Alejandra Villamil

Von Willebrand factor could be an index of endothelial dysfunction in patients with cirrhosis: relationship to degree of liver failure and nitric oxide levels.

BACKGROUND/AIMS The aim of this study was to evaluate the relationship between plasma levels of von Willebrand factor (vWF), a marker of endothelial cell activation, and nitric oxide, a powerful vasodilator synthesized by endothelial cells, in 27 patients with cirrhosis at different stages of the disease. These results were compared with those of age-matched normal, healthy subjects (n=10). METHODS vWF:antigen was measured by electro-immunodiffusion test and serum nitrite and nitrate levels, the stable end products of nitric oxide metabolism, were determined by an enzymatic procedure. RESULTS vWF:antigen and nitrite/nitrate levels were significantly higher in cirrhotic patients (367+/-185% and 29.3+/-10.8 micromol/l) than in healthy subjects (92+/-20% and 19.2+/-8.3 micromol/l, p<0.05, respectively). Higher levels of vWF:antigen and nitrites/nitrates were observed in patients with more advanced degrees of liver failure, as reflected by quantitative Child-Pughs score (516+/-154% and 38.3+/-7.8 micromol/l in Child-Pugh > or = 9 vs 227+/-61% and 21.0+/-6.1 micromol/l in Child-Pugh <9, p<0.001, respectively). Moreover, both endothelial-related factors were higher in patients with ascites than those without ascites (543+/-158% and 37.8+/-8.9 micromol/l vs 262+/-103% and 24.4+/-8.8 micromol/l, p<0.001, respectively). In the overall series, a highly significant linear correlation between nitrites/nitrates and vWF:antigen levels was observed in patients with cirrhosis (r=0.79, p<0.001). CONCLUSIONS These results support a cirrhosis-related endothelial dysfunction and suggest that plasma vWF measurement could be useful as a marker of endothelial disturbance in patients with cirrhosis.

Catastrophic antiphospholipid syndrome complicating orthotopic liver transplantation

Catastrophic antiphospholipid syndrome (CAPS) is an acutely devastating situation characterized by widespread thrombotic microangiopathy in the presence of elevated titers of antiphospholipid antibodies. We describe a 57-year old woman who underwent liver transplantation for primary sclerosing cholangitis and developed this malignant variant of the antiphospholipid syndrome.

Sicker Patients for Liver Transplantation: Meld, Meld Sodium, and Integrated Meld’s Prognostic Accuracy in the Assessment of Posttransplantation Events at a Single Center from Argentina

Background. MELD or MELD sodium promotes sicker patients for earlier liver transplantation (LT); the balance between pre- and post-LT outcomes is still controversial. Aim. To compare MELD and related scores’ risk assessment of short-term morbidity and mortality after LT. Methods. We included only transplanted cirrhotic patients from 6/2005 to 6/2010 (). Immediate pre-LT MELD, integrated MELD (iMELD), and two MELD sodium formulas “MELD Na1” and “MELDNa2” were calculated. Results. Pre-LT scores for nonsurvivors were higher than those for survivors: MELD (28 ± 8 versus 22 ± 7, ), MELD Na1 (33 ± 8 versus 27 ± 10, ), and iMELD (51 ± 6 versus 46 ± 8, ). Patient survival assessment was performed by AUROC analysis (95% CI): MELD 0.694 (0.56–0.82; ), MELD Na1 0.682 (0.56–0.79; ), MELD Na2 0.651 (0.54–0.76; ), and iMELD 0.698 (0.593–0.80; ). Patients with MELD ≥25 points had longer intensive care stay (mean 10 versus 7 days, ) and longer mechanical ventilatory support (5.4 versus 1.9 days, ). Conclusions. The addition of serum sodium to MELD does not improve assessment of mortality after LT. Patients with higher MELD may preclude higher morbidity after transplantation.

A MELD-SCORE BASED LIVER ALLOCATION SYSTEM HAS A NEGATIVE IMPACT ON WAITING LIST MORTALITY AND IS ASSOCIATED WITH LOWER POST-TRANSPLANT SURVIVAL IN A COUNTRY WITH A UNIQUE, LARGE GEOGRAPHIC ORGAN PROCUREMENT AREA: 1029

Since June 2005 liver allocation in Argentina has incorporated MELD score to stratify patients in the waiting list. Due to an uneven distribution of transplantation centers no organ allocation areas were established, with a unique national waiting list serving a population of 39 million inhabitants. Aim: To evaluate the impact of MELD score in drop out, transplants and 1 year survival post transplantation. Patients and Methods: We included 707 consecutive patients registered in the waiting list. Period Pre-MELD: Listed June 1998/May 2005 in categories elective and urgency according to clinical and biochemical criteria (n=377). Period MELD: Listed June 2005/December 2008 stratified by MELD score (n=325). Overall and subgroup analysis was performed. Comparison between groups for quantitative variables was based on the test of t Student and for qualitative variables with Chi2 test. Actuarial probability of survival and drop out from the waiting list were calculated by Kaplan-Meier and compared using Mantel-Cox test. Results:In MELD period there was a 78 % increase in annual registration of patients without differences between etiologies or presence of HCC (15.3 vs 12.0 %). Mean age at registration was significantly higher in Period MELD (53.35 ±13 vs 49.11±14 years, p<0.05). 59 % of patients in period MELD were listed with MELD scores 12 to 19 (mean MELD16±6), while previously 72 % were listed in elective category. Number of transplants/year remained unchanged (35.2 vs 33.3). Yet time to transplantation was significantly shorter in Period MELD (8.7m vs 14.2m, p<0.001). Mean MELD at transplantation in Period MELD was 24.13±7.6 and 19.63±9.7 at drop out (p <0.001). Drop out was significantly higher in period MELD (18.4 to 14.5%. p<0.001). Rates of listed/transplanted patients decreased for cholestatic disease post MELD (66 to 23 %, p<0.05)and increased for HCC (17 to 91 %, p<0.001). One year patient and graft survival post transplant decreased from 93.1 to 83.5 % (p <0 .001). Mean MELD of patients dying within 3 months post-transplant: was 27.8±5.6 compared to 23.2±7.4 in survivors (p <0.01). Conclusion: Application of MELD score in Argentina has demonstrated a negative impact on waiting list mortality and has been associated with lower early post transplant survival. Further tuning of the application of the system should be performed to optimize results.

MELD PRIORITIZATION FOR PATIENTS WITH CIRRHOSIS AND SMALL UNRESECTABLE HEPATOCELLULAR CARCINOMA HAS A MORE POSITIVE IMPACT IN WAITING TIME AND POST TRANSPLANT RECURRENCE FREE SURVIVAL THAN LIVING DONOR LIVER TRANSPLANTATION: 618

A.G. Villamil, O.A. Galdame, J.C. Bandi, P.C. Casciato, M. Reig, V. Ardiles, E. de Santibañes, A.C. Gadano Liver Transplantation Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina Introduction: A selected group of patients with cirrhosis and small hepatocellular carcinoma (HCC) can be cured by liver transplantation. Yet, organ shortage and long waiting time may preclude transplantation due to disease progression. Aim: To evaluate the impact of living donor liver transplantation (LDLT) and MELD prioritization on pre and post LTx outcome of patients listed for cirrhosis and HCC. Patients and methods: 55 consecutive patients with small unresectable HCC fulfi lling the Milan Criteria (single nodule <5 cms or up to 3 nodules <3cms without vascular invasion) and a normal chest CT and bone scan were listed for LTx between Jan 2001 and Sept 2006. Outcome was analyzed in 2 different time periods: Jan 2001-June 2005 (Group A, all patients were offered the possibility of LDLT) and July 2005-Sept 2006 (Group B, all patients were given a MELD score of 22 and an additional point every 3 months in the waiting list). No differences in ethiology and severity of cirrhosis were observed between groups. Results were also analyzed within Group A between patients with or without an available living donor. Results: In Group A only 7:32 patients had an adequate living donor and received a LDLT. Median waiting time was signifi cantly longer in Group A compared with Group B (24.3 ± 10.3 vs 2.8 ± 1.6 months, p< 0.05). Within Group A waiting time was signifi cantly different between patients with an adequate living donor compared with those without a living donor (6.8 ± 2.1 vs 27.8 ± 13.7 months, p<0.05). Recurrence free survival was lower for patients in Group A compared to Group B (19/32 (59.3%) vs 19/23 (82.6%), p<0.05). Results

[186] BENEFIT OF PLASMAPHERESIS AND ANTICOAGULATION IN PATIENS TRANSPLANTED FOR END-STAGE LIVER DISEASE WITH HIGH RISK FOR ANTIPHOSPHOLIPID-ASSOCIATED VASCULAR EVENTS

BENEFIT OF PLASMAPHERESIS AND ANTICOAGULATION IN PATIENS TRANSPLANTED FOR END-STAGE LIVER DISEASE WITH HIGH RISK FOR ANTIPHOSPHOLIPID-ASSOCIATED VASCULAR EVENTS. Alejandra Villamil, Paola Casciato, Walter Scorso, Felix Nunez, Daniel Bustos, Daniel Alvarez, Eduardo de Santibanes, Adrian C Gadano. Liver Transplantation Unit, Hospital Italiano, Buenos Aires, Argentina; Transfusional Unit; Immunoserology Laboratory; Radiology Unit. Circulating antiphospholipid antibodies (aPL) are often present in patients with end-stage liver disease and are associated with post-OLT morbidity and graft loss. Risk is increased in patients with pre-OLT thrombotic events or high titer circulating aPL. Plasmapheresis is an adequate therapy after the development of vascular complications post transplant. Aim: To evaluate the impact of pre-OLT plasmapheresis associated with post-OLT anticoagulation in patients transplanted for end-stage liver disease with positive aPL and high risk for vascular complications. Methods: 14 patients with positive aPL and high risk criteria for vascular thrombosis who have undergone OLT (1998-2004) for chronic liver disease were included. Patients were divided into Group A (n=7): patients with no plasmapheresis pre-OLT and low dose aspirin ± low weight heparin post-OLT, and Group B (n=7)): patients who received plasmapheresis with fresh frozen plasma 12 hours pre-OLT followed by post-OLT anticoagulation, maintained for at least 6 months. Clinical and Doppler US evaluations were performed before OLT and at different time-points during the first six months post-OLT (weekly the first month and monthly thereafter). Etiology and severity of cirrhosis and immunosuppression did not differ between both groups. Immunosuppressive regimen included cyclosporine (n=8) or tacrolimus (n=6) + mycophenolate + steroids. Results: 5/7patients in group A developed complications post-OLT related to aPL (cerebrovascular ischemia n=2, humeral thrombosis n=1, hepatic artery thrombosis n=1, intestinal ischemia n=1, catastrophic antiphospholipid syndrome n=2) that resulted in grafts loss (n=1) and death (n=1). Median time post-OLT was 2.8 ± 1.4 months. In 4/5 patients the complications developed within 2-16 days post severe acute cellular rejection. In Group B 1/7 patients developed an antiphospholipid-associated complication post-OLT: extensive intestinal ischemia + livedo reticularis at 4.5 months post-OLT, resulting in patient ́s death with multiorgan failure unresponsive to repeated plasmapheresis. Conclusion: Plasmapheresis pre-OLT associated with anticoagulation postOLT may be an effective strategy to prevent aPL associated vascular complications in high risk patients. CONCURRENT SESSION 67: PEDIATRIC LIVER TRANSPLANTATION