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One liver for two: Liver regeneration in living donors and recipients
Vol. 9, No. 4 2005
administration also increased resting hepatic energy stores as determined by an increase in cellular ATP (P ⬍ 0.05) with a concomitant decrease in uncoupling protein 2 (UCP2) prior to I/R (P ⬍ 0.05). Finally, there was an increased level of glutathione (GSH) in the EGCG treated mice as compared to the vehicle treated mice both at baseline and following I/R. Taken together, this study demonstrates that treatment with EGCG by either oral or i.p. administration, significantly protects the liver following I/R possibly by reducing hepatic fat content, increasing hepatic energy status and functioning as an antioxidant.
41 ONE LIVER FOR TWO: LIVER REGENERATION IN LIVING DONORS AND RECIPIENTS Burckhardt Ringe, MD, Felix Braun, MD, Michael Moritz, MD, Gillian Zeldin, MD, Humberto Soriano, MD, William Meyers, MD, Drexel University College of Medicine, Philadelphia, PA Apart from balancing risk versus benefit, the principle of living donor liver transplantation is to split one liver, and to maintain sufficient liver mass and function for two patients-the donor and the recipient. For long-term survival, adequate regeneration of both liver lobes is essential. Published data on volume restoration after living donor liver resection and transplantation are limited and inconclusive. To investigate and compare the recovery of residual left lobes, and right lobe grafts, a consecutive series of adults—22 donors and 22 recipients—were included in a prospective analysis with serial volumetry by magnetic resonance imaging before and 3, 7, 14, 28, 60, 90, 180, and 360 days following right hemihepatectomy or partial liver transplantation. Actual donor and recipient liver volumes were measured (ALV), and calculated in relation to preoperative total donor liver volume (RLV), liver volume at the time of surgery (LVI), and body weight (LBR). Liver regeneration rates (LRR) were determined within the first 28 days. Immunosuppression was tacrolimus based, and completely steroid free in most cases. Overall, the kinetics of liver volume restoration after resection and transplantation of right lobes showed three phases: a rapid early increase within 28 days, an intermediate phase, and slow adaptation tending towards preoperative data. Liver regeneration was not completed after 1 year. There was a significant difference between donors and recipients. In donors, volume of residual left lobes increased continuously within one year after resection, from 45% to 93% RLV after 360 days. Recipients showed a 2-3fold faster and stronger response with an overshoot reaction beyond 100% RLV within the first week after transplantation, and subsequent volume decrease of right lobe grafts. In conclusion, liver volume restoration after resection and transplantation seems to be regulated and controlled by different liver and host factors. In live donors, this process is comparable to liver regeneration, whereas the volume changes in recipients are multifactorial. Further studies are needed to assess the long-term results in these patients.
42 LONG-TERM FOLLOW-UP OF LIVING DONOR LIVER TRANSPLANTATION: 12 YEARS OF EXPERIENCE Sukru Emre, MD, Manuel Rodriguez-Davalos, MD, Raphael Maurette, MD, Sasan Roayaie, MD, Gabriel Gondolesi, MD, Myron Schwartz, MD, Charles Miller, MD, Mount Sinai School of Medicine, New York, NY Our aim was to evaluate the long-term results of living donor liver transplantation (LDLT) in an experienced center; 186 patients (103 adults and 83 pediatrics) underwent LDLT in our center from June 1993 to March 2004. We retrospectively analyzed the indications for transplant, type of graft, recurrence of hepatitis C, outcome in
Abstracts
537
hepatocellular carcinoma (HCC), biliary complications, and patient and graft survival. Donor age was 35.8 (range 19-64). Recipient age was 52.8 (19-74) in adults and 2.7 (4 months-18 years) in pediatrics. Liver grafts consisted in 93 (90.3%) right lobes, and 10 (9.7%) left lobes in the adults; in pediatrics, 68 (81.9%) received a left lateral segment graft, 10 (12%) a left lobe and 5 (6%) a right lobe. The most common indication for transplant in the adult was Hepatitis C. in 47 (45.6%). In the pediatrics 42 (40.7%) had diagnosis of biliary atresia, followed by acute liver failure 19 (22.9%). Of the 47 patients with hepatitis C, 3(6.4%) died early in their postoperative course, 1(2.1%) patient required retransplantation within the first week of transplant for primary graft non-function. Of the 43 long-term survivors, 29 (67.4%) have evidence of recurrent Hepatitis C, 2(6.9%) required retransplantation. 38(36.9%) patients had HCC, 19 (50%) exceeded Milan criteria. Among the long-term survivors, freedom of recurrence is 82.2% at 1 year and 63.9% at 2 years. Incidence of overall biliary complications were 45.6% in adults and 14.5% in pediatrics. Incidence of biliary complications in the left lobe grafts were higher than the right lobe grafts (60% vs 15.1%). Biliary leak occurred early postoperative period and resulted in significant morbidity and mortality: 19% of patients with bile leak died secondary to infectious complications. On the other hand, bile duct strictures occurred in late postoperative period and mainly treated by interventional radiology without increasing mortality. In children underwent LDLT with the diagnosis of fulminant hepatic failure, overall survival was 80%. The 5-year patient and graft survival were 90%-82% in pediatrics and 67-63% in adults. Living donor liver transplantation is a viable option for patients waiting for liver transplantation. Selected patients with hepatocellular carcinoma exceeding Milan criteria may benefit from living donor liver transplantation. Biliary complications are still the Achilles’ heel of living donor liver transplantation. Early biliary complications have higher incidence of morbidity and mortality. Living donor liver transplantation is a life saving procedure in pediatric patients with fulminant hepatic failure.
43 PREDICTING POST-TRANSPLANT GRAFT SURVIVAL IN LIVER TRANSPLANT RECIPIENTS USING PERIOPERATIVE CHARACTERISTICS UNDER THE NEW MELD SYSTEM Derek E. Moore, MD, MPH, Irene D. Feurer, PhD, D. Lee Gordon, MD, J. Kelly Wright, Ravi S. Chari, MD, C. Wright Pinson, MD, Vanderbilt University, Nashville, TN The ever widening gap between donor organs and the number of liver transplant candidates requires optimization of post-transplant outcomes by matching donors and recipients on perioperative factors that maximize graft survival. The aim of this study was to evaluate graft survival based on preoperative donor, “situational,” and recipient characteristics under the new MELD allocation system and devise a practical model with which to predict posttransplant survival. Demographic, clinical, and survival data were extracted from the UNOS Standard Transplant Analysis and Research files for adult, cadaveric liver transplants. Potential risk factors influencing outcomes included donor age, cold ischemia time (CIT), recipient age, MELD score, and previous transplant. Data were analyzed via Kaplan-Meier and Cox proportional hazards regression methods. There were 8,000 grafts transplanted between February 2002 and May 2004. The mean follow up was 8 ⫹ 3 months. One-year graft survival for recipients of donors ⬍60 vs. ⬎60 years old was 83% and 75%, respectively (P ⬍ .001). Recipients of grafts with ⬍12 vs. ⬎12 hours of CIT had 1-year survivals of 83% and 75%, respectively (P ⬍ .001). Recipients with MELD scores ⬍30 had 1-year survivals of 84% compared to 77% for those with MELD scores ⬎30 (P ⬍ .001). Multivariate analysis with Cox
administration also increased resting hepatic energy stores as determined by an increase in cellular ATP (P ⬍ 0.05) with a concomitant decrease in uncoupling protein 2 (UCP2) prior to I/R (P ⬍ 0.05). Finally, there was an increased level of glutathione (GSH) in the EGCG treated mice as compared to the vehicle treated mice both at baseline and following I/R. Taken together, this study demonstrates that treatment with EGCG by either oral or i.p. administration, significantly protects the liver following I/R possibly by reducing hepatic fat content, increasing hepatic energy status and functioning as an antioxidant.
41 ONE LIVER FOR TWO: LIVER REGENERATION IN LIVING DONORS AND RECIPIENTS Burckhardt Ringe, MD, Felix Braun, MD, Michael Moritz, MD, Gillian Zeldin, MD, Humberto Soriano, MD, William Meyers, MD, Drexel University College of Medicine, Philadelphia, PA Apart from balancing risk versus benefit, the principle of living donor liver transplantation is to split one liver, and to maintain sufficient liver mass and function for two patients-the donor and the recipient. For long-term survival, adequate regeneration of both liver lobes is essential. Published data on volume restoration after living donor liver resection and transplantation are limited and inconclusive. To investigate and compare the recovery of residual left lobes, and right lobe grafts, a consecutive series of adults—22 donors and 22 recipients—were included in a prospective analysis with serial volumetry by magnetic resonance imaging before and 3, 7, 14, 28, 60, 90, 180, and 360 days following right hemihepatectomy or partial liver transplantation. Actual donor and recipient liver volumes were measured (ALV), and calculated in relation to preoperative total donor liver volume (RLV), liver volume at the time of surgery (LVI), and body weight (LBR). Liver regeneration rates (LRR) were determined within the first 28 days. Immunosuppression was tacrolimus based, and completely steroid free in most cases. Overall, the kinetics of liver volume restoration after resection and transplantation of right lobes showed three phases: a rapid early increase within 28 days, an intermediate phase, and slow adaptation tending towards preoperative data. Liver regeneration was not completed after 1 year. There was a significant difference between donors and recipients. In donors, volume of residual left lobes increased continuously within one year after resection, from 45% to 93% RLV after 360 days. Recipients showed a 2-3fold faster and stronger response with an overshoot reaction beyond 100% RLV within the first week after transplantation, and subsequent volume decrease of right lobe grafts. In conclusion, liver volume restoration after resection and transplantation seems to be regulated and controlled by different liver and host factors. In live donors, this process is comparable to liver regeneration, whereas the volume changes in recipients are multifactorial. Further studies are needed to assess the long-term results in these patients.
42 LONG-TERM FOLLOW-UP OF LIVING DONOR LIVER TRANSPLANTATION: 12 YEARS OF EXPERIENCE Sukru Emre, MD, Manuel Rodriguez-Davalos, MD, Raphael Maurette, MD, Sasan Roayaie, MD, Gabriel Gondolesi, MD, Myron Schwartz, MD, Charles Miller, MD, Mount Sinai School of Medicine, New York, NY Our aim was to evaluate the long-term results of living donor liver transplantation (LDLT) in an experienced center; 186 patients (103 adults and 83 pediatrics) underwent LDLT in our center from June 1993 to March 2004. We retrospectively analyzed the indications for transplant, type of graft, recurrence of hepatitis C, outcome in
Abstracts
537
hepatocellular carcinoma (HCC), biliary complications, and patient and graft survival. Donor age was 35.8 (range 19-64). Recipient age was 52.8 (19-74) in adults and 2.7 (4 months-18 years) in pediatrics. Liver grafts consisted in 93 (90.3%) right lobes, and 10 (9.7%) left lobes in the adults; in pediatrics, 68 (81.9%) received a left lateral segment graft, 10 (12%) a left lobe and 5 (6%) a right lobe. The most common indication for transplant in the adult was Hepatitis C. in 47 (45.6%). In the pediatrics 42 (40.7%) had diagnosis of biliary atresia, followed by acute liver failure 19 (22.9%). Of the 47 patients with hepatitis C, 3(6.4%) died early in their postoperative course, 1(2.1%) patient required retransplantation within the first week of transplant for primary graft non-function. Of the 43 long-term survivors, 29 (67.4%) have evidence of recurrent Hepatitis C, 2(6.9%) required retransplantation. 38(36.9%) patients had HCC, 19 (50%) exceeded Milan criteria. Among the long-term survivors, freedom of recurrence is 82.2% at 1 year and 63.9% at 2 years. Incidence of overall biliary complications were 45.6% in adults and 14.5% in pediatrics. Incidence of biliary complications in the left lobe grafts were higher than the right lobe grafts (60% vs 15.1%). Biliary leak occurred early postoperative period and resulted in significant morbidity and mortality: 19% of patients with bile leak died secondary to infectious complications. On the other hand, bile duct strictures occurred in late postoperative period and mainly treated by interventional radiology without increasing mortality. In children underwent LDLT with the diagnosis of fulminant hepatic failure, overall survival was 80%. The 5-year patient and graft survival were 90%-82% in pediatrics and 67-63% in adults. Living donor liver transplantation is a viable option for patients waiting for liver transplantation. Selected patients with hepatocellular carcinoma exceeding Milan criteria may benefit from living donor liver transplantation. Biliary complications are still the Achilles’ heel of living donor liver transplantation. Early biliary complications have higher incidence of morbidity and mortality. Living donor liver transplantation is a life saving procedure in pediatric patients with fulminant hepatic failure.
43 PREDICTING POST-TRANSPLANT GRAFT SURVIVAL IN LIVER TRANSPLANT RECIPIENTS USING PERIOPERATIVE CHARACTERISTICS UNDER THE NEW MELD SYSTEM Derek E. Moore, MD, MPH, Irene D. Feurer, PhD, D. Lee Gordon, MD, J. Kelly Wright, Ravi S. Chari, MD, C. Wright Pinson, MD, Vanderbilt University, Nashville, TN The ever widening gap between donor organs and the number of liver transplant candidates requires optimization of post-transplant outcomes by matching donors and recipients on perioperative factors that maximize graft survival. The aim of this study was to evaluate graft survival based on preoperative donor, “situational,” and recipient characteristics under the new MELD allocation system and devise a practical model with which to predict posttransplant survival. Demographic, clinical, and survival data were extracted from the UNOS Standard Transplant Analysis and Research files for adult, cadaveric liver transplants. Potential risk factors influencing outcomes included donor age, cold ischemia time (CIT), recipient age, MELD score, and previous transplant. Data were analyzed via Kaplan-Meier and Cox proportional hazards regression methods. There were 8,000 grafts transplanted between February 2002 and May 2004. The mean follow up was 8 ⫹ 3 months. One-year graft survival for recipients of donors ⬍60 vs. ⬎60 years old was 83% and 75%, respectively (P ⬍ .001). Recipients of grafts with ⬍12 vs. ⬎12 hours of CIT had 1-year survivals of 83% and 75%, respectively (P ⬍ .001). Recipients with MELD scores ⬍30 had 1-year survivals of 84% compared to 77% for those with MELD scores ⬎30 (P ⬍ .001). Multivariate analysis with Cox