Ectopic variceal bleeding — emergency tips alone is not enough

Category 2:

Cirrhosis and its complications, pathophysiology and clinical aspects

~ 2 - ' ] THE EFFECT OF PROPRONOLOL ON INCIDENCE OF SPONTANOUS BACTERIAL PERITONITIS (SBP) IN CIRRHOTIC PATIENTS WITH ASClTES Ali Riza Soylu, Gulbin Dokmeci, Ahmet Tezel, Humeyra Amuca, E Ozguner. Univ. Thrace, Clinics of Gastroenterology, Edirne, Turkey It is suggested that a beta-receptor antagonit, propranolol may decrease the incidence of SBP by diminishing portal hypertensive congestion in gut wall and increasing intestinal motility. In this study, we aimed to compare the incidences of SBP in cirrhotic patients with ascites taking propranolol with those who were not taking it. The medical records of 73 cirrhotic patients with ascites (mean age: 55 4- 14 yrs and M/F: 56/17) were reviewed retrospectively. Thirty-six patients (49%) who were taking propranolol for variceal bleeding prophylaxis comprised the first group and those 37 patients (%51) who did not need to take it were group 2. The clinical and laboratory features of groups were homogenous except for the predominance of male patients (87% vs 66%) in the first group. When the incidences of SBP between two groups were compared using chi-square test (The rate of SBP 17/36 in the first group vs 20/37 in the second), there was no statistically significant difference (p < 0.73) determined, but SBP was observed less in number in the first group. The reason for we do not observe the decrement in SBP incidence in patients under propranolol prophylaxis may be due to ineffective doses of propranolol. So it is necessary to design longer-term, placebo-controlled, prospective trials where the efficiency of propranolol dose is demonstrated by HVPG measurements.

- ~ A NEW TECHNIQUE OF THORACENTESIS IN MASSIVE I'IYDROTHORAX Marco Sperandeo ] , Eugenio Caturelli 2, Giuseppe Sperandeo 3, Antonio CamagnaÂ. 1Department of Internal Medicine, Casa Sollievo

della Sofferenza, San Giovanni Rotondo (Foggia); 2Department of Gastroenterology, Casa Sollievo della Sofferenza, San Giovanni Rotondo (Foggia); 3Department of Radiology, Casa Sollievo della Sofferenza, San Giovanni Rotondo (Foggia), Italy Hepatic hydrothorax, a rare complication related to ascites, occurs in about 5-12% of cirrhotic patients not affected with primary cardiac or pulmonary disease. Sometimes it is associated with respiratory failure, and a prompt effective treatment is mandatory. The purpose of the present study was to evaluate the efficacy and safety of a new method to rapidly remove respiratory symptoms in patients with massive hydrothorax. Twelve patients (7 males and 5 females, age ranging from 51 to 78 years) affected with hepatic hydrothorax and respiratory failure were treated by means of echo-guided thoracentesis using an aspirator endowed with a regulator of pressure. A 17-18 G needle was inserted in the chest wall, choosing the most suitable site by ultrasound guide. Two to 2.5 L of pleural effusion were rapidly drained applying the appropriate negative pressure. A prompt relief from respiratory symptoms was achieved in all patients. No major complication occurred. In all patients the diagnosis of hepatic hydrothorax was confirmed by analysis of the drained effusion. The utilization of ultrasound guide and adjustable aspirator to perform thoracentesis is a safe and rapid method allowing to remove respiratory symptoms in patients with massive hydrothorax.

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MOXONIDINE THERAPY IN CIRRHOTIC PORTAL HYPERTENSION

Mihnea Strain 1, Bogdan Mut-Vitcu 2, Stefan Dragulescu 2 , Radu Strain I .

I Dept. of Gastroenterology, Univ. of Medicine, Timisoara; 2Cardiology Institute, Univ. of Medicine, Timisoara, Romania Aim: In the late 90's it has been suggested that moxonidine (Imidazole(I) l/ alpha-2 receptor agohist) may have a lowering effect on cirrhotic portal hypertension. The purpose of this study is to see if moxonidine is an effective treatment in cirrhotic portal hypertension.

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Methods: The study was realized in 10 consecutive cirrhotic patients admitted to our department Exclusion criteria: age < 18 or >70 years, presence of hepatocellular carcinoma or portal vein thrombosis, severe hepatic failure (bilirubin > 5 mg/dl, prothrombin rate < 40%), renal disease (creatinine > 1.5 mg/dl), and refusal to be enrolled. Unfortunately, 3 patients did not complete the study (lost from follow-up), so only 7 patients completed the study: 3 E 4 M, mean age 52.4 4- 8.6 Child laugh Class A/B/C 4/2/1 Etiology Alcohol/HBV/HCV 3/2/2 Hepatic venous pressure gradient (HVPG), systemic hemodynamics and renal function were assessed before starting and after 4 weeks of treatment with moxonidine 0.3 mg/day. We started with a moxonidine dosis of 0.2 mg/day, titrating the dose to maintain a systolic hood pressure >90 nun Hg, but no more than 0.4 mg/day. Results: Moxonidine did not reduce HVPG: baseline 22 4- 4.3 mm Hg, after 4 weeks of treatment 21.8 4- 4.8 mm Hg. Mean arterial pressure did not significantly change (88 4- 13 mm Hg vs. 88 4- 9.8 mm Hg), as did not change renal function. There were no side-effects reported. Conclusion: Despite the low number of patients included and the high drop-out rate, our preliminary results suggest that moxonidine has no place in the portal hypertension armamentarium.

~-5"~ FREQUENCY OF HEPATO-PULMONARY SYNDROME IN CIRRHOTIC PATIENTS Aldo Torre., Marco Antonio Olivera. Instituto Nacional de Ciencias

Medicas y Nutricion 'Salvador Zubiran', Mexico D.F., Mexico Introduction: The hepato-pulmonary syndrome (HPS) is defined by the triad: hepatic disease, increased arterial-alveolar oxygen gradient, and evidence of intrapulmonary shunts. The frequency of HPS in patients with chronic hepatic disease is 4-47%. The diagnosis can be made by technetium-labeled macroaggregated albumin, pulmonary arteriography, and contrast enhanced echocardiogram. Aim: To study the prevalence of HPS in cirrhotic population by etiology (primary biliar cirrhosis (PBC), autoinmmune hepatitis (AIH), alcohol induced cirrhosis (AC), and posthepatitis cirrhosis (PC) and by disease severity according to Child classification. Material and Methods: A transthoracic echocardiogram study was performed in cirrhotic patients showing three or more of he following signs and symptoms: platipnea, orthodeoxia, severe hypoxemia (PaO2 < 50 mmHg), digital clubbing, and spider angiomata. Results: Eighty seven patients were included: PBC = 19, AC = 18, AIH = 20, and PC = 30, mean age 52 years. Fifteen patients (17.24%) presented fight-left shunts, PBC = 2, AC = 4, AIH = 5, and PC = 4. The most frequent clinical findings were digital clubbing (80%) and orthodeoxia (73.3%). The frequency was Child A = 0, B = 5, and C = 10. Conclusions: HPS is more frequent in AIH and AC. Its prevalence correlates directly with the severity of the disease, predominantly cirrhotic patients in Child C.

~4-6] ECTOPIC VARICEAL BLEEDING - EMERGENCY TIPS ALONE IS NOT ENOUGH Marcello Vangeli 1, David Patch ] , Neil Davies 2, Anthony Watkinson 2, John Tibballs 2, Andrew K. Burroughs I . 1Liver Transplantation Unit

Royal Free Hampstead NHS Trust, London; 2Dept Radiology Royal Free Hampstead NHS Trust London, UK Introduction/Method: Controlling bleeding from ectopic varices (not oesophageal or gastric varices) is a rare but well documented problem in cirrhotic patients, particularly after abdominal surgery. TIPS have been proposed as a useful treatment in these patients. We report our experience of 18 patients with ectopic varices who underwent TIPS for haemorrhage refractory to conservative management. Results: The study group consisted of 9 Child B, 9 Child C patients. Mean age was 51 years (range 19-76). Site of varices bleeding was: rectal 8, stomal 5, colonic/caecal 2, jejunal 1, duodenal 1, and ileal 1. Portal vein

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Poster Sessions

puncture was unsuccessful in 2 (small livers); both died. Mean HVPG before TIPS was 21 mmHg (range 10-31) and after was 9.4 mmHg. In 5, post procedural HVPG was >12 mmHg, but with a drop of more than 20%. Bleeding stopped with TIPS alone in 7/16 (43.7%). However in 9/16 (56.2%) variceal embolisation (coils plus alcohol) was required following TIPS placement to arrest bleeding, 5 of whom had an HVPG < 12 mmHg. 3 patients rebled (colon, duodenal and jejunal varices) following initial embolisation, requiting a second embolisation session. 1 patient with ileostomy varices rebled 4 times, despite an HVPG < 12 mmHg and 3 embolisations. In this patient a surgical porto-caval shunt was performed, but he continued to bleed, and died of liver failure. Conclusion: In patients with ectopic variceal bleeding, a significant reduction in portal pressure alone via TIPS is often insufficient to stop bleeding, and selective variceal catheterisation and embolisation is required.

Category 3: Molecular and cell biology (gene expression, signalling, fibrosis) ~-~

ALTERED CALCIUM SIGNALING IN FRESHLY ISOLATED AORTIC SMOOTH MUSCLE CELLS FROM BILE DUCT-LIGATED RATS

Noemi Atucha, David Iyu, Ravshan Utyamyshev, Javier Nadal, Joaquin Garcia-Estan. Depto. Fisiologia, Fac. Medicina, Murcia, Spain We have studied the mechanisms of entry and intracellular release of calcium in smooth muscle cells (SMC) freshly isolated from the abdominal aorta of rats with bile duct ligation (DBL, 4th week). The SMC were obtained on the day of the experiment after digestion with collagenase and incubation with fura-2. Intracellular calcium levels [Ca]i were measured in individual cells by fluorescence microscopy. Basal [Ca]i was slightly but significantly lower in SMC from BDL rats (70.14 4- 2.02 nM, n = 51) than in controls (80.77 4- 3.52, n = 44). The application of the purinergic agonists ATP and Lrrp (10, 30 and 100 microM) produced a very rapid peak of calcium and a slow return to baseline. However, those responses were significantly lower in the B DL cells. Thus, 100 microM of ATP produced a peak of 1280.8 4- 288.0 nM in control and of 559.6 4- 121.5 in BDL cells. The area under the curve of these responses during 5 minutes was always lower in BDL cells than in controls. Similar results were obtained with UTP, although the alteration of the BDL cells was more important than that observed with ATP. In the absence of extracellular calcium, both agonists induced responses of similar shape but of lower magnitude. The peak obtained with 100 microM ATP was of 188.0 4- 25.3 in controls and of 11 !.5 -I- 20.7 in SMC from BDL. These alterations were reverted by incubation with the nitric oxide synthesis inhibitors L-NNA (300 microM) and L-NIL (30 microM). We conclude that, in smooth muscle ceils freshly isolated from bile duct-ligated rats, both the entry of extracellular calcium and the intracellular mobilization of calcium are defective in response to purinergic agonists. Nitric oxide of an inducible origin is involved in these alterations.

ure (portacaval anastomosis). The impairment occurs at the level of activation of soluble guanylate cyclase by NO. The impairment of this pathway may be responsible for some of the neurological alterations found in hyperammonemia and hepatic encephalopathy. Soluble guanylate cyclase is also present in lymphocytes. Activation of guanylate cyclase by NO is also altered in lymphocytes from hyperammonemic rats or from portacaval anastomosis rats. We studied in lymphocytes from seventy-seven patients with liver disease and seventeen controls whether activation of soluble guanylate cyclase was also altered. The basal content of cGMP in lymphocytes was decreased in patients with liver disease. In contrast, cGMP in plasma was increased. Activation of guanylate cyclase by NO was also altered in liver disease and was higher in lymphocytes from patients with cirrhosis or hepatitis than in lymphocytes from controls. Successful interferon treatment of patients with hepatitis C reversed all the above alterations. Altered modulation of soluble guanylate cyclase by NO in liver disease may play a role in the neurological and hemodynamic alterations found in these patients.

~ 7 - ~ PAl"tERN OF EXPRESSION OF THE GNT1 GENE AND ACTIVATIONOF UGTIA DURING THE PERINATAL DEVELOPMENT IN RAT Francisco J. Cubero ] , Agustin Ortiz ], Helena Cantarino 1, Elvira Arza I , Nieves Mula 3, Socorro Garefa Barrutia 2, Paloma Maganto 3, Rosa M a Arahuetes I . ~Dpto. Biolog(a Animal II, Facultad de Biologfa,

Universidad Complutense, Madrid 28040; 2Dpto. Biologfa Celular, Facultad de Biolog(a, Universidad Complutense, Madrid 28040; 3Servicio de Cirugfa Experimental, Clinica Puerta de Hierro, c/San Martin dePorres n°4 Madrid 28035, Spain Glucuronoconjugation in the endoplasmic reticulum by the microsomal enzyme bilirubin-UDP-glucuronosyltransferase (UGT1A) is an essential step in the clearance of bilirubin. Complete or near complete deficiency of UGT 1A activity results in severe disorders such as Crigler-Najjar syndrome type 1. The Gunn rat is an accurate model of this disease. The aim of the present study was to determine the pattern of expression of GNT1 (gene encoding UGT1) and evidence the start of the protein activation in the perinatal development with the purpose to use fetal hepatocytes in a near future, in the most suitable stage of development for transplantation into Gunn rats. Female Wistar rats with timed pregnancy rats between 13 and 22 days of gestation (E13-E22) and neonatal rats (N1-N30) were used. For the detection of GNT1 mRNA, total RNA was extracted from the livers according to the method of Chirgwin (1979). Slot blotting was carried out to analyze the expression of GNT1. The assay of the UGT1A activity was based on the method described by Viollon-Abadie et al (1999) for microsomes: The activation of the microsomal fraction was carded out by the addition of Brij-56 followed with the incubation at 37 ° C in the presence of bilirubin and glucuronic acid. Finally, diazotization of glucuronides were done and the formed azo-derivates were quantified spectrophotometrically. The results show that at day 13 of gestational life there is already GNTl gene expression, however activity is not evident until day 20 of gestation when gradually increases until birth and it reaches adult levels during the first month of life. (This work was financed by grant UCM PR 52/00-8901 and FIS 01/0001-02)

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ALTERED cGMP CONTENT AND ACTIVITY OF SOLUBLE GUANYLATE CYCLASE IN LIVER DISEASE

Regina Corbalan ], Carmina Montoliu 2, Maria Dolores Minana 3, Juan Del Olmo 2, Miguel Serra 2, Luis Aparisi 2, Jose Rodrigo 2, Vicente Felipo J .

1Departament of Neurobiology, Instituto de lnvestigaciones Otologicas, FVIB, Valencia; 2Hepatology Unit, Hospital Clinico Universitario, Valencia; 3lnstituto de Biologia Celular, OPVI, Valencia, Spain The glutamate-NO-cGMP pathway is impaired in brain in vivo animal models of chronic moderate hyperammonemia without and with liver fail-

IL-10 STIMULATES IL-8 SECRETION IN ACETALDEHYDE-TREATEDHepG2 CELLS

Luis Gomez-Quiroz l , David Kershenobich2, Concepcion Gutierrez-Ruiz I . 1Departamento de ciencias de la salud,

DCBS, Universidad Autonoma Metropolitana Iztapalapa, Mexico, D.E ; 2Departamento de Gastroenterologia, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico, D.E, Mexico

Backgrounds: Neutrophils are recruited in response to liver tissue injury by IL-8. Acetaldehyde (Ac) and reactive oxygen species induce 1L-8 secretion in HepG2 cells.