Hepatic Distribution Criteria: MELD/PELD CIT Regionalization  Buenos Aires, November 29, 2011  Liver Transplantation: Towa...
Current Status of Liver Transplantation <ul><li>Increased patient´s access to the procedure  </li></ul><ul><li>Expansion o...
Liver Transplantation in Argentina MELD 1.4 2.2 204 290 648 289 40% 123%
Disproportion between the number of candidates listed and the number of available donors <ul><li>Decreased applicability o...
¿How can we increase applicability of OLT? <ul><li>Optimize organ procurement </li></ul><ul><li>Maximize the utilization o...
¿How can we decrease waitlist mortality? Organ allocation policy Severity of liver disease is the major determinant of wai...
Liver Allocation Policy Based on CTP Before 2000 there were only 3 categories of disease severity for patients with CLD <u...
Liver Allocation Policy Based on MELD In 2000 the US Department of Health and Human Services adopted the Final Rule Distri...
Liver Allocation in Argentina  Argentina was the first country after the US to adopt the MELD/PELD allocation model in Jul...
2 2 3 9 18 Centers  (21 Programs) 1 1 <ul><li>Adults: 7 </li></ul><ul><li>Children: 4 </li></ul><ul><li>Both: 7 </li></ul>...
MELD Exceptions in Adults HCC HPS FAP T2 (Milan Criteria) PaO 2  <60 mmHg breathing air Motor impairment  Visceral neuropa...
MELD Score  Model for End-Stage Liver Disease 9.57 x log e   creatinine  (mg/dL) + 3.78 x log e   bilirubin  (mg/dL) + 11....
¿To Child or to MELD?  Model design Validation  Objectivity Reproducibility  Discriminatory ability Calculation + + + +  +...
Four cirrhotics with encephalopathy and severe ascites (6 points) and creatinine of 1 mg/dL Discriminatory Ability of CTP ...
 Wiesner R et al 2003 6 8 12 14 MELD and CTP at the Time of Listing 60 50 40 30 20 10 0 CTP Score MELD          ...
Kamath PS and Kim WR (2007) Efficacy of MELD to Predict Survival <ul><li>NASH-related cirrhosis </li></ul><ul><li>HCV-cirr...
MELD and Mortality on the Waiting List 3437 adults added to the list in the US at 2A or 2B Status between 11/99 and 12/01 ...
Three-Month Waitlist Mortality According to  MELD  at Listing in Argentina 1406 patients C-statistic: 0.89 (p<0.001) % Ruf...
The Survival Benefit of OLT 12996 adults listed between 2001 and 2003 Direct organs to those more likely to benefit from O...
No allocation system and no prognostic score is perfect Around 20% of cirrhotics with severe ascites or recurrent encephal...
Can the MELD score be improved? Do complications of portal hypertension increase the ability of MELD to predict death? Con...
Waitlist Mortality in Patients With or Without Hyponatremia MELD Score % Ruf AE et al (2005)
Addition of Serum Sodium Into the MELD Score **p<0.05 vs. MELD Ruf AE et al (2005) <0.001 0.908** MELD + serum sodium <0.0...
Efficacy of MELD-Na vs. MELD to Predict Mortality - <0.001 0.883 0.868 7171 Biggins 23.8 0.69 0.88 0.86 753 Biggins - 7.8 ...
Is MELD the ideal score to allocate donor livers? No…. but is the best we have The Challenge for the Future <ul><li>Adding...
Thank you
<ul><li>Estratificar a los pacientes de acuerdo a la severidad de la cirrosis y al riesgo de muerte </li></ul><ul><li>Adju...
Algunas Ventajas del MELD <ul><li>Fue el primer paso en el diseño de políticas de distribución de órganos basadas en la ev...
Algunas Desventajas del MELD <ul><li>No es buen predictor del riesgo de muerte en alrededor del 20% de los pacientes </li>...
El Desafío para el Futuro <ul><li>Agregar otras variables objetivas a la fórmula </li></ul><ul><li>Reevaluar los coeficien...
Malinchoc et al, Hepatology 2000 Survival (%) Years post-TIPS 100 80 60 40 20 0.5 1.0 1.5 2.0 High risk (RS >1.8)  Low ris...
MELD Parameters at Time of Listing in Patients who Survived or Died While on the Waiting List Wiesner R et al (2003) Bilir...
% Mortalidad a los Tres Meses en Lista de Acuerdo al MELD  Argentina (Fundación Favaloro)
Impacto de la Utilización de Distintas Tromboplastinas en el INR y Factor V Ruf AE y col (ILTS, 2007) 45 pacientes con cir...
INR MELD Mediana (percentilos 25-75) del  INR  y  MELD  Obtenidos con las Diferentes  Tromboplastinas  p <0.001 p <0.001 p...
Variación del Score de MELD de Acuerdo a los Valores de INR  Número de Pacientes 27 % 2 13 11 1 18 0 5 10 15 20 > 1 punto ...
Trotter J y col (2007) 5 muestras de sangre a 14 laboratorios en EEUU Variaciones del INR y MELD en Distintos Laboratorios...
Mediana (percentilos 25-75) del  of  Factor V  Obtenido con las Diferentes  Tromboplastinas  160 140 120 100 80 60 40 20 0...
Ruf AE y col (TTS 2009) Mortalidad a los Tres Meses en Pacientes con Cirrosis de Acuerdo al INR, Factor V, MELD y MELD mas...
Can the CTP score be improved? Giannini E et al (2004) Does the superiority of MELD rely solely on the inclusion of serum ...
 
Regulations for Updating MELD and PELD Scores on Waitlisted Patients Laboratory tests to be performed at the transplant ce...
MELD/PELD Exceptions Exceptions by request (INCUCAI Liver Committee) <ul><li>Hepatoblastoma </li></ul><ul><li>HCC </li></u...
Data Source Liver Transplantation in Argentina  National System of Procurement  and Transplantation Database (SINTRA) of I...
Liver Transplantation in Argentina 81 170 204 115 289 Number of DDLT  MELD
Liver Transplantation in Argentina 204 290 648 289 MELD 1.4 2.2 40% 123%
1864 patients listed  Death/Removal from WL  (19.4%) Listed Alive  (36.3%) Liver Transplantation in Argentina  Analysis of...
MELD  al Listing (2005-2008) Ruf A et al (2010) 1406 patients  MELD: 17    7  41% MELD <15
PELD  al Listing (2005-2008) 255 patients  PELD: 14    3  51% PELD <15 Ruf A et al (2010)
Death or Removal from the Waitlist Ruf A et al (2010) 361/1864  (19.4%)  listed from 2005-2008 p<0.01 p<0.01 p=NS p=NS % M...
Three-Month Waitlist Mortality According to  PELD  at Listing Ruf A et al (2010) % 255 patients C-statistic: 0.76 (p<0.001...
MELD Scores at Listing According to Outcome at 3 Months % Ruf A et al (2010) 20 19 16 15 p<0.001 n=198 n=547 n=63 n=598 MELD
Liver Transplantation in Argentina  Ruf A et al (2010) % n=547 LDLT DDLT Males Females n=826 Emer-gency MELD/PELD Emer-gen...
Liver Transplantation in Argentina  Ruf A et al (2010) 826 liver transplants p<0.01 p<0.01 % n=547 n=142 n=581 n=139 MELD ...
MELD Scores at the Time of OLT (2010) 223 patients  % MELD Score 78.5% MELD >20
1623 patients listed from 2005-2009 MELD Exceptions in Adults 234  (15%)  requests for supplemental points McCormack L et ...
1623 patients listed from 2005-2009 MELD Exceptions in Adults 234  (15%)  requests for supplemental points McCormack L et ...
Split Liver Transplantation <ul><li>Left lobe: 70  </li></ul><ul><li>Right lobe: 60 </li></ul>130 recipients of a partial ...
Accuracy of MELD and CTP to Assess 3-Month Mortality on the Waiting List Wiesner R et al (2003) p<0.001 Concordance
Liver Allocation Policy Based on MELD In 2000 the US Department of Health and Human Services adopted the Final Rule Distri...
Prognosis of Decompensated Cirrhosis Low risk of death It would be more useful to look at predictors of decompensation rat...
Predictors of Clinical Decompensation in Patients with Compensated Cirrhosis Ripoll C et al (2007) Ascites (22%) Encephalo...
Predictors of Clinical Decompensation in Patients with Compensated Cirrhosis Ripoll C et al (2007) Multivariate Analysis (...
Development of Complications of Cirrhosis in Patients with NASH or Hepatitis C Sanyal AJ et al (2006) 152 patients with NA...
Can the CTP score be improved? Giannini E et al (2004) Does the superiority of MELD rely solely on the inclusion of serum ...
MELD-Na:   Prediction Model Kim WR et al (2008) 6769 adults with cirrhosis listed in the US in 2005 of which 31% had hypon...
MELD-Na:   Validation Kim WR et al (2008) 7171 adults with cirrhosis listed in the US in 2005 of which 2159 underwent OLT ...
Is MELD the best prognostic score? <ul><li>In the transplant setting MELD is superior to CTP to: </li></ul><ul><ul><li>Ran...
 
Mortalidad en Lista de Espera en Pacientes con y sin Hiponatremia Categoría de MELD  % Ruf AE et al (2005)
Prevalencia de Hiponatremia y de Elevación de la Creatinina de Acuerdo al MELD
Eficacia Pronóstica del MELD y Sodio Sérico (Muerte a los 3 meses) p<0.05 vs. MELD <0.001 0.908** MELD + sodio sérico <0.0...
El Beneficio de Incorporar el Sodio Sérico a la Fórmula del MELD <0.001 0.88 0.87 7171 Biggins 23.8 0.69 0.88 0.86 753 Big...
MELD <ul><li>A pesar que la protrombina expresada como INR es menos tromboplastina-dependiente que en segundos, el uso de ...
MELDSTJ  MELDMODJ  MELDENZ  MELDCOMJ   BIL< 5.9  mg/dL MELD difference 0 to  3 points   MELDSTJ  MELDMODJ  MELDENZ  MELDCO...
¿Cómo compensar en los niños la “desventaja” del menor PELD?  <ul><li>M ayor sobrevida del PELD sobre el MELD </li></ul>ME...
Validación del MELD y del Child Kamath y col (2001); Wiesner R y col (2003) El Child nunca fue validado prospectivamente p...
<ul><li>Los receptores pediátricos tienen prioridad  en  los donantes pediátricos </li></ul><ul><li>Situaciones  donde l o...
Key Questions How severe is my cirrhosis? What problems will I encounter in the near future? How will my life expectancy b...
The Most Practical Classification of Cirrhosis Liver insufficiency Complications of portal hypertension <ul><li>Ascites </...
The Benefits of Using Prognostic Indexes No prognostic score will entirely replace good clinical judgment and common sense...
To Child or to MELD?  An Ongoing Debate   Both scores have proponents and detractors Physicians working in transplantation...
To Child or to MELD?   Model Design <ul><li>Variables and cut-off values selected empirically </li></ul><ul><li>Each varia...
To Child or to MELD?   Objectivity <ul><li>Includes 2 very subjective variables such as ascites and encephalopathy: </li><...
To Child or to MELD?   Reproducibility <ul><li>Severity of ascites and encephalopathy relies on clinical judgment and lack...
To Child or to MELD?   Reproducibility <ul><li>Although prothrombin time expressed as INR is less thromboplastin-dependent...
To Child or to MELD?   Discriminatory Ability <ul><li>Narrow range of disease severity: 3 classes and 10 levels of differe...
To Child or to MELD?   Discriminatory Ability Four patients with decompensated cirrhosis and with severe ascites and encep...
To Child or to MELD?   Calculation <ul><li>Easy to calculate </li></ul><ul><li>Most physicians clearly understand the diff...
Prognostic Indicators of Survival in Patients with Cirrhosis D’Amico G et al (2006) <ul><li>Analysis of all reported progn...
Prognostic Indicators of Survival in Patients with Cirrhosis D’Amico G et al (2006) <ul><li>CTP was the most consistent an...
Compensated Cirrhosis
MELD in Compensated Cirrhosis Kamath PS et al (2001) Viral Cirrhosis (n=491 PBC  (n=491 Concordance Statistic
MELD in Compensated Cirrhosis Said A et al (2004) 1611 patients with cirrhosis Compensated cohort: no ascites, VB or HE  ...
Prognosis of Decompensated Cirrhosis Low risk of death It would be more useful to look at predictors of decompensation rat...
Predictors of Clinical Decompensation in Patients with Compensated Cirrhosis Ripoll C et al (2007) Ascites (22%) Encephalo...
Predictors of Clinical Decompensation in Patients with Compensated Cirrhosis Ripoll C et al (2007) Multivariate Analysis (...
Development of Complications of Cirrhosis in Patients with NASH or Hepatitis C Sanyal AJ et al (2006) 152 patients with NA...
Liver Transplantation
Non-Transplant Patients
CTP and MELD in Non-Transplant Patients with Cirrhosis Said A et al (2004) Most studies to validate MELD have looked at pa...
CTP and MELD in Non-Transplant Patients with Cirrhosis Said A et al (2004) 1611 relatively well-compensated cirrhotics <ul...
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Federico Villamil - Argentina - Tuesday 29 - Liver Transplantation Towards New Horizons

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  • Empeorando la situación de un país en vias de desarrollo, se encuentra la centralización de los promas de tx, en nuestros país existen 21 equipos de trasplante hepático de los cuales 15 están localizados en bs as, 12 en capital y 3 en la provincia 10 equipos de adultos 7 pediátricos y 4 ambos.
  • El desarrollo del MELD marcó un importante avance en la habilidad para predecir la mortalidad en los pacientes con cirrosis hepática Basado en tres variables de laboratorio, de fácil obtención, reproducibles, cuantitativas y objetivas, su fórmula consiste en multiplicar el log natural de las variables (bili-creati-INR) a un coeficiente de regresión que expresa el peso o poder que tiene cada variable en la mortalidad. Su variante pediátrico el PELD tiene como variables la edad, el retraso en el crecimiento, Albúmina, bilirrubina, INR
  • Aunque existe una relación directa entre el valor del meld y el Child como se aprecia en esta línes, el gráfico muestra tanbien que los dos scores varían significativamente para cada valor. Por ejemplo pacientes con un score CTP 10 el meld varía entre 8 y 46
  • Utilizando un análisis de regresión de Cox se identificaron 4 variables pronósticas como predictoras de sobrevida en una población de 231 pacientes sometidos a TIPS para prevenir el resangrado o tratar Ascitis refractaria, con las cuales se diseñó un modelo llamado inicialmente Mayo TIPS Model y que luego de pequeñas modificaciones resultó el MELD. El Modelo fue validado en una población independiente de 71 pacientes sometidos a TIPS (holanda) en donde La utilización del Mayo TIPS Model permitió estratificar según el riesgo de muerte de los pacientes en dos grupos: 1- Grupo de elevado riesgo con una sobrevida media &lt; 3 meses (R&gt;1.8) 2- Grupo de bajo riesgo con una sobrevida media mayor a 3 meses (R&lt;1.8).... Para ambos grupos de pacientes la sobrevida observada y la esperada (estimada con el modelo) fueron similares P NS de (p=.88 y .41).
  • Here are the results of the first group : Median values (25-75 percentiles) and range of INR and MELD Score were obtained using 4 thromboplastins with each of in the 45 patients . You can see that the INR and MELD significantly differed (p&lt;0.001) when comparing TBP-1 vs. 2; 2 vs. 3, and 4 vs. 1, 2 and 3.
  • Here are the variations of the MELD scores in Group 1, indicating the span between the 2 most divergent INRs of each patient. Variation of 1 point of MELD occurred in 13 patients, of 2 points in 18, 3 points in 11, and 7 points in one patient. The median variation of MELD was 2 points, although in a quarter of the patients, it was equal to or greater than 3.
  • In contrast to INR, Factor V activity was similar in all groups irrespective of the thromboplastin used.
  • El Sistema Nacional de Información de Procuración y Trasplante de la República Argentina (SINTRA), es el sistema informático para la administración, gestión, fiscalización y consulta de la actividad de procuración y trasplante de órganos, tejidos y células en el ámbito nacional. Un sistema de información con escalones jurisdiccionales, regionales e integrado nacionalmente, que permite el registro en tiempo real de la actividad, la gestión de pacientes en diálisis, listas de espera y asignación de órganos y tejidos con fines de implante en nuestro país, con el fin de permitir el monitoreo y evaluación permanente, así como ofrecer a la sociedad la garantía de transparencia de la actividad Período de 3 años desde el inicio de la era MELD
  • Como se compensa la diferencia entre el valor numérico del PELD/MELD en la práctica: 1-En primer lugar por la observación de una mayor sobrevida del PELD sobre el MELD a un determinado valor numérico. Como ejemplo un paciente adulto con un MELD de 30 tiene una sobrevida del 55% a los tres meses, en cambio un PELD similar tiene una sobrevida del 85%.
  • En segundo lugar se consideró basado en evidencias claras que demostraron mejores resultados de los injertos pediátricos en receptores pediátricos darle prioridad a los receptores pediátricos en los donantes pediátricos. Por último pueden ingresar en categoría de emergencia los pacientes con enfermedades crónicas (MELD o PELD &gt;25) que presenten descompensación aguda (EPS-AR- SHR- HDA-Infecciones) estos últimos puestos en práctica en US y por definirse en argentina si previamente pasaran cada caso en particular por un “Comité Asesor de expertos Honorarios”
  • Federico Villamil - Argentina - Tuesday 29 - Liver Transplantation Towards New Horizons

    1. 1. Hepatic Distribution Criteria: MELD/PELD CIT Regionalization Buenos Aires, November 29, 2011 Liver Transplantation: Towards New Horizons 2011 Organ Donation Congress Federico G. Villamil Liver Transplantation Unit Buenos Aires British Hospital
    2. 2. Current Status of Liver Transplantation <ul><li>Increased patient´s access to the procedure </li></ul><ul><li>Expansion of indications and decrease in the number of contraindications </li></ul><ul><li>Increased number of transplant centers </li></ul>
    3. 3. Liver Transplantation in Argentina MELD 1.4 2.2 204 290 648 289 40% 123%
    4. 4. Disproportion between the number of candidates listed and the number of available donors <ul><li>Decreased applicability of OLT </li></ul><ul><li>Increased waitlist mortality </li></ul>Current Status of Liver Transplantation
    5. 5. ¿How can we increase applicability of OLT? <ul><li>Optimize organ procurement </li></ul><ul><li>Maximize the utilization of deceased donors with extended criteria </li></ul><ul><li>Split livers/domino OLT </li></ul><ul><li>Live donor liver transplantation </li></ul>Increase the number of donors
    6. 6. ¿How can we decrease waitlist mortality? Organ allocation policy Severity of liver disease is the major determinant of waitlist mortality “ The sickest first”
    7. 7. Liver Allocation Policy Based on CTP Before 2000 there were only 3 categories of disease severity for patients with CLD <ul><li>Waitlist time became an important factor as a tiebraker within each category </li></ul><ul><li>Particularly problematic for Status 2B including patients with a broad range of disease severity </li></ul> 10, ICU, <7 days to live 2A  10 2B  7 3 CTP Score Status
    8. 8. Liver Allocation Policy Based on MELD In 2000 the US Department of Health and Human Services adopted the Final Rule Distribute livers in the order of medical urgency minimizing the role of waitlist time and use of subjective variables MELD-based allocation policy
    9. 9. Liver Allocation in Argentina Argentina was the first country after the US to adopt the MELD/PELD allocation model in July, 2005 Categorical System MELD/PELD Emergency Emergency Elective Urgency A Urgency MELD PELD (<12 yrs, 2007) Urgency B Elective Elective 1988 1998 2000 12-07-2005
    10. 10. 2 2 3 9 18 Centers (21 Programs) 1 1 <ul><li>Adults: 7 </li></ul><ul><li>Children: 4 </li></ul><ul><li>Both: 7 </li></ul>Liver Transplantation in Argentina 12/18 (67%) National Single Waiting List Allocation by MELD
    11. 11. MELD Exceptions in Adults HCC HPS FAP T2 (Milan Criteria) PaO 2 <60 mmHg breathing air Motor impairment Visceral neuropathy (electrophysiologic or urodynamic studies) 20 16 One additional point every 3 months 22
    12. 12. MELD Score Model for End-Stage Liver Disease 9.57 x log e creatinine (mg/dL) + 3.78 x log e bilirubin (mg/dL) + 11.20 x log e prothrombin (INR) + 6.43 Malinchoc M et al (2000) Kamath P et al (2001) Patients undergoing TIPS (n=231)
    13. 13. ¿To Child or to MELD? Model design Validation Objectivity Reproducibility Discriminatory ability Calculation + + + + + +++ +++ +++ +++ +++ +++ ++ CTP MELD
    14. 14. Four cirrhotics with encephalopathy and severe ascites (6 points) and creatinine of 1 mg/dL Discriminatory Ability of CTP and MELD 33 15 C 3.5 30 30 15 C 3.0 20 25 15 C 2.5 10 21 15 C 2.2 4 Score Class MELD CTP INR Bil
    15. 15.  Wiesner R et al 2003 6 8 12 14 MELD and CTP at the Time of Listing 60 50 40 30 20 10 0 CTP Score MELD                                                                                                                                                                                             r=0,66 p<0.001 10 n=3437  8 46
    16. 16. Kamath PS and Kim WR (2007) Efficacy of MELD to Predict Survival <ul><li>NASH-related cirrhosis </li></ul><ul><li>HCV-cirrhosis </li></ul><ul><li>Alcoholic hepatitis </li></ul><ul><li>Chronic hepatitis B </li></ul><ul><li>Fulminant hepatitis </li></ul><ul><li>Variceal bleeding </li></ul><ul><li>Bacterial infections </li></ul><ul><li>Hepatorenal syndrome </li></ul><ul><li>ICU-bound cirrhotics </li></ul><ul><li>TIPS procedure </li></ul><ul><li>Resection for HCC </li></ul><ul><li>Cardiac surgery </li></ul><ul><li>Abdominal operations </li></ul>
    17. 17. MELD and Mortality on the Waiting List 3437 adults added to the list in the US at 2A or 2B Status between 11/99 and 12/01 Wiesner R et al (2003)  9 MELD Score % C-statistic: 0.83
    18. 18. Three-Month Waitlist Mortality According to MELD at Listing in Argentina 1406 patients C-statistic: 0.89 (p<0.001) % Ruf A et al (2010) MELD Score
    19. 19. The Survival Benefit of OLT 12996 adults listed between 2001 and 2003 Direct organs to those more likely to benefit from OLT Merion RM et al (2005) Mortality of OLT recipients compared to candidates on the list Survival Benefit Transition Point
    20. 20. No allocation system and no prognostic score is perfect Around 20% of cirrhotics with severe ascites or recurrent encephalopathy have mild synthetic dysfunction and normal creatinine and therefore are not well served by MELD Can the MELD score be improved?
    21. 21. Can the MELD score be improved? Do complications of portal hypertension increase the ability of MELD to predict death? Concordance Ascites Variceal Bleeding SBP Encephalopathy Wiesner RH et al (2001)
    22. 22. Waitlist Mortality in Patients With or Without Hyponatremia MELD Score % Ruf AE et al (2005)
    23. 23. Addition of Serum Sodium Into the MELD Score **p<0.05 vs. MELD Ruf AE et al (2005) <0.001 0.908** MELD + serum sodium <0.001 0.905** MELD + hyponatremia <0.001 0.894 MELD <0.001 0.784 Serum sodium <0.001 0.753 Hyponatremia p Concordance Variable
    24. 24. Efficacy of MELD-Na vs. MELD to Predict Mortality - <0.001 0.883 0.868 7171 Biggins 23.8 0.69 0.88 0.86 753 Biggins - 7.8 - 4.93 RR <0.001 0.85 0.62 303 Wanamaker 0.46 0.92 0.88 513 Biggins <0.05 0.79 0.69 507 Heuman <0.001 0.91 0.89 262 Ruf MELD-Na MELD p Concordance N° Author
    25. 25. Is MELD the ideal score to allocate donor livers? No…. but is the best we have The Challenge for the Future <ul><li>Adding to its formula other objective components </li></ul><ul><li>Reassessing the coefficients for each variable </li></ul><ul><li>Standardizing the methods to measure INR and serum creatinine </li></ul>To further refine the MELD model to increase its accuracy and reproducibility by:
    26. 26. Thank you
    27. 27. <ul><li>Estratificar a los pacientes de acuerdo a la severidad de la cirrosis y al riesgo de muerte </li></ul><ul><li>Adjudicar los órganos prioritariamente a los pacientes que más lo necesitan </li></ul>El MELD es superior al Child en la evaluación de candidatos a trasplante ya que permite: Hay casos en los que ningún índice mide bién la severidad de la cirrosis El MELD y el Child pueden tener similar eficacia en pacientes con cirrosis compensada o mínimamente descompensada Conclusiones
    28. 28. Algunas Ventajas del MELD <ul><li>Fue el primer paso en el diseño de políticas de distribución de órganos basadas en la evidencia (variables objetivas) </li></ul><ul><li>El incremento rápido del score indica un peor pronóstico (delta-MELD) </li></ul><ul><li>La actualización frecuente del score limita el ascenso rápido en la lista por fluctuaciones transitorias y reversibles de sus variables </li></ul>Conclusiones
    29. 29. Algunas Desventajas del MELD <ul><li>No es buen predictor del riesgo de muerte en alrededor del 20% de los pacientes </li></ul><ul><li>No “ayuda” a todos los candidatos por igual. A un mismo valor de MELD el riesgo de muerte puede no ser el mismo </li></ul><ul><li>Algunos pacientes con MELD “bajo” tienen enfermedad severa y progresiva que puede representar una contraindicación para el trasplante (desnutrición) </li></ul>Conclusiones
    30. 30. El Desafío para el Futuro <ul><li>Agregar otras variables objetivas a la fórmula </li></ul><ul><li>Reevaluar los coeficientes de cada variable </li></ul><ul><li>Estandardizar los métodos para medir el INR y la creatinina </li></ul>Mejorar el modelo MELD para incrementar su eficacia y reproducibilidad El MELD es “lo mejor que tenemos” Conclusiones
    31. 31. Malinchoc et al, Hepatology 2000 Survival (%) Years post-TIPS 100 80 60 40 20 0.5 1.0 1.5 2.0 High risk (RS >1.8) Low risk (RS <1.8) Validation of MELD in Patients Undergoing TIPS Observed survival Estimated survival n=71
    32. 32. MELD Parameters at Time of Listing in Patients who Survived or Died While on the Waiting List Wiesner R et al (2003) Bilirubin 4.2 8 12 INR 1.6 1.9 2.2 Creatinine 1.2 1.4 2 p<0.01 p<0.01 p<0.01
    33. 33. % Mortalidad a los Tres Meses en Lista de Acuerdo al MELD Argentina (Fundación Favaloro)
    34. 34. Impacto de la Utilización de Distintas Tromboplastinas en el INR y Factor V Ruf AE y col (ILTS, 2007) 45 pacientes con cirrosis avanzada en lista de espera de trasplante Todas las muestras estudiadas con las 4 TBP 2.22 Cerebro de conejo Bioppol 1.03 Placenta humana Thromborel 0.93 Recombinante humana Innovin 1.31 Cerebro de conejo Neoplastine ISI Orígen Tromboplastina
    35. 35. INR MELD Mediana (percentilos 25-75) del INR y MELD Obtenidos con las Diferentes Tromboplastinas p <0.001 p <0.001 p<0.001: TBP-1 vs. 2; TBP-2 vs. 3 and TBP-4 vs. 1, 2 and 3 TBP-1 TBP-2 TBP-3 TBP-4 5 10 15 20 25 30 35 40 TBP-1 TBP-2 TBP-3 TBP-4 p<0.001 p<0.001 0 1 2 3 4 5 6
    36. 36. Variación del Score de MELD de Acuerdo a los Valores de INR Número de Pacientes 27 % 2 13 11 1 18 0 5 10 15 20 > 1 punto en 67% (mediana: 2 puntos) Sin cambios 1 punto 2 puntos 3 puntos 7 puntos
    37. 37. Trotter J y col (2007) 5 muestras de sangre a 14 laboratorios en EEUU Variaciones del INR y MELD en Distintos Laboratorios La variabilidad del INR fue mayor en pacientes con coagulopatía severa e INR elevado (p=0.017) 16-25 (9) 2.4-5.1 Muestra 5 14-21 (7) 1.9-3.7 Muestra 4 12-20 (8) 1.7-3.4 Muestra 3 10-17 (7) 1.4-2.5 Muestra 2 8-14 (6) 1.2-2.0 Muestra 1 Rango de MELD Rango de INR
    38. 38. Mediana (percentilos 25-75) del of Factor V Obtenido con las Diferentes Tromboplastinas 160 140 120 100 80 60 40 20 0 TBP-1 TBP-2 TBP-3 TBP-4 59 56 62 64 p=NS
    39. 39. Ruf AE y col (TTS 2009) Mortalidad a los Tres Meses en Pacientes con Cirrosis de Acuerdo al INR, Factor V, MELD y MELD mas Factor V <0.001 0.92 MELD + V <0.001 0.76 Factor V <0.001 0.92 MELD-V <0.001 0.92 MELD <0.001 0.86 INR Valor de p C-statistic Marcador
    40. 40. Can the CTP score be improved? Giannini E et al (2004) Does the superiority of MELD rely solely on the inclusion of serum creatinine? 145 patients with cirrhosis a p=0.04 vs. CTP b p=0.01 vs. CTP and 0.04 vs. CTP-Creatinine 0.90-0.98 0.95 b MELD 0.77-0.89 0.83 a CTP-Creatinine 0.68-0.82 0.76 CTP 95% CI Concordance Variable
    41. 42. Regulations for Updating MELD and PELD Scores on Waitlisted Patients Laboratory tests to be performed at the transplant center <30days 12 months MELD/PELD ≤10 <14 days 3 months MELD/PELD 14-11 <7 days 30 days MELD/PELD 15-19 <48 hours 7 days MELD/PELD >20 Date of Labs Interval to Update Category
    42. 43. MELD/PELD Exceptions Exceptions by request (INCUCAI Liver Committee) <ul><li>Hepatoblastoma </li></ul><ul><li>HCC </li></ul><ul><li>HPS </li></ul><ul><li>CLD-ICU </li></ul><ul><li>Metabolic </li></ul><ul><li>HCC </li></ul><ul><li>HPS </li></ul><ul><li>FAP </li></ul>Children Adults
    43. 44. Data Source Liver Transplantation in Argentina National System of Procurement and Transplantation Database (SINTRA) of INCUCAI Data of the pre-MELD period (1988-2005) is not available for comparison (no electronic registry)
    44. 45. Liver Transplantation in Argentina 81 170 204 115 289 Number of DDLT MELD
    45. 46. Liver Transplantation in Argentina 204 290 648 289 MELD 1.4 2.2 40% 123%
    46. 47. 1864 patients listed Death/Removal from WL (19.4%) Listed Alive (36.3%) Liver Transplantation in Argentina Analysis of the INCUCAI database (SINTRA) from July, 2005 to July, 2008 Ruf A et al (2010) 361 826 677 Transplanted (44.3%)
    47. 48. MELD al Listing (2005-2008) Ruf A et al (2010) 1406 patients MELD: 17  7 41% MELD <15
    48. 49. PELD al Listing (2005-2008) 255 patients PELD: 14  3 51% PELD <15 Ruf A et al (2010)
    49. 50. Death or Removal from the Waitlist Ruf A et al (2010) 361/1864 (19.4%) listed from 2005-2008 p<0.01 p<0.01 p=NS p=NS % MELD/PELD Emer-gency PNF/ HAT FHF Excep-tions MELD/PELD PELD MELD
    50. 51. Three-Month Waitlist Mortality According to PELD at Listing Ruf A et al (2010) % 255 patients C-statistic: 0.76 (p<0.001) PELD Score
    51. 52. MELD Scores at Listing According to Outcome at 3 Months % Ruf A et al (2010) 20 19 16 15 p<0.001 n=198 n=547 n=63 n=598 MELD
    52. 53. Liver Transplantation in Argentina Ruf A et al (2010) % n=547 LDLT DDLT Males Females n=826 Emer-gency MELD/PELD Emer-gency MELD/PELD
    53. 54. Liver Transplantation in Argentina Ruf A et al (2010) 826 liver transplants p<0.01 p<0.01 % n=547 n=142 n=581 n=139 MELD PELD MELD/PELD Excep-tions LDLT 14 (2.6%) 63 (44%)
    54. 55. MELD Scores at the Time of OLT (2010) 223 patients % MELD Score 78.5% MELD >20
    55. 56. 1623 patients listed from 2005-2009 MELD Exceptions in Adults 234 (15%) requests for supplemental points McCormack L et al (2010) 141 requests (60%) approved Other (16%) HPS (4%) FAP (1%) HCC (79%) 22 2 6 111 Died/Removed from WL (13%) 14 OLT (85%) Listed (2%) 94 2
    56. 57. 1623 patients listed from 2005-2009 MELD Exceptions in Adults 234 (15%) requests for supplemental points McCormack L et al (2010) Explant Analysis (n=94) <ul><li>No HCC: 20 (22%) </li></ul><ul><li>HCC-T2: 41 (44%) </li></ul><ul><li>HCC-T1: 9 (10%) </li></ul><ul><li>HCC-T3: 23 (24%) </li></ul>141 requests (60%) approved Other (16%) HPS (4%) FAP (1%) HCC (79%) 22 2 6 111 Died/Removed from WL (13%) 14 OLT (85%) Listed (2%) 94 2
    57. 58. Split Liver Transplantation <ul><li>Left lobe: 70 </li></ul><ul><li>Right lobe: 60 </li></ul>130 recipients of a partial graft Number
    58. 59. Accuracy of MELD and CTP to Assess 3-Month Mortality on the Waiting List Wiesner R et al (2003) p<0.001 Concordance
    59. 60. Liver Allocation Policy Based on MELD In 2000 the US Department of Health and Human Services adopted the Final Rule Distribute livers in the order of medical urgency (MELD) minimizing the role of waitlist time and use of subjective variables <ul><li>Decrease in the number of newly listed patients (12% in 2002) </li></ul><ul><li>Higher transplant rates </li></ul><ul><li>Reduction in waitlist mortality (from 2046 in 2001 to 1364 in 2005) </li></ul><ul><li>Higher rate of combined liver-kidney transplants </li></ul>
    60. 61. Prognosis of Decompensated Cirrhosis Low risk of death It would be more useful to look at predictors of decompensation rather than at predictors of death
    61. 62. Predictors of Clinical Decompensation in Patients with Compensated Cirrhosis Ripoll C et al (2007) Ascites (22%) Encephalopathy (8%) Variceal bleeding (3%) Median follow-up of 51 months 213 patients with compensated cirrhosis 62% HCV-positive, 24% ALD HVPG  6 mmHg (no esophageal varices) Median MELD of 8 (7-10) Median CTP of 5 (88% Class A) Decompensation in 62 patients (29%)
    62. 63. Predictors of Clinical Decompensation in Patients with Compensated Cirrhosis Ripoll C et al (2007) Multivariate Analysis (several models to avoid colinearity and overfitting) CTP score was not an independent predictor of decompensation <0.0001 0.22-0.62 0.37 Albumin 0.014 1.03-1.29 1.75 MELD 0.001 1.05-1.17 1.11 HVPG p Value 95% CI HR Variable
    63. 64. Development of Complications of Cirrhosis in Patients with NASH or Hepatitis C Sanyal AJ et al (2006) 152 patients with NASH and 150 with hepatitis C No ascites (n=198) Ascites (n=54, 27%) No EV (n=153) No HE (n=258) EV (n=45, 29%) HE (n=41,16%) <ul><li>MELD </li></ul><ul><li>HE </li></ul><ul><li>MELD </li></ul><ul><li>Platelets </li></ul><ul><li>MELD </li></ul>PREDICTORS
    64. 65. Can the CTP score be improved? Giannini E et al (2004) Does the superiority of MELD rely solely on the inclusion of serum creatinine? 145 patients with cirrhosis Mean Mean to mean + 1SD > Mean + 1SD >1.8 1.2-1.8  1.1 Creatinine <40% 70-40% >70% Prothrombin <3.0 3.0-3.5 >3.5 Albumin >3.0 2.0-3.0 <2.0 Bilirubin Grade III-IV Grade I-II None Encephalopathy Tense Mild/Mod Absent Ascites 3 2 1 Variable
    65. 66. MELD-Na: Prediction Model Kim WR et al (2008) 6769 adults with cirrhosis listed in the US in 2005 of which 31% had hyponatremia (<135 mmol/L) HR for death was 1.21 per MELD point (p<0.001) and 1.05 per 1-unit decrease in sodium (p<0.001) The effect of sodium was greater in patients with low MELD scores Multivariate Cox Regression Analysis MELD – Na – [0.025 x MELD x (140 – Na)] + 140 Formula of MELD-Na
    66. 67. MELD-Na: Validation Kim WR et al (2008) 7171 adults with cirrhosis listed in the US in 2005 of which 2159 underwent OLT and 477 (7%) died If the MELD-Na had been used, 7% of the 477 deaths (n=32) might have been prevented 477 66 159 189 58 5 Total 66 66 40 116 116 30-39 165 43 (26%) 122 20-29 121 67 (55%) 54 10-19 9 4 (44%) 5 <10 40 30-39 20-29 10-19 <10 Total MELD-Na MELD
    67. 68. Is MELD the best prognostic score? <ul><li>In the transplant setting MELD is superior to CTP to: </li></ul><ul><ul><li>Rank patients according to disease severity and risk of death </li></ul></ul><ul><ul><li>To preferentially allocate organs to those in more urgent need </li></ul></ul><ul><li>In non-transplant patients with compensated or mildly decompensated cirrhosis MELD and CTP may provide equal prognostic information </li></ul>Both MELD and CTP may be unsatisfactory in certain patient populations Probably yes, but it is not perfect
    68. 70. Mortalidad en Lista de Espera en Pacientes con y sin Hiponatremia Categoría de MELD % Ruf AE et al (2005)
    69. 71. Prevalencia de Hiponatremia y de Elevación de la Creatinina de Acuerdo al MELD
    70. 72. Eficacia Pronóstica del MELD y Sodio Sérico (Muerte a los 3 meses) p<0.05 vs. MELD <0.001 0.908** MELD + sodio sérico <0.001 0.905** MELD + hiponatremia <0.001 0.894 MELD <0.001 0.784 Sodio sérico <0.001 0.753 Hiponatremia p C-statistic Parámetro
    71. 73. El Beneficio de Incorporar el Sodio Sérico a la Fórmula del MELD <0.001 0.88 0.87 7171 Biggins 23.8 0.69 0.88 0.86 753 Biggins 7.8 4.93 RR <0.001 0.85 0.62 303 Wanamaker 0.46 0.92 0.88 513 Biggins <0.05 0.79 0.69 507 Heuman <0.001 0.91 0.89 262 Ruf MELD-Na MELD p Concordancia N° Autor
    72. 74. MELD <ul><li>A pesar que la protrombina expresada como INR es menos tromboplastina-dependiente que en segundos, el uso de diferentes reactivos también se asocia a variaciones significativas del INR y del MELD </li></ul><ul><li>En pacientes con marcada elevación de la bilirrubina la creatinina puede variar de acuerdo al método utilizado para su dosaje (es preferible el enzimático al colorimétrico) </li></ul>¿Child o MELD? Reproducibilidad
    73. 75. MELDSTJ MELDMODJ MELDENZ MELDCOMJ BIL< 5.9 mg/dL MELD difference 0 to 3 points MELDSTJ MELDMODJ MELDENZ MELDCOMJ MELDSTJ MELDMODJ MELDENZ MELDCOMJ BIL: 11.7-23.4 mg/dL MELD difference 0 to 5 points MELDSTJ MELDMODJ MELDENZ MELDCOMJ BIL ≥ 23.4 mg/dL MELD difference 0 to 7 points Variaciones del MELD de Acuerdo a la Bilirrubina y Creatinina (Método) p=0.14 p<0.05 p<0.05 BIL: 5.9-11.7 mg/dL MELD difference 0 to 4 points p<0.05
    74. 76. ¿Cómo compensar en los niños la “desventaja” del menor PELD? <ul><li>M ayor sobrevida del PELD sobre el MELD </li></ul>MELD/PELD Freeman y col (2004) Sobrevida a 3 meses (%) MELD PELD 85% 55% 100 20 40 60 80 0 -20 -10 0 10 20 30 40 50 60 70
    75. 77. Validación del MELD y del Child Kamath y col (2001); Wiesner R y col (2003) El Child nunca fue validado prospectivamente para estimar la sobrevida en pacientes con cirrosis avanzada o candidatos a trasplante 0.83 3437 Lista de espera (UNOS) 0.84 1179 Grupo heterogéneo (no TH) 0.80 326 CBP (ambulatorios) 0.80 491 No colestática (ambulatorios) 0.87 282 Avanzada (hospitalizados) C-statistic Nº Tipo y Severidad de Cirrosis
    76. 78. <ul><li>Los receptores pediátricos tienen prioridad en los donantes pediátricos </li></ul><ul><li>Situaciones donde l os candidatos  18 años con una enfermedad crónica (PELD >25) pueden categorizar para emergencia: </li></ul>¿Cómo compensar en los niños la “desventaja” del menor PELD? <ul><li>Hemorragia digestiva incontrolable </li></ul><ul><li>Ascitis refractaria o síndrome hepatorenal </li></ul><ul><li>Sepsis de orígen biliar que requiera inotrópicos </li></ul><ul><li>Encefalopatía hepática grado III-IV </li></ul><ul><li>Asistencia respiratoria mecánica </li></ul>
    77. 79. Key Questions How severe is my cirrhosis? What problems will I encounter in the near future? How will my life expectancy be affected? Will I require a liver transplant soon? Cirrhosis is an heterogeneous disease
    78. 80. The Most Practical Classification of Cirrhosis Liver insufficiency Complications of portal hypertension <ul><li>Ascites </li></ul><ul><ul><li>SBP, HRS </li></ul></ul><ul><li>Variceal bleeding </li></ul><ul><li>Encephalopathy </li></ul>Slow deterioration? Rapid decline? Compensated Decompensated 5-7% per year
    79. 81. The Benefits of Using Prognostic Indexes No prognostic score will entirely replace good clinical judgment and common sense for individual decision making Use of objective prognostic scores is essential for the design of good clinical trials or to prioritize organ allocation to the sickest patient listed for transplantation At the Bed Side At a Population Level
    80. 82. To Child or to MELD? An Ongoing Debate Both scores have proponents and detractors Physicians working in transplantation believe that patients are better served by MELD In the non-transplant setting many still prefer the more familiar and friendly CTP What are the benefits and limitations of CTP and MELD scores? <ul><li>I work in transplantation </li></ul><ul><li>I do like MELD </li></ul>Disclosure
    81. 83. To Child or to MELD? Model Design <ul><li>Variables and cut-off values selected empirically </li></ul><ul><li>Each variable given the same weight </li></ul><ul><li>Both albumin and PT measure liver dysfunction  overweight their impact on the final score </li></ul>CTP MELD <ul><li>Variables found to be statistically significant predictors of death in a multivariate Cox model </li></ul><ul><li>Bilirubin, INR and creatinine were appropriately weighted and expressed in log to avoid the impact of extreme values on the final score </li></ul>MELD has been more rigorously validated
    82. 84. To Child or to MELD? Objectivity <ul><li>Includes 2 very subjective variables such as ascites and encephalopathy: </li></ul><ul><ul><li>Rely heavily on physical exam for diagnosis and grading </li></ul></ul><ul><ul><li>Difficult to standardize </li></ul></ul><ul><ul><li>Subject to inter-observer variations </li></ul></ul>CTP MELD <ul><li>Mathematical formula based on 3 simple, objective and widely available laboratory tests, thus excluding the influence of individual judgments </li></ul><ul><li>Incorporates serum creatinine, a validated predictor of death in patients with cirrhosis </li></ul>
    83. 85. To Child or to MELD? Reproducibility <ul><li>Severity of ascites and encephalopathy relies on clinical judgment and lacks reproducibility: </li></ul><ul><ul><li>How much ascites is moderate ascites? </li></ul></ul><ul><ul><li>Does sleep reversal or personality changes constitute established encephalopathy? </li></ul></ul><ul><li>Albumin levels are influenced by nutritional status and transvascular escape (ascites, sepsis) and may vary when using electrophoresis or the colorimetric method </li></ul><ul><li>PT in seconds is highly thromboplastin-dependent and is not routinely employed in most centers </li></ul>CTP
    84. 86. To Child or to MELD? Reproducibility <ul><li>Although prothrombin time expressed as INR is less thromboplastin-dependent, use of different reagents is associated with significant variations of INR and MELD </li></ul><ul><li>In patients with high bilirubin values serum creatinine and MELD may vary significantly when using the colorimetric or enzymatic method (preferable) </li></ul>MELD
    85. 87. To Child or to MELD? Discriminatory Ability <ul><li>Narrow range of disease severity: 3 classes and 10 levels of difference between the least sick (5 points) and the most sick (15 points) </li></ul><ul><li>Maximum of 3 points per component, a value that remains fixed above the defined threshold </li></ul><ul><li>Continuous system with no floor or ceiling effects. The score progressively increases with worsening of the 3 variables </li></ul><ul><li>Patients allocated to 35 disease severity categories (6 to 40 points) </li></ul>CTP MELD
    86. 88. To Child or to MELD? Discriminatory Ability Four patients with decompensated cirrhosis and with severe ascites and encephalopathy, as defined by CTP, and creatinine levels of 1 mg/dL 33 15 C 3.5 30 30 15 C 3.0 20 25 15 C 2.5 10 21 15 C 2.2 4 Score Class MELD CTP INR Bil
    87. 89. To Child or to MELD? Calculation <ul><li>Easy to calculate </li></ul><ul><li>Most physicians clearly understand the difference between CTP classes A, B and C </li></ul>CTP MELD <ul><li>Mathematical model and is thus less user-friendly </li></ul><ul><li>Requires computation or access to internet </li></ul>Today, in the era of handheld computers and web access through mobile phones, this issue is much less relevant
    88. 90. Prognostic Indicators of Survival in Patients with Cirrhosis D’Amico G et al (2006) <ul><li>Analysis of all reported prognostic studies of cirrhosis (815 references) </li></ul><ul><li>Criteria for elegibility included survival analysis, follow-up >6 months and multivariate analysis of predictors of mortality </li></ul>Review of 118 elegible studies (23797 patients) 75% 8/9 MELD 63% 67/118 CTP Independent Predictor of Mortality N° Studies with MV analysis Variable
    89. 91. Prognostic Indicators of Survival in Patients with Cirrhosis D’Amico G et al (2006) <ul><li>CTP was the most consistent and robust predictor of death </li></ul><ul><li>It is not surprising that the MELD score (which incorporates creatinine in addition to markers of liver dysfunction) has become a valuable method to allocate organs </li></ul><ul><li>It is predictable that the MELD score would not be useful to predict survival in patients with compensated cirrhosis </li></ul>
    90. 92. Compensated Cirrhosis
    91. 93. MELD in Compensated Cirrhosis Kamath PS et al (2001) Viral Cirrhosis (n=491 PBC (n=491 Concordance Statistic
    92. 94. MELD in Compensated Cirrhosis Said A et al (2004) 1611 patients with cirrhosis Compensated cohort: no ascites, VB or HE  9 MELD Score Mortality C-Statistic p=NS
    93. 95. Prognosis of Decompensated Cirrhosis Low risk of death It would be more useful to look at predictors of decompensation rather than at predictors of death
    94. 96. Predictors of Clinical Decompensation in Patients with Compensated Cirrhosis Ripoll C et al (2007) Ascites (22%) Encephalopathy (8%) Variceal bleeding (3%) Median follow-up of 51 months 213 patients with compensated cirrhosis 62% HCV-positive, 24% ALD HVPG  6 mmHg (no esophageal varices) Median MELD of 8 (7-10) Median CTP of 5 (88% Class A) Decompensation in 62 patients (29%)
    95. 97. Predictors of Clinical Decompensation in Patients with Compensated Cirrhosis Ripoll C et al (2007) Multivariate Analysis (several models to avoid colinearity and overfitting) CTP score was not an independent predictor of decompensation <0.0001 0.22-0.62 0.37 Albumin 0.014 1.03-1.29 1.75 MELD 0.001 1.05-1.17 1.11 HVPG p Value 95% CI HR Variable
    96. 98. Development of Complications of Cirrhosis in Patients with NASH or Hepatitis C Sanyal AJ et al (2006) 152 patients with NASH and 150 with hepatitis C No ascites (n=198) Ascites (n=54, 27%) No EV (n=153) No HE (n=258) EV (n=45, 29%) HE (n=41,16%) <ul><li>MELD </li></ul><ul><li>HE </li></ul><ul><li>MELD </li></ul><ul><li>Platelets </li></ul><ul><li>MELD </li></ul>PREDICTORS
    97. 99. Liver Transplantation
    98. 100. Non-Transplant Patients
    99. 101. CTP and MELD in Non-Transplant Patients with Cirrhosis Said A et al (2004) Most studies to validate MELD have looked at patients with advanced cirrhosis and analyzed 3-month survival 1611 patients with relatively well-compensated cirrhosis both in the outpatient and inpatient settings (median follow-up of 24 months) Impact of MELD on survival (for each 10 points) 1.24-1.71 1.46 >11 months 2.76-3.81 3.25 Initial 95% CI HR Variable
    100. 102. CTP and MELD in Non-Transplant Patients with Cirrhosis Said A et al (2004) 1611 relatively well-compensated cirrhotics <ul><li>A single MELD measurement should not be used to predict survival beyond 1 year of F/U </li></ul><ul><li>MELD and CTP scores provide equally good prognostic information </li></ul>Predictors of Mortality 1.30 (0.0006) 1.09 (<0.0001) 1-Year 1.12 (NS) 1.04 (0.0009) Entire Follow-up CTP MELD HR (p value) Mortality

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