J. C. Bandi

Use of Liver Grafts From Anti-Hepatitis B Core-Positive Donors: A Multicenter Study in Argentina

Liver transplantation success is limited by the availability of donors. To overcome this limitation, anti-core-positive donors are increasingly being accepted, but underutilization of this resource still occurs. We performed the current study to determine the prevalence of anti-core-positive donors in our region and to describe the management of these donors and their recipients. Between January 2005 and July 2011, the national transplant database included 2,262 registered liver donors among whom 106 (4.7%) were anti-core-positive including 59 (56%) discarded and 47 (44%) implanted organs. A median of 14.5 offers (range 4-60) were rejected before harvesting and implanting the accepted grafts. The only difference between the implanted and the discarded grafts was found for the alanine aminotransferase level, which was higher among the discarded ones (50 ± 59 UI/L vs 25 ± 16, P < .05). Among 40 recipients included in the study, 5 (12.5%) did not receive any prophylaxis; 18 (45%) a nucleos(t)ide analog 11 (25.5%), heptitis B immunoglobulin and nucleos(t)ide analogs and 6 (15%) pretransplant hepatitis B vaccination. Over a mean follow-up of 871 ± 585 days, 4 de novo hepatitis B cases were identified at 545, 720, 748, and 1,080 days posttransplantation. None of these patients had received any prophylaxis. In all cases entecavir successfully controlled viral replication. We believe that better utilization of these donors and careful management of their recipients represent safe strategies to expand the liver donor pool in Argentina.

Chronic hepatitis C liver microenvironment: role of the Th17/Treg interplay related to fibrogenesis

The role of the different lymphocyte populations in liver microenvironment of chronic hepatitis C (CHC) patients is still matter of debate. Since Th17 and Treg have opposite functions, their balance could affect disease progression. The aim was to explore liver microenvironment and its peripheral blood counterpart in adult CHC patients. CD4+ lymphocytes were predominant in the liver, with high Foxp3+ but low IL-17A+ frequency. IL-17A+ lymphocytes and IL-17A+/Foxp3+ ratio displayed association with advanced fibrosis (pu2009=u20090.0130; pu2009=u20090.0236, respectively), while Foxp3+ lymphocytes and IL-10 expression level inversely correlated with fibrosis severity (pu2009=u20090.0381, pu2009=u20090.0398, respectively). TGF-β/IL-6 ratio correlated with IL-17A+/Foxp3+ ratio (pu2009=u20090.0036, ru2009=u20090.5944) and with IL-17A+ lymphocytes (pu2009=u20090.0093; ru2009=u20090.5203). TNF-α and TGF-β were associated with hepatitis severity (pu2009=u20090.0409, pu2009=u20090.0321). Peripheral blood lymphocyte frequency was not associated with liver damage. There are functionally different immune cell populations actively involved in liver damage, but the liver cytokine milieu actually drives the pathogenesis. The intrahepatic Foxp3+ lymphocytes predominance beside the low IL-17A+ lymphocytes frequency, delineate a skewed IL-17A+/Foxp3+ balance towards Foxp3+ lymphocytes. However, the IL-17A+ lymphocytes association with advanced fibrosis denotes their role in the pathogenesis. Therefore, the interplay between Th17 and Treg conditions liver fibrogenesis.

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