254 DISSOCIATION OF URSODEOXYCHOLATE-INDUCED BILE FLOW AND BILE ACID OUTPUT, DURING THE PREREPLICATIVE PHASE (St) OF REGENEHATING RAT LIVER.

J~J. Garcia-Marin~ F. Perez-Barriocanal, J.C. Perez-Antona, P. Regueiro, G.R. Villanueva, A. Esteller. Department of Physiology and Pharmacology, University of Salamanca, Spain.

Ursodeoxycholic acid (UDCA) induces hypercholeresis in the rat, related to an increase in bi l iary bicarbonate secretion (BBS), due to proton extrusion from bile. We studied bile formation induced by infusion of UDCA (300 nmol/min/calculated l iver weight, LW) or sodium taurocholate (TC; 150 nmol/min/calculated LW) in control (C) male Wistar (250 g) rats, and in 63% hepatectomized rats, lh, 6h or 12h before the experiments. The calculated LW was signif icantly different to the actual LW only in the 12h group (+22%). The results are expressed per actual LW and compared to the control group (*: P<O.05). The TC-induced increase in bile flow (BF; C:1.13, lh:1.04, 6h:0.97, 12h:0.90 ~I/min/g LW) and in bile acid secretion (BAS; C:140, lh:182", 6h:136, 12h:164 nmol/min/g LW) were not impaired during St. However, UDCA-induced BF was progressively decreased during St (C:3.62, lh:2.91", 6h:2.40", 12h:1.46" ~I/min/g LW). BBS induced by UDCA was also reduced (C:206, lh:159", 6h:115, 12h:60" nmol/min/g LW). No significant change in hepatic carbonic anhydrase act ivi ty was detected during St. The slight decrease in plasma bicarbonate concentration observed (C:25, lh:27, 6h:23, 12h:21" mmol/l) might only part ial ly account for the lowered BBS. In spite of the reduced choleretic effect, the BAS induced by UDCA was higher during St than in control rats (C:114, lh:99, 6h:346", 12h:222" nmol/min/g LW). Thin-layer chromatography of bile (6h group) showed that the increase in BAS was mainly due to tauroursodeoxycholate (61%) and glycoursodeoxycholate (32%). Only 7% of the increase in BAS was UDCA. These results suggest that the increase in conjugated BAS might be involved in the impairment of UDCA-induced BF and BBS during St, i f the cholehepatic shunt does play a role in the choleretic effect of UDCA.

255 EXPRESSION OF LYMPHOCYTE ACTIVATION ANTIGENS IN PATIENTS WITH HBV-RELATED LIVER

DISEASE. C.Garcla Monz6n*rR.Moreno Otero*,L.Garcla Buey*,N.Ortiz de Land~zuri**,M.L6pez- Botet**,F.Sanchez-Madrid**,J.M.Pajares Garcla*. Servicios de N.I.-Digestivo* e Inmunologia**.Hospital de la Princesa.Universidad Aut6noma de Madrid.Espa~a.

Recent studies have suggested that activated human lymphocytes may be involved in the patho- genesis of certain viral and autoimmune diseases.The aim of the present study was to deter- mine whether peripheral blood lymphocytes(PBL)from patients with HBV-related liver disease (HBV-RLD)expressed lymphocyte activation antigens(LAA)as detected by specific monoclonal an- tibodies(mAbs).PATIENTS:12 patients with HBV-RLD(4 chronic persistent hepatitis,5 chronic active hepatitis,2 active hepatic cirrhosis and 1 fulminant acute hepatitis)were investiga- ted.11 patients were HBsAE+,8 patients were HBeAE+ and 1 patient was anti-HBc+.lO patients with alcoholic chronic liver disease(ACLD) and a control group of 25 healthy subjects were also studied.All patients with HBV-RLD were studied twice at intervals of 3-12 months. ME- THODS:PBL were separated from heparinized blood by centrifuEation on a Ficoll-Paque density gradient.Expression of LAA was assessed by an indirect immunofluorescence technique usin E specific mAbs(MAR 93(anti-Tac),FGl/6(anti-TR-R),TSl/2(anti-HLA-DR)and TS2/7(anti-VLA-l).Nea- surements were performed by Flow Cytometry(EPICS-C).Data from the different groups were com- pared by the Mann-Whitney test.RESULTS:The expression of LAAwas significantly higher in 6 patients with HBV-RLD(DR+:I9±6~;TR+R+:6±3~;Tac+:5+_4%;VLA-I+:5+_3~)than in controls(DR+:14±_6~ p<O.O5;TR-R+:O.I±0.3~ p<O.Ol;Tac+:O.5~_0.6~ p<O.OI;VLA-1+:O.3+_0.4% p<O.O1).No siEnificative difference with controls was found in the other 6 patients with HBV-RLD and in patients with ACLD.CONCLUSIONS:I!)50~ of patients with HBV-RLD expressed LAA.2~)No correlation was found between expression of LAA and either histological liver injury or serological markers;howe- ver,sequential studies indicated that 80~ of patients expressing LAA showed higher levels of tPansaminases(ALT,AST)than when LAA were not detectable in the same patients.3!)These preli- minary results require further biochemical confirmation in purified T lymphocytes.

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