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Predictors and outcome of early allograft dysfunction (EAD) following orthotopic liver transplantation (OLT)
HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995
139A
AASLD A B S T R A C T S
129 EXTENDED COLD ISCHAEMIA IS NOT ASSOCIATED WITH
IMPAIRED GRAFT FUNCTION AND BILIARY COMPLICATIONS. DF Mirza, BK Guns0n, BH Ferraz Neto, AD Mayer, JAC Buckels, P McMaster. The Liver Unit, Queen Elizabeth Hospital, Birmingham, UK. Prolonged cold preservation has been reported to result in ischaemic type biliary complications and impaired initial graft function after orthotopic liver transplantation(OLT). Consequently, many centres have shortened cold ischaemia time(CIT)periods. Methods: From April 1988 to April 1995, 658 elective adult OLTs were carried out in 512 patients with a median CIT of 740(97-1665) min; 279 grafts with a CIT <740 min(Group 1), median CIT 585(97-740) min, median follow up 30 months; and 279 >740 min(Group 2) with a median CIT 855(740-1665) min, median follow up 26 months. Donor in-situ aortic perfusion was with 3-4 litres Marshall's solution(n=474) or University of Wisconsin solution (UWs)(n=84) at 100 mm Hg. Portal venous and back table perfusion was with UWs. The median follow-up was 30 and 26 months respectively. Results: Eady graft function and biliary complications(BC) were similar in both groups: Group 1 Group 2 p Primary nonfunction 5(1.8%) 3(1.1%) ns Peak AST day 1-5 575(66-7270) 699(81-12080) ns Peak bilirubin day 1-6 149(24-812) 151(17-1540) ns Bile leak 24 27 ns Biliary stricture/obstruction 30 31 ns Re-operation for BC 25(9%) 28(10%) ns Intra-operative blood product use, hospital stay, and one year graft(79% vs 80%) and patient(86.6% vs 82.6%) were identical in the two groups. Conclusion: Extended preservation alone does not lead to impaired graft function or biliary complications.
130 PREDICTORS AND OUTCOME OF EARLY ALLOGRAFT
DYSFUNCTION (EAD) FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION (OLT). JR Lake, R Krom, S Belle and the NIDDK Liver Transplantation Database. University of California; San Francisco, Mayo Clinic and University of Pittsburgh, Pittsburgh, PA. EAD has been shown to increase the frequency of graft loss and death after OLT. However, the definition of EAD has been based on indices of liver injury rather than of liver function. In addition, the impact of EAD on outcomes other than patient and graft survival has not been determined. Methods: We used the N1DDK Liver Transplantation Database, a 5-year collection of data which included 738 liver only, non-fulminant adult transplant recipients from 3 centers: UCSF, the Mayo Clinic, and the Univ. of Nebraska. Our definition of EAD included at least 1 of the following: bilirubin >10 rag% during day 4-10, prothrombin time >_17sec day 0-10, encephalopathy during day 0-t 0, clinical diagnosis of poor function during day 0-10, or death or re-OLT because of liver failure day 0-10. 724 recipients had sufficient data sets. Results: 179 (24.7%) recipients met the definition. One:year patient and graft survival were 80% and 69% in recipients with EAD compared to 91% and 89% in patients without EAD,p<.001. Median hospital stay was 23 days for recipients with EAD, 15 days for those without EAD. 41% of recipients with EAD and 14% of recipients without EAD had an ICU stay > 4 days. Differences in survivals and lengths of stay remain when the analysis is confined to Child's class A and B patients only. By univariate analysis, pre-operative and donor factors predictive of EAD were: PRE-OP FACTORS MALE KARNOFSKY_>8 UNOS STATUS 1 CHILD CLASS C ACUTE LIV FAIL
P .04 .001 .001 .001 .001
PRE43P FACTORS RENAL FAK..URE (31 BLEED/NG ENCEPHAI~PATH BILIRUBIN BUN PROTIME
P .006 .005 .001 .001 .001 .001
DONOR FACTORS AGE-> 50 RACE-NONWHiTE SURGEON ASSESS COLDISCHEMIA
P .001 .04 .001 .001
By multivariate analysis, factors independently associated with EAD and their respective odds ratios were bilirubin (1.04 per mg% increase), PT >15 sec (1.72), donor age >_50yr. (2.53), ABO mismatch (2.38),pre-procurement acidosis (1.54) and cold ischemia time (1.11 per 1 heour increase). SUMMARY: EAD has important effects on a variety of post-OLT outcomes and requires more hospital resources.
131 DETECTION OF ALBUMIN mRNA IN BLOOD AFTER LIVER
132 PORTAL FLOW AFTER ORTHOTOPIC LIVER TRANSPLANT
TRANSPLANTATION IN PATIENTS WITH BENIGN LIVER DISEASE H.G.M.Niesters'. D.J.Bac 2. S.W.Schalm 2, H.W.Tilanus s end J.N.M.IJzermans 3. Dept. of Virology', Internal Medicine II2 and Surgery 3, University Hospital Rotterdam, The Netherlands.
EVALUATED BY PER-RECTAL PORTAL SCINTIGRAPHY WITH TECHNETIUM-99M PERTHECHNETATE. A.D'Artenzo. LCelentano**. L.Cimino*. F.Manouso. G.piirrilli*, D.Mattara. M.Di Pieno. G.V'cinanza. G;Budillon*. (3.M=w-t=~.r_~, I e *11 Cattadra di Gastrnentarologia, ** Cattadrs di Medicine Nudeara, University "Fededco Ir', Naples, Italy.
Albumin mRNA is a liver-specific cell marker. It has been suggested that a positive albumin mRNA-PCR in blood in patients with a hepatocellular carcinoma may indicate shedding of liver tumourcells into the circulation. Thus, the test may identify a subgroup of patients with hepatocellular carcinoma that has a high risk of tumour recurrence after livertransplantation [LTx]. Using a highly sensitive mRNA-PCR assay, we studied the cell release in relation to LTx. Peripheral and central blood samples were.taken at regular intervals from consecutive patients undergoing LTx for benign liver disease, and mixed with guanidinium-iso-thiocyanate to isolate total nucleic acids. The results demonstrate t h a t albumin-mRNA could be detected in central as well as peripheral blood samples collected after recipient hepatectomy, but not before liversurgery. Furthermore, a semi-quantitative analysis shows an increase after reperfusion of the donor liver. As histological examination of the hepatectomized livers confirmed the absence of any malignancy, we conclude that a positive albumin-mRNA PCR test has no specific predictive value for hepatocellular carcinoma. Additonal specificity should be obtained before making clinical decisions.
In patients with orthotopic liver transplant (OLT) portal pressure normalizes even though a splenomegaly and hypersplenism may persist. Per-rectal portal sdntigraphy with Technetium-99m perthechnetate (99mTc-tast) is useful to evaluate the development of activated shunts from the infedor mesentedc vein to the inferior vena ceva due to the development of portal hypertension in cint,mtJc patients: an haemodynemic recording of hepatic and cardiac imaging was obtained after the rectal release of 1 ml 99m-Tc-perthecr~tate (specific activity 7.5 mCi/ml). The ratio between heart radioactivity and the sum of heart and liver radioactivity in the first 30 seconds of observation is defined as Shunt Index (S.I.). (No0Tnalvalue: <20%). In order to evaluate the changes in portal flow alter OLT, we studied 10 male patients (mean age +_SD: 52+_9)who had undergone OLT due to cirrhosis, Child B or C, viral etiology, with marked signs of penal h ~ , us~g the 99mTc-taat. The test was parformed 1 to41 months after OLT (mean +_SD:23+_13).The mean +_SDplatalet count was 123.900+_30.428/ram3. All patients showed an imaging pattern virtually identical to that of healty subjects with an S.I. below 19% (mean _+SD: 12.07+-4.60). A s i ~ inverse correlation was observed between the S.I. values and the platatet counts (y=176890-4390x, r= -0.66, p= 0.036). Our data demonsnta a normalization of the mesentadc flow after OLT v~ll the clostxe of the shunts even in the patients in which signs of h y p e r ~ persist. Lower S.I. values are observed in patients ~dth normal platlet counts.
139A
AASLD A B S T R A C T S
129 EXTENDED COLD ISCHAEMIA IS NOT ASSOCIATED WITH
IMPAIRED GRAFT FUNCTION AND BILIARY COMPLICATIONS. DF Mirza, BK Guns0n, BH Ferraz Neto, AD Mayer, JAC Buckels, P McMaster. The Liver Unit, Queen Elizabeth Hospital, Birmingham, UK. Prolonged cold preservation has been reported to result in ischaemic type biliary complications and impaired initial graft function after orthotopic liver transplantation(OLT). Consequently, many centres have shortened cold ischaemia time(CIT)periods. Methods: From April 1988 to April 1995, 658 elective adult OLTs were carried out in 512 patients with a median CIT of 740(97-1665) min; 279 grafts with a CIT <740 min(Group 1), median CIT 585(97-740) min, median follow up 30 months; and 279 >740 min(Group 2) with a median CIT 855(740-1665) min, median follow up 26 months. Donor in-situ aortic perfusion was with 3-4 litres Marshall's solution(n=474) or University of Wisconsin solution (UWs)(n=84) at 100 mm Hg. Portal venous and back table perfusion was with UWs. The median follow-up was 30 and 26 months respectively. Results: Eady graft function and biliary complications(BC) were similar in both groups: Group 1 Group 2 p Primary nonfunction 5(1.8%) 3(1.1%) ns Peak AST day 1-5 575(66-7270) 699(81-12080) ns Peak bilirubin day 1-6 149(24-812) 151(17-1540) ns Bile leak 24 27 ns Biliary stricture/obstruction 30 31 ns Re-operation for BC 25(9%) 28(10%) ns Intra-operative blood product use, hospital stay, and one year graft(79% vs 80%) and patient(86.6% vs 82.6%) were identical in the two groups. Conclusion: Extended preservation alone does not lead to impaired graft function or biliary complications.
130 PREDICTORS AND OUTCOME OF EARLY ALLOGRAFT
DYSFUNCTION (EAD) FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION (OLT). JR Lake, R Krom, S Belle and the NIDDK Liver Transplantation Database. University of California; San Francisco, Mayo Clinic and University of Pittsburgh, Pittsburgh, PA. EAD has been shown to increase the frequency of graft loss and death after OLT. However, the definition of EAD has been based on indices of liver injury rather than of liver function. In addition, the impact of EAD on outcomes other than patient and graft survival has not been determined. Methods: We used the N1DDK Liver Transplantation Database, a 5-year collection of data which included 738 liver only, non-fulminant adult transplant recipients from 3 centers: UCSF, the Mayo Clinic, and the Univ. of Nebraska. Our definition of EAD included at least 1 of the following: bilirubin >10 rag% during day 4-10, prothrombin time >_17sec day 0-10, encephalopathy during day 0-t 0, clinical diagnosis of poor function during day 0-10, or death or re-OLT because of liver failure day 0-10. 724 recipients had sufficient data sets. Results: 179 (24.7%) recipients met the definition. One:year patient and graft survival were 80% and 69% in recipients with EAD compared to 91% and 89% in patients without EAD,p<.001. Median hospital stay was 23 days for recipients with EAD, 15 days for those without EAD. 41% of recipients with EAD and 14% of recipients without EAD had an ICU stay > 4 days. Differences in survivals and lengths of stay remain when the analysis is confined to Child's class A and B patients only. By univariate analysis, pre-operative and donor factors predictive of EAD were: PRE-OP FACTORS MALE KARNOFSKY_>8 UNOS STATUS 1 CHILD CLASS C ACUTE LIV FAIL
P .04 .001 .001 .001 .001
PRE43P FACTORS RENAL FAK..URE (31 BLEED/NG ENCEPHAI~PATH BILIRUBIN BUN PROTIME
P .006 .005 .001 .001 .001 .001
DONOR FACTORS AGE-> 50 RACE-NONWHiTE SURGEON ASSESS COLDISCHEMIA
P .001 .04 .001 .001
By multivariate analysis, factors independently associated with EAD and their respective odds ratios were bilirubin (1.04 per mg% increase), PT >15 sec (1.72), donor age >_50yr. (2.53), ABO mismatch (2.38),pre-procurement acidosis (1.54) and cold ischemia time (1.11 per 1 heour increase). SUMMARY: EAD has important effects on a variety of post-OLT outcomes and requires more hospital resources.
131 DETECTION OF ALBUMIN mRNA IN BLOOD AFTER LIVER
132 PORTAL FLOW AFTER ORTHOTOPIC LIVER TRANSPLANT
TRANSPLANTATION IN PATIENTS WITH BENIGN LIVER DISEASE H.G.M.Niesters'. D.J.Bac 2. S.W.Schalm 2, H.W.Tilanus s end J.N.M.IJzermans 3. Dept. of Virology', Internal Medicine II2 and Surgery 3, University Hospital Rotterdam, The Netherlands.
EVALUATED BY PER-RECTAL PORTAL SCINTIGRAPHY WITH TECHNETIUM-99M PERTHECHNETATE. A.D'Artenzo. LCelentano**. L.Cimino*. F.Manouso. G.piirrilli*, D.Mattara. M.Di Pieno. G.V'cinanza. G;Budillon*. (3.M=w-t=~.r_~, I e *11 Cattadra di Gastrnentarologia, ** Cattadrs di Medicine Nudeara, University "Fededco Ir', Naples, Italy.
Albumin mRNA is a liver-specific cell marker. It has been suggested that a positive albumin mRNA-PCR in blood in patients with a hepatocellular carcinoma may indicate shedding of liver tumourcells into the circulation. Thus, the test may identify a subgroup of patients with hepatocellular carcinoma that has a high risk of tumour recurrence after livertransplantation [LTx]. Using a highly sensitive mRNA-PCR assay, we studied the cell release in relation to LTx. Peripheral and central blood samples were.taken at regular intervals from consecutive patients undergoing LTx for benign liver disease, and mixed with guanidinium-iso-thiocyanate to isolate total nucleic acids. The results demonstrate t h a t albumin-mRNA could be detected in central as well as peripheral blood samples collected after recipient hepatectomy, but not before liversurgery. Furthermore, a semi-quantitative analysis shows an increase after reperfusion of the donor liver. As histological examination of the hepatectomized livers confirmed the absence of any malignancy, we conclude that a positive albumin-mRNA PCR test has no specific predictive value for hepatocellular carcinoma. Additonal specificity should be obtained before making clinical decisions.
In patients with orthotopic liver transplant (OLT) portal pressure normalizes even though a splenomegaly and hypersplenism may persist. Per-rectal portal sdntigraphy with Technetium-99m perthechnetate (99mTc-tast) is useful to evaluate the development of activated shunts from the infedor mesentedc vein to the inferior vena ceva due to the development of portal hypertension in cint,mtJc patients: an haemodynemic recording of hepatic and cardiac imaging was obtained after the rectal release of 1 ml 99m-Tc-perthecr~tate (specific activity 7.5 mCi/ml). The ratio between heart radioactivity and the sum of heart and liver radioactivity in the first 30 seconds of observation is defined as Shunt Index (S.I.). (No0Tnalvalue: <20%). In order to evaluate the changes in portal flow alter OLT, we studied 10 male patients (mean age +_SD: 52+_9)who had undergone OLT due to cirrhosis, Child B or C, viral etiology, with marked signs of penal h ~ , us~g the 99mTc-taat. The test was parformed 1 to41 months after OLT (mean +_SD:23+_13).The mean +_SDplatalet count was 123.900+_30.428/ram3. All patients showed an imaging pattern virtually identical to that of healty subjects with an S.I. below 19% (mean _+SD: 12.07+-4.60). A s i ~ inverse correlation was observed between the S.I. values and the platatet counts (y=176890-4390x, r= -0.66, p= 0.036). Our data demonsnta a normalization of the mesentadc flow after OLT v~ll the clostxe of the shunts even in the patients in which signs of h y p e r ~ persist. Lower S.I. values are observed in patients ~dth normal platlet counts.