[ P/C01/25 ]

ELAD: REPORT OF CELLULAR FUNCTION DURING AND AFTER PATIENT THERAPY J.M. Millis 1, D.C. Cronin ~, H. Conieevaram ~, T. Faust ~, J. Charette 1, R. Johnson 2, C. Conlin ~, J. Brotherton ~, D. Triglia 2, P. Maguire ~ ~University of Chicago, USA. 2VitaGen Inc, La Jolla, CA, USA.

The ELAD artificial liver device is a hollow fiber cartridge utilizing immortalized C3A cells in a clinical trial to bridge patients to transplant in acute liver failure. Three patients have been supported continuously from 18 to 80 hours. Methods: During support, cartridges containing the hepatocytes are continuously monitored for oxygen utilization, glucose consumption and pH.. Following treatment all cartridges were immediately analyzed for glucose utilization (g/d/ELAD), galactose elimination (lamol/min/ELAD), and MEG-X production (~mol/min/ELAD) at the clinical site. After these studies were completed the cartridges were cooled to 40 C and sent back to the manufacturing facility and tested for additional metabolic function for 14 days. Results: Oxygen consumption, glucose utilization, A pH were normal and stable throughout the treatment period. The data regarding metabolic function prior to treatment, immediately after treatmem and after shipment is shown in the following Table.

Pre Treatment Immediately' post Treatment After shipping Albumin 240.5 ND 236 (mg/d/ELAD) Transferrin I 17 ND 118 (mg/d/ELAD) AFP (mg/d/ELAD) 43.3 ND 45.5

Glucose Utilization 18.2 16.8 18.7 Galactose Elimin. 24.6 25.4 30.0 MEG-X Production 0.55 0.47 0.56 Conclusions: The cartridges continued to be metabolically active throughout patient treatment - even up to g0 hours of treatment. The cartridges continued to meet release characteristics immediately after treatment and upon arrival hack to the manufacturing facility. The cartridges continued to function for up to 14 days after treatment. We conclude that the cells used in the ELAD maintain metabolic function during and after exposure to patients with fulminant hepatic failure.

Liver transplantation, surgery, acute liver failure

I P/C01/27 I

PROGNOSTIC RELEVANCE OF PROLIFERATION AND CELL AD- HESION MARKERS IN LIVER TRANSPLANTATION FOR META- STATIC NEUROENDOCRINE TUMORS

J. Rosenau, M.J. Bahr, R. v Wasielewski ~, M. Mengel 1, B. Nashan 2, J. Klempnauer 2, M.P. Manns, K.H.W. BOker Gastroenterology & Hepatology, Medical School Hannover, Germany l- Pathology, Medical School Hannover, Germany. 2Visceral & Transplant Surgery, Medical School Hannover, Germany.

Neuroendocdne carcinomas often present with irresectable muiti- Iocular hepatic metastases. The role of orthotopic liver transplanta- tion (OLT) in these cases is not well defined. We retrospectively analyzed all 19 patients who received a liver graft until 12/97 for metastatic neuroendocdne tumors (NET) at the Medizinische Hochschule Hannover (1.6 % of all transplants). Fol- low-up was 23-146 months after OLT (mean 56) and 2-84 months before OLT. 6/19 patients died (2 shortly, 4 patients 41-58 months after OLT). All long-term deaths were tumor-associated. Recurrence was diagnosed in 12/19 patients 2 to 48 months after OLT. 3/6 pa- tients without tumor recurrence are alive more than 8 years after OLT. Hepatic metastases at OLT were analyzed immuno-histochemically for call proliferation (p53 Ki67) and adhesion markers (E-cadhedn). Histology was classified in favorable (group A: p53 and Kt67 <2% +re cells and regular E-cadhedn staining) and unfavorable (group B: p53 or Ki67 >5% +ve cells or aberrant E-cadherin staining). Of 10 patients with more than 5 years follow-up all 5 patients with tumor related deaths belonged to group B. Log rank testing for survival of the two groups using Keplan-Meier estimates was significant (p=0.01). The only other significant prognostic factor was histologi- cally proven regional lymph node metastases at OLT (p=0.02). NET show a substantial recurrence rate after OLT with a highly van- able clinical course. We have identified histological markers that may allow estimation of prognosis. This may lead to a better char- actedzation of NET patients elegible for OLT. Our data should be validated by a multi-center analysis.

L P/C01/26 J

RETRANSPLANT OF THE LIVER (RLT) IN RECURRENT HEPA- TITIS C VIRUS (HCV) INFECTION: RETROSPECTIVE MUL- TICENTRIC STUDY

R. B~iroena 1, D. Pares, L. Grande, M. Prieto, C. Barrios, E. Fraga, E Suarez, E. Ffi.brega, C. Loinaz, A. Bilbao, E Pareia, J.I. Herrero, A. Can- delas IServicio de Gastroenterologia, Madrid, Spain. H. Ram6n y Cajal, Mad- rid, Spain.

1hem amjustf~,=~aboutkerMra'~aalalontRL'l)inreeu~i I-E:V ~ m a ~ a ~ a t 0 n b n o t ~ bt~pmtt~. AII~ To compare ~le evolulbn ¢fRLTr,~ ~ d b j ~ ~ h RLT bl/oll~r _r~____N~ in spin PATIENTS AND METI-K:¢~ Ra~pe0ke s~:ly ¢fRLT l~Bilsfmm 12 d b m t Hoclab cadml ou[ dudngb~o ~as, IggS.gf, a n d ~ up unll I~ June, 99. V~ have ~__r)~_ _ i ' n r ~ lheral~, t~e urli RLT, s4pecvi~,-,c,~ deeSz n~_ _~_~. p~emcumt a n d i n R L T S ~ p = m L T ~ ( a ~ d h ~ , ~ ,L.~.~ ?.~_ _. ma M'ml ins~r¢ienoA penr, mencein i~,,,~vecare unl md hospileltqr~e. RESULT~ V~ have oolea~ dela t~m 9 ~ OL.T and 90 R1L 610 rmles, meen age 48~0 ~ms. ~ ~ e HCV,,.: 213 males, mere age ~,5:~ (o< 0.01). 35'90 I~ . .v .~eH~.Thec~u~s~RTl .~ l~ . Rivuy gralt rlm.flxct~(PGNF) 18 ~s~, Vascz~mnTIk:aiom 0,%') 23, ¢hnmic mjeff~on (CR) 20, RHCV 12 and tiber causes 14. In OLT 87% m ¢ ~ l o/dospaln ~0% tCle t~ral~ The frne unli RTL ~¢s m ~ t in I-L'V+ (~0eTal d a ~ wd in HCV. (,leat66ett). "this i r e ~ s O ~ m m ~ t ~ t ~ - ~ ' v 0 a ~ a ~ a n ~ r ~ t a a ~ * a ~ 0 a r d ~ t o ~

~ar, md was simlar for I -L '~ md I-L"V- p~f~ls ~ in R-ICV ~ms 68,6% at tst yeer ard 50% at t td yem, ttem ~es not bebveen t~is rale of sup~vMmoe ard Ire ;;__.,~,~ed for PGMF, ~ or CR In R-L-'V ~,~.==~ ~e have not found p~r t t rva lua for ,= mv)~mmin ~eaf¢in, b[mdan, al~urr~n or ~,~,,.,, ~ , free I M I s ~ RTLima.

RHCV b ~ c~Be of 1,2% oi OLT md 13,~e/o oi Rll.. S ~ M ~ - , ~ , ~,_ , ~ ot club, pem~nm~ in hoq~l ~rm, and poS-RTL oxnl~alom are siTilarin RHCV and olher c~___~__ of RTL

[ P,c01 s ]

EARLY STEATOSIS AND PAST HBV INFECTION PREDICT FI- BROSIS PROGRESSION IN LIVER TRANSPLANT RECIPIENTS WITH RECURRENT HCV INFECTION

M. Angelico, G. Palmieri, D. Di Paolo, E. Torri, G. Iaria, L. Baiocchi, A. Anselmo, S. Mensi, C.U. Casciani, G. Tisone Gastro Unit and Liver Transplantation Center, Tot Vergata University, Rome, Italy.

Recurrent HCV infecUon is almost universal after liver transplantation, yet disease progression varies from minimal changes to severe chronic hepatitis rapidly evolving to cirrhosis. Predictors of such disparate outcomes are unknown. Early hepatic steatusis is a specific sign of recurrent HCV inf~tion in the graft, often preceding necroinflammation. Occult HBV infection has been sugges~d as a possible promoter of the evolution of chronic hepatits C. Accordingly, the aim of this study was to investigate the role of early hepatic steatosis and of past HBV infection on the progression of liver fibrosis in a cohort of HCV-infected transplant recipients. Methods. Thirty-three patients (mean age 52+6 yrs, M/F:23/8) transplanted for HCV-cirrhosis 25 to 84 (median 49) months earlier were studied. Standard immunosuppression was based on Neoral and azathiopnne. Protocol liver biopsies were obtained at 3 months and then yearly. A total of 150 biopsies were scored for steatosis (0 to 3), necroinflammatory changes and stage of fibrosis (Ishak). Results. HbcAb was found in 18 (54°/.) patients, in 11 (33%) of whom associated with HBsAb. Early (3-month) hepatic steatosis was absent in 15 patients (group A), mild or moderate in 16 (group B) and severe in 6 (group C). The groups did not differ for donor and recipient age, body mass index and gender, nor for HCV genotypcs. At univariate analysis patients with severe early steatosis had a higher total necro-inflammatory score vs groups 1 and 2 at one and two years after transplant (p= 0.04 and 0.003, respectively). The fibrosis score was also higher (p<0.004) in group C (2.25) than in group A (1.25) and B (1.0) from year two. Among several parameters examined by multiple regression, the 3-year score of fibrosis was independently predicted by only 3 variables: early hepatic steatosis (p:0.019), presence of I-lbcAb (p:0.015) and absence of HBsAb (p=0.019). Conclusion. 3-month steatusis and past (perhaps occult) HBV infection predict a faster progression of HCV-related liver disease after transplaE.t

55