LIVER - IMMUNOSUPPRESSION, ACUTEICHRONIC REJECTION, GVH, PEDIATRICS I
`
`Poster Board #-Session: P78-I
`Abstract# 265
`(23-690 days). Conclusions: lmmunoprophylaxis with SimulectB in combination
`with cyclosponne and steroids is safe with a one year graft rejection rate of 26.59.
`Q U E S l l O N 0 F ~ R O I D ~ ~ W ~ U N D E R T A C R O L M U S M ) R
`The observed rejections were mild to moderate and resolved after therapy: no organ
`PRIMARY BILIARY CIRRHOSIS (PBC), PRIMARY SCLEROSING
`was lost due to graft rejection.
`CHOLAGITIS (PSC) AND AUTOIMMUNE HEPATITIS (-1)
`A F E R
`LIVER TRAMPLANTATION AND LONG-TERM SURVIVAL. Ashdc B.
`Jain,' Randeep S. Kashyap,' Santosh Potdar,' John J. Fung.' 'Surgery,
`T.E.Starz1 Transplantatron Institution, Pittsburgh, PA.
`Recurrence of autoimmune process after liver transplantation (LTx) HAS BEEN
`documented. Use of steroids have been suggested lo prevent the recurrence of
`disease. Aim: To examine the long-term outcome after LTX for PBC. PSC and A1
`under lacrolimus and the need to use steroid with baseline immunosuppression.
`Material and Methods: Between August 'R9 to Dec. '92. 16R patients underwent
`LTx for PBC (n=83). PSC (n=60), and AI (n=2S). All patients were followed up to
`March 2OOO. Mean follow -up 8.Rf 0.7 year (median 8.9. range 7.2 to 10.5). Their
`postoperative course and base line immunosuppression was retrospectively
`reviewed. Results: Total 43 patients died and 26 underwent retransplantation for
`PNF (n=14), HAT ( n 4 ) Biliary complications (n=4), rejection. acute /chronic
`rejection (n=3) and denovo HCV (n=I). Overall patient survival was 74.9% a1 mean
`follow up of 9 years. Survival for each diagnosis is given in figure below.
`
`100
`7 80
`> 60
`L:
`
`f ;~pscl
`
`I-cPHCl
`
`,
`
`,
`
`- - -
`
`,--_I
`-1
`
`Poster Board #-Session: P80-I
`Abstract# 267
`TACROLMUS PI URhlACOKhITICX N TI IE EARLY PHASE AITER
`LIVER TRANSPLANTATION. Felix Brdun,' Beatrice Peters,' Ekkehard
`Schiitz,' Thomas Lorf.' Giuliano Ramadori.' Michael Oellerich.2 Burckhardt
`Klinik fur Tronspluntationschirurgie,
`Ringe.' 'Geor,~:4-Au~ii.~t-Univer.~itut.
`Gdrtingen, Germunv: 'Geor,s-Au,srist-Unri~ersitut. Ahteilrtng Kltnisrhe
`
`Chemie. Gottingen. Germany. 'Geor~-Au~ust-Uni~,ersifat. Ahterlung fur
`Gasfroenterologie iind Endokrrnolngie. Giittin,qen. Germany.
`Tacrolimus (Tac) trough level adjusied do\ing I* recanimended. hecause of its inter-
`and intraindividual variable hioavailahility. Therefore, we studied Tac
`pharmacokinetic (PK) profiles in the early phase after liver transplantation (LTx).
`Seventeen patients underwent LTx including 4 graft\ with primary nonfunction. Tac
`was started orally at a dosige of 2x0.0.5 mg&/d. Thereafter. Tac dosages were adjusted
`toatargetrangeof10-1S~~.Tac-PKs(T0.0.S.l.2.3.4.6.R.Y,10,11. 12h)were
`drawn after the first dose t PK I I, during the second week (PKZ), and at 3 months after
`LTx (PK3) Tac blood concentration\ were measured hy MElA 11.
`Tac pharmacokinetic data are depicted in the tahlc below. Companng the 3 PK-profiles.
`the AUC between PK I and PK2 showed a significant increase (p=0.003) and there
`was a significant difference in tmax between PKI and PK3 (p=O 003). The correlation
`hetween Tac trough levels and Tac-AUCs were r=O.Y7 PK I , r=O.Y7 PK I (PF). M.99
`PKI (PNF). r=O.RO PK2. and r=O.KS PK3 Patients with PNF had a delayed tmax.
`The Tac trough levels had a good correlation toTac-AUCs after first dose (PK I). and
`dunng the early and late steady state (PKZ and PK3). This finding implicates that the
`first Tac trough levels are good indicators of systemic exposure. Interestingly. a shift
`towards an earlier tmax was *een hetween the first PK and the PK at 3 months afier
`LTx. The first Tac trough level\ might already he taken into consideration for dose
`adjustment.
`Table. Tac pharmacokinetic data after liver transplantution. (Abbreviations: PF =
`pnmary lunction. PNF = primary nonfunction. AUC = area under the curve, t =time,
`c = concentration)
`
`8
`
`0
`
`
`
`0
`
`1
`
`2
`
`3
`
`Years Posttransplant
`
`4
`
`5
`
`1
`
`6
`
`-
`
`v
`
`-
`
`7
`
` -
`
`8
`
`9
`
`
`
`Their current liver function is shown in the table.
`ALT dml
`AIL Po4 ulml GGTP ulml
`Bill mg/dl AST ulml
`P B C 0 6 i o z
`4 1 1 1 ~ 5 3 5 s 0 4 f 4 7 i
`i 7 1 i t i 5 3
`i i z ~ i 1 1 0 8
`172f206
`9 4 i X 3
`4 9 5 t 4 7
`1 2 1 i 1 1
`PSC 0 6 i 0 2
`07+03 3ZflI
`I I Y t 4 4
`1XT16
`1 1 2 i Y 2
`Al
`In all patients, steroid was withdrawn at some time point after LTx. However in 31
`(24.8%) it was reintroduced for recurrence of disease Rate of reintroduction was 18
`(2%) for PBC. 6 (30%) for A1 and 7( 16.2%) for PSC. All patients showed impmvement
`in biochemcial profile upon reintroduction of steroid. In addition 6 (13%) patients
`with PSC received steroid to control colitis. Conclusion: 9-year actuarial patient
`survival for PBC, PSC and Al hepatitis is 76.7%. 73.2% and KO% respectively.
`Maintenance of steroid is not necessary in all patients. 24.8% of patients may require
`re-introduction of steroid with recurrent autoimmune process with a satisfactory
`biochemical response without any nsk to allograft.
`
`Poster Board #-Session: P79-I
`Abstract# 266
`IMWUNOPROPHYLAXIS WITH SIMULECTa (BASILIXIMAB) IN
`COMBINATION WITII CYCLOSPORINE AND STEROIDS IN LIVER
`TRANSPLANTATION. Genit Grannas,' Rainer Lueck,' Thomas Becker,'
`Ernst Kuse,! Juergen K1empnauer.l Bjoern Nashan.' 'Klinik fuer Visieral-
`und Transplantafronschirurgie, Mediiinisc'he Hochschule. Hannover.
`G e m n y .
`Basiliximab is a high affinity chimenc monoclonal antibody directed against the IL-
`2 receptor (CDZS). In order to evaluate efficancy and outcome 102 consecutive adult
`liver transplant recipients receiving basiliximab were analysed. Patients and
`Methods: From 01/99 to II/OO 109 liver transplanlalions were performed in 102
`patients, seven patients were retransplanted. Immunosuppression consisted of two
`iv bolus injections of ZOmg Simulectm on day 0 and day 4 were given and cyclosponne
`and steroids. 5 of the 102 patients received an additional kidney transplant. 92 full-
`size livers, 7 split livers. X living related livers (segments V-VIII) and 2 domino liven
`were transplanted. The median age was 47 years ( I 8-65), The primary objective was
`to assess the incidence of acute graft rejection (AR) post transplantation. Results:
`& 27 patients (26.5%) had an AR , 25 of the ARs (89.3%) occurred in the first 6
`months post transplantation with a median of day I 5 (7- 139). 16 of the 25 AR (64%)
`occurred between post operation day 7 and day 2 I All ARs were biopsy confirmed,
`no severe AR was found. 1 Patient got a graft versus host disease. & u g d
`W b r u t i o r r s : 12 out of I 0 9 tranplantations ( I 1%): 2 leakage of cystic duct, I
`leakage of bile duct anastomosis, I bleeding of right hepatic artery and I bleeding of
`caval anastomosis: 5 dehiscence of abdominal wall and 2 thrombosis of the hepatic
`
`artery All complications were reoperated. Cmudumoorlons with Re -= 7 from 102
`
`patients (6.9%): 4 initial non functions of the transplant, 1 chronic graft rejection, I
`HCV reinfection and I patient had an ischemic necrosis of parenchyma of unknown
`ongin.
`12 cholangitis ( 1 I%), 12 CMV infection ( I 1%)).
`I I
`'
`wound infection (10%). 6 pneumonia (6%). Ileaths, 5 patients ( 5 . 7 1 ) died. 4 of a
`septic multi organ failure between post op day 49 and 99 (median 64) and I patient
`died on post op day 7 with an intracerebral bleeding in case of a vacculitic due to
`CryoglObUIinemia. auLpme Graft survival was 93. I%. median follow-up: R.7 months
`(1-690 days): patient survival was 94.3% with a median follow up of 10.3 months
`
`Poster Board #-Session: PSI4
`Abstract#268
`OPTIMAL DOSING OF MYCOPIIENOLATE MOFETIL (MMF)
`IS NECESSARY TO DELAY IlEPATlTIS C RECURRENCE (IIEP
`CR) IN LIVER TRANSPLANT RECIPIENTS (OLT). Carlos G.
`Fasola,' George J. Netto,' Linda W. Jenntngs,' Laura L. Christensen.)
`Ernest0 P. Molmenti.' Edmund Q. Sanchez,' Shigeru Marubashi.' Brian
`M. Gogel.' Thomas A. Gonwa,' Robert M. Goldstein.' Marlon F. Levy.1
`Goran B. Klintmalm.l 'Baylor University M e d i t d Center, Dallas, 7x.
`Purpose: To determine MMF dose resulting in lesser graft fihrosis IGF) Methods:
`HepC 1994 -I WR OLT analy7ed. Group I (n=l26): Cyclo*ponne(CSA)+Steroids(P).
`Group Il(n46). CSA+P+MMF MMF used post rejection IACRl or renal sparing.
`Expowe ratio\ (ER) estahlished (MMF dose x MMF cxposure period/study perid)
`todetect optimal ratioat which no \evere HepCR occur. Criierion fulfilled by ERz1.9.
`Group 11 wbdivided in IIA: ER<1.9(n=3S) and llR>I.Y(n=I I ) . Parameters:
`Demographics. hospital stay. infections. tests. patient(PS) and graft(GS) survivals.
`Protocol liver histology at I . 2 and 5 years post OLT. Hep CR criteria hy GF scores
`(Stages[S]:O-4) as in A J S. Path 19(12)~14(W. 1995 Analyses with Chi-square and
`Kaplan-Meier. A p valued O.OS=\ignificant. Rcwlts. As expected. severe ACR
`incidence at 2 years was higher in Groups IIA. Y/IX(SO'IC) and IIB. Sn(71%) vs
`Group I: 7/x2(9% )(p=O.t)003). No statistical diffcrcnccs found for other parameters.
`Incidences of Hep CR at 2-year follow up (tahle).
`HEPATITIS C REWRREW'E AT SECOND YEAR OF FOI.I.OW Ill'
`Patknl. m MMF Ior I 2 nonlhi
`E R q I . 9
`No.MMF
`E R Z I . 9
`AxULbdu IAlI
`n I%I
`n i % l
`n l + I
`rlenc ,(if*& 11,
`1 h I l V 5 % 1 4121'11
`II(Il%l
`1-2)
`'J 147'6,
`u,dcrrt< I ( i , a I k S
`h l l l U V & l
`$11 lh19.,l
`(crcrr IGrdc- 1 4 1
`O i 1 l I l
`I h l I ' l 5 I I 6 l 1 2 S I
`uudLmux
`h IIf'II
`42 1 5 1 1 1
`I 1 1 7 I l
`\#,In 1st.pr
`Ill
`?4 I ' V I ,
`v $47*1,
`< I X I ' Z ,
`Uldcmlc islagc' 1-21
`I1 lI5P
`\cvcrr l S l l p 141
`I1 111'1 I
`10 1211'8 I
`1 I Ih% 1
`Conclu\ion\. OLT with MMF EW2l 9 no wverc Al or hridging fibro\is (S3) and no
`cirrhow 6 4 ) at 2-year follow up. Although not stiitistical qnificant. the lower GF
`incidence for ERZl Y may he me:ininglul given the higher pcrcentage of graft injury
`before MMF(7IQ ACR). The% findings indicatc that dosing nhove 1.9 g/d/yeW
`*hould carry a lesser CF Larger and randomiied trials arc neccrsary to confirm thew
`finding*
`
`p v d w
`
`0 I
`
`202
`
`

`

`LIVER - IMMUNOSUPPRESSION, ACUTE/CHRONIC REJECTION, GVH, PEDIATRICS I
`
`Poster Board #-Session: PS2-I
`Abstract# 269
`S I R O L l M u S ~ ~ ~ P ~ I O N I N L I V E R T R A N S P L A N T A T I O N
`AVOIDING CALCINEURIN INHIBITOR NEURO- AND
`NEPHROTOXICITY. Daniel H. Kosoy,l Glenda Meeberg,) David L. Bigam,[
`AM James Shaptro,' Winnie Wong,' Mang Ma? KlausGutfreund: Vincent
`Bain? Norman M. Kneteman.' 'Dept of Surgery; 2Dept of Medicine; 'Liver
`Transplant Program. Universiry of Alberta, Edmonton. AB, Canada.
`PURPOSE: To review our results using sirolimus-based immunosuppression to
`avoid calcineurin inhibitor toxicity in liver transplant patients. METHOD: We
`retrospectively reviewed data from 35 patients who were given sirolimus as their
`primary immunosuppressant in the 4 year penod from Dec 1996 to Dec 2000. Nephro-
`and neurotoxicity were assessed by changes in creatinine, need for dialysis. and
`changes in neurologic symptoms. Sirolimus toxicity was assessed by changes in
`hemoglobin. WBCs. platelets, cholesterol and triglycerides, therapy with
`erythropoietin. G-CSF, and lipid-lowering agents, as well as forced changes in
`sirolimus dosing. Impact of immunosuppression was evaluated by episodes of
`rejection, infection and malignancy, and graft and patient survivals. RESULTS: In
`the nephrotoxicity group (n=29), 19 patients (66%) showed significant improvement
`in renal function. with 14 returning to a normal creatinine within 1-3 weeks of
`beginning therapy. Six patients maintained stable renal function, while 2 showed
`further deterioration. Two patients who were dialysis dependent at initiation of therapy
`died. Of the 7 dialysis dependent patients post-transplant, all 5 who survived
`discontinued dialysis. In the neurotoxicity group (n=7), 6 patients (86%) showed
`significant improvement in their neurologic status. 3 with complete resolution of
`symptoms, and 2 with only minor ongoing complaints. Of the entire group, 15 patients
`(43%) required at least one transfusion. while 10 (28%) and 4 patients (I 1%) requued
`erythropoietin and G-CSF respectively, for anemia, leukopenia. and/or
`thrombocytopenia. Nine patients (26%) required a dose reduction and 4 (1 1%) had
`therapy discontinued. Ten patients (28%) required lipid-lowering agents for
`hyperlipidemia. There were 17 episodes of rejection in I 1 patients (31%). all steroid
`sensitive, 54 episodes of infection (35 bacterial. 16 vual. 3 fungal) in 24 patients
`(68%). and 2 caws of PTLD. Patient survival was 74% in this challenging cohort.
`Graft survival was 72%. I graft was lost to recurrent HCV. CONCLUSION: Pnmary
`sirolimus immunosuppression was effecuve rescue therapy in liver transplant patients
`not tolerating, or not expected to tolerate calcineurin inhibitors. It effectively reduces
`nephro- and neurotoxicity while mamtaining adequate immunosuppression. patient,
`and graft survival.
`
`Poster Board #-Session: PS4-I
`Abstract# 271
`AN OPENLABEL,AC"lVECONTROLLEDSTUDY TOEVALUATETHE
`IN POST LIVER
`USE OF MYCOPHENOLATE MOFETIL (-)
`TRANSPLANT PATIENTS WITH RENAL IMPAIRMENT WHO ARE
`CURRENTLY ON CYCLOSPORINE / FK506. David J. Reich,' Pierre A.
`Clavian? Leona Kim-Schluger,' Emest E. Hedge: for the Renal Dysfunction
`after Liver Transplantation Study Group. 'Albert Einstein Med. Ctr.,
`Philadelphia; 2Duke Univ., Durham; 'Mt. Sinai Med. Ctr., NYC; 4Roche
`Laboratories. Nurley, NJ.
`Purpose: W o parallel Phase IlIb trials investigated the ability of mycophenolate
`mofehl (MMF. CellCepta) as maintenance immunosuppression in pts with renal
`impairment after liver transplantation (LT). thereby reducmg exposure to cyclosporine
`(CyA) or tacrolimus (FK). Methods: Rs on CyA or FK (parallel trials) who were 3-
`27 mos post LT with a serum creatinine 1.8-4.0 mdml or a creatinine clearance of 20-
`60 mumin (with either representing >20% declme in renal function post LT) were
`randomized to discontinuation (Group I) or 50% reduction (Group 11) of macrolide.
`At randomization pts received MMF 1.5 g bid, and prednisone 10-15 mg/d (<6 mos
`post LT) or 5-15 mdd (26 mos post LT). Azathiopme, if present, was discontmued.
`The primary efficacy end point was glomerulofiltration rate (GFR); secondary end
`points included biopsy proven rejection (BPR). and pt & graft survival. Results: In
`the CyA tnal 26 pts were randomized into Groups I & 11; 13 pts completed 52 wks
`follow-up [Group I(61, Group I1 (7)]. Reasons for early termination will be presented
`indetail. InGroupI(meanage51 yr)meanGFRsatbaseline& wk52were35.0f16.5
`mVmm & 57.8320.1 mumin [>15% improvement (5/6). unchanged (l/6)]. In Group II
`(mean age 51 yr) mean GFRs were 46.6f20.4 ml/min & 56.of29.1 mUmtn [>15%
`improvement (2/7). unchanged (2P). >15% detenoration (3/7)]. In the FK tnal14 pts
`were randomized into Groups I & 11; 12 pts completed 52 wks follow-up [Group I(5).
`Group I1 (7)]. In Group I (mean age 59 yr) mean GFRs at baseline & wk 52 were
`55.4f13.7 mumin & 56.M8.9 m h i n [>15% improvement (2/5). unchanged (3/5)]. In
`Group 11 (mean age 56 yr) mean GFRs were 46.7f11.8 mumin & 60.2f9.7 mumin
`[ >I58 improvement (4/7), unchanged (3/7)]. BPR in the CyA trial occurred in 50%
`of Group I pts & 9% of Group I1 pts, and in the FK trial in 14% of pts in each Group.
`All BPRs were mild or moderate, and successfully treated with steroids andlor
`macrolide increase or reinitiation. h & graft survivals were 100% in both trials.
`Conclusion: Both trials show that MMF safely allows for macrolide reduction or
`cessation i n pts with renal impairment post LT. resulting in improvement or
`stabilization of renal function in a significant majonty of the PIS.
`
`Poster Board #-Session: P85-I
`Abstract# 212
`DoF.SEARLYTRFATMF.NTOFHCVIRUS(HCV)WITHANTI-
`VIRALTHERAPY A L T E R U S E O F I D R U G S O R
`RISK OF ACUTE REJECTION IN LIVER TRANSPLANT (OLT)
`RECIPIENTS? David J. Heffeman,l Mandana Khalili,' Kathy Bollinger,'
`Nancy L. Ascher: John P. Roberts,'Norah A. Terrau1t.l 'Dept. ofMedicine.
`UCSF, Sun Francisco; 2Depr. of Surgery. UCSF, Sun Francisco.
`Limited data suggests that initiation of Interferon ( E N ) early post-OLT reduces
`the risk of recurrent disease. However IFN, especially early post-OLT. may increase
`rejection directly (upregulation of HLA expression) or indirectly (IF"-induced side
`effects, especially BM suppression. limiting immunosuppression). Aims:To compare
`( I ) rates of acute rejection and (2) immunosuppressive drug dosefievels. in HCV-
`infected OLT recipients on early post-OLT IFN versus no IFN Methods: Prospeclive
`study of all HCV-infected OLT patients from 12/98 to 10/00. Standard
`immunosuppression(1MS): tacrolimus, mycophenolate mofetil(MMF), prednisone.
`with goals to taper prednisone to 5mg by Swks and stop MMF by 3mos. Rejection
`diagnosed by liver biopsy; performed for abnormal liver tests. Results: 56 patients
`(38 male, median age 5Oyrs); median follow-up 12.2mo; 33 received EN+/-Ribavirin.
`Median time from OLT to IFN 1.38 mos (0.3-8.5); median IFN therapy 7.qO.2-2 I)mob.
`24 rejection episodes in 19(34%) patients. No difference in rejection rates in those
`starting IFN <4wks(7/21) versus Awks post-OLT (2/12). All but 2 pts had rejection
`pre-IFN treatment.
`
`Any IFN (n=33, No IFN (n=241
`N plr with Relcclion (%I
`Y (21%)
`10 142411
`I 11%)
`Npls w l h >I episode 1%)
`3 ( 1 7 % )
`I ~
`2-7 5 )
`Median lime 10 1st Releclian (mar)
`
`I
`I
`R q Srveriiy mtldlmWscvere
`41411
`6/4/0
`s 115%)
`Rx steroids only
`111141
`RI sleroidq + additional drug'
`2 mi
`0 71
`1 ( Y B I
`MMF dobe PI I mo (gmrlO')
`
`0 I t
`62 128-911
`67 131-Y3)
`MMF OR 81 ?ma port-OLT
`5 12S%I
`X 121%)
`0 5 5
`n 38
`I moY 0
`Tierolimus level lmedinnl 11
`5 2
`n 72
`I 0
`Time 10 pred Smg (mosl
`X
`Conclusions: Early post-OLT IFN does not increase nsk or severity of acute rejection.
`Overall incidence of acute rejection dunng and after IFN therapy is low (6%). No
`significant difference in IMS between IFN and non-IFN patients. implying IFN-
`associated side effects do not compromise IMS in the early post-OLT period.
`
`p value
`n 2s
`0 s
`I nsto 2-1 4)
`0 41
`
`0 81
`
`Poster Board #-Session: P83-I
`Abstract# 270
`MEASUREMENTOFEFSTEDI-BARVIRUS(EBV)GENOMICTlTREIN
`BLOOD OF PAEDIATRIC LIVER TRANSPLANT RECIPIENTS
`RECEIVING EITHER CYCLOSPORIN (NEORAL) ORTACROLIMUS
`(TAC)-BASED IMMUNOSUPPRESSION. David Mutimer,' Narinder bur,'
`the European Paediatric Tacrolimus vs. Cyclosporin Microemulsion Liver
`Transplant Study Group. 'The Liver and Hepatobrliary Unit, Universriy of
`Birmingham. Queen Elizabeth Ho~ppltal, Birmingham. United Kingdom.
`Primary EBV exposure is associated with post-transplant lymphoproliferative
`disease (PTLD). EBV-driven cell proliferation may be assessed by the determinahon
`of the blood EBV genomic titre. Methods: We have used a quantitative PCR-based
`assay to measure EBV genomic titre in the blood of paediatric liver transplant
`recipients. This analysis is based on samples of children who were enrolled in a
`European multicentre trial and received either CyA or TAC-based
`immunosuppression. Recipient blood was sampled at the time of LTx (tlol, then at
`I. 3, 6 and 12 months. At the time of the analysis, 324 specimens from 134
`recipients (67 CyA. 67 TAC) have been examined (unit of measurement is EBV
`genomic titre/million PBMC's, results are expressed as mepiSn with interquarrrk
`range). Pre-LTx, 53/134 patients were EBV seropositive (R+); 52/134 seronegative
`recipients received livers from EBV-seropositive donors (D+/R-). for 29/134 patients
`the serology was not known
`Results: For R+ patients. EBV titres at the 5 time points were t,, 49 0-210; I,
`0-
`0-4100. For D+/R-. titres were t, p O-IIO;
`1080 t, 46p 0-1520 1, L6a 0-650 t,,
`0-930; 1, lua 70-4010 1,
`280-9850,t,I
`1500-9770. For the entire
`I,
`cohort (134 patients) and for each of the R t and D+/R- groups, the EBV titre of
`patients who received CyA and TAC were compared. In these 3 analyses, there were
`no significant differences between CyA and TAC-treated patients in EBV titres
`measured at any of the 5 time points. At 1,: titres for D+/R- were 1l6e 3970-7502
`I805-/31lM (TAC group). At the time of this analysis, 155
`(CyA group) and
`patients had completed I2 months treatment; 4 patients (3 patients D+/R-, I unknown)
`had developed FTLD. Peak titreb for the 3 D+/R- were 41 100, 18800, and 16500.
`These titres were not different from other LWR- patients. Conclusions: Blood EBV
`tines are higher in D+/R- patients than in R+ patient?. Dunng the first post-LTx year,
`EBV titres are not significantly different between CyA and TAC-treated children. The
`incidence of FTLD wa? low. EBV genomic titre measurements post LTx could not
`distingutsh between D+/R- patients who did or did not develop F'TLD.
`
`203
`
`

`

`LIVER - INFECTIONS, COMPLICATIONS, RECURRENT DISEASE, SURGICAL TECHNIQUES I
`
`Poster Board #-Session: P86-I
`Abstract# 273
`APROTI"USEINPEDIATRICLIVERTRANSPLANTATI0N.E~.
`D. Bigam, A. Senthilselcan, C. Tang, J. Shapiro, N. Kneteman. 'Surgery.
`University of Alberta Hospital. Edmonton, AB, Canada.
`Aprotinin has been shown to reduce blood loss and transfusion requirements dunng
`adult liver transplantation. as well as in pediatric heart and lung mansplantation.
`The objective of this study i s to establish whether aprotinin reduces the need for
`transplantation, and to
`blood product transfusions specifically in pediatric liver
`determine whether there are any adverse effects to the use of aprotinin in this
`setting. Transfusion of blood products (red blood cells, fresh frozen plasma,
`platelets. and cryoprecipitate) was analyzed intra-operatively and post-operatively
`in 67 consecutive pediatric liver transplants. Aprotinin (A) was used in 45
`transplants. and no aprotinin (NA) was used in 22 cases. There were no significant
`differences in mean intra-operative or post-operative transfusion requirements
`between the two groups. There was however a concerning trend towards an increase
`in hepatic artery thromboses in the aprotinin group ( I in NA vs. 6 in A: p = 0.4)
`and overall incidence of serious thrombotic complications (2 in NA vs. 10 in A; p
`4 . 3 ) . There was no significant difference in hemorrhagic complications or mortality
`between the two groups. In a subgroup analysis. comparing patients under two
`years of age (8 in NA: 28 in A), who are at greatest risk for vascular ana\tomotic
`thrombosis, there were no thrombotic complications in the NA group, and nine in
`the A group, with six hepatic artery thromboses (p a . 2 ) . This study demonstrates
`no reduction in blood transfusion requirements with the use of aprotinin in pediatric
`liver transplants. There is however a trend toward an increase in serious thrombotic
`complications, most of which require retransplantation,
`reoperation. or are fatal.
`Based on these results. we feel that aprotinin should he used with caution in
`pediatric liver transplantation. particularly in those patients less than 2 years of
`age.
`
`Poster Board #-Session: P87-I
`Abstract# 274
`NEW METHOD FOR DETERMINATION OF EBV VIRAL LOAD IN
`TRANSPLANT RECIPIENTS. David Wine? Pam Green,? John Bucuvalas,'
`Fred Ryckman,' Maria A1onso.l Thomas Gross.' 'Pediatric Liver Care
`Center, Division of Pathology. Childrens Hospital Medical Center.
`Cincinnatr, OH.
`The potential benefits of accurate determination of EBV viral burden in
`immunocompromised patients include not only more effective monitoring and early
`recognition of EBV infection but also new opportunities for preemptive therapy to
`prevent the complication\ of post-transplant lymphoproliferative disease (PTLD).
`As a result a number of assays using a variety of technologies have been developed
`for semiquantitative or quantitative determination of EBV DNA levels. Many of
`these PCR bared assays are based on an endpoint determination requinng serial
`dilution analysis or the use of competitive internal standards rather than using a
`kinetic approach. We set out to develop a quantitative assay to determine EBV copy
`number that would be a practical alternative method for monitoring these high nsk
`patients.
`Methods: We have developed a quantitative EBV assay using the Lightcycler PCR
`system which I\ based on continous real-time monitoring of PCR product. verified by
`flourophore labeled prohe specific hybridization and quantitated during the log-
`linear phase of the reaction. This improves the dynamic range in which \ampla can
`be analyzed (<I0 copies to 10'). has reduced substantially the turnaround time (< I
`hour), is highly reproducible (coefficient of vmation 4%). and i s less labor intensive.
`Whole blood sample\ were used to extract purified genomic DNA and the EBNA
`region was amplified for analysis. Using this assay we have monitored senal blood
`samples from over 80 pediatric patients at high risk for developing EBV disease.
`Results: Monitoring of serial blood samples frequently revealed a dynamic and
`sometimes complex panern of transient elevation\ followed by a rapid decline in EBV
`copy numbers in the peripheral blood. Peak EBV levels ranged from SO to 6 3 . 0
`copieshg DNA We found no consistent single value predictive of PTLD. Of the 2X
`patients with EBV copy numbers >SO0 only 3 developed clinical evidence of PTLD.
`We also found that rising levels in the blood EBV copy numhers frequently correlated
`with the onset of clinical EBV disease and declining EBV viral burden in the blood.
`as a result of treatment intervention was observed in three patients treated for PTLD.
`Therefore, determination of blood EBV copy number5 al random isolated time poinL\
`may not effectively identify significant clinical EBV disease. The results of this study
`suggest that effective management of patients at high nsk for EBV PTLD may require
`serial monitoring of blood EBV copy number\ and other factors wch as EBV T-cell
`immunity are probably important to determining predictive value of EBV viral load
`and PTLD.
`
`POSTER SESSION I:
`
`LIVER - INFECTIONS, COMPLICATIONS,
`RECURRENT DISEASES, SURGICAL
`TFTHNIOI IF3 1
`
`Poster Board #-Session: P88-I
`Abstract# 275
`SPLIT-LIVER TRANSPLANTS FOR 2 ADULT RECIPIENTS; AN
`INITIAL EXPERIENCE. Abhi Humar,' Raja Kandaswamy,' Timothy
`Sielaff.' Rainer Gruessner.' Marci Knaak,' Jack Lake,' William Payne.'
`'Surgery. University of Minnesota. Minneapolis. MN.
`Background: The shortage of cadaver donor livers has been most severe for adult
`patients with end-stage liver disease. Split-liver transplants (SLTs) are one method
`to expand the donor pool. To dale. most split\ have been performed for transplantation
`into an adult and a child However, if this technique is to have a significant impact
`on the waiting list, it need\ to he applied for 2 adult recipients. Herein we describe
`our initial experience with SLT\ for 2 adult recipients.
`Methods We \plit liver\ from 5 cadaver donor\, and transplanted the segments into
`10 adult ,170 recipients. All splits were performed in situ with transection through
`the midplane of the liver. resulting in a right lohe graft and a left lobe graft: the middle
`hepatic vein and main trunks of the hilar structures(common hepatic artery. portal
`vein. and common bile duct) were retained with the left graft. Graft weight to recipient
`weight (GW/RW) ratio\ were obtained for all recipients. Outcomes were analyzed.
`Results: Mean donor age was 20.4 years; mean donor weight was 81.9 kg. Mean
`recipient age was 39.2 yean: mean weight of right lobe recipients was 85.2 kg; of left
`lohe recipients, 57.6 kg. All procurements were multiorgan. involving a thoracic and
`abdominal \urgical team. All donors were hemdynamically stable and had normal
`liver function test\ pre-procurement. Mean operative time for the procurement was 1.5
`hours. Average blood loss during the transection of the liver was 4%) ml. Mean GW/
`RW ratio for all recipient\ wa\ 0 . X X I : for right lohe recipients. O.X9%; for left lobe
`recipients, O.X7%.
`With mean follow-upof 6 months. patient and graft sutvival rates were XOFJF and 80%.
`There were 2 death\. I after hepatic artery thromhosis (HAT) and subsequent
`multiorgan Pailure, and the other after HAT, liver retransplant and subsequent gram
`negative \epsis. The remaining X patients are doing well We oh\erved no cases of
`pnmary nonfunction. All grafts functioned immediately. with a drop in the serum
`bilirubin levels and INR. Other \urgical complications included, bile leak and/or
`steno\i\ (n=3). bleeding from the Roux loop(n=l). hleedingafter percutaneous biopsy
`(n=l), and inchiondl hernia (n=l ).
`Conclusions~ SLT\, using I cadaver liver for 2 adult recipients. can be performed
`\uccesdully. Proper donor and recipient \election is crucial for the success of this
`procedure
`
`Abstract#276
`Poster Board #-Session: P89-I
`NEED FOR RlBAVlRlN DOSE ADJUSTMENT IN RELATION
`TORENALFUNCTIONFORTREATMENTOFRECURRENT
`IlCV INFECTION IN POST LIVER TRANSPLANT PATIENTS.
`Ashok B. Jain,' Randeep S Kashyap.' Forrest Dodson,' Akhtar Khan,'
`Obaid Shakil.' John J. Funp.' 'Surgery, T.E.Star.-l Trunsplantution
`Institute. Pitrshiirgh, PA.
`Currently hepatitis C viral (HCV) infection is the commonest cause for liver transplant
`(LTx) Recurrence of HCV infection after successful liver transplantation is almost
`uniform. There are \everal reports to wggest heneficial effect of Ribavirin in
`combination with interferon a(lNF). Although Ribavirin isexcretated by the kidney,
`very little is pubhhed in terms of incidence of hemoly\i\ due to rihavirin treatment
`and it\ rclation\hip to renal function in post LTx patients. Alm: To examine the
`incidenceof hemolysis (drop in hematocnt 2 IS%) and its relationship to renal function
`at the time of initiation of riboviran and INF-a treatment. Material and methods:
`Between Aug 96 to July XXX) 72 post LTx recipient\ (M-SH, F-14. mean age 49.2
`f X.?) received lNFa ( 3 million unit% three time ii week subcutaneously) and
`Kibavirin 4 M l mg twice a day orally for recurrent HCV infection. All patients were
`followed until Nov. 2(X)O. mean follow up 39.9 f 2 I .7 months. Thc Patient population
`was divided according to \erum creatinine 5 I .(I mgldl (Group A) and serum creatinine
`> 1.0 mgldl (Group B) and incidence of hcmoly\i.; was calculated in both groups.
`Similarly =rum creatinine was examined with those who had hemolysis (Group I)
`and those who did not have hemolysis (Group II) Results: 4%h2 5 % ) patients had
`drop in hematocrit of > I SWGroup I), and 27 (373%)) patients had drop in hematwnt
`of cIS%(group 11). Mean serum ureatinine for goup I was 1.32f 0.45 m/dl compmd
`to I .W f 0.32 for group I1 (p=0.02). Similarly 32(44.4%,) paticnts had s. creatinine s
`I .O mgldl (group A) and 40 (55.6%) paiients had s. creatinine 21 .O mg.dl (Group B).
`IfXSOOk) patients in-group A and 29(72.5'%) in-group B experienced hemolysis
`(p=OOS). Findings are shown in the tahle
`Hrrnolyrw niS 1 Mron d c i r c i r ~ S E ~ C Y I mcun+SD
`nl? 1
`P >.I"<
`I" 1 1 ~ 1 1
`~ c i i i 5 % 1 4 v 6 2 51 n 8
`o n ?
`2 7 i t n q
`I I ? t o 4 5
`F M ~ I idcrrcarr
`m H & i r l 5 % 1 27111 5 1 n a
`(I I12
`I IIWII 12
`Croup II I&C~C.Y
`5 7 + 4 5
`O I
`I ~
`1 5 i l l y 4
`I ~ I J J J I i h 1 5 1 i 1
`I I X ~ O I
`GruupA I C k r r a l S l 1111
`0.0s
`19.6fl 1 . 1
`GroupB(S.creat>l.O)
`29 (72.51
`l.Sf0.7
`40(55.6)
`Conclusion: Our data sugge\t that the dose of ribovirin should he adjusted according
`to renal function to reduce the degree of hemolysi\. A prospective study t o measure
`the rihavinn concentration in relation to creatinine clearunce may he helpful to develop
`the algorithm for ribavirin don- adjustment i n relation to renal function.
`
`204
`
`

`

`L I V t i i - INFtG 1 IONS, GUMPLICATIONS, RECURRENT DISEASE, SURGICAL TECHNIQUES I
`
`Group III (n=l10): Progressive (increasing S) and Group IV (n=103): Aggressive
`(1st year 2 S2: 2nd year 2 S3). Donor(DF)hecipient(RF) factors: demographics, cause
`of death, serology, weight, ICU/hospital stay, pressors, liver tests (LIT'S). UNOS
`status, rejection, infections. steroids, antibodies. immunosuppression and survivals.
`In selected OLT quantitative Hep C RNA sera assessed. Chi-square and Kaplan-
`Meier used for analyses. A p value < 0.05 = significant. !&A&:
`No statistical
`differences found for most DF and RF studied but RFLFT's. Table shows relevant
`medians.
`TABLE: PATTERNS OF HEPATITIS C RECURRENCE
`GROUPS
`n
`RECIPIENT TESTS
`p "she
`I
`IV
`ill
`I o
`I n
`n 8s
`II xn
`u nnni
`1 months post OLT T 6th (mg/dl)