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P496 OSTEOPONTIN IS A NEW NON-INVASIVE PARAMETER OF PORTAL HYPERTENSION IN PATIENTS WITH LIVER CIRRHOSIS
POSTERS P494 LIVER AND SPLEEN STIFFNESS ASSESSED BY QUANTITATIVE REAL-TIME SUPERSONIC SHEAR WAVE ELASTOGRAPHY (SWE™) CORRELATE WITH CLINICAL STAGES AND PORTOHYPERTENSIVE COMPLICATIONS IN PATIENTS WITH LIVER CIRRHOSIS I. Grgurevic1 , T. Bokun1 , D. Brnic2 , Z. Puljiz2 , R. Heinzl3 , M. Milosevic4 , B. Luksic5 , M. Kujundzic1 . 1 Department of Gastroenterology, University of Zagreb School of Medicine, University Hospital Dubrava, Zagreb, 2 Department of Gastroenterology, University of Split School of Medicine, University Hospital Center Split, Split, 3 Department of Pathology, University of Zagreb School of Medicine, University Hospital Dubrava, 4 University of Zagreb, School of Medicine, Andrija Stampar School of Public Health, Zagreb, 5 Department for Infectious Diseases, University of Split School of Medicine, University Hospital Center Split, Split, Croatia E-mail: [email protected] Background and Aims: To investigate possible relation of liver (LS) and spleen stiffness (SS) assessed by Supersonic Shear wave elastography (SWE™) to clinical stage of liver cirrhosis (LC) and the presence of portohypertensive complications such as esophageal varices (EV) and ascites. Methods: Patients with biopsy-proven or clinicaly defined LC (upon clinical, ultrasound, biochemical and endoscopic criteria) of different ethiologies underwent SWE of the liver (SWEH) and spleen (SWEL) on Aixplorer® Ultrasound system. The results were compared to Child–Pugh (CP) stage of LC and the presence of EV and ascites. Results: Of 111 pts were 71.2% male and 28.8% female in CP stages A (47.7%), B (31.5%) and C (20.7%). LS and SS were significantly different between CP stages A-C (p < 0.001): cut-off values between compensated (CP A) and decompensated cirrhosis (CP B/C) were 31 kPa (AUC 0.857) and 35 kPa (AUC 0.782) for SWEH and SWEL respectivelly. LS and SS correlated to each other (r = 0.319; p = 0.001), most signifficantly in CP stage A (r = 0.662, p < 0.001) and much weaker or absent in stages B/C. LS and SS differed significantly in patients without and with EV or ascites (p < 0.001 both), with SWEH and SWEL cut-off values 24 kPa (AUC 0.747) and 31 kPa (AUC 0.797) for EV and 31 kPa (AUC 0.843) and 35 kPa (AUC 0.785) respectivelly for ascites. SWEH or SWEL could not discriminate between patients with small and large/bleeding EV. Conclusions: By SWE™ it was possible to discriminate between compensated and decompensated LC and the presence of EV and ascites. P495 INCREASED EXPRESSION OF PROLIFERATION AND STEM CELL MARKERS IN CELLS LINING DILATED PERIBILIARY GLANDS N. Goossens1 , L. Spahr1 , R. Breguet2 , L. Rubbia-Brandt3 . 1 Division of Gastroenterology and Hepatology, 2 Division of Radiology, 3 Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland E-mail: [email protected] Background and Aims: PBG dilatation is a common finding in end-stage liver disease (ESLD) and is related to MELD. We aimed to characterise the expression profile of individual cells in dilated PBGs and to assess radiological performance in the diagnosis of dilated PBGs. Methods: Explanted livers of patients transplanted for ESLD were included. The expression of epithelial cell adhesion molecule (EpCAM), MIB-1 and of cytokeratin 19 (CK19) were studied by immunochemistry on formalin-fixed tissue at the hilum. We manually counted all positively staining cells in PBGs in large (>1000 mm diameter) and small-sized PBGs (<200 mm diameter). A blinded radiologist reviewed pre-transplant CT and MRIs and we assessed the diagnostic performance of imaging to diagnose histologically-proven dilated PBGs. Results: Clinical characteristics of the 74 included patients were: average age: 52 years, mean MELD: 14. 18/74 patients (24%) had S234
large PBGs, 65/74 patients (88%) had small PBGs. The proportion of cells staining for EpCAM within large PBGs was significantly increased compared to small PBGs (69% vs 28% respectively, p < 0.001) as was the proportion of cells staining positive for MIB-1 (2.8% vs 0.5% respectively, p < 0.001). Sensitivity/specificity for diagnosis of >1000 mm dilated PBG was 29%/90% for CT-based diagnosis (89% of patients) and 0%/72% for MRI-based diagnosis (39% of patients). Conclusions: Cells lining dilated PBGs display increased expression of markers associated with stem/progenitor cells and cellular proliferation which could be linked to attempts at liver regeneration. Cross-sectional imaging by CT or MRI was a specific but insensitive test to assess for histologically-proven PBG dilatation. P496 OSTEOPONTIN IS A NEW NON-INVASIVE PARAMETER OF PORTAL HYPERTENSION IN PATIENTS WITH LIVER CIRRHOSIS R. Bruha, M. Jachymova, J. Petrtyl, L. Vitek, P. Urbanek, K. Dvorak. Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic E-mail: [email protected] Background and Aims: Portal hypertension leads to major complications of cirrhosis. Until now, the invasive measurement of hepatic venous pressure gradient (HVPG) has been the only method used for accurate evaluation of portal hypertension. Osteopontin is a new biomarker with possible relationship to pathogenesis of fibrosis, cirrhosis and hepatocelular carcinoma. The aim was to evaluate the relationship of serum osteopontin and the severity of portal hypertension in patients with cirrhosis. Methods: 154 patients with liver cirrhosis (112 ethylic, 108 men, age 34–72 years) were enrolled. The diagnosis of liver cirrhosis was confirmed by liver biopsy. HVPG measurement, laboratory and ultrasound examination were performed in all patients. HVPG was measured by standard cathetrisation balloon wedged technique. Osteopontin was measured by standard ELISA technique. Control group for comparison of ostepontin levels consisted of 59 healthy age- and sex-matched individuals. Results: The mean value of HVPG was 16.2±5.6 mm Hg. The values of osteopontin in cirrhotic patients were significantly higher than values in controls (145±114 vs. 56.3±17.1 ng/ml; p < 0.001). The levels of osteopontin in cirrhotic patients were positively related to the HVPG values (p = 0.0022). Moreover, the osteopontin 80 ng/ml treshold was able to discriminate the patients with significant portal hypertension (HVPG >10 mmHg) with 73% sensitivity and 60% specificity (AUC 0.72). No relation of osteopontin to ultrasound hemodynamic parameters (portal vein diameter, portal vein flow, spleen size) was found. Conclusions: Osteopontin is closely related to HVPG and might serve as a non-invasive marker of portal hypertension. It could also discriminate the patients with clinically significant portal hypertension. Supported by IGAMZCR NT 12290/4, 11247/4 and SVV UK-3362.
Journal of Hepatology 2014 vol. 60 | S215–S359
large PBGs, 65/74 patients (88%) had small PBGs. The proportion of cells staining for EpCAM within large PBGs was significantly increased compared to small PBGs (69% vs 28% respectively, p < 0.001) as was the proportion of cells staining positive for MIB-1 (2.8% vs 0.5% respectively, p < 0.001). Sensitivity/specificity for diagnosis of >1000 mm dilated PBG was 29%/90% for CT-based diagnosis (89% of patients) and 0%/72% for MRI-based diagnosis (39% of patients). Conclusions: Cells lining dilated PBGs display increased expression of markers associated with stem/progenitor cells and cellular proliferation which could be linked to attempts at liver regeneration. Cross-sectional imaging by CT or MRI was a specific but insensitive test to assess for histologically-proven PBG dilatation. P496 OSTEOPONTIN IS A NEW NON-INVASIVE PARAMETER OF PORTAL HYPERTENSION IN PATIENTS WITH LIVER CIRRHOSIS R. Bruha, M. Jachymova, J. Petrtyl, L. Vitek, P. Urbanek, K. Dvorak. Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic E-mail: [email protected] Background and Aims: Portal hypertension leads to major complications of cirrhosis. Until now, the invasive measurement of hepatic venous pressure gradient (HVPG) has been the only method used for accurate evaluation of portal hypertension. Osteopontin is a new biomarker with possible relationship to pathogenesis of fibrosis, cirrhosis and hepatocelular carcinoma. The aim was to evaluate the relationship of serum osteopontin and the severity of portal hypertension in patients with cirrhosis. Methods: 154 patients with liver cirrhosis (112 ethylic, 108 men, age 34–72 years) were enrolled. The diagnosis of liver cirrhosis was confirmed by liver biopsy. HVPG measurement, laboratory and ultrasound examination were performed in all patients. HVPG was measured by standard cathetrisation balloon wedged technique. Osteopontin was measured by standard ELISA technique. Control group for comparison of ostepontin levels consisted of 59 healthy age- and sex-matched individuals. Results: The mean value of HVPG was 16.2±5.6 mm Hg. The values of osteopontin in cirrhotic patients were significantly higher than values in controls (145±114 vs. 56.3±17.1 ng/ml; p < 0.001). The levels of osteopontin in cirrhotic patients were positively related to the HVPG values (p = 0.0022). Moreover, the osteopontin 80 ng/ml treshold was able to discriminate the patients with significant portal hypertension (HVPG >10 mmHg) with 73% sensitivity and 60% specificity (AUC 0.72). No relation of osteopontin to ultrasound hemodynamic parameters (portal vein diameter, portal vein flow, spleen size) was found. Conclusions: Osteopontin is closely related to HVPG and might serve as a non-invasive marker of portal hypertension. It could also discriminate the patients with clinically significant portal hypertension. Supported by IGAMZCR NT 12290/4, 11247/4 and SVV UK-3362.
Journal of Hepatology 2014 vol. 60 | S215–S359