HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995 AASLD ABSTRACTS 297A

761 TIPS vs Sc lerotherapy + Propranolo i in the prevent ion of var icea l rebleeding : pre l iminary results of a muit icenter r a n d o m i z e d trial. Groupe d 'Etude des Anas tomoses ln t ra -Htpa t iques (Toulouse , Bondy, Lille, Nice, Cr~teil, Paris) F R A N C E

This study a imed to compare T IPS and selerothempy + propranolol (SE+P) in the prevent ion o f var ieeal rebleeding in patients with Child C cirrhosis. Methods : 65 consecut ive patients (46 males , 19 females , mean age = 51 ,4 years) wi th Child C cirrhosis (94% f r o m alcohol abuse) admit ted with bleed ing f r o m rap tu red oesophageal var ices were t reated with emergency sclerotherapy, then r andomized to be t reated by TIPS (32 patients), which had to be per fo rmed whithin 4 days af ter bleeding, or e lec t ive sc lero therapy associa ted wi th propranolol (33 patients) . The patients were fol lowed for 1 year or until death or l iver transplantation. Rebleed ing was def ined as any d iges t ive hemor rhage necessi tat ing a transfusion of 2 o r more blood units. R e s u l t s : 5 7 % of the pat ients w e r e ac t ive ly b leed ing at initial endoscopy. Mean hematocr i t on admission was 19i-6%, and a median of 5 blood units ( range : 0-40) were Deeded to maintain and/or increase it to 25%. Pat ients t r ea ted wi th SE+P had a m e a n o f 4 .5 selerotherapy sessions and were g iven a m e a n daily dose o f 96 m g o f propranolol. In 2 patients, T I P S could not be per fo rmed (1 technical failure, 1 portal vein thrombosis). So far 53 patients comple ted the study. 13 of the 32 patients (41%) randomized to be treated wi th T IPS experienced rebleeeding, as c o m p a r e d to 20 o f 33 in the SE+P group (61%) (NS). T h e 2 T IPS failures were treated with SE+P and both rebled. Accordingly, among the patients actually treated w i thTIPS rebleeding rate was 37%, as compared ~.o 63% among the patients actually treated by SE+P (p<O.05). 30 patients (46%) died whithin a m e a n o f 71 days : 16 (50%) in the TIPS group and 14 (42%) in the SE+P group (hiS). Rebleeding was the cause o f death in

.... 15 p a t i e ~ (8 treated with TIPS, and 7 treated with SE+P). C o n e l n s i o n : according to these pre l iminary results, there is a trend toward a greater effieay of TIPS in preventing varieeal rebleeding (-20%). Mortali ty was similar in both groups o f patients.

762 TIPS and paracentesis for the treatment of refractory ascites (RA): Intedros analysis of a randomized controlled trial A. OcHs, A. L. GENES *, K. HAAG, J. HULL*, K. H. HALrENSTEIN, T. WAGGERSHAUSEN*, M. REISER*, G. PAUMGARTNER*, H. E. BLUM, M. R~SSLE. Depts. of Medicine and Radiology Klinikum Groghadern, University of Munich* and Medizinische and Radiologisebe

Universi~tsklinik Freiburg, Germany. Aim: Recently we and others have shown that TIPS can be an effective therapy for RA in patients with cirrhosis (N. Engl. J. Med. 1995;332:1192-97). In order to further define the clinical value of TIPS for RA, a randomized controlled trial has been conducted comparing TIPS and large volume pameentesis (PARA) with i. v. albumin substitution (8 g per liter aseites removed). We here report an interims analysis upon inclusion of half of the calculated number of patients. Patients: RA was defined as diuretic resistant, diuretic intractable or reeidivant aseites. Severe hepatic or renal failure, malignancy, spontaneous bacterial peritonitis or previous overt hepatic encephalopathy were exclusion criteria. Treatment failure was defined as persistence of tense ascites (TIPS) or need of >_ one large volume paracentesis per week (PARA). Results: (mean +- SD) 33 patients were randomized (19 pts. for TIPS, 14 pts. for PARA): 84 % alcoholic cirrhosis, age 59 + 9 yrs. 67 % male gender, Child Pugh score 8.9 +- 1.2, duration ofRA 8 + 7 months, follow-up 206 5:152 days.

TIPS Paracenlssis p value Child Pugh score Technical success mean follow up + SD #* of paracentesis

9±1.3 8.65:1,2 100% 100%

210 5:156 202 + 153 0.9 5:1.5 .

hospital days 31 5:21 4/21% death (#)/%

1 year survival** # of TF/1 year free of'IF**

e.s.

8 + 9.4 0.002 51 5:41 0.08 4/28% n.s.

0,79 0.78 1/0.94 5/0.37

a.s. I -/0.02

TF= Treatment failure * number, **Kaplan-Meier analysis, log-rank test

Four of 5 ptatients with treatment failures in the paracentesis group responded to TIPS treatment, I patient in the TIPS group rejected revision and received PARA. Conclusion: TIPS seems to be more effective than paracantesia with 36% treatment failure. In addition, patients tend to spend more time in the hospital following paracentesis. Survival is not different between the groups.

763 THE ACHILLESHEEL OF TIPS, PAREHCHYMALTRACT STEHOSISAND OCCLUSION, IS CAUSED BY BILIARY-TIPS FISTULAE. K.Benner. n.Saxon. K.Flora t H.Barton r J.Rabkin, M.Reed, F.Keller. ~.nosch. Oregon Health Sciences University, Dept of Medicine and Dotter Inst., Portland, OR

TIPS provides effective control of continued active variceal bleeding, prevention of recurrent variceal bleeding and treatment of refractory ascites. However, etenosie of both the parenchymal tract and the hepatic vein results in recurrence of portal hypertension and its complications in >50% of patients within 1 year. Histology suggests that parenchymal tract stenosis within the etent lumen is associated with bile duct injury. We studied the correlation of parenchymal tract stenosis and occlusion with bile duct fistulae. Methods= Between 1990 and 1995, 222 TIPS procedures were performed at OHSU. Follow-up included 222 venograms in 94 patients and histologic evaluation of TIPS at explant or autopsy in 21 patients. Suspected biliary-stent fistulae were investigated by contrast injection into the occluding thrombua (5 patients), ERCP (1 patient) or balloon venography of the steer lumen using a double occlusion (I patient). Resulte$ Follow-up venography demonstrated parenchymel tract stenosis or obstruction in 35, hepatic vein stenosie in 35 and patent stents in 25. Among 12 patients who developed obstructing or occluding thrombus of the parenchymal tract ~30 days after TIPS, 7/8 patients evaluated had biliary-stent fistulae (5 detected by thrombosis injection, 1 by ERCP, 1 by double occlusion balloon). Among 21 TIPS which were histologically evaluated, 6/7 with venographic or gross pathologic evidence of parenchymal tract stenosis had histologic evidence of bile duct cowauunication. Hone of 14 patent TIPS had histologic evidence of biliary fistula {p<O.001). Conclusions= 1) Parenchymal tract etenosis is a common cause of TIPS stenosls. 2) Billary tract communication with the TIPS can be demonstrated in most patients with early parenchymal tract throgabosls by intra-thrombus injection, ERCP or double occlusion balloon techniques. 3) Parenchymal TIPS stenoais is strongly correlated with histologic evidence of billary- TIPS communication. 4) Techniques to minimized biliary- TIPS fistulae, such as covered stents, should be developed to improve TIPS patency.

764 THE GLYCOSYLoPHOSPHATIDYLINOSITOL (GPI)-LINKED MEMBRANE PROTEIN PRDTECTIN IS INDUCIBLE ON THE BASOLATERAL DOMAIN OF HUMAN HEPATOCYTES. |-Y Scoazee*, A-F Bringuier*, G Peidmann ~, *INSERM U327, Facult~ Xavier Bichat, Paris, France We have previously shown that the complement regulatory protein 'protectin is induced on the besolateral domain of hepatocytes in various inflammatory diseases of the liver. Protectin is a GPl-linked membrane, protein, inserted in the membrane by a lipid anchor. In most polarized epithelial cells, except thyroid follicular cells, GPI- linked membrane proteins are restricted to the apical membrane. So far, like other GPlolinked proteins, protectin has been detected only along the apical domain of most polarized epithelial cells. Its basolateral distribution at the surface of hepatocytes is therefore unexpected. Three hypotheses might be proposed: (a) the existence of a non GPI-ltnked hepatocyte isoform of protectin, (b) an alteration of the intracellulas rouiage of canalicular proteins in the pathological situations associated with protectin induction,/c) a particular intracellular footage of GPl-linked proteins in bepatocytes. To test these hypotheses, we first determined whether protestin was inserted in the hepatocyte membrane by a GPl-anehor by using the property of GPI- linked proteins to be specifically cleaved by Pl-phospholipase C (PIPLC). Sections of frozen liver tissue were treated by 1U/ml PIPLC and stained by indirect immunoperoxidase for protectin, the transmembrane lateral protein E-cadherin, the transmembrane apical protein aminopeptidase N (CD13), and a GPl-linked protein expressed by sinusoidal endothelial cells, CD14. After treatment, protectin and CD14 were undetestable. In contrast, E-cadherin and CD13 remained detectable. We also verifed that the treatment by PIPLC of HepG2 ceils, which constitutionnally express protectin., reduced by 60 % the amount of protein measured by cellular ELISA. Protectin expressed by human hepatocytes therefore behaves as a GPl-linked protein. In a second step, we verified by confocal laser microscopy that hepatocytes presenting a basolateral induction of protectin retained a normal localization of canallcular proteins, such as CD13. We therefore excluded a general alteration of the routage of canalicular proteins in the pathological situations associated with pmtectin induction. Our results thereforo support the hypothesis of a particular routage of the GPI-linked protectln in induced hepatocytes, tn thyroid follicular cells, the basolateral routage of GPl-linked proteins has been attributed to the lack of caveo]in, which might prevent the formation of specific apically targeted carrier vesicles. We therefore searched for caveolin in hepatocytes by immunohistochemistry on frozen liver sections and by Western blotting of HepG2 cell lysates. No caveolin expression was detected in hepatocytes, while the protein was readily detected in situ in blEary epithelial cells and endothelial cells. In conclusion, the GPI-linked protectin is expressed on the baselateral domain of human hepatocytes. This is likely the result of a particular intraceUular routage of GPI-Enked membrane proteins, which might be related to the absence ef caveolin in hepatocytes.