[245] HEPATIC VENOUS PRESSURE GRADIENT (HVPG) PREDICTS THE FIRST CLINICAL DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIS C (CHC)-RELATED CIRRHOSIS

02B. CIRRHOSIS AND COMPLICATIONS months) until SBP occurrence, lost of follow-up or death. At inclusion, 29 patients (16%) were Child-Pugh class A, 108 (61%) were class B and 40 (23%) were class C. Cirrhosis was of alcoholic origin in 126 cases (7 I %). Serum ferritin was determined at entry and every six months during follow-up. Hyperferritinemia was defined as serum ferritin higher than 500 ng/ml. SBP-free survival was evaluated by the Kaplan-Meier method and survival curves obtained in patients with and without hyperferritinemia were compared (log-rank test). Predictive variables of SBP were evaluated by Cox regression model. Results: 79 patients (45%) had hyperferritinemia at entry. Their mean Child-Pugh score (8.9f1.8 vs 7.8f1.7, p<0.01) as well as MELD 0.001) were significantly higher than score ( 1 6.4f5.7 vs I3.2f5.5; p i in patients without hyperferritinemia. 43 patients (24%) presented SBP during follow-up, with a significantly higher incidence in those with hyperferritinemia (32% vs 18% respectively; p = 0.04). Free-SBP survival was significantly lower in patients with hyperferritinemia than in those with normal serum ferritin (47 vs 75 months, log-rank = 0.003), even adjusting for liver disease severity and for continued alcohol abuse during follow-up. In Cox regression analysis serum ferritin was an independent predictor of survival besides low ( i l . 5 g/dl) ascitic protein concentration and MELD index. Conclusions: Hyperferritinemia is associated with a greater risk of SBP, independently of liver disease severity and alcohol consumption. The hypothetical beneficial effects of iron depletion on the incidence of SBP should be prospectively evaluated.

12431 THE LONG TERM SAFETY AND EFFICACY OF BALLOON OCCLUDED RETROGRADE TRANSVENOUS OBLITERATION (BRTO): A COMPARISON STUDY WITH THE TRANSJUGULAR INTRAHEPATIC PORT0 SYSTEMIC SHUNT (TIPS) M.K. Park’, J.H. Lee’, Y.S. Choi’, M.S. Choi’, S.W. Paik’, K.C. Kohl, B.C. Yoo’, J.C. Rhee’, Y.S. Do2, S.W. Choo’, S.W. Shin’, J.S. Lee3.

’Depurtnzent of Medicine, Sumsung Medical Center; Sungkyunkwun

linioersiiy School of‘ Medicine, Seoul; 2Department of‘ Radiology and Center ,fir Imaging Science, Sumsung Medical Center; Sung!gmnkwan Unioer~sit?/ School of Medicine, Seoul; ”Depurtnzent oflnternal Medicine, Inje liniuersity llsan Paik Hospital, Kyunggido, South Korea E-mail: [email protected] Background and Aims: Balloon occluded Retrograde Transvenous Obliteration (BRTO) is known to be an effective treatment for gastric variceal bleeding; however there is limited information on its efficacy, safety and long-term outcomes. Methods: A retrospective study of 64 patients (18 patients in the TIPS group vs. 46 patients in the BRTO group) with gastric variceal bleeding was carried out. Analysis of the patient groups included: clinical characteristics, mortality, rebleeding and complications. Results: Bleeding was successfully controlled in 15 of 18 (83.3%) patients in the TIPS group and 42 of 46 (91.3%) patients in the BRTO group. The overall survival rate was not significantly different in comparisons between the two groups (78.9%, 62.0% and 49.6% vs. 84.8%, 64.5%, and 56.2% at six weeks, 2 years and 3 years). Multivariate analysis showed that survival in the BRTO was reduced in patients with impaired hepatic and renal function (Hazard ratio = 7.44, 95%CI 1.10-99.08, and 9.07, 95%C1 I .77-46.47). The incidence of esophageal variceal (EV) rebleeding in the BRTO group was higher than in the TIPS group. The presence of large EVs was an independent risk factor for EV rebleeding after BRTO (Hazard ratio = 2.77, 95%CI 1.01-7.64). Conclusions: BRTO was found to be as effective as TIPS to control gastric variceal bleeding. However, mortality remained high in patients with impaired hepatic and renal function. In addition, subsequent esophageal variceal bleeding was a problem particularly in patients with large EVs at the time of GV bleeding.

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B) CLINICAL ASPECTS

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12441 CHANGES IN THE PROFILES OF CAUSATIVE AGENTS AND ANTIBIOTIC RESISTANCE RATE FOR SPONTANEOUS BACTERIAL PERITONITIS: AN ANALYSIS OF CULTURED MICROORGANISM IN RECENT 12 YEARS M.K. Park’, J.H. Lee’, Y.H. Byun’, J.H. Song’, B.C. Yoo’, G.Y. Gwak’, M.S. Choi’, K.C. Kohl, S.W. Paik’ , J.C. Rhee’, J.S. Lee’. ‘Department

of‘ Medicine, Sumsung Medical Center, Sungkyunkwun linioersity School of

Medicine, Seoul; ’Department of Internal Medicine, Inje Uniuersih~

llsan Paik Hospital, Kyunggido, South Korea E-mail: [email protected] Background and Aims: The causative agents for spontaneous bacterial peritonitis (SBP) and antibiotic resistance rate vary in different localities and change over time. We aimed to analyze the recent changes in the profiles of microorganisms and antibiotic resistance rate in Korea. Methods: We analyzed the clinical records of 1018 episodes of ascitic fluid infection from November, I994 to December, 2005, retrospectively. The profiles of causative agents for SBP and the rate of antibiotic resistance were compared in every 4-year-term. Results: Microorganisms were isolated in 394 of 1018 episodes (38.7%). Gram negative and positive organisms constituted 7 1.6% and 2 1.3%, respectively. The five most frequently isolated organisms were E. coli (35.8%), K. pneumoniae (1 5.5%), Viridans streptococci (10.4%), S. pneumoniae (4.8%), Aeromonas group (4.6%). The rate of E. coli resistant to cefotaxime (0%, 5.4%, 7.4%) and ciprofloxacin (4.3%, 21.6%, 28.4%) increased significantly in recent years. Five isolates of E. coli producing extended spectrum beta-lactamase (ESBL) have appeared in the last 4-year-terms. The gram negative organisms other than E. coli and K. pneumoniae also showed resistance to cefotaxime (36.4%, 34.6%, 41.9%), to ciprofloxacin (0%, 26.9%, 16.I %) and increasing rate of ESBL-production (9.l%, I1.5%, 38.7%). The overall rate of ESBL producing gram negative organisms was on the rise (2.2%, 16.7%, IS.O%). In the gram positive organisms, every isolates of Viridans streptococci and Pneumococci were sensitive to cefotaxime and ciprofloxacin. Recently, methicillin-resistant Staphylococcus aureus (MRSA) (5/19, 28%) and vancomycin-resistant Enterococci (VRE) (4/13, 31%) have been isolated. In each 4-year-term, the overall antibiotic resistance rates to cefotaxime were 12.5%, 14.0%, 14.8%, to ciprofloxacin were 3.1%, 16.7%, 18.0, and to imipenem were 4.7%, 7.0%, 4.2%, respectively. Conclusions: Cefotaxime may still be the choice of primary empirical antibiotic for the treatment of SBP in Korea since the resistance rate is acceptable. However, a notice should be given to the recent increase in ciprofloxacin-resistant E. coli, ESBL-producing gram negative bacilli, MRSA and VRE.

12451 HEPATIC VENOUS PRESSURE GRADIENT (HVPG) PREDICTS THE FIRST CLINICAL DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIS C (CHC)-RELATED CIRRHOSIS

D. Rincon, 0. Lo Iacono, A. Hernando, J. Gomez, M. Salcedo, M.V. Catalina, C. Sanz, G. Clemente, A. Matilla, 0. Nunez, R. Banares. Liuer and Transplant Unit, Hospital General Uniuer~xiturioGregorio Maranon, Mudrid, Spain E-mail: [email protected] Background and Aims: The transition from compensated to decompensated CHC-related cirrhosis occurs at a rate of 5-7% per year, and determines a significantly worse prognosis. Therefore, predictors of clinical decompensation (CD) are needed to optimize the management of these patients. The aim of this study was to evaluate HVPG as a predictor of CD in patients with previously compensated CHC-related cirrhosis. Methods: All patients with CHC who underwent a hepatic hemodynamic study (HHS), as part of the routine clinical workup, between 112001 and

POSTERS

S l00

12/2005 were included. The endpoint was the development of CD defined as the apparition of ascites, variceal bleeding or hepatic encephalopathy. Results: In the study period, 364 patients with CHC underwent HVPG measurements. Thirty-seven non-cirrhotic patients were excluded and 20 were lost after the HHS. The final population was composed of 307 CHC cirrhotic patients (69% genotype l), 145 (47%) of them with compensated disease. Median HVPG [19.1(5.3) vs. 13(6.3), p=0.0001] and MELD score [14.4(6.4) vs. 9.8(4.7),p=0.0001] at the time ofHHS were greater in patients with baseline decompensated cirrhosis. Median follow-up was 22 (range 1-66) months. Twenty-eight out of 145 patients (19.5%) developed CD during follow-up: 24 (86%) ascites; 3 ( 1 1%) hepatic encephalopathy; I (3%) variceal bleeding. The probability of CD was 12%, 22%, 37% at I , 2, 3 years respectively. In univariate analysis WR, bilirrubin, serum sodium, albumin, MELD score and HVPG were significantly related to CD. In multivariate analysis 3 predictors of CD were identified: HVPG [HR 1.069 ( I .01-1 . I 3) p=0.03]; MELD [HR 1.073 ( I .01-1.14) p = 0.0261; and serum sodium [HR 0.088 (0.78-0.99) p=0.04]. A HVPG value of
12461 HAPLOTYPES TACG AND CACG FROM GLUTAMINASE GENE PROTECT AGAINST HEPATIC ENCEPHALOPATHY M. Romero-Gomez' , J.J. Galan2, M . Jover' , 1. Camacho', L. Grandel, C. Trabadelal, E. Hoyas', A. Ruiz2, J.D. Bautista' . '7JCM Digestioe Diseuses, Hospital Uniuersiturio de Vulme, Seuilla; 'Department of Structural Genomic, Neocodex, Seuilla, Spain E-mail: [email protected] Background: PAG has been found increased in the duodenum of cirrhotic patients suffering from minimal hepatic encephalopathy (MHE) (J Hepatol 2004). Oral glutamine challenge (OGC) together with M H E predicts risk for overt HE and survival (Hepatology 2004). PAG gene (OMIM: 138280) is found in chromosome 2 (2q32-q34) showing 84675 pd. Aims: To know the influence of PAC polymorphisms in liver function, intestinal ammonia production alter glutamine intake, psychometric test performance and risk for overt HE. Methods: We analysed four intragenic polymorphisms within PAC gene (rs37713 10, rs6743496, rs2883713, rs3088307) in 103 cirrhotics and 103 healthy controls. The presence of MHE was diagnosed by psychometric hepatic encephalopathy score (PHES). Intestinal ammonia production was measured by OGC after intake of lograms of L-glutamine and liver function by MELD and Child-Pugh. Risk for overt hepatic encephalopathy was calculated taking together MHE and altered OGC. We conducted single marker analyses using tests adapted from Sasieni, utilizing multiple testing corrections. Besides, linkage disequilibrium and haplotypic analyses of available markers were conducted using Thesias software. The association between haplotypes and MHE, OGC, Child was expressed as odds ratio from the intercept and with quantitative variables as ammonia production, MELD and PHES as the difference between each haplotype and the intercept. All comparison were corrected by sex and age. Results: Genotype CC in rs28837 13 found in intron 9 was over-expressed in cirrhotics vs. controls (26.2% vs. 13.6%; p=0.036). No difference was seen between cirrhotics and controls in the frequency of haplotypes TACG (19% vs. 14%) and CACG (24.5% vs. 22%). TACG and CACG haplotypes were related to lower ammonia intestinal production alter glutamine intake (-2 I Kg/dl and -22 ygidl respectively), better liver function (MELD: -2.29 0.00006 and p 0.0005 respectively). Moreover, and -2.59 points; p i the risk for HE decreased to a third (CACG: O.R.=0.32 (0.14-0.73); p <0.006) or a quarter (TACG: O.R.=0.24 (0.1-0.58); p iO.OO1).

Conclusions: These data support a key role of PAG in the pathogenesis of hepatic encephalopathy TACG and CACG haplotypes of PAG gene promote lower ammonia production, better liver function and thus, decrease risk for overt HE. The genotype CC (rs2883713) seems to be related to cirrhosis development Acknowledgements PI040384 form ISClll

12471 CIRCULATING RETINOL BINDING PROTEIN 4 IS REDUCED IN LIVER CIRRHOSIS AND NOT ASSOCIATED WITH INSULIN RESISTANCE E. Yagmur', R. Weiskirchen' , A.M. Gressner', C. Trautwein2, F. Tacke2. 'Institute of Clinical Chemistry and Puthohiochemistry; 'Department of Medicine 11L RWTK Universiw Hospital Aachen, Aachen, Gevniany E-mail: [email protected] Background and Aims: Retinol Binding Protein 4 (RBP4) has been identified as a novel adipokine mediating systemic insulin resistance, and increased RBP4 expression by adipocytes has been proposed to mediate its pro-diabetogenic effects (Yang et al, Nature 2005; 436:356). Moreover, elevated serum RBP4 indicated overt or impending insulin resistance in lean, obese and type 2 diabetic subjects (Graham et al, NEJM 2006; 354:24). As insulin resistance is present in nearly all patients with liver cirrhosis and dysregulation(s) of adipocytolcines have been shown in cirrhosis, we evaluated RBP4 in patients with chronic liver diseases (CLD). Methods: Serum RBP4 was measured in I I 1 non-diabetic CLD patients and 99 age- and gender-matched healthy controls, alongside other adipocytokines and various clinical and laboratory parameters. Findings in patients were confirmed in an animal model of cirrhosis (bile duct ligation) by quantification of RBP4 gene expression by real-time PCR in normal and cirrhotic rat liver. Results: Serum RBP4 was significantly reduced in CLD patients compared 0.001), and closely correlated with the stage with healthy controls (p i of liver cirrhosis (Child-Pugh or MELD score). CLD patients without cirrhosis showed normal RBP4 concentrations, which correlated with serum glucose, insulin secretion and inversely with insulin sensitivity. In patients with Child A-C liver cirrhosis, however, RBP4 was not correlated with glucose metabolism or other adipokines such as adiponectin, resistin or ghrelin, but closely linked to the hepatic biosynthetic capacity (albumin, cholinesterase, prothrombin time), fibrotic changes in liver histology or clinical complications of cirrhosis such as portal hypertension. In an animal model of experimental cirrhosis, hepatic RBP4 gene expression decreased in cirrhotic liver. Conclusions: RBP4 appears, unlike in obesity or type 2 diabetes, not to be a relevant systemic factor in the pathogenesis of insulin resistance in liver cirrhosis. Furthermore, RBP4 may not be a clinically useful marker indicating overt or impending insulin resistance, in the case of a concomitant liver dysfunction.

12481 HCC-RISK AFTER TIPS-IMPLANTATION: BARE STENTS VERSUS PTFE COVERED STENTS G. Ulbrich', B. Angermayr' , F. Karne13, A. Koch13, M. Schmook2, M. Cejna2, M. Peck-Radosavljevic' . 'Depavtnient of' Gastroenterology and Hepatology; 'Depavtment of' Radiology, Medical University Vienna, Vienna; "Department of Interoentional Radiology, KFJ Vienna, Vienna, Austria E-mail: [email protected] Objective: Transjugular intrahepatic portosystemic stent shunt (TIPS) is a very effective method for lowering the hepatovenous pressure-gradient in patients with livercirrhosis and a well established method for the treatment of complications of portal hypertension especially variceal bleeding and refractory ascites. In a recent retrospective study (Banares et al, Hepatology 2005) it was reported that TIPS-implantation of bare stents could