2011 Organ Donation Congress Buenos Aires, November 27-30, 2011 Graft and Patient Outcomes Challenges in Liver Transplanta...
Priorities in Liver Transplantation The Past <ul><li>Acute and chronic rejection </li></ul><ul><li>Infectious complication...
<ul><li>Increase the number of donors and optimize organ allocation </li></ul><ul><li>Minimize long-term adverse effects o...
1980 1990 CsA Tac MMF 1960 Steroids AZA Steroids Steroids AZA Tac: 88.8%  , CsA 5.7% Tac + MMF + Steroids: 54.7% SRTR Annu...
Challenges in Liver Transplantation Hepatitis B
OLT for Hepatitis B : “A happy story” HBV Recurrence 1980’s No inmunoprofilaxis 80-90% HBIg  monotherapy 20-30% HBIg +  LA...
Challenges in Liver Transplantation Hepatitis C
Accelerated fibrogenesis  (30% cirrhosis at 5 years) Natural History of Recurrent Hepatitis C Decreased patient and graft ...
Effect of Donor Age on Severity of HCV Recurrence Following OLT Berenguer et al (2002) % HCV-related graft cirrhosis Donor...
Is CsA antiviral in vivo?  Are mTor inhibitors anti-fibrogenic? Immunosuppression in Hepatitis C Changes in immunosuppresi...
The HCV- Diabetes -Kidney Connection HCV Diabetes (IR) Renal failure HCV is an Independent predictor of renal failure and ...
Accelerated fibrogenesis  (30% cirrhosis at 5 years) Natural History of Recurrent Hepatitis C Decreased patient and graft ...
Histological Outcome of Patients  With SVR  Post-OLT Inflammation Fibrosis %
Antiviral Therapy Improves Long-Term Outcome of HCV Recurrence * Significant differences SVR NR Treated Untreated 100%* 93...
Efficacy of PEG-Ribavirin Therapy for HCV Recurrence 25 reported studies including 835 patients 8% 55% SVR   (all genotype...
There is an urgent need for more safe and effective antiviral agents  SVR in Naive Genotype 1 Patients Triple therapy Trip...
Garg V et al. Hepatology 2011  AUC increase x 70 Tacrolimus + telaprevir Tacrolimus  Impact of Telaprevir on CNI Exposure
Hepatocellular Carcinoma Challenges in Liver Transplantation
Liver Transplantation for HCC Mazzaferro V y col (1996) Imaging studies with a single nodule <5 cm or up to 3 nodules <3 c...
Recommendations for OLT for HCC International Consensus Conference Clavien PA et al (2011) <ul><li>Milan criteria are  cur...
Is tumor biology the answer? Can we safely go beyond Milan Criteria?
Results of OLT in HCC and non-HCC Patients According to Immunosuppression Toso C et al NS 78% 79% NS 70% 68% MMF <0.001 79...
5-Year survival Toso C et al (2010) Results of OLT in HCC Patients According to Immunosuppression Multivariate Analysis (H...
Secondary Objectives SILVER Study (RCT) Primary Objective <ul><li>Patient survival </li></ul><ul><li>Time-to-recurrence </...
Challenges in Liver Transplantation NASH
Metabolic Syndrome and Liver Transplantation Metabolic syndrome in up to 60% of post-transplant patients 30-40% 20-75% DM ...
Present and Future Demand for Liver Transplantation for NASH % of LT Charlton MR, Clin Gastro & Hep  3:2005.
 
<ul><li>Most likely, ETV and TDV will replace LAM and ADV both pre- and post-OLT </li></ul><ul><li>In the era of antiviral...
Actuarial Rates of Fibrosis in Patients with HCV Recurrence Fundación Favaloro 1995-2007 72 consecutive HCV+ patients with...
HCV Infection is Associated with Decreased Post-OLT Survival HCV-Neg (n=6597) HCV-Pos (n=4439) 81.8% 76.6% 77.8 69.9 p<0.0...
Strategies for Management of Patients with HCV Recurrence <ul><li>Identification of reliable predictors of severe recurren...
Tumor Size is a Surrogate Marker for Histological Predictorsof Recurrence Figueras J et al (2001) Tumor diameter of main n...
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Federico Villamil - Argentina - Tuesday 29 - Graft and Patient Outcomes

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  • Reasons may be prevalence related, but may be impacted on disease term availablility in SRTR data.
  • Federico Villamil - Argentina - Tuesday 29 - Graft and Patient Outcomes

    1. 1. 2011 Organ Donation Congress Buenos Aires, November 27-30, 2011 Graft and Patient Outcomes Challenges in Liver Transplantation Federico G. Villamil Liver Transplantation Unit Buenos Aires British Hospital
    2. 2. Priorities in Liver Transplantation The Past <ul><li>Acute and chronic rejection </li></ul><ul><li>Infectious complications </li></ul>Survival Prophylaxis Therapy <ul><li>90% at 1 yr </li></ul><ul><li>80% at 5 yrs </li></ul>10-20% 2-3%
    3. 3. <ul><li>Increase the number of donors and optimize organ allocation </li></ul><ul><li>Minimize long-term adverse effects of immunosuppressive agents </li></ul><ul><li>Prevent or effectively treat recurrent disease </li></ul>The Present Priorities in Liver Transplantation
    4. 4. 1980 1990 CsA Tac MMF 1960 Steroids AZA Steroids Steroids AZA Tac: 88.8% , CsA 5.7% Tac + MMF + Steroids: 54.7% SRTR Annual Report 2009 (n=5826) ATG, Anti-IL2, Campath, Rituximab Sirolimus, everolimus Belatacept, sotrastaurin 2011 At present CNI-free IS in liver transplantation is the exception rather than the rule  Minimization <ul><li>Nephrotoxicity </li></ul><ul><li>Hypertension </li></ul><ul><li>Hyperlipidemia </li></ul><ul><li>Neurotoxicty </li></ul><ul><li>Diabetes mellitus </li></ul>¿Calcineurin-free immunosupression?
    5. 5. Challenges in Liver Transplantation Hepatitis B
    6. 6. OLT for Hepatitis B : “A happy story” HBV Recurrence 1980’s No inmunoprofilaxis 80-90% HBIg monotherapy 20-30% HBIg + LAM 5-10% HBIg + ADV (  LAM) 2-5% HBIg +ETV o TDF ?? From an absolute contraindication to a universally accepted indication 1990 2000 2005 2010 HBIg-free prophylaxis?
    7. 7. Challenges in Liver Transplantation Hepatitis C
    8. 8. Accelerated fibrogenesis (30% cirrhosis at 5 years) Natural History of Recurrent Hepatitis C Decreased patient and graft survival Strategies for Management of Patients with HCV Recurrence <ul><li>Identify reliable predictors of severe HCV recurrence (fibrosis) to minimize their impact on allograft disease </li></ul>
    9. 9. Effect of Donor Age on Severity of HCV Recurrence Following OLT Berenguer et al (2002) % HCV-related graft cirrhosis Donor Age
    10. 10. Is CsA antiviral in vivo? Are mTor inhibitors anti-fibrogenic? Immunosuppression in Hepatitis C Changes in immunosuppresion over time should be slow and gentle  Avoid intense imunosuppression followed by rapid withdrawal For mild episodes of rejection intensification of baseline immunosuppression should be attempted before administering steroid boluses
    11. 11. The HCV- Diabetes -Kidney Connection HCV Diabetes (IR) Renal failure HCV is an Independent predictor of renal failure and may accelerate the progression of diabetic nephropathy HCV increases the risk of DM Diabetes (IR) increases the severity of HCV
    12. 12. Accelerated fibrogenesis (30% cirrhosis at 5 years) Natural History of Recurrent Hepatitis C Decreased patient and graft survival Strategies for Management of Patients with HCV Recurrence <ul><li>Identify reliable predictors of severe HCV recurrence (fibrosis) to minimize their impact on allograft disease </li></ul><ul><li>Antiviral therapy </li></ul>
    13. 13. Histological Outcome of Patients With SVR Post-OLT Inflammation Fibrosis %
    14. 14. Antiviral Therapy Improves Long-Term Outcome of HCV Recurrence * Significant differences SVR NR Treated Untreated 100%* 93%* NA 43% 69% NA NA 74%* 92.5%* NA 30 Kornberg (08) 62% 89 Berenguer (08) 66% 165 Veldt (08) Patient Survival (5-7 Years) N Author
    15. 15. Efficacy of PEG-Ribavirin Therapy for HCV Recurrence 25 reported studies including 835 patients 8% 55% SVR (all genotypes): 259/835 (31%)
    16. 16. There is an urgent need for more safe and effective antiviral agents SVR in Naive Genotype 1 Patients Triple therapy Triple therapy Telaprevir Boceprevir %
    17. 17. Garg V et al. Hepatology 2011 AUC increase x 70 Tacrolimus + telaprevir Tacrolimus Impact of Telaprevir on CNI Exposure
    18. 18. Hepatocellular Carcinoma Challenges in Liver Transplantation
    19. 19. Liver Transplantation for HCC Mazzaferro V y col (1996) Imaging studies with a single nodule <5 cm or up to 3 nodules <3 cm Recurrence-free survival 90% 86% 83% 83% HCC recurrence: 8% % “ Milan Criteria”
    20. 20. Recommendations for OLT for HCC International Consensus Conference Clavien PA et al (2011) <ul><li>Milan criteria are currently the benchmark for the selection of HCC patients for OLT </li></ul><ul><li>In patients following LDLT outside the accepted criteria for DDLT, re-OLT for graft failure using a deceased donor organ is not recommended </li></ul>Are the Milan Criteria too restrictive?
    21. 21. Is tumor biology the answer? Can we safely go beyond Milan Criteria?
    22. 22. Results of OLT in HCC and non-HCC Patients According to Immunosuppression Toso C et al NS 78% 79% NS 70% 68% MMF <0.001 79% 73% NS 69% 69% CsA <0.001 73% 79% NS 68% 70% Tac NS 78% 79% <0.01 68% 74% Anti-CD25 NS 79% 74% <0.05 69% 83% Sirolimus p No Yes p No Yes No HCC (n=12167) HCC (n=2491) 5-Year Survival Droga “ Anti-cáncer agent”
    23. 23. 5-Year survival Toso C et al (2010) Results of OLT in HCC Patients According to Immunosuppression Multivariate Analysis (HCC patients) Sirolimus: HR 0.53 (0.31-0.92) p<0.05 Anti-CD25: HR 0.64 (0.45-0.9) p<0.01
    24. 24. Secondary Objectives SILVER Study (RCT) Primary Objective <ul><li>Patient survival </li></ul><ul><li>Time-to-recurrence </li></ul><ul><li>Tumor progression </li></ul><ul><li>Renal function </li></ul><ul><li>De novo malignancies </li></ul>Recurrence-free survival
    25. 25. Challenges in Liver Transplantation NASH
    26. 26. Metabolic Syndrome and Liver Transplantation Metabolic syndrome in up to 60% of post-transplant patients 30-40% 20-75% DM or IGT 60-70% 67% Hypertension 50-70% 12-85% Elevated lipids OLT NAFLD
    27. 27. Present and Future Demand for Liver Transplantation for NASH % of LT Charlton MR, Clin Gastro & Hep 3:2005.
    28. 29. <ul><li>Most likely, ETV and TDV will replace LAM and ADV both pre- and post-OLT </li></ul><ul><li>In the era of antivirals high dose IV HBIg regimens are no longer necessary: </li></ul><ul><ul><li>Low doses </li></ul></ul><ul><ul><li>IM or SC </li></ul></ul><ul><ul><li>Finite course in low-risk patients </li></ul></ul><ul><li>HBIg-free prophylaxis? </li></ul>Prophylaxis of HBV Recurrence
    29. 30. Actuarial Rates of Fibrosis in Patients with HCV Recurrence Fundación Favaloro 1995-2007 72 consecutive HCV+ patients with mean follow-up of 69 months and 5  2 protocol biopsies 97% 81% 49% 21% F1 F2 F3 F4
    30. 31. HCV Infection is Associated with Decreased Post-OLT Survival HCV-Neg (n=6597) HCV-Pos (n=4439) 81.8% 76.6% 77.8 69.9 p<0.0001 HCV recurrence is the major cause of graft loss and death Forman L et al (2002)
    31. 32. Strategies for Management of Patients with HCV Recurrence <ul><li>Identification of reliable predictors of severe recurrence to minimize their impact on allograft disease </li></ul>
    32. 33. Tumor Size is a Surrogate Marker for Histological Predictorsof Recurrence Figueras J et al (2001) Tumor diameter of main nodule (n=305) %

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