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136Analysis of fibrosis in pediatric liver transplant recipients
C-34
Sixth Congress o f the ILTS
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U R G E N T L I V I N G D O N O R L I V E R T R A N S P L A N T A T I O N IN C H I L D R E N W I T H F U L M I N A N T HEPATIC F A I L U R E OR ACUTE D E C O M P E N S A T E D C I R R H O S I S . C L M a c k . EA A l o n s o , PF Whitington. M Abecassis and RA Superina, Depts. O f Pediatrics and S u r g e r y , Childrenls M e m o r i a l Hospital, C h i c a g o , Illinois, United States. Purpose: Liver transplantation is the standard of care for children with liver failure secondary to fulminantacute hepatic failure. Because of the unpredictable timing of cadaverie organ donation, we have considered living donor liver transplantation (LDLTI in this critically ill group of children with multiple organ system failure (MOSFI. This report describes our initial experience in this unique group of children. Methods: A retrospective review of those who had LDLT for fulminant failure or acute deeompensation o! chronic disease in a two-year period was carried out. MOSF was defined as the failure of at least two organ systems according to standard criteria. Preoperative data including laboratory values and specific organ system function was collected. Outcome measures were graft and patient survival and cause of patient death. Data on donor information and outcome was also reviewed. Results: Seven patients (6 boys) underwent urgent LD[,T. The indications for transplantation included idiopathic fulminant failure (31. aaerial thrombosis ( I ). primary non-function ( I ). and acute decompensated cirrhosis (2). All patients were listed as UNOS status I. MOSF was present in all patients prior to transplantation. Six patients were on mechanical ventilation. 3 had renal failure. 3 required inotropic support. I had hypoplastic bone marrow, I had severe GI hemorrhage and all were encephalopathic (grades H-IV). Mean laboratory values prior to liver transplantation: PT 39.5sees, SGOT 4.400 IU/L, bilirubin 14.5mg/dl. and ammonia 102umol/L. The median age at transplantation was 3.2 years. The median waiting time between admission to our hospital and LDLT was 3 days. All donors were discharged From the hospital within 3 days of donation with no serious complications. Recipient and graft survival was 71% (5 survivors) with a mean follow-up of 12.5 months. None required mtransplantation. In the two non-sun, ivora, death ~curred after 24 hours in one (intracranial hemorrhage) and after 83 days in the other (pancreatilis and fungal sepsis). Median ICU stay for survivors was 20 days after transplantation. All survivors recovered fully with no residual organ dysfunction. Conclusions: We conclude that living related donor liver transplantation is justified even in the presence of MOSF in this high-risk group of children. Improved survival from that previously reported may be due to more timely transplantation because of graft availability,.
LIVING RELATED LIVER TRANSPLANTATION IN ACUTE AND CHRONIC PEDIATRIC LIVER FAILURE LG Podestfi, JJ "Frentadue, CD Luque. OC Andriani, MC Galloppo. D D'Agostino, MO Silva, M Genoud, FG Villamil. Liver Unit, Fundaci6n Favaloro, Buenos Aires, Argentina. l.iving related liver transplantation (LRLT) for chronic liver disease (CLDI has been widely accepted but controversial in acute cases when cadaverlc organs may be available. The incidence of fulmmant hepatzc failure (FHF) secondary to hepatitis A in the pediatric population is unusually high m Argentina. Furthermore the number of cadaveric organ donors is very. limited and many are marginal and therefore unsuitable for reducuon or splitlng. E~.!: Analyze the results of LRLT m acute and CLD compared w~th cadavenc organ liver transplant. Methods: From june 1995 to december 1999 46 I.T were earned out in 44 recipients under 17 years of age. 19 of these were for fulmmant hepatic failure. LRLT choice was based on seventy ol clinical condition, prolonged listing for cadavcric organ, and the exlstunce ot family member who was physically, socialy and psychologically prepared to be the donor. Results are expresed in terms of actuarial survival as a KaplanMeier curve. Results: 44 pacients received in total 46 grafts. Mean age: 5.5 years (range 0.5-17), 29 (66'/o) were female. Status at the time of transplanl was: Status I (FHF), 19 patients: status 2-3, 5 patients; and status 4 (bomebound), 20 patients with CLD, Cadaveric organ grafts were implanted in 25 cases (54 %): 11 for CLD and 14 for FHF. 21 (45%) received I . R H : 14 for CLD and 7 for FHF. The mean age of I,RLT receipients was 2.2 y I~ 0.5 to I I). The diagnosis For the group as a whole were: 19 FHF. 13 bihar', atresias and 6 autoimmune hepatdts, 2 retransplants and 6 mtscelaneous LRLT recipient diagnoses were: 10 bihary atresla. 7 FltF and 4 others. O f 21 patients first listed for Fill:, 2 died while waiting for the transplant. 19 were transplanted (90.4 %), of them 7 were LRLT. Mean waiting period tot cadaveric organ in FtlF cases was: median I day (r 1-6) and for LRLT 4.5 days (r 2-111. I year actuarial surviva] as a whole was 93%, 82% Ibt cadaveric LT in FHF, 86% for I.RLT in FHF. and 100% for cadaverlc Lq and LRLT in CLD. LRLT donors had minimal morbidity: stretching of the braquial plexus in 3 cases and I biliary fistula from de cut surface thai resolved with drainage. Conclusions: LRLT increases the aplicability of L'I in CLD but particularly in FHF. Minimal donor morbidity in FHF case.~ justifies the use of LRLT when other sources of organs are not allway~ available.
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ANALYSIS OF FIBROSIS IN PEDIATRIC LIVER TIL~NSPLANT RECIPIENTS P.M.J.G. Peelers, E. Sicders, M. van den Ileuvel. C.M.A. Bijleveld" K.P. de Jong, E.M. TenVergert, M.J.H. Slooff, and A.S.H, Gouw. Liver Transplant Group, University Hospital Groningen, The Netherlands
PEDIATRIC LIVER TRANSPLANTATION: 10 YEARS E U R O T R A N S P L A N T EXPERIENCE. GC Wiesenbaan-StallinRwerff'~J M A Smits, J de Boer, ~ Persijn. MJH Slooff. Eurotransplant Intemational
Purpose. Recent histopathological studies showed an unexpected high incidence of pathological changes in asymptomatic survivors after pediatric liver transplantation. The aim of this study was to analyze the occurrence of histological abnormalities one year posttransplantatinn, to assess the clinical significance, and to identify predictive factors for these pathological changes. Methods. The first annual protocol graft biopsies of 84 consecutive liver transplants were analyzed and correlated with concomitant liver function tests. Identification of predictive factors was performed by analyzing variables related to the recipient, donor, and transplantation procedure in an univariate analysis as well as a multivariate logistic regression analysis. Resuhs. The incidence of portal fibrosis (PF) was 3 I%. The mean values of alkaline phosphatase, -f glutamyl transferase, ASAT, ALAT, and direct and total bilrubin showed an increase in the PF group compared to the group without PF. The mean albumin was lower in the PF group compared with the group without PF. Mean values of alkaline phosphalase and direct bilirubin were 435 U/L and 23 pmol/L, respectively, in the PF group and 264 U/L and _: pmol/L, respectively, in the normal group (P=0.04 for both comparisons). Eight of 19 univariantly tested variables were entered into a logistic regression model: cold ischemia time (CIT), preservation solution, type of allograft (full size versus parial size graft), cytomegalovirus (CMV) recipient status, type of biliary reconstruction, biliary complications, graft complications, and rejection. A significant positive correlation with PF was found for CIT more than 10 hours (Relative Risk 3.5, Odds Ratio 5.7), biliary complications (RR 2.5, OR 3.4), and CMV status (RR 2.1, OR 4.3). Acute rejection showed a negative correlation (RR 0.3, OR 0.2). Conclusions. The incidence of PF within one year after pediatric liver transplantation was 31%. This finding was accompanied by cholestatic liver function test abnormalities. Factors predisposing to PF were a prolonged CIT, biliary complications, and a positive CMV recipient status. Acute rejection seemed to prevent for PF.
Foundation, Leiden, The Netherlands Purpose: To describe the pattern of pediatric liver transplantation in the Eurutmnsplant area during the years 1989 till 1998 and to analyse the impact of several donor/match and recipient factors on graft and patient outcome. Patients and methods: All children (<16 y) that received a liver transplant between Jan 1, 1989 and Dec 31, 1998 were included in the descriptive analysis. Graft and patient outcome analysis was restricted to the transplants performed till Dec 31, 1996, allowing for a 3 year follow-up period. Results: During these 10 years, 1012 children received a first and 223 a retransplantation. In the early nineties, cadaver whole liver transplantation was the only treatment option for children, while at the end of the decade halt of the pediatric transplants were performed with a split liver transplant. A borderline significant difference (.0=0.07) was observed with relation to graft outcome for liver transplantations performed with split liver [N=68], a living related [N=84] and whole (or reduced size) cadaver liver [N=657], at 3 years the rates were respectivily 51%, 67% and 61%. In the subset of first, non urgent, whole cadaver liver transplantations [N=427], a significant assocation between patient survival and donor age was seen (p=0.002). Children, who receive a liver transplant from a donor aged between 6 to 15 years [N=149], had a survival rate at 3 years of 90%, compared to 75% for children transplanted with liver from a donor under 6 [N=156], and 74% if the donor was older than 16 [N= 129]. A clear rank order was observed between the age of the patient and the patient survival rates: the younger the child, the lower the outcome. Patient survival rates at 3 years were for the children under l : 71%, 79% for the I to 5 year old patients, 86% and 84% for respectivily 6-10 ~lnd 11-15 year old children.(p=0.03) Conclusion: Outcome of liver transplantation in pediatric recipients is g o o d , at least for children over the age of 1, and seems to justify the shift in liver transplantation techniques te enlargen the (small) pediatric donor pool. Optimal non-immunological matching might further improve the succes rates.
Sixth Congress o f the ILTS
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U R G E N T L I V I N G D O N O R L I V E R T R A N S P L A N T A T I O N IN C H I L D R E N W I T H F U L M I N A N T HEPATIC F A I L U R E OR ACUTE D E C O M P E N S A T E D C I R R H O S I S . C L M a c k . EA A l o n s o , PF Whitington. M Abecassis and RA Superina, Depts. O f Pediatrics and S u r g e r y , Childrenls M e m o r i a l Hospital, C h i c a g o , Illinois, United States. Purpose: Liver transplantation is the standard of care for children with liver failure secondary to fulminantacute hepatic failure. Because of the unpredictable timing of cadaverie organ donation, we have considered living donor liver transplantation (LDLTI in this critically ill group of children with multiple organ system failure (MOSFI. This report describes our initial experience in this unique group of children. Methods: A retrospective review of those who had LDLT for fulminant failure or acute deeompensation o! chronic disease in a two-year period was carried out. MOSF was defined as the failure of at least two organ systems according to standard criteria. Preoperative data including laboratory values and specific organ system function was collected. Outcome measures were graft and patient survival and cause of patient death. Data on donor information and outcome was also reviewed. Results: Seven patients (6 boys) underwent urgent LD[,T. The indications for transplantation included idiopathic fulminant failure (31. aaerial thrombosis ( I ). primary non-function ( I ). and acute decompensated cirrhosis (2). All patients were listed as UNOS status I. MOSF was present in all patients prior to transplantation. Six patients were on mechanical ventilation. 3 had renal failure. 3 required inotropic support. I had hypoplastic bone marrow, I had severe GI hemorrhage and all were encephalopathic (grades H-IV). Mean laboratory values prior to liver transplantation: PT 39.5sees, SGOT 4.400 IU/L, bilirubin 14.5mg/dl. and ammonia 102umol/L. The median age at transplantation was 3.2 years. The median waiting time between admission to our hospital and LDLT was 3 days. All donors were discharged From the hospital within 3 days of donation with no serious complications. Recipient and graft survival was 71% (5 survivors) with a mean follow-up of 12.5 months. None required mtransplantation. In the two non-sun, ivora, death ~curred after 24 hours in one (intracranial hemorrhage) and after 83 days in the other (pancreatilis and fungal sepsis). Median ICU stay for survivors was 20 days after transplantation. All survivors recovered fully with no residual organ dysfunction. Conclusions: We conclude that living related donor liver transplantation is justified even in the presence of MOSF in this high-risk group of children. Improved survival from that previously reported may be due to more timely transplantation because of graft availability,.
LIVING RELATED LIVER TRANSPLANTATION IN ACUTE AND CHRONIC PEDIATRIC LIVER FAILURE LG Podestfi, JJ "Frentadue, CD Luque. OC Andriani, MC Galloppo. D D'Agostino, MO Silva, M Genoud, FG Villamil. Liver Unit, Fundaci6n Favaloro, Buenos Aires, Argentina. l.iving related liver transplantation (LRLT) for chronic liver disease (CLDI has been widely accepted but controversial in acute cases when cadaverlc organs may be available. The incidence of fulmmant hepatzc failure (FHF) secondary to hepatitis A in the pediatric population is unusually high m Argentina. Furthermore the number of cadaveric organ donors is very. limited and many are marginal and therefore unsuitable for reducuon or splitlng. E~.!: Analyze the results of LRLT m acute and CLD compared w~th cadavenc organ liver transplant. Methods: From june 1995 to december 1999 46 I.T were earned out in 44 recipients under 17 years of age. 19 of these were for fulmmant hepatic failure. LRLT choice was based on seventy ol clinical condition, prolonged listing for cadavcric organ, and the exlstunce ot family member who was physically, socialy and psychologically prepared to be the donor. Results are expresed in terms of actuarial survival as a KaplanMeier curve. Results: 44 pacients received in total 46 grafts. Mean age: 5.5 years (range 0.5-17), 29 (66'/o) were female. Status at the time of transplanl was: Status I (FHF), 19 patients: status 2-3, 5 patients; and status 4 (bomebound), 20 patients with CLD, Cadaveric organ grafts were implanted in 25 cases (54 %): 11 for CLD and 14 for FHF. 21 (45%) received I . R H : 14 for CLD and 7 for FHF. The mean age of I,RLT receipients was 2.2 y I~ 0.5 to I I). The diagnosis For the group as a whole were: 19 FHF. 13 bihar', atresias and 6 autoimmune hepatdts, 2 retransplants and 6 mtscelaneous LRLT recipient diagnoses were: 10 bihary atresla. 7 FltF and 4 others. O f 21 patients first listed for Fill:, 2 died while waiting for the transplant. 19 were transplanted (90.4 %), of them 7 were LRLT. Mean waiting period tot cadaveric organ in FtlF cases was: median I day (r 1-6) and for LRLT 4.5 days (r 2-111. I year actuarial surviva] as a whole was 93%, 82% Ibt cadaveric LT in FHF, 86% for I.RLT in FHF. and 100% for cadaverlc Lq and LRLT in CLD. LRLT donors had minimal morbidity: stretching of the braquial plexus in 3 cases and I biliary fistula from de cut surface thai resolved with drainage. Conclusions: LRLT increases the aplicability of L'I in CLD but particularly in FHF. Minimal donor morbidity in FHF case.~ justifies the use of LRLT when other sources of organs are not allway~ available.
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ANALYSIS OF FIBROSIS IN PEDIATRIC LIVER TIL~NSPLANT RECIPIENTS P.M.J.G. Peelers, E. Sicders, M. van den Ileuvel. C.M.A. Bijleveld" K.P. de Jong, E.M. TenVergert, M.J.H. Slooff, and A.S.H, Gouw. Liver Transplant Group, University Hospital Groningen, The Netherlands
PEDIATRIC LIVER TRANSPLANTATION: 10 YEARS E U R O T R A N S P L A N T EXPERIENCE. GC Wiesenbaan-StallinRwerff'~J M A Smits, J de Boer, ~ Persijn. MJH Slooff. Eurotransplant Intemational
Purpose. Recent histopathological studies showed an unexpected high incidence of pathological changes in asymptomatic survivors after pediatric liver transplantation. The aim of this study was to analyze the occurrence of histological abnormalities one year posttransplantatinn, to assess the clinical significance, and to identify predictive factors for these pathological changes. Methods. The first annual protocol graft biopsies of 84 consecutive liver transplants were analyzed and correlated with concomitant liver function tests. Identification of predictive factors was performed by analyzing variables related to the recipient, donor, and transplantation procedure in an univariate analysis as well as a multivariate logistic regression analysis. Resuhs. The incidence of portal fibrosis (PF) was 3 I%. The mean values of alkaline phosphatase, -f glutamyl transferase, ASAT, ALAT, and direct and total bilrubin showed an increase in the PF group compared to the group without PF. The mean albumin was lower in the PF group compared with the group without PF. Mean values of alkaline phosphalase and direct bilirubin were 435 U/L and 23 pmol/L, respectively, in the PF group and 264 U/L and _: pmol/L, respectively, in the normal group (P=0.04 for both comparisons). Eight of 19 univariantly tested variables were entered into a logistic regression model: cold ischemia time (CIT), preservation solution, type of allograft (full size versus parial size graft), cytomegalovirus (CMV) recipient status, type of biliary reconstruction, biliary complications, graft complications, and rejection. A significant positive correlation with PF was found for CIT more than 10 hours (Relative Risk 3.5, Odds Ratio 5.7), biliary complications (RR 2.5, OR 3.4), and CMV status (RR 2.1, OR 4.3). Acute rejection showed a negative correlation (RR 0.3, OR 0.2). Conclusions. The incidence of PF within one year after pediatric liver transplantation was 31%. This finding was accompanied by cholestatic liver function test abnormalities. Factors predisposing to PF were a prolonged CIT, biliary complications, and a positive CMV recipient status. Acute rejection seemed to prevent for PF.
Foundation, Leiden, The Netherlands Purpose: To describe the pattern of pediatric liver transplantation in the Eurutmnsplant area during the years 1989 till 1998 and to analyse the impact of several donor/match and recipient factors on graft and patient outcome. Patients and methods: All children (<16 y) that received a liver transplant between Jan 1, 1989 and Dec 31, 1998 were included in the descriptive analysis. Graft and patient outcome analysis was restricted to the transplants performed till Dec 31, 1996, allowing for a 3 year follow-up period. Results: During these 10 years, 1012 children received a first and 223 a retransplantation. In the early nineties, cadaver whole liver transplantation was the only treatment option for children, while at the end of the decade halt of the pediatric transplants were performed with a split liver transplant. A borderline significant difference (.0=0.07) was observed with relation to graft outcome for liver transplantations performed with split liver [N=68], a living related [N=84] and whole (or reduced size) cadaver liver [N=657], at 3 years the rates were respectivily 51%, 67% and 61%. In the subset of first, non urgent, whole cadaver liver transplantations [N=427], a significant assocation between patient survival and donor age was seen (p=0.002). Children, who receive a liver transplant from a donor aged between 6 to 15 years [N=149], had a survival rate at 3 years of 90%, compared to 75% for children transplanted with liver from a donor under 6 [N=156], and 74% if the donor was older than 16 [N= 129]. A clear rank order was observed between the age of the patient and the patient survival rates: the younger the child, the lower the outcome. Patient survival rates at 3 years were for the children under l : 71%, 79% for the I to 5 year old patients, 86% and 84% for respectivily 6-10 ~lnd 11-15 year old children.(p=0.03) Conclusion: Outcome of liver transplantation in pediatric recipients is g o o d , at least for children over the age of 1, and seems to justify the shift in liver transplantation techniques te enlargen the (small) pediatric donor pool. Optimal non-immunological matching might further improve the succes rates.