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En el congreso de la AASLD de este año se dedicaron específicamente al trasplante hepático dos sesiones plenarias (comunicaciones 1-12) y tres sesiones paralelas (donación y distribución de órganos [parallel 7], trasplante en hepatocarcinoma y enfermedades no virales [parallel 17]  y trasplante hepático en las hepatitis virales [parallel 27]). Además, las sesiones poster incluyeron 182 comunicaciones relacionadas con el trasplante (poster session I desde la numero 517 hasta la 699).

En las siguientes líneas se exponen de forma resumida las comunicaciones de mayor interés agrupadas por sesiones. Es inevitable omitir en un resumen de estas características muchas comunicaciones relevantes; el denso libro de abstracts y la página web de la AASLD ofrecen al lector la posibilidad de establecer un itinerario propio con el objetivo de acceder a otras comunicaciones que puedan ser de su interés.

Transplant plenary I:

1. Improved efficacy of antiviral therapy in liver transplant (LT) patients treated at earlier stages of fibrosis. V. Aguilera1, 3; A. Rubin1, 3; C. Ortiz2, 3; M. Gimenez2, 3; M. Prieto1, 3; M. Berenguer1, 3 1. Hepatology and Liver Transplant Unit, Hospital la Fe, Valencia, Spain.2. Experimental Immunity Unit, Hospital la Fe, Valencia, Spain. 3. Ciberehd, Instituto de Salud Carlos III, Valencia, Spain.

Background: We recently published worse sustained viral responses (SVR) in HCV-LT patients treated in recent years compared to those treated in earlier cohorts (Liver Transpl 2009; 15:738). We hypothesized that this was mostly caused by an increase number of patients treated at advanced stages of fibrosis. Based on these data, we changed our treatment policy in order to start therapy at earlier time-points. Aim: To assess whether these changes have resulted in improved SVR. Methods: Efficacy (rapid, early-EVR-, end-of-treatment, SVR) and tolerability were compared between patients treated with pegIFN-ribavirin (RBV) in 2005-06 (group 1, n= 52) and those treated more recently (group 2, 2007-09, n=76) after changing the center policy. Tolerability measures included initial IFN/RBV doses, premature treatment discontinuation, dose reductions, anemia, growth factors, and transfusions. Baseline factors potentially predictive of SVR included renal function (MDRD), immunosuppression (cyclosporine vs tacrolimus, MMF, steroids), type of interferon (alfa 2a vs alfa2b), stage of fibrosis and degree of inflammation, donor and recipient age, gender, history of preLT antiviral therapy, time from LT to therapy, genotype, viral load, body mass index (BMI), diabetes and laboratory values. On-treatment factors included viral kinetics and tolerability-related factors. Results: SVR increased from 31% in group 1 (n=16/52) to 49% in group 2 (n=37/76) (p=0.04). Baseline factors associated with SVR were younger donor (p=0.02) and recipient age (p=0.05), BMI (p=0.03) and mild fibrosis (F 0-1) (p=0.003) while treatment-related variables were treatment duration > 80% (p<0.001), RBV full dose at initiation (p=0.02) and RBV cumulative dose > 80% (p<0.001). Finally viral kinetics predicted SVR. Comparison of those treated in the early as opposed to the more recent cohort revealed no differences in most baseline variables with the exception of the stage of fibrosis with a decrease number of patients treated at advanced stages of fibrosis in 2007-2009: 53% compared to 2005-06: 71%(p=0.04), baseline IFN and RBV doses with an increase of those treated with full doses (IFN: group 1, 86% vs group 2, 99%, p=0.008; RBV: 67% vs 89%, p=0.002). In addition, those treated more recently developed anemia (86% vs 69% ; p=0.01) and required erythropoietin (80% vs 63%; p=0.03) and transfusions (46% vs 25%, p=0.01) more frequently. Conclusions: Treatment at earlier stages of fibrosis is associated with higher SVR. Our results warrant strict disease progression monitoring. A more aggressive approach, particularly regarding RBV appears also to improve treatment efficacy.

Comentario: el momento más oportuno para iniciar el tratamiento de la hepatitis recurrente por VHC en el  post-trasplante sigue siendo un tema debatido. Un argumento podría ser la posibilidad de obtener mejor respuesta cuando se inicia el tratamiento en estadios más precoces.

 

2. Results of Liver Transplantation in a Large Cohort of more than 100 HIV Infected Patients – A Monocentric Experience.J. Duclos-Vallée1, 3; M. Tateo1, 3; E. Teicher4; A. Roque-Afonso2, 5; M. Sebagh1, 3; T. Antonini1; A. Coilly1; R. Sobesky1; E. Vibert1, 3; C. Salloum1; R. Adam1; D. Azoulay1; D. X. Castaing1; D. Vittecoq4; D. Samuel1, 2 1. Centre Hepato-Biliaire, AP-HP Hopital Paul Brousse, Villejuif, France. 2. UMR-S785, Univ Paris-Sud, Villejuif, France. 3. Unite 785, Inserm, Villejuif, France.4. Service Maladies Infectieuses, AP-HP Hopital Paul Brousse, Villejuif, France. 5. Laboratoire de Virologie, AP-HP Hopital Paul Brousse, Villejuif, France.

Liver disease progression to cirrhosis is much faster in HIV infected patients and liver transplantation (LT) is now an accepted therapeutic option for HIV infected patients with end stage liver disease. Until now, results of small series have demonstrated that LT is feasible in HIV infected patients; however, severity of recurrence of HCV infection on the liver graft constitutes the main problem. Methods: we have analyzed the outcome of more than 100 patients in terms of survival according the indication of LT, the degree of recurrence of HCV infection on the liver graft and the response to anti HCV therapy. Results: 105 HIV infected patients (mean age: 45 yrs ± 5.9; male: n=88 (83%) have been transplanted in our center between December 1999 and July 2010. Indications of LT were as follows: HCV cirrhosis: n=59 (56%); hepatocellular carcinoma: n=20 (19%); HBV cirrhosis: n=8 (7.6%); HBV/HCV cirrhosis: n=5 (4.7%), HBV/HDV cirrhosis: n=1 (0.9%), fulminant hepatitis: n=2 (1.9%), nodular regenerative hyperplasia: n=4 (3.8%), hemochromatosis: n=1 (0.9%), hepato-pulmonary syndrom: n=3 (2.8%) and secondary biliary cirrhosis: n=2 (1.9%). The mean MELD score at the time of LT was 18.9 ± 8.73 [7-49]. Mean CD4 cell count at LT was 291.3 ± 194.37 cells/mm3 [10-1020]. The mean delay of follow-up was 3 years ± 2.3 [0-10.2]. The overall cumulative survival was 55 % at 5 years. Nine (8.5%) patients have been retransplanted. The survival of patients transplanted for HCV cirrhosis, HCC and HBV cirrhosis were 45 %, 49% and 100% at 5 yrs, respectively. At the end of follow-up, fibrosis score was >2 in 14 (13.2%) of the overall population and in the group of patients transplanted for HCV cirrhosis 14/51 (27.4%), respectively. Anti-HCV therapy (PegIFN + Ribavirin) was given in 36/58 (62%) patients who had a recurrence of HCV infection on the liver graft; the response rates were as follows: no response: n= 24 (66.6%); partial response: n=2 (5.5%); sustained virological response: n=4 (11%) and complete response: n= 2 (5.5%). Conclusions: survival at 5 yrs after LT in a cohort of 105 HIV infected patients is 55%. Because of a low rate of sustained virological response after LT with PegIFN and Ribavirin, new drugs against HCV viral infection must be tested in a very near future.

Comentario: una evidencia más de los desfavorables resultados a cinco años del trasplante en los pacientes VIH, especialmente en el subgrupo de coinfectados por VHC.

3. The Role of Cardiac Catheterization and Percutaneous Coronary Intervention in Pre-Operative Assessment and Management of Patients prior to Orthotopic Liver Transplantation
H. Maddur1; P. D. Bourdillon3; S. Liangpunsakul1; A. Tector2; J. A. Fridell2; M. Ghabril1; M. A. Lacerda1; R. Vianna2; R. Vinayek1; H. Yoo1; P. Y. Kwo1. 1. Division of Gastroenterology/Hepatology, Indiana University Medical Center, Indianapolis, IN, United States. 2. Transplantation Surgery, Indiana University School of Medicine, Indianapolis, IN, United States. 3. Cardiology Division, Indiana University Medical Center, Indianapolis, IN, United States.
There is limited data regarding the optimal risk assessment strategy for evaluating candidates for orthotopic liver transplant (OLT). At this center a policy has been adopted over the last few years of performing cardiac catheterization with coronary arteriography (CATH), followed by percutaneous coronary intervention (PCI) for angiographically significant coronary artery disease in patients with predefined risk factors as part of the preoperative evaluation, even in the presence of negative stress tests. The risk factors considered included age, family history, smoking history, diabetes, hypertension, prior history of coronary artery disease, and obesity. Our AIM was to assess the effect of this policy on cardiovascular complications and survival rates post – OLT. Methods: Single center retrospective study of all patients who underwent OLT between 2000 and 2010. Data was abstracted including one year all cause and cardiovascular (CV) mortality, post-operative myocardial infarction (MI), and frequency of CATH and PCI. The time frame of the study was divided into three sub-periods: 2000-2004(A); 2005-2008(B); and 2009-2010(C), to reflect the changes in policy over this period of time in which the frequency of invasive cardiac catheterization in period B was intermediate between that of A and C as the evaluation policy evolved. Results: 1235 patients underwent OLT during this period. 38 of the 56 patients requiring PCI had normal stress tests. The numbers of patient undergoing OLT, and the all cause mortality, CV mortality, MI, CATH and PCI rates (%) for these time periods are indicated in the table. Conclusions: A significant improvement in overall survival rates over the three time periods analyzed was noted. An increase in the frequency of CATH and PCI corresponded with a significant decrease in CV mortality and post-operative MI. Further analyses of the role of stress testing and CATH, for evaluating and treating patients prior to OLT are required to optimize this process

Comentario
: esta comunicación propone una conducta agresiva en el manejo de la enfermedad coronaria ya que la cardiopatía isquémica no controlada tiene un impacto significativo en la mortalidad cardiovascular post-trasplante. Este hecho se debe tener en cuenta en la evaluación pre-trasplante.

 

Transplant plenary II

4. The Influence of Inter-Center Competition on Liver Transplant Outcomes. J. B. Halldorson1; H. Paarsch2; A. Segre3; J. P. Roberts4 1. Surgery, University of Washington, Seattle, WA, United States. 2. Economics, University of Melbourne, Melbourne, VIC, Australia. 3. Computer Science, University of Iowa, Iowa City, IA, United States. 4. Transplant Surgery, University of California, San Francisco, CA, United States.   

Background: The number of Liver Centers within a Donor Service Area (DSA) varies between 1 and 6 centers across the United States. Given that donor offer match lists are shared within a DSA, transplant centers in which there is more than one center/DSA compete locally for the limited number of cadaveric livers that become available. When multiple centers compete for a liver on a single match list, an individual center may often face a conflicted choice between either accepting a suboptimal donor/recipient match for a particular liver offer or “losing the liver offer” to a competing center. Conversely, centers in which there is no competition for local offers have greater freedom to optimize risk profiles for individual donor/recipient matches. As the number of centers competing within a DSA increases, the probability of a single center having multiple potential recipients for a liver offer decreases and optimal donor/recipient matching is impaired. We hypothesize that competition for the limited resource of donor livers under a “sickest first” allocation scheme impairs optimal donor recipient/ matching, increases average disease severity and worsens expected and observed survival after liver transplantation. Methods: National transplant center summary statistics were accessed from publicly available data at us.transplant.org. Three year observed, expected and the ratio of observed/expected patient survival were analyzed. Results: 22.7% of liver transplant centers operate in a DSA without a competitor. Centers without competition had superior observed and expected patient survival at 3 years compared to centers within a competitive environment. 80.7% vs 77.4% expected survival p<0.0001 and 81.8% vs. 76.9% observed p<0.0008. Observed/Expected Survival was not significantly different. As the number of centers/DSA increases, expected 3 year patient survival decreases with each competitor center added within a DSA. Conclusions: While competition has been advocated in many fields as a stimulus to process improvement, our findings suggest that under current conditions in which a severly limited resource is allocated by a “sickest first” mechanism, competition may negatively influence patient survival. The potentially negative impact of inter-center competition on outcome should be a considered when changes in liver allocation strategies are proposed.

Comentario: esta comunicación pone de manifiesto los problemas de justicia distributiva en el reparto de órganos en los Estados Unidos. Las áreas con un solo centro generador/receptor de órganos se ven claramente beneficiados frente a las áreas con varios hospitales que compiten simultáneamente por el mismo órgano. Un viejo problema en la distribución de órganos de difícil solución.

 

5Utilization of Simultaneous Liver-Kidney Transplants Varies Dramatically by Region and Does Not Correlate with MELD Score
P. J. Gaglio1; S. S. Florman1; T. Kato1; L. Kim-Schluger1; M. Kinkhabwala1; G. Morgan1; M. Orloff1; P. Sheiner1; L. Teperman1; S. DeLair1. 1. New York Center for Liver Transplantation, East Greenbush, NY, United States.

Introduction: Over the last several years, the number of deceased donor simultaneous Liver-Kidney transplants (SLK) have increased. However, guidelines for SLK, including when these combined transplants are appropriate based on serum creatinine, underlying liver and renal disease, etiology of renal dysfunction and time on dialysis are contentious. Inappropriate SLK removes an organ from the donor pool which would more appropriately be utilized for a patient awaiting kidney transplantation, and failure to provide SLK to a patient who requires prolonged dialysis and kidney transplantation following isolated LT is similarly inappropriate. We hypothesize that the use of SLK varies by region, and may be related to mean MELD at the time of transplantation. Methods: Utilizing data provided by UNOS, we performed a retrospective review of all SLK performed from 2002-2010, analyzed the percentage of SLK performed in each region based on total number of liver transplants (LT) performed, the ratio of % SLK performed to mean MELD at the time of transplantation, and assessed rate of change in number of SLK by year by region. Results: During this time period, 2975 SLK and 45,120 isolated LT were performed. Nationally, the ratio of SLK to LT was 6.5%. This ratio was dramatically different when comparing regions, with the highest ratio in regions 1, 5 and 7 (12, 8.8 and 12.5% respectfully) and lowest in regions 6, 9, and 11 (3.6, 4, and 3.9%). The mean increase per year in number of SLK performed between 2002 and 2010 was 14.7, but also varied dramatically by region, with an increase of 32, 31, and 27 SLK in regions 3, 7, and 5 respectively, and 2, 3, and 3 SLK in regions 6, 1 and 2. When analyzing the ratio of % of SLK versus total LT to mean MELD score at the time of transplantation in each region, significant differences were also found, with the highest ratios in regions 1 and 7 (.375 and .403) and lowest in regions 6, 9, and 11(.138, .125, .144). Conclusions:

1) Utilization of SLK varies significantly when comparing UNOS regions
2) The increased utilization of SLK does not appear to correlate to increased wait list MELD score at the time of transplantation in regions performing the highest % of SLK. In fact, lowest utilization of SLK is occurring in regions with some of the highest wait list MELD scores.
3) These findings suggest that a uniform policy related to utilization of SLK should be adopted

Comentario: resulta especialmente llamativa la gran variabilidad en la utilización del trasplante  hepato-renal entre los distintos centros. Por ello se propone una política común para establecer la indicación de este tipo de trasplantes.

 

Paralell 7: Donation and allocation

6. How a Broader Regional Sharing and Relative Size of Liver Transplant Centers Impact Patient Survival in a Simplified Liver Allocation Model (SLAM): Is It Share and Share Alike? J. Schwartz1; H. F. Thiesset1; J. B. Sorensen1; T. D. Box2; W. R. Hutson2; R. D. Kim1; F. R. Adler3 1. Department of General Surgery Section of Transplantation, University of Utah, Salt Lake City, UT, United States. 2. Department of Gastroenterology, University of Utah, Salt Lake City, UT, United States.3. Department of Mathematics, University of Utah, Salt Lake City, UT, United States.

PURPOSE: Recent analysis indicates that liver transplant (tx) candidates with a MELD >35 have waitlist mortalities similar to Status 1 candidates, for whom sharing of organs occurs on a regional basis. Plans to broaden distribution have proven controversial due to concerns that changes would not be born equally by all localities. We offer a simple mathematical model using probabilistic rates to ascertain how changes in organ allocation may impact patients at the individual liver tx center level. METHODS: Data on 105 adult liver tx centers from July 1, 2009, to June 30, 2010 was extracted from the SRTR. Patients were categorized based upon MELD score (<21, 21-30, and 31-40). Using the observed rates (OR) of entry onto the waiting list in each of the three categories, the OR at which organs became available, and the OR of death stratified by MELD score, wait list dynamics were modeled using a stochastic process. As the primary endpoint, we examined the probability of death before tx for three strategies: no sharing, regional sharing of organs at MELDs >30, and regional sharing at MELDs > 20 (Figure). RESULTS: Broader regional sharing at a MELD > 30 resulted in a substantially reduced risk of death (RR <1.0) on the waiting list for high MELD patients (>30) across all centers and regions. Centers performing a higher fraction of transplants in their respective regions benefited less than their smaller counterparts. After correcting for this factor, a center’s regional affiliation had no impact on results. Lower MELD patients show a slightly smaller, but still consistent benefit when included in sharing. However, a regional effect is now evident. CONCLUSION: This model can be easily applied to individual tx centers. Patients listed at high MELD scores benefit from broader regional sharing, with the largest benefits occurring in relatively small centers. In an effort to develop an equitable organ allocation policy, the availability of this approach may help inform policy discussions in conjunction with existing models.

Comentario: se trata de una idea atractiva por la cual los enfermos más graves logran un claro beneficio de supervivencia cuando pueden acceder a un pool regional de órganos más amplio.

 

7. The Comparative Effectiveness of Donation after Cardiac Death versus Donation after Brain Death Liver Transplantation: Recognizing Who Can Benefit C. L. Jay1, 2; V. Lyuksemburg1, 2; D. Ladner1, 2; E. Wang1, 2; J. L. Holl3; G. Hazen4, 1; M. M. Abecassis1, 2; A. I. Skaro1, 2 1. Northwestern University Transplant Outcomes Research Collaborative (NUTORC), orthwestern University Feinberg School of Medicine, Chicago, IL, United States. 2.Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United States. 3. Institute for Healthcare Studies, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.4. McCormick School of Engineering and Applied Science, Northwestern University Feinberg, Chicago, IL, United States.

Background: Given continuing organ scarcity and waitlist mortality, utilization of donation after cardiac death DCD livers have increased. However, which group of patients benefit from DCD liver transplantation has not been identified. We examined the relative cost-effectiveness of DCD compared with donation after brain death (DBD) liver transplantation according to recipient disease severity. Methods: We constructed a Markov model comparing DCD transplantation with remaining on the waitlist until death or a DBD liver becomes available. We examined differences in life-years, quality-adjusted life-years (QALYs), and costs according to recipient disease severity measured by the Model for End-stage Liver Disease (MELD) score and for HCC patients with and without exception points. Results: For patients with a MELD <15, DCD transplantation resulted in both greater cost and reduced effectiveness. Patients with a MELD 15-20 experienced an improvement in effectiveness (+0.06 QALYs) with DCD liver transplantation, but at an incremental cost effectiveness ratio (ICER) of > $2million/QALY. Patients with MELD 21-30 and >30 also derived a QALY benefit from DCD transplantation (+0.25 and +0.83 QALYs) with ICERs of $519K/QALY and $163K/QALY, respectively. Monte Carlo simulation and sensitivity analyses demonstrated stable results for the MELD <15 and >20 patients, but there was significant uncertainty regarding the preferred strategy for patients with MELD 15-20 (Figure 1). DCD transplantation was associated with increased costs and decreased survival for HCC patients receiving exception points, but was associated with an additional +0.26 QALY and ICER of $552K/QALY for those patients not receiving exception points. Conclusions: DCD liver transplantation results in decreased survival for patients with a MELD <15 and HCC patients receiving exception points, but provides a survival benefit to patients with MELD >20 and HCC patients not receiving exception points compared with remaining on the waitlist. However, all ICERs were beyond conventional willingness-to-pay thresholds. In the current era of healthcare reform and focus on comparative effectiveness, these findings have important policy implications regarding the utilization of DCD livers.

Comentario: es bien conocido que el trasplante de donante a corazón parado es un trasplante más problemático. En esta comunicación se aportan ideas para establecer quién debería ser el receptor potencial más adecuado para un donante de estas características.

 

Paralell 17: Transplantation for HCC and Non viral Diseases

8. Incidence, Progression and Predictors of Metabolic Syndrome and Cardiovascular Outcomes Before and After Liver Transplantation L. Sauers2; J. Heimbach4; C. Fan3; R. A. Dierkhising3; E. Coss2; M. Charlton1; K. D. Watt1 1. Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, United States. 2. Internal Medicine, Mayo Clinic, Rochester, MN, United States. 3. Biostatistics, Mayo Clinic, Rochester, MN, United States. 4. Surgery, Mayo Clinic, Rochester, MN, United States.  

Our ability to predict the long-term complications of obesity, metabolic syndrome (MS), and cardiovascular disease (CVD) in the post transplant (LT) population is suboptimal. AIM: To characterize the prevalence, progression and predictors of MS and CVD post transplant. 482 adults receiving a liver transplant from 1998 to 2004 were analyzed for demographics, pre and post LT MS components, as well as pre LT echocardiogram findings, and post LT immunosuppression. CVD is defined as unstable angina, MI, CHF, cardiac arrest, CVA, or arrhythmia. RESULTS: Pre LT MS has increased annually (OR 1.29, p=0.0008, per year), but not post LT MS (p=NS). Mean body mass index (BMI) increased progressively through the first 3 years post LT (p<0.0001). Patients with BMI>30 increased from 23% at 4 months to 40% at 3 years. Pre LT BMI, a diagnosis of NAFLD or cryptogenic cirrhosis, pre LT diabetes, cyclosporine use, and tacrolimus use were significantly associated with weight gain post-transplant. Age, steroid use, insulin use, and post LT diabetes were not. Weight gain was associated with development of MS at 1 and 3 years (OR 1.1, p=0.0009 and OR 1.05 p=0.04 per BMI point). Overall, 14.4% of surviving patients had CVD within 1 year, 22.4% by 3 years, 30.1% by 5 years, and 58.0% within 8 years. BMI was not independently associated with CVD. Post-transplant diabetes at 1 year (OR 2.0, p=0.027) was associated with CVD by 1 year. Post-transplant hypertension was associated with CVD at 5 and 8 years post LT (OR 2.34, p=0.038, and OR 2.97, p=0.009, respectively). Dyslipidemia was not independently associated with CVD. Tacrolimus use was associated with lower risk of CVD at 1 year (OR 0.25, p<0.001), 3 years (OR 0.44, p=0.0015) and 5 years (OR 0.55, p=0.08). Conversely, cyclosporine use was associated with increased risk of CVD at 1 year (OR 2.72, p=0.03) and 3 years (OR 2.66, p=0.042). Steroid use was not associated with CVD. Pre-transplant left ventricular ejection fraction < 50% was predictive of CVD by 1 and 3 years (OR 9.32, p=0.018; OR 10.62, p=0.025). Pre-transplant left ventricular hypertrophy was predictive of CVD at 3 and 5 years after transplantation (OR 2.84, p=0.002; OR 2.49, p=0.007). CONCLUSION: Pre-existing MS has increased over time and is associated with post transplant MS and CVD. The degree of weight gain after transplant is influenced by immunosuppression and is strongly associated with post transplant MS. Independent of MS, immunosuppression used and pre transplant echocardiographic findings are important risk factors associated with post transplant CVD.

Comentario: el síndrome metabólico es un componente muy relacionado con la mortalidad cardiovascular post-trasplante. En este estudio es destacable el valor predictivo de la ecocardiografía pre-trasplante.

 

9. Liver Transplantation for Familial Amyloidosis; the 20-year report from the Familial Amyloidotic Polyneuropathy World Transplant Registry (FAPWTR). H. E. Wilczek2; A. J. Stangou1; O. Suhr3; M. E. Larsson2; B. Ericzon2 1. NHS Amyloid Treatment Programme, Liver Unit & Centre for Rare Diseases, Queen Elizabeth Hospital, University Hospital Birmingham, Birmingham, United Kingdom. 2. Transplantation Surgery, Center for Surgical Sciences, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.3. Department of Medicine, Umea University Hospital , Umea, Sweden.   

Liver transplantation (LT) is the only available treatment for familial amyloid polyneuropathy (FAP). The Familial Amyloid Polyneuropathy World Transplant Registry (FAPWTR), established shortly after LT was introduced as potential treatment for FAP in 1990, is a centralised service based in Karolinska Institute in Sweden for the collection, monitoring and analysis of international data on LT for FAP. We present here the long-term FAPWTR results on the 20 years anniversary of LT for FAP. Between April 1990 and January 2010, data on 1782 liver transplant procedures and regular follow-up were reported to the registry from 70 transplant centres in 18 countries. Annual international transplant activity for FAP has remained stable at 80-120 procedures since 1996. Amongst those 866 liver transplants were performed in Portugal, 216 in France, 130 in Sweden, followed by USA 79, UK 78, Brazil 77, Spain 74, Japan 65. The Mediterranean Val30Met transthyretin (TTR) mutation was identified in 83% of cases. A further 50 different variants were reported, collectively referred to as non-ValMet30, and additionally a dozen of non-TTR mutations such as Glu526Val and ApoA1 Gly26Arg. The Ser77Tyr and Thr60Ala mutations appear to be the commonest amongst non-Val30Met variants. Median age at LT was 38 years (range 21-72 years), 57% of patients were male. Median disease duration prior to transplantation was 3 years (range 0-30 years). Of patients in the Val30Met group 98% received isolated LT, while 11% of non-Val30Met cases required either simultaneous (9%) or sequential heart and liver transplant (2%). Overall 1, 3, 5, and 10 year survival after LT in the entire FAP population including all variants was 86.9%, 81.8%, 77.6% and 71%. Five-year and 10 year survival in the Val30Met group was 80.9 % and 73.4% respectively, significantly superior to 57.8 % and 43.9% in the non-Val30Met group ( p<0.001). Commonest cause of death was cardiac related events (24%), followed by sepsis (23%) or liver related complications (14%). Multivariate analysis in the entire cohort including all variants identified disease duration prior to transplantation, initial presentation with autonomic rather than peripheral neuropathy, TTR mutation, and modified body mass index (mBMI) of less than 600, indicating poor nutritional status, as significant factors influencing survival after LT (p<0.01).

Comentario: un dato relevante de este registro es la demostración de la peor supervivencia de los pacientes trasplantados con variantes no-Val30Met.

 

Paralell 27: Viral Hepatitis and Transplantation

10. Sirolimus-based immunosuppression is associated with improved sustained virologic response(SVR) to antiviral treatment for patients with recurrent hepatitis C (HCV)infection post-liver transplant(LT). S. Asthana1; K. W. Burak2; J. Bailey2; R. P. Myers2; G. Meeberg1; A. L. Mason3; V. G. Bain3; N. M. Kneteman1 1. Transplantation Surgery, University of Alberta Hospital, Edmonton, AB, Canada. 2. Hepatology, Southern Alberta Liver Transplant Clinic, Calgary, AB, Canada. 3. Hepatology, University of Alberta Hospital, Edmonton, AB, Canada.

The impact of calcineurin inhibitor (CNI) immunosuppression (IS) on success of anti-HCV therapy post-LT has been studied,but data on the impact of sirolimus (SRL) is lacking. This study assessed the impact of SRL on antiviral response rates post-LT and determined the effect of SVR on patient survival. Methods: This intention-to-treat analysis included patients with biopsy-proven recurrent HCV post-LT, who commenced anti-HCV therapy(Peg IFN+ribavirin) between July 2002-Dec 2010.SRL was considered to be the primary IS for patients on both SRL and CNI at the time of HCV therapy. Results: Of 100 patients (81% men,72% genotype 1),36 were unable to complete treatment.Forty patients were on SRL IS, 35 on tacrolimus, 24 on cyclosporine (1=MMF alone). More patients with previous rejection (ACR) discontinued treatment prematurely (46% vs.72% of ACR patients, p=0.03). SVR was achieved in 47% of patients-60% on SRL vs. 43% on tacrolimus & 29% on cyclosporine. SRL IS [OR 2.41 (95%CI1.1-5.5)], female sex [OR 2.99(95%CI1.-8.7)] and non-genotype 1 infection [OR2.67(95%CI 1.1-6.7)] impacted SVR.On multivariate analysis, only non-genotype 1 infection significantly influenced SVR [OR 2.66 (95% CI 1.1-6.6); p=0.034]. However, on per protocol analysis of patients who completed treatment (n=64), SRL-based IS was the only factor that affected SVR [OR 4.6 (95%CI1.3-16); p=0.02]. At a median follow-up period of 77.6 months (IQR39.9-115.5), patients with SVR had significantly improved survival than non-SVR(p=0.03)[Fig-1].SRL IS did not impact patient survival[HR 1.74(95% CI (0.7-4.3);p=0.2].  Conclusion: SRL IS is associated with significantly higher SVR rates following antiviral therapy for recurrent HCV post-LT. Achieving SVR was associated with improved post-treatment survival.

Comentario: aunque el número de enfermos es limitado y el estudio plantea dudas sobre el grado de control de las covariables sí es una evidencia más de la ausencia de un efecto perjudicial de los mTOR sobre la replicación viral y la recurrencia post-trasplante.

 

Poster Session ( Abstractsform 517-699).

De las 182 comunicaciones presentadas en la sesión de poster,19 han conseguido una presidential distinction. En las siguientes líneas se destacan algunas de las de mayor interés.

517. Liver Resection For Hepatocellular Carcinoma: A Western Series of 313 Patients M. Kluger; J. Salceda; A. Laurent; C. Tayar; C. Duvoux; T. Decaens; A. Luciani; J. Tran Van Nhieu; D. Azoulay; D. Cherqui

Comentario: una amplia serie donde se muestra una experiencia occidental en resección hepática. Se destaca que la recurrencia tumoral se relaciona, tal y como se ha descrito anteriormente, no sólo con el tamaño sino con la biología tumoral

 518. Greater Degree of Met-Enkephalin Immunohistochemical Staining Expression is Found in Patients with More Severe Recurrent Hepatitis C Post Liver Transplantation J. D. Fender; T. D. Schiano; M. J. Sanchez; N. V. Bergasa; M. Fiel

Comentario: una interesante aportación  del valor potencial que los receptores opioides pueden tener en la replicación viral y en la recurrencia de la hepatitis C post-trasplante

548. Evaluation of diagnostic performance of non invasive biomarkers, scores and transient elastography for the assessment of liver fibrosis after liver transplantation. A. Pissaia Junior; D. Samuel; C. Duvoux; P. Bernard; L. Quinquis; O. Chazouilleres; B. Terris; Y. Calmus; S. Grabar; F. Conti

Comentario: esta comunicación pone de manifiesto la baja exactitud diagnóstica de los marcadores no invasivos de fibrosis en el post-trasplante y propone la combinación de varios métodos ( elastografía + marcadores) para una valoración mas objetiva

 549. Acute Tubular Necrosis is Present in the Majority of Patients Undergoing Liver Transplantation. S. K. Asrani; W. Kim; J. Heimbach; C. B. Rosen; M. M. Berndt; R. H. Wiesner; B. Kim; Z. El-Zoghby; N. Leung; J. P. Grande

Comentario: un elevado porcentaje de pacientes llega al trasplante con datos histológicos de necrosis tubular aguda. El número de enfermos incluidos en el estudio es escaso (25); aunque los resultados no son del todo inesperados estaría justificado realizar estudios más amplios.

551. The Framingham Risk Score is Strongly Associated with Cardiovascular Events After Liver Transplantation A. Chaney; M. Heckman; C. Thomas; M. Herman; S. Pungpapong; A. Keaveny

Comentario: los componentes del Framinghan Risk Score son edad, sexo, colesterol total, TA sistólica, hábito tabáquico y tratamiento de la HTA. Este score también se correlaciona estrechamente con el índice de eventos cardiovasculares en el enfermo post-trasplante.

552. Preformed donor-specific HLA alloantibodies predict early allograft rejection in ABO-compatible liver transplant recipients C. Pigott; R. Agni; A. Powell; G. E. Leverson; D. F. Lorentzen; A. M. D’Alessandro; M. R. Lucey; A. Musat

Comentario: una interesante aportacion por la cual se establece una relación entre anticuerpos preformados y el desarrollo de rechazo celular agudo.

553. Emergence of YMDD lamivudine resistance after transplantation of anti-HBc positive donor livers into anti-HBc negative recipients using lamivudine monotherapy prophylaxis. H. E. Bohorquez ; A. J. Cohen; I. C. Carmody; D. S. Bruce; S. Joshi; B. B. Borg; N. Girgrah; G. E. Loss V

Comentario: el tratamiento con lamivudina es altamente efectivo en los enfermos que reciben un hígado anti-core positivo. Se destaca la potencial aparición de  cepas lamivudin resistentes, probablemente en relación con una baja replicación viral no detectable.

554. De Novo Malignancies after Liver Transplantation: A Single Center Population Controlled Study H. Chatrath; K. Berman; R. Vuppalanchi; H. Yoo; M. A. Lacerda; R. Vinayek; S. Liangpunsakul; N. P. Chalasani; R. S. Mangus; R. Vianna; J. A. Fridell; P. Y. Kwo; A. Tector; M. Ghabril.

Comentario: interesante estudio donde se describe una mayor incidencia medida por SIR (ratio de incidencia estandarizada) de tumores cutáneos (SIR: 5.80), tumores sólidos ( SIR: 2.65) y neoplasias hematológicas (SIR: 5.80) en pacientes sometidos a trasplante.

556. Diagnostic Algorithm to improve the differentiation between Rejection (ACR) and Recurrent Hepatitis C(RH) after Liver transplantation. J. de la Peña; Tome S; F. Gude; J. Pons; M. Miras; P. Ramirez; J. Bermejo; E. Varo; J. Forteza; P. Parrilla View Presentation

Comentario: se presenta un algoritmo que considera fundamentalmente la variable tiempo desde el trasplante en combinación con determinados parámetros anatomopatológicos para facilitar el diagnóstico diferencial entre hepatitis recurrente y rechazo

651. Time-course of apoptosis in liver transplantation: a study based on serum keratin concentrations A. Gonzalez-Quintela; J. Loureiro; L. Vizcaino; I. Abdulkader; E. Varo; Tome. S.

Comentario: comunicación que estudia el valor de la monitorización de las keratinas séricas  medidas por TPS y M30 con el objeto de valorar necrosis y apoptosis. También se indica el potencial valor que estos marcadores puedan tener en la diferenciación entre rechazo y hepatitis recurrente.

 652. Liver resection for hepatocellular carcinoma: a multicenter evaluation of the AASLD and EASL guidelines recommendation. M. F. Silva; G. Sapisochin; S. I. Strasser; S. Hewa-Geeganage; J. Chen; A. J. Wigg; R. S. Alencar; R. M. Jones; L. Kikuchi; F. J. Carrilho; P. R. Fontes; R. Charco

Comentario: esta comunicación confirma las recomendaciones de la AASLD y de la EASL con respecto a la supervivencia de los hepatocarcinomas sometidos a resección en pacientes con buena función hepática y sin HTP. Este estudio multicéntrico demuestra que la supervivencia en este subgrupo de pacientes sometidos a resección es similar a la de los pacientes trasplantados.

 

Santiago Tomé

Unidad de Hepatología

Complejo Hospitalario Universitario de Santiago

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