C-35 Program Abstracts 138 139 AGING RELATED CHANGES REVERSE IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS WITH OLDER DONOR LIVERS F Innocenti, L Burgart, O Freese, A Cohen, C Rosen, M EI-Youssef, IV Ishitani Mayo Clinic, Rochester, MN USA Background: The direct effect aging may have on liver function is unknown and may be important when utilizing older liver donors in the pediatric liver transplant population. Lipofuscin granules have been identified as a marker of aging and may suggest aging related liver enzymatic dysfunction. The aim of this study is to present the histhopathological changes in lipofuscin quantity and distribution in livers transplanted from old donors into young recipients. Methods: Donor and post OLT follow up biopsies were graded (0-4) for quantity and distribution of lipofuscin granules in nineteen patients. Group A (n--6), pediatric patients who received a young donor graft; Group B (n=6), old patients who received an old donor graft; Group C (n=7), pediatric patients who received an old donor graft. Results: The one-year graft survival and the incidence of acute rejection were similar within each of the three groups. Peripheral and gastrointestinal eosinophilia after pediatric liver transplantion, Rune Romero, Todd Pilh:n, Rebecca Tutt, Carkrs Abrarnovsky. Grcgg Smallwood, Thomas G. Heffron. Emory University School of Medicine. Atlanta, GA. Introduction: Pronounced peripheral and gastroint~tinal eosinophilia has been rc~rted after liw:r transplantathm. We ~.-xaminedpossible predisposing factors to aid in the prospective idc'ntification of patients at risk for the development of peripheral or gestroint~tinal eosinophilia, defined as eosinophilie infil~ation ofgestrointestinal epithelia. Methods: The medical records of all pediatric liver transplant recipients at our institution from 1-97 to 12-09 were rcviewcd. Paramders abstracted included patient characteristics, pretransplant peripheral eosinophilia (PE), history of food/drug allergy, type of immunosuppr~sian, number of biopsy -proven rejections episode, prior abdominal surgeri~, liver transplant type, endoscopic procedures, and pathologic diagnoses. Fifty of a possible 53 records were reviewed. For continuous data, a two-tailed students "t"tcst was used. For nominal data Chi square analysis was performed except where Fisher's eaact t~t was appropriate. Results: All 50 patients had normal protransplantation peripheral cosinophil counts. PE of> 10% dt,wclopcd in 15 of 50 patients (30%) at a mean post-transplantation date of 417 days +/- 240 days. Paticnts with PI" were youngcr at the time of transplantation (3.7 +/- 5.5 y ~ r s vs. 7.3 +/- 6.3 years, p =0.05). Rejections episodes were marc common in the PE group (2.46/patient vs. 0.9/patienL p=0.01 ). Bilia~' atresia accounted for 9 of the 15 cas~ (60%) in the PE and only 14 of the 35 (40%) tmaffected children, but this did not reach statistical significance (p=0.32). Reduced segment gratis were used in 10 of 15 (67 %) patients in the PE group, and 14 of 35 (40%) unaffected children (t}=0.63). Prior alk:rgic history or immunosuppr~sive regimens did not differ significantly in the 2 groups. Gastroint~tinal endoscopy was performed in 23 wansplanted patients, 6 had PE and all had cosinophilic gastr(xmtcritis. Conclusions: PE is common after pediatric liw.'r transplantation. Young patients with frequent rcjcction episode appear to be at risk. Symptomatic eosinophilie inflammation of the GI tract is common in pediatric patients with Pt" after transplantation. Whether innate immune rt.~ponsiveness combined with increased antigenic stimuli account for this apparently acquired condition merits further twaluation. Group Donor Age (yr) A (n=6) 3 (2--4) B (n=6) 68.6 (59-74) C (n=7) 61.1 (53-76) Li ~ofuscin accumulation Group Donor 1 week Recipienl Age (yr) 3.3 (0-9) 57 (53-65) 9 (0-17) 6 mo 1 yr 2 yr , Kuppfer cells A 0 0 ,0 0 0 B 3.6(3-4) 3(2-4) 3(2-4) 3 3 C 3.3(2-4) 2.5(2-4) 2(1-3) 1.4(0-3) 1 • Significant macrophagic lipofuscin seen in 4/6 patients at 6 months and in 2/6 at 2 years. Conclusion: We found that older donor age-related changes persist in older recipients and eventually resolve in younger recipients. Based on these observations, we have speculated that lipofuscin may be a marker of aging but its presence may be influenced by hepatocyte independent mechanisms. Further studies are needed to determine if this pattern is followed by other metabolic or structural changes in the transplanted liver. 140 141 LACTATE LEVELS DURING LIVER TRANSPLANTATION CORRIELATE WITH UNDERLYING DIAGNOSIS, MASSIVE BLOOD TRANSFUSION, A N D OUTCOME NJ Wilkes. SI" MalletL T Peachev. C Beard. Department qf Anaesthesta. Royal Free Hospital london NW3 2QG. United Kingdom Introduction: The liver is the main site for clearance of" lactate. During oahotopic liver transplantation (OLT) serum lactate levels rise due to impaired clearance during the dissection and anhepatic stages. The rate of decline of serum lactate following reperfusion may be an early marker of initial graft function) "~ The aim of the current study was to analyse the influence of clinical variables, such as the aetiology of the liver disease, blood transfusion, and graft fimeLion on the intraoperative lactate profile. Methods: We analysed the records of 84 consecutive adult patients that had undergone liver transplantation at our institution for a variety of indications. Lactate was measured on three occasions during the dissection stage, two occasions during the anhepatic stage, and three occasions during the neohepatic stage using an amperometnc biosensor (reference range 0.6 - 2.4 mmol.l'~). For statistical analysis we used paired Studeat's t-tests. Results: Baseline mean lactate was lower in patients with cholestatic compared to cirrhotic disease (0.7 vs. 13 mmol.I"1, p=0.001) and remained lower at end of surgery (2.0 vs. 4.5 mmol.I"~, p=0.002). In patients that had received massive blood transfusion (>12 units), lactate levels were significantly higher than in those patients that had received < 12 units (6. I vs. 4.2 mmol.I"~, p=0.042), A duration of stay < three days on the Intensive Therapy Unit (ITU) was associated with a significantly lower lactate at end of surgery than a stay of :~ three days (4.0 vs. 5.4 mmol.I"j, p=0.035) Patients with a short ITU stay also demonstrated a decline of lactate during reperfusion (5.0 to 4.0 mmol.f ~, p=0.089). A primary non-functioning graft (PNFG) was associated with a steep rise in lactate to 12.3 mmol.Ia. Discussion: The aetiology of the underlying liver disease affects levels of serum lactate during OLT. The volume of intraoperative red cell transfusion determines the rate of increase of serum lactate. In the neohepatic stage, lactate levels decrease rapidly in patients with good initial graft function reflected by an ITU stay of less than 3 days. A suboptunal graft may be associated with a longer ITU stay. These patients demonstrate higher intraoperative lactate levels and a smaller decline during reperfusion. A continued rise of lactate levels following reperf~sion may indicate a PNFG. The absolute level of lactate at the time of reperfusioo is of less importance prognostieally than the subsequent rate of clearance and fall in lactate NON-HEPATIC GLUCOSE PRODUCTION IN HUMANS DURING T H E ANHEPATIC PHASE OF LIVER TRANSPLANTATION A. Pulvirenti, J. Coppa, A. Banez.zatf. L Luai', D.E. Matthews', R. Romito. M. Schiavo, E. Regalia, V Mazzaferro National Cancer Institute and S. Raffaele Institute'. Milan, Italy Background Aim of this study is to assess whether humans can produce significant amounts of glucose independently from the liver, Methods: Four patients who underv,'cnt liver transplantation for localized hepatocellular carcinoma in hepatic cirrhosis were studied. The conversion ol gluconeogcnic substmtes when the liver is physically absent, i.e. during the anhepatic phase of liver transplantation ~as measured. A bolus of 13-13 CI alaninc and [6,6-2H21glucosc was administered after the removal of the native liver In the time windows (approx. 60 rain.) prior to graft reperfusion` blood v,,as sampled to follow the decay of the bolus and to determine the appearance of labelled carbons into glucose. Glucose and alanine kinetics were described using two compartmental models plus one compartment representing a dela} between the glucose and the alanine subsystems. Results were not corrected for the carbon exchange in the Krebs cycle. Results: During the anhepatie phase, the concentration of insulin, glucagon. cortisol and GH were 40~2 ItU/ml, 301±101 pg/ml, 481± 66 pg/l and 9:1:2 pg/ml, respectively. The concentration of glucose, alanine, glutamine and lactate wcre169~30 mg/dl, 819-~129 pmolll, 742~:48 wnol/I and 8.9~2.9 mmol/I.The individual values ofalanine and ucose kinetics were: Subject Alanine Rd" ghtcose RD°" % alanme Rd % glucose Ra from OzmolI Kg~mm) (rag Kg ram) to glucose ialonme 2.96 0.$6 # I 8.6 4.2 6.32 15.07 #2 11.5 1.3 3.62 4.78 #3 10.5 07 #4 16.8 3.9 0.94 0.361 mcan~SE 11.9--+-1.8 25±0.9 3.46"4-I. I 1 2.69"~:1.29 "'Ra: rate ofappcaranee Rd: rate of disappearance Conclusions; In summary, humans can produce significant amounts ol glucose during the anhepatic phase of liver transplantation possibly from the kidney and small bowel. A minor proportion of glucose comes from alaninc.