Expression of immune adhesion molecules in human liver grafts

229 CHRONIC EFFECTS OF PROPRANOLOLAND VERAPAMIL IN PORTAL HYPERTENSIVERATS.

230 SERUM HYALIJRONATE RELIABLY PREDICTS CIRRHOSIS IN CHRONIC LIVER DISEASE U. Steiger and R. Preisiq, Dept. of Cllnlcal Pharma-

R.E.Stauber,F.W.Ruthardt,R.Kuhlen,D.H.Van Thiel Dlv.of Gastroenteroiogy, Univ. of Pittsburgh,USA.

cology,

The aim of the present study was to evaluate the influence of a ID-day-longsystemic infusion of propranololor verapamilon the developmentof portal-systemicshunting (PSS) in rats. Methods: Forty-threerats underwentpartial portal vein ligationand subsequentlyS.C. implantationof an osmotic minipump for continuousdelivery of either propranolol(20 mglkgfd),verapamil (80 mglkgld), or saline.Ten days later, heart rate (HR), mean arterialblood pressure (MAP), and portal venous pressure (PVP) were determinedunder ketamine anesthesia;PSS was measured following ileocolic injectionof radioactivemicrospheres.Results: Group(n) sa;;.a;;l") P;;;:2$15) verapT113) HR (blmin) 3@!? BET10 B2TlO MAP(mn Hg) 15971.2 13.Ox2.Q* PVP(mm Hg) 12.472.1* PSS (%) 85X13 + 64t16 83717 )p
University

Since

of Berne.

t'yaluronate

(Hy)

Berne

Swtzerland

- a glycosamnoglycan

synthezisedby fibroblastsand drsposed from circulation hy the hepatic RES system - has been nominated as a marker of hepatic fibrosis,we tested the predictive value of serum Hy for the cirrhotic stage of liver disease in 145 outpatients (R5 males, 60 females, age 17-75).Based on histology, quantitative liver function tests (GEC. ABT) and radiology they were classified as non-cirrhotic (HCLD; n-73) and cirrhotic (CLD: n-72). i!edianHy levels were significantlyhigher (p
231 EXPRESSIONOF IMMUNE ADHESION MOLECULES IN HUMAN LIVER GRAFTS G.Steinhoff,M.Behrend,R. Pichlmayr,K1in.f. Abd. u. Transplantationschirurgie,Med.Hochsch.Hannover

232 ANTIMITOCHONDRIALANTIBODIES (AMA) IN PATIENTS WITH CHRONIC GRAFT VERSUS HOST DISEASE (GvHD) AND LIVER INJURY. R.Stemerowicr.W.Siegert. U.tiopf,D.KUther, D.Huhn. Dent. of InternalMedicine. Universitatskliniku Rudolf Virchow, Berlin-West

The tissue expressionof immune adhesion molecules (LFA-l,CD2)and their 1;9ands (ICAM-l,LFA-3)was studied after human liver transplantation.Liver biopsies (n=50) were compared to normal liver(n=lO) and severe liver diseases (n=4D). Results: (1) In normal liver hepatocytes,bile ducts and endothelia were lCAM-1 and LFA-3 negative. (2) In biopsies taken during transplantation(n=20) the expression of ICAM- on sinusoidallining cells was increased. Also the number of LFA-1 positive leucocyteswas increasedin the sinusoids.(3) Without compiications after transplantationthe tissue distribution of adhesionmolecules resembledthat of normal liver. (4) With complications(rejection,viraland bact. infections)ICAM- was induced on hepatocytes, bile ducts and endothelia.In biopsies with severe the !CAM-1 inductionon hepatocyteswas rejection generalized.Only in irreversiblerejected grafts a focal inductionof LFA-3 was found on hepatocytes. Most infiltratingcells and Kupffer ceils stained LFA-!+, a subset also expressed CD2. (5) In endstage liver disease (PBC,HBV)hepatocytes,Kupffer cells and endotheliawere found ICAM-lt. Some bil'e ducts expressed ICAM-1. Only in a few cases LFA-3 was inducedde nova on hepatocytes.bile ducts, endotheliaand Kupffer cells. These results show that the expressionof lCAM-1 in liver grafts is upregulatedduring a variety of different inflammatory processes.The inductionof LFA-3 was less freauent and could deoend on additional factors.

Patients with chronic GvHD after allogeneicbone marrow transplantation(EMT) show frequentlychoiestatic and inflammatoryreactions in the liver mimicking primary biliary cirrhosis (PBC) or primary sclerosingcholangitis.PBC is associatedwith defined AMA, which recognize equivalententerobacterial proteins (Lancet 1988;ii:1166).Gut flora might play a pathogeneticrole in PBC (Lancet 1989; ii:1419) and in GvHD (Annu Rev Fled1984;35:11). Therefore we studied antibody activity against mitochondriaand enterobacteriain 11 patients with chronic GvHD after BMT and elevated markers of cholestasis.Liver biopsies were performed in 3 patients and showed non-suppurativecholangitis. Methods: Sera were tested by immunoblottingwith bovineheart mitochondriaand E. coli lysates as antigens and by immunofluorescence technique with kidney and liver sections from mouse. Results: 9 of the 11 patients developed AMA recognizmchondrial proteins at 22 kD in 8 cases, at 36 kD in 4 cases. at 50 kD in 5 cases, and at 70-80 kD in 2 cases. Using immunofiuorescencetest AMA became detectable only in one patient. All 11 patients had antibodies against various enterobacterialproteins. Conclusions:The data support the hypothesis of an etiopathogeneticrelationshipbetween liver injury in chronic GvHD and PBC. S58