. Xu, J.-H. Qi, K.-L. Qian, X.-F. Shi. Department of Infectious Diseases, Second Affiliated Hospital to Chongqing Medical University, Chongqing, China E-mail: [email protected] Objectives: To investigate the antifibrotic effects of small interfering RNA(siRNA) targeting tissue inhibition of metalloproteinase −1(TIMP-1) on hepatic fibrogenesis and its mechanism in rats.
Journal of Hepatology 2010 vol. 52 | S183–S317
S209
POSTERS Methods: A total of 32 male rats were randomly and averagely divided into 4 groups: normal group, model group, TIMP-1siRNA treated group (0.25 mg/kg), negative control group (0.25 mg/kg). Carbon tetrachloride and high-fat diet were used to induce liver fibrosis. All the rats were sacrifced at 8 week to collect liver tissue specimens. The pathological changes of liver tissues were observed after HE. The protein expression of TIMP-1, collagen type I, collagen type III were analyzed by Western blot and immunohistochemistry and the mRNA expression were detected by quantitative real-time polymerase chain reaction (QRT-PCR). Results: The tissue of liver in the siRNA treated group has normal structure, with a small number of inflammatory cell infiltrating, and there is no obvious proliferation of collagen fibers. Immunohistochemistry showed that the protein expression of TIMP-1 collagen typeI, collagen typeIII were decreased (2.68±0.47vs6.23±0.32, 6.45±0.13; 2.52±0.14vs 6.78±0.98, 6.84±0.21, p < 0.01). Western blot showed that the protein expression of TIMP-1 was decreased significantly (2.85±0.32vs 5.73±0.87, 5.96±0.92; p < 0.01). QRT-PCR showed that the mRNA expression of TIMP-1, collagen type I, collagen type III were decreased significantly compared with model group and negative group (0.47±0.23 vs 0.85±0.31, 0.89±0.22; 0.55±1.32 vs 0.91±1.52, 0.92±1.20, 0.20±0.32 vs 0.56±0.89, 0.51±0.56, p < 0.01). Conclusions: TIMP-1 siRNA can targetedly inhibit the expression of TIMP1, promote extracellular matrix degradation on the modle of the liver fibrosis of rats induced by CCL4, which can effectively prevent the occurrence and development of liver fibrosis. 523 HEMODYNAMIC EFFECTS OF TEZOSENTAN, A DUAL ENDOTHELIN RECEPTOR ANTAGONIST, IN PATIENTS WITH CIRRHOSIS D. Lebrec1 , J. Bosch2 , R. Jalan3 , F.J. Dudley4 , R. Jesic5 , J.C. GarciaPagan6 , R. Mookerjee3 , R. Moreau7 , P.L.M. van Giersbergen8 , A. Kusic-Pajic8 , J. Dingemanse8 . 1 INSERM, Clichy, France; 2 Idibaps, Barcelona, Spain; 3 Institute of Hepatology, London, UK; 4 Dept of Gastroenterology, Alfred Hospital, Melbourne, VIC, Australia; 5 Klinicki Centar Srbije, Belgrad, Serbia; 6 Liver Unit Hospital Clinic, 7 CiberEHD, Barcelona, Spain; 8 Actelion Pharmaceuticals Ltd., Allschwil, Switzerland E-mail: [email protected] Background and Aims: In patients with cirrhosis, portal hypertension develops as a consequence of both hyperdynamic circulation and increased hepatic resistance mediated by several neurohormones, including endothelins. Elevated plasma concentrations of endothelin (ET) are found in patients with cirrhosis and are correlated to the severity of cirrhosis and to the hepatic venous pressure gradient (HVPG). The aim of this investigation was to assess the effect of tezosentan, a dual ET receptor antagonist, on portal and systemic hemodynamics in patients with cirrhosis. In addition, the safety, pharmacokinetics, and pharmacodynamics of tezosentan were evaluated. Patients and Methods: The population consisted of patients with cirrhosis with clinically significant portal hypertension. This was a randomized, double-blind, multicenter study. The patients were randomized 3:1 to tezosentan (3 mg/h for 2–3 h) or placebo. HVPG, hepatic blood flow (HBF, ICG method) and arterial pressures were measured before and after tezosentan administration. Plasma concentrations of tezosentan and ET-1 were determined peripherally and in the hepatic vein. Results: 18 patients received tezosentan and 6 placebo. Clinical, biochemistry, and basal hemodynamic characteristics were not significantly different between the 2 groups. There was no significant treatment effect on HPVG. The extraction coefficient, the plasma clearance of ICG, and the HBF did not show any relevant changes during the infusion of tezosentan and there were no differences between placebo- and tezosentan-treated patients. A linear relationship was observed between the maximum-fold S210
increase in ET-1 concentration and the steady-state tezosentan plasma concentration (r = 0.82). There was a strong correlation between plasma clearance of ICG and that of tezosentan (r = 0.88). Arterial pressure and heart rate did not significantly change in both groups. Conclusion: In patients with portal hypertension secondary to cirrhosis, a 2- or 3-hour tezosentan infusion was safe and well tolerated and reduced the hepatic venous pressure gradient only in some patients. Tezosentan infusion had no influence on the extraction coefficient and plasma clearance of ICG and did not change HBF. 524 HEPATIC VENOUS PRESSURE GRADIENT DOES NOT CORRELATE WITH THE PRESENCE AND THE SEVERITY OF PORTAL HYPERTENSIVE GASTROPATHY IN PATIENTS WITH LIVER CIRRHOSIS T.-H. Lee, Y.-W. Kang. Konyang University, Daejeon, Republic of Korea E-mail: [email protected] Background and Aims: Portal hypertensive gastropathy (PHG) is common finding in patients with liver cirrhosis and portal hypertension, which might give rise to severe complication such as gastrointestinal bleeding associated with prognosis of patients with liver cirrhosis. Despite portal hypertension remains the crucial trigger for the development of PHG, the relationship between portal hypertension and PHG has not been widely investigated. Patients and Methods: Ninety-four cirrhotic patients (84 males, mean age 53 years) who were performed hepatic vein catheterization to Konyang university hospital between November 2006 and May 2009 were prospectively included in this study. The degree of PHG was assessed according to the Third Baveno International Consensus Workshop, and classified three degrees as no, mild and severe. The hepatic venous pressure gradient (HVPG) was calculated by subtracting the free hepatic venous pressure (FHVP) from the wedged hepatic venous pressure (WHVP). These pressure measurements were performed by triplicate in each case, and results were given as arithmetic means of the three determinations. Results: Baseline characteristics were not statistically significant between the patients with no(39 cases), mild(45 cases), severe(10 cases) PHG including age, gender, etiology, Child score, MELD score, esophageal varies and gastric varices (Table 1). HVPG values were different between the patients with no(12.7±4.4 mmHg), small (13.7±3.7 mmHg), medium(16.2±4.7 mmHg) and large(15.6±3.6 mmHg) esophageal varices (p = 0.029). HVPG values did not differ between the patients without PHG (14.1±4.7 mmHg), those with mild PHG (15.7±4.1 mmHg), and those with severe PHG (15.2±2.9 mmHg, p = 0.221). Conclusions: Our data show that the presence and the severity of PHG doesnot correlate with the degree of HVPG in patients with liver cirrhosis despite good correlation with esophageal varices. Further studies are required to better understand the pathogenesis of the gastric lesions in patients with portal hypertension. 525 THE EXPRESSION OF IGFBPRP1 IN LIVER TISSUE FROM PATIENTS WITH HEPATIC CIRRHOSIS AND ITS RELATIONSHIP WITH TGF-b1/SMAD PATHWAY L.-X. Liu1,2,3 , H.-Y. Zhang1 , L.-Y. Liu1 . 1 Experimental Center of Science and Research of The First Teaching Hospital, 2 Institute of Liver Disease, 3 Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, Taiyuan, China E-mail: [email protected] Background and Aims: TGF-b1 is at present the key cytokine in process of liver cirrhosis. Smad3 is a downstream molecular and
Journal of Hepatology 2010 vol. 52 | S183–S317
521 THE VASOPRESSIN-2-RECEPTOR ANTAGONIST SATAVAPTAN IMPROVES PORTAL HYPERTENSION IN THE NON-ASCITIC THIOACETAMIDE CIRRHOTIC RAT WITHIN A NARROW SAFE AND EFFECTIVE DOSE-RANGE W. Laleman1 , J. Trebicka2 , L. Van Landeghem1 , I. Vander Elst1 , T. Sauerbruch2 , D. Cassiman1 , F. Nevens1 . 1 Hepatology, University Hospital Gasthuisberg, Leuven, Belgium; 2 Internal Medicine I, University of Bonn, Bonn, Germany E-mail: [email protected] Background and Aims: The highly selective vasopressin-V2receptor-antagonist satavaptan is effective in the management of ascites (HypoCAT-trial), but encountered safety concerns upon validation (SPARE-1-trial). This indicates a narrow safe and effective dose-range in controlling water balance and suggests heterogeneous effects on splanchnic and systemic hemodynamics in cirrhosis. We aimed to elucidate the effect and safety of multiple doses of satavaptan on the portal hypertensive syndrome in nonascitic cirrhotic rats. Methods: A dose-finding study was performed in a ratmodel of TAA-cirrhosis with free access to water. Satavaptan (0.01–0.05–0.1–1 mg/kg, n = 6/group) or vehicle was injected intraperitoneally 6 hrs prior to portal (PP) and mean arterial pressure (MAP) measurements. Aquaretic effects, liver and renal function were evaluated. In the most effective and safe dose, hemodynamic assesment was performed by systemic microspheres (n = 17), plasma-volume-calculation and in-situ-liver perfusion. Results: Hemodynamic and lethal effects of 0.01–0.05–0.1–1 mg/kg are shown in table 1. The dose of 0.1 mg/kg was considered most valuable. Further hemodynamic characterization with 0.1 mg/kg showed a decrease in PP (9.9±0.8 mmHg vs 15±1.0 mmHg for TAA alone, P < 0.001) without affecting MAP, cardiac output or systemic vascular resistance. The decrease in PP was associated with a decrease in hepatic vascular resistance (1.6±0.3 vs 2.9±0.5 mmHg*min*100g/ml, P = 0.02), also confirmed by in-situliver perfusion, and a decrease in plasma-volume (P = 0.008) and an increase in portal tributary flow (P = 0.01), mesenteric shunting (P = 0.03) and hepatic artery flow (P = 0.04). Satavaptan further increased renal blood flow (P = 0.02) which correlated with urine excretion and inversely with urine osmolality. No liver or renal impairment was observed. Conclusion: Satavaptan improves portal pressure without incapacitating systemic hemodynamics by a potential intrahepatic effect. However, the effective and safe dose for these effects is narrow-ranged, which might explain largely the adverse events encountered in clinical trials. These findings warrant further studies using vaptans for ascites and portal hypertension. Dose-effects after 6 hrs of satavaptan Body weight decrease (g) Urine volume (mL) Portal pressure reduction (%) MAP reduction (%) Mortality (%)
0.01 mg/kg
0.05 mg/kg
0.1 mg/kg
1 mg/kg
5.7±2.3 2.2±0.2 −3.8
5.7±3.4 6.8±1.4 −10.4
5.8±6.3 16.2±4.9 −36.9
49.5±1.2 41.5±0.6 +23.5
12 0
10 0
−3 0
−24 83
522 EXPERIMENT STUDY OF TIMP-1 SIRNA ON LIVER FIBROSIS IN RATS Q. Lang, N. Xu, J.-H. Qi, K.-L. Qian, X.-F. Shi. Department of Infectious Diseases, Second Affiliated Hospital to Chongqing Medical University, Chongqing, China E-mail: [email protected] Objectives: To investigate the antifibrotic effects of small interfering RNA(siRNA) targeting tissue inhibition of metalloproteinase −1(TIMP-1) on hepatic fibrogenesis and its mechanism in rats.
Journal of Hepatology 2010 vol. 52 | S183–S317
S209
POSTERS Methods: A total of 32 male rats were randomly and averagely divided into 4 groups: normal group, model group, TIMP-1siRNA treated group (0.25 mg/kg), negative control group (0.25 mg/kg). Carbon tetrachloride and high-fat diet were used to induce liver fibrosis. All the rats were sacrifced at 8 week to collect liver tissue specimens. The pathological changes of liver tissues were observed after HE. The protein expression of TIMP-1, collagen type I, collagen type III were analyzed by Western blot and immunohistochemistry and the mRNA expression were detected by quantitative real-time polymerase chain reaction (QRT-PCR). Results: The tissue of liver in the siRNA treated group has normal structure, with a small number of inflammatory cell infiltrating, and there is no obvious proliferation of collagen fibers. Immunohistochemistry showed that the protein expression of TIMP-1 collagen typeI, collagen typeIII were decreased (2.68±0.47vs6.23±0.32, 6.45±0.13; 2.52±0.14vs 6.78±0.98, 6.84±0.21, p < 0.01). Western blot showed that the protein expression of TIMP-1 was decreased significantly (2.85±0.32vs 5.73±0.87, 5.96±0.92; p < 0.01). QRT-PCR showed that the mRNA expression of TIMP-1, collagen type I, collagen type III were decreased significantly compared with model group and negative group (0.47±0.23 vs 0.85±0.31, 0.89±0.22; 0.55±1.32 vs 0.91±1.52, 0.92±1.20, 0.20±0.32 vs 0.56±0.89, 0.51±0.56, p < 0.01). Conclusions: TIMP-1 siRNA can targetedly inhibit the expression of TIMP1, promote extracellular matrix degradation on the modle of the liver fibrosis of rats induced by CCL4, which can effectively prevent the occurrence and development of liver fibrosis. 523 HEMODYNAMIC EFFECTS OF TEZOSENTAN, A DUAL ENDOTHELIN RECEPTOR ANTAGONIST, IN PATIENTS WITH CIRRHOSIS D. Lebrec1 , J. Bosch2 , R. Jalan3 , F.J. Dudley4 , R. Jesic5 , J.C. GarciaPagan6 , R. Mookerjee3 , R. Moreau7 , P.L.M. van Giersbergen8 , A. Kusic-Pajic8 , J. Dingemanse8 . 1 INSERM, Clichy, France; 2 Idibaps, Barcelona, Spain; 3 Institute of Hepatology, London, UK; 4 Dept of Gastroenterology, Alfred Hospital, Melbourne, VIC, Australia; 5 Klinicki Centar Srbije, Belgrad, Serbia; 6 Liver Unit Hospital Clinic, 7 CiberEHD, Barcelona, Spain; 8 Actelion Pharmaceuticals Ltd., Allschwil, Switzerland E-mail: [email protected] Background and Aims: In patients with cirrhosis, portal hypertension develops as a consequence of both hyperdynamic circulation and increased hepatic resistance mediated by several neurohormones, including endothelins. Elevated plasma concentrations of endothelin (ET) are found in patients with cirrhosis and are correlated to the severity of cirrhosis and to the hepatic venous pressure gradient (HVPG). The aim of this investigation was to assess the effect of tezosentan, a dual ET receptor antagonist, on portal and systemic hemodynamics in patients with cirrhosis. In addition, the safety, pharmacokinetics, and pharmacodynamics of tezosentan were evaluated. Patients and Methods: The population consisted of patients with cirrhosis with clinically significant portal hypertension. This was a randomized, double-blind, multicenter study. The patients were randomized 3:1 to tezosentan (3 mg/h for 2–3 h) or placebo. HVPG, hepatic blood flow (HBF, ICG method) and arterial pressures were measured before and after tezosentan administration. Plasma concentrations of tezosentan and ET-1 were determined peripherally and in the hepatic vein. Results: 18 patients received tezosentan and 6 placebo. Clinical, biochemistry, and basal hemodynamic characteristics were not significantly different between the 2 groups. There was no significant treatment effect on HPVG. The extraction coefficient, the plasma clearance of ICG, and the HBF did not show any relevant changes during the infusion of tezosentan and there were no differences between placebo- and tezosentan-treated patients. A linear relationship was observed between the maximum-fold S210
increase in ET-1 concentration and the steady-state tezosentan plasma concentration (r = 0.82). There was a strong correlation between plasma clearance of ICG and that of tezosentan (r = 0.88). Arterial pressure and heart rate did not significantly change in both groups. Conclusion: In patients with portal hypertension secondary to cirrhosis, a 2- or 3-hour tezosentan infusion was safe and well tolerated and reduced the hepatic venous pressure gradient only in some patients. Tezosentan infusion had no influence on the extraction coefficient and plasma clearance of ICG and did not change HBF. 524 HEPATIC VENOUS PRESSURE GRADIENT DOES NOT CORRELATE WITH THE PRESENCE AND THE SEVERITY OF PORTAL HYPERTENSIVE GASTROPATHY IN PATIENTS WITH LIVER CIRRHOSIS T.-H. Lee, Y.-W. Kang. Konyang University, Daejeon, Republic of Korea E-mail: [email protected] Background and Aims: Portal hypertensive gastropathy (PHG) is common finding in patients with liver cirrhosis and portal hypertension, which might give rise to severe complication such as gastrointestinal bleeding associated with prognosis of patients with liver cirrhosis. Despite portal hypertension remains the crucial trigger for the development of PHG, the relationship between portal hypertension and PHG has not been widely investigated. Patients and Methods: Ninety-four cirrhotic patients (84 males, mean age 53 years) who were performed hepatic vein catheterization to Konyang university hospital between November 2006 and May 2009 were prospectively included in this study. The degree of PHG was assessed according to the Third Baveno International Consensus Workshop, and classified three degrees as no, mild and severe. The hepatic venous pressure gradient (HVPG) was calculated by subtracting the free hepatic venous pressure (FHVP) from the wedged hepatic venous pressure (WHVP). These pressure measurements were performed by triplicate in each case, and results were given as arithmetic means of the three determinations. Results: Baseline characteristics were not statistically significant between the patients with no(39 cases), mild(45 cases), severe(10 cases) PHG including age, gender, etiology, Child score, MELD score, esophageal varies and gastric varices (Table 1). HVPG values were different between the patients with no(12.7±4.4 mmHg), small (13.7±3.7 mmHg), medium(16.2±4.7 mmHg) and large(15.6±3.6 mmHg) esophageal varices (p = 0.029). HVPG values did not differ between the patients without PHG (14.1±4.7 mmHg), those with mild PHG (15.7±4.1 mmHg), and those with severe PHG (15.2±2.9 mmHg, p = 0.221). Conclusions: Our data show that the presence and the severity of PHG doesnot correlate with the degree of HVPG in patients with liver cirrhosis despite good correlation with esophageal varices. Further studies are required to better understand the pathogenesis of the gastric lesions in patients with portal hypertension. 525 THE EXPRESSION OF IGFBPRP1 IN LIVER TISSUE FROM PATIENTS WITH HEPATIC CIRRHOSIS AND ITS RELATIONSHIP WITH TGF-b1/SMAD PATHWAY L.-X. Liu1,2,3 , H.-Y. Zhang1 , L.-Y. Liu1 . 1 Experimental Center of Science and Research of The First Teaching Hospital, 2 Institute of Liver Disease, 3 Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, Taiyuan, China E-mail: [email protected] Background and Aims: TGF-b1 is at present the key cytokine in process of liver cirrhosis. Smad3 is a downstream molecular and
Journal of Hepatology 2010 vol. 52 | S183–S317