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Cardiac evaluation in adult liver transplant candidates
210A
413
PROPOSAL
AASLD ABSTRACTS
FOR
A
STANDARDISED
: CLINICOPATHOLOGICAL
CLASSIFICATION OF LlYER TRANSPLANT FAILURE John Devlin. Ro~er Williams. Instituteof Liver Studies, Kings CollegeSchool of Medicine ~d Dentistry, London,U K
414
A standardised classificationof liver Iransplant(Tx) failure is required. Such a scheme,if basedaround the underlyingelinico-pathological processes,should promote interpretation Of published results, facilitate audit and seientific communication and allow identification of changing clinieal patterns. Methode An analysis of 126 consecutive Tx failuresexperiencedbetween I/I/90 and 31/12/93 was performed.Followingdocumentationof the clinical syndromes considered to be the primary and predominant morbid events leading to retransplantationor death, a c!inieo-pathologicalclassificationis proposed. R,=sult,=From the 126 transplant failures, 101 (80%) weredue to patient death and.25 (20%i retransplantati0n. All0graftrejection,vascular thromboses,diseaserecurrence,sepsisand abdominalHeeding were the major events. Other causes included unexpectedsystemiccomplications, GVHD, non-thrombotic graft infarction, pulmonaryhaemorrhage,Stevens-Johnson syndrome and de novo malignancy. An 8 eategury classification of the predominantunderlyingclinico-pathogenicprocessesbased upon examination of the natural historyof each ease is prolmSed:.
and infection) or unfavourablepretransplantcharacteristics, such as severe malnutrition, leading to Tx failure were placed in group l. Primary graft dysfunction encompasses the spectrum of disordered function reflecting impaired organ viability. Immunologicalfailure includes rejection and graftversus-host processes. Events initiated or aggravated significantly by immunosuppressionare placed in category 6. Failure of a systemic organ system,in the absenceof graft failure or any of the other category processes (e.g. unexplainedGI bleeding),are classifiedunder the umbrella term 'organsystem' transplant failure. Finally, a 'miscellaneous' group is proposed. Con©luelon A consensusin nomenclaturesurroundingfailure of a liver transplantwouldbe valuable. The present proposalhas the meritof identifying and eategurisingthe predominantaetiologicalfactors involved rather than the less informativeend-stageclinical episode.
UNRECOGNIZED ALPIIA-I-ANTITR~PSIN CARRIAGE IN L I V E R DONORS. C a l d w e l l SH, N o r m a n s e l l DE, Stace 7
E, Ishitani MB. Dickson RC, Stevenson WC. O l i v e i r a W, G a f f e r M, Iezzoni JC. M c C u l l o u u h CS. Sue M, Driscoll C, P r u e t t TL. I n t e r n a l Medicine, P a t h o l o g y and Surgery, U n i v e r s i t y of Virginia, Charlottesville, Va., USA. C a r r i a g e of an abnormal a l p h a - l - a n t i t r y p s i n (AIA) p h e n o t y p e may p o t e n t i a t e p r o g r e s s i o n of c h r o n i c liver disease. C a r r i a g e is o f t e n silent and h e n c e may go u n r e c o g n i z e d in d o n o r organs. P u r p o s e : To d e t e r m i n e the p r e v a l e n c e of a b n o r m a l AIA p h e n o t y p e s in d o n o r livers. Methods: We c o n s e c u t i v e l y p h e n o t y p e d r e c l p i e n t and d o n o r serum from 34 p a t i e n t s u n d e r g o i n g 36 liver t r a n s p l a n t a t i o n s . Specimens were s t o r e d at -70°c until assayed. PI type was determined by isoelectric focusing performed on A m p h o l i n e p l a t e s (Fharmacia) at p H 4-5. 15cc of c y s t i e n e r e d u c e d s e r u m was applied to a p r e f o c u s e d gel and focused for 3 hours at 30W, 1400V, 50mA. P. R e s u l t s : i0 of 33 (30%) r e c i p i e n t s had a b n o r m a l PI types; 6 were MS, 1 was MZ, 1 was MF, I was SS and 1 was ZZ. A m o n g the d o n o r organs, 9 of 34 (26%) had a b n o r m a l PI types; 6 were MS, 2 were MZ and 1 was ZZ. The latter p a t i e n t e x p r e s s e d a b n o r m a l l y low serum A I A p o s t - o p e r a t i v e l y . He died at six m o n t h s from lymphoma, conolusioms: A b n o r m a l a l p h a - l - a n t i t r y p s i n p h e n o t y p e is common in our liver r e c i p i e n t s w i t h v a r i o u s liver d i s e a s e s and in o t h e r w i s e h e a l t h y a p p e a r i n g d o n o r livers. L o n g t e r m f o l l o w u p of r e c i p i e n t s of c a r r l e r organs w i l l be n e c e s s a r y to assess the c l i n i c a l s i g n f i c a n c e of t h e s e o b s e r v a t i o n s on graft function.
CARDIAC EVALUATION IN ADULT LIVER TRANSPLANT CANDIDATES Donovan CL. Brown KA. Punch JD. Marcovitz PA. Bach DS, Armstron~ WF. Lucev MR. Departments of Internal Medicine and Surgery, )dniversity-of Michigan Medical Center, Ann Arbor, Michigan, 48108. The prevalence and clinical significance of cardiac dysfunction among patients with chronic end stage liver disease (ESLD), undergoing evaluation for orthotopic liver transplantation (OLT) are unknown. We prospectively evaluated 190 adults with ESLD referred for OLT using 2 dimensional echocardiography (n=190), Dobutamine stress echo (n=165), and cardiac catheterization (n=18). There were 92 (48%) males and 98 (52%) females. 85 patients had alcoholic cirrhosis. Other risk factors for cardiac disease were as follows : Diabetes Mellitus 30 (16 %), hypertension 43 (22%), family history 52 (27 %), hyperlipidemia 33 (17%), known coronary artery disease 7 (4%). Results: There were no significant differences between alcoholic and non alcoholic candidates in left ventricular volume and diameter, either in systole or diastole, or in ejection fraction. 13 patients had an ejection fraction of < 50%, of whom 8 were non alcoholic and 5 were alcoholic. OLT was denied because of the cardiac evaluation in 8 patients for the following reasons : alcoholic cardjomyopathy (n=2), coronary artery disease (n=3), pulmonary hypertension (n=3). 71 patients received an OLT. Cardiac complications after OLT included myocardial infarction (h=l), acute left ventricular dysfunction (n=4), arrhythmia (n=10), and pulmonary edema (n=39). No preoperative echocardiographic parameters predicted untoward cardiac events after OLT. Conclusions : 1) the majority of ESLD patients evaluated for OLT have structurally normal hearts on echocardiography, 2) few patients are excluded on cardiac grounds, 3) major postoperati,/e cardiac events are not predicted by preoperative echocardiography, 4) in this population, alcoholic cardiomyopathy is rare, and alcoholism does not confer an increased risk of perioperative cardiac events.
1. Pretransplant recipient slinlcal status (n=la) 2. Primary gr'eft dysfunction (n=12) 3. Technical Complications (n=25) 4. immunological failure (n=34) 5: Disease recurrence (n=13) 6. Immunosupprecsion-related (n=12} 7. Primary[ organ system fa ure (n=10) 8. Msce aneous (n=6)[ Established pathology present at Tx (e.g. cardiovascular, cerebral disorde~'s
415
HEPATOLOGY October 1995
416
E P S T E I N - B A R R VIRUS - RELATED POST TRANSPLANT L Y M P H O P R O L 1 F E R A T I V E D I S E A S E O F DONOR ORIGIN IN T W O ORTHOTOPIC LIVER TRANSPLANT RECIPIENTS. °RM Iemmolo, *G Gerund% *R Merenda *D Neri, ~A Poletti, ^E D'Andrea, ^B Comeo, AM Montagna, AC Menin, ^A Del Mistro and °M Strazzaboseo. Institutes of °Internal Medicine, *General Surgery I," AOneology and §Pathology, University of Padova, Padova, Italy.
Post transplant lymphoproljferative disease (PTLD) is a potential complication of solid organ transplantation in recipients on cyclosporine A/prednisone regimen. We report the genetic and virological characterization of two PTLD cases presenting 4 and 6 months after orth0topic liver transplant (OLTX) as non-Hodgkin large cells lymphomas located at the hilum hepatis. The lymphomatous tissue was analyzed for clonality of IgI-I gene rearrangement by Southern blot and "semi-nested" PCR; the presence of Epstein-Barr Virus (EBV) genetic material was assessed by Southern blot with a Xho I probe (case #1) and by PCR with primers specific for EBV sequences. Both tumors were sustained by clonal proliferation of B cells that contained type A EBV DNA (in episomal configuration in case #1). In addition, in situ hybridization with a digoxiganin-labelled EBV large internal repeat probe showed a strong nuclear signal in the neoplastic cells. Finally, PCR amplification of DNA microsatellites at three different genetic loci detected alleles of donor origin in both tumor samples, suggesting that neoplastic B cells were of donor origin. EBV-infected donor B lymphocytes may thus be responsible for intragraft PTLD in OLTx recipients. Since 20 to 30% post-transplant lymphomas involve the graft itself, donor-derived PTLD may be a relatively frequent phenomenon and prospective studies should be planned to identify possible risk factors.
413
PROPOSAL
AASLD ABSTRACTS
FOR
A
STANDARDISED
: CLINICOPATHOLOGICAL
CLASSIFICATION OF LlYER TRANSPLANT FAILURE John Devlin. Ro~er Williams. Instituteof Liver Studies, Kings CollegeSchool of Medicine ~d Dentistry, London,U K
414
A standardised classificationof liver Iransplant(Tx) failure is required. Such a scheme,if basedaround the underlyingelinico-pathological processes,should promote interpretation Of published results, facilitate audit and seientific communication and allow identification of changing clinieal patterns. Methode An analysis of 126 consecutive Tx failuresexperiencedbetween I/I/90 and 31/12/93 was performed.Followingdocumentationof the clinical syndromes considered to be the primary and predominant morbid events leading to retransplantationor death, a c!inieo-pathologicalclassificationis proposed. R,=sult,=From the 126 transplant failures, 101 (80%) weredue to patient death and.25 (20%i retransplantati0n. All0graftrejection,vascular thromboses,diseaserecurrence,sepsisand abdominalHeeding were the major events. Other causes included unexpectedsystemiccomplications, GVHD, non-thrombotic graft infarction, pulmonaryhaemorrhage,Stevens-Johnson syndrome and de novo malignancy. An 8 eategury classification of the predominantunderlyingclinico-pathogenicprocessesbased upon examination of the natural historyof each ease is prolmSed:.
and infection) or unfavourablepretransplantcharacteristics, such as severe malnutrition, leading to Tx failure were placed in group l. Primary graft dysfunction encompasses the spectrum of disordered function reflecting impaired organ viability. Immunologicalfailure includes rejection and graftversus-host processes. Events initiated or aggravated significantly by immunosuppressionare placed in category 6. Failure of a systemic organ system,in the absenceof graft failure or any of the other category processes (e.g. unexplainedGI bleeding),are classifiedunder the umbrella term 'organsystem' transplant failure. Finally, a 'miscellaneous' group is proposed. Con©luelon A consensusin nomenclaturesurroundingfailure of a liver transplantwouldbe valuable. The present proposalhas the meritof identifying and eategurisingthe predominantaetiologicalfactors involved rather than the less informativeend-stageclinical episode.
UNRECOGNIZED ALPIIA-I-ANTITR~PSIN CARRIAGE IN L I V E R DONORS. C a l d w e l l SH, N o r m a n s e l l DE, Stace 7
E, Ishitani MB. Dickson RC, Stevenson WC. O l i v e i r a W, G a f f e r M, Iezzoni JC. M c C u l l o u u h CS. Sue M, Driscoll C, P r u e t t TL. I n t e r n a l Medicine, P a t h o l o g y and Surgery, U n i v e r s i t y of Virginia, Charlottesville, Va., USA. C a r r i a g e of an abnormal a l p h a - l - a n t i t r y p s i n (AIA) p h e n o t y p e may p o t e n t i a t e p r o g r e s s i o n of c h r o n i c liver disease. C a r r i a g e is o f t e n silent and h e n c e may go u n r e c o g n i z e d in d o n o r organs. P u r p o s e : To d e t e r m i n e the p r e v a l e n c e of a b n o r m a l AIA p h e n o t y p e s in d o n o r livers. Methods: We c o n s e c u t i v e l y p h e n o t y p e d r e c l p i e n t and d o n o r serum from 34 p a t i e n t s u n d e r g o i n g 36 liver t r a n s p l a n t a t i o n s . Specimens were s t o r e d at -70°c until assayed. PI type was determined by isoelectric focusing performed on A m p h o l i n e p l a t e s (Fharmacia) at p H 4-5. 15cc of c y s t i e n e r e d u c e d s e r u m was applied to a p r e f o c u s e d gel and focused for 3 hours at 30W, 1400V, 50mA. P. R e s u l t s : i0 of 33 (30%) r e c i p i e n t s had a b n o r m a l PI types; 6 were MS, 1 was MZ, 1 was MF, I was SS and 1 was ZZ. A m o n g the d o n o r organs, 9 of 34 (26%) had a b n o r m a l PI types; 6 were MS, 2 were MZ and 1 was ZZ. The latter p a t i e n t e x p r e s s e d a b n o r m a l l y low serum A I A p o s t - o p e r a t i v e l y . He died at six m o n t h s from lymphoma, conolusioms: A b n o r m a l a l p h a - l - a n t i t r y p s i n p h e n o t y p e is common in our liver r e c i p i e n t s w i t h v a r i o u s liver d i s e a s e s and in o t h e r w i s e h e a l t h y a p p e a r i n g d o n o r livers. L o n g t e r m f o l l o w u p of r e c i p i e n t s of c a r r l e r organs w i l l be n e c e s s a r y to assess the c l i n i c a l s i g n f i c a n c e of t h e s e o b s e r v a t i o n s on graft function.
CARDIAC EVALUATION IN ADULT LIVER TRANSPLANT CANDIDATES Donovan CL. Brown KA. Punch JD. Marcovitz PA. Bach DS, Armstron~ WF. Lucev MR. Departments of Internal Medicine and Surgery, )dniversity-of Michigan Medical Center, Ann Arbor, Michigan, 48108. The prevalence and clinical significance of cardiac dysfunction among patients with chronic end stage liver disease (ESLD), undergoing evaluation for orthotopic liver transplantation (OLT) are unknown. We prospectively evaluated 190 adults with ESLD referred for OLT using 2 dimensional echocardiography (n=190), Dobutamine stress echo (n=165), and cardiac catheterization (n=18). There were 92 (48%) males and 98 (52%) females. 85 patients had alcoholic cirrhosis. Other risk factors for cardiac disease were as follows : Diabetes Mellitus 30 (16 %), hypertension 43 (22%), family history 52 (27 %), hyperlipidemia 33 (17%), known coronary artery disease 7 (4%). Results: There were no significant differences between alcoholic and non alcoholic candidates in left ventricular volume and diameter, either in systole or diastole, or in ejection fraction. 13 patients had an ejection fraction of < 50%, of whom 8 were non alcoholic and 5 were alcoholic. OLT was denied because of the cardiac evaluation in 8 patients for the following reasons : alcoholic cardjomyopathy (n=2), coronary artery disease (n=3), pulmonary hypertension (n=3). 71 patients received an OLT. Cardiac complications after OLT included myocardial infarction (h=l), acute left ventricular dysfunction (n=4), arrhythmia (n=10), and pulmonary edema (n=39). No preoperative echocardiographic parameters predicted untoward cardiac events after OLT. Conclusions : 1) the majority of ESLD patients evaluated for OLT have structurally normal hearts on echocardiography, 2) few patients are excluded on cardiac grounds, 3) major postoperati,/e cardiac events are not predicted by preoperative echocardiography, 4) in this population, alcoholic cardiomyopathy is rare, and alcoholism does not confer an increased risk of perioperative cardiac events.
1. Pretransplant recipient slinlcal status (n=la) 2. Primary gr'eft dysfunction (n=12) 3. Technical Complications (n=25) 4. immunological failure (n=34) 5: Disease recurrence (n=13) 6. Immunosupprecsion-related (n=12} 7. Primary[ organ system fa ure (n=10) 8. Msce aneous (n=6)[ Established pathology present at Tx (e.g. cardiovascular, cerebral disorde~'s
415
HEPATOLOGY October 1995
416
E P S T E I N - B A R R VIRUS - RELATED POST TRANSPLANT L Y M P H O P R O L 1 F E R A T I V E D I S E A S E O F DONOR ORIGIN IN T W O ORTHOTOPIC LIVER TRANSPLANT RECIPIENTS. °RM Iemmolo, *G Gerund% *R Merenda *D Neri, ~A Poletti, ^E D'Andrea, ^B Comeo, AM Montagna, AC Menin, ^A Del Mistro and °M Strazzaboseo. Institutes of °Internal Medicine, *General Surgery I," AOneology and §Pathology, University of Padova, Padova, Italy.
Post transplant lymphoproljferative disease (PTLD) is a potential complication of solid organ transplantation in recipients on cyclosporine A/prednisone regimen. We report the genetic and virological characterization of two PTLD cases presenting 4 and 6 months after orth0topic liver transplant (OLTX) as non-Hodgkin large cells lymphomas located at the hilum hepatis. The lymphomatous tissue was analyzed for clonality of IgI-I gene rearrangement by Southern blot and "semi-nested" PCR; the presence of Epstein-Barr Virus (EBV) genetic material was assessed by Southern blot with a Xho I probe (case #1) and by PCR with primers specific for EBV sequences. Both tumors were sustained by clonal proliferation of B cells that contained type A EBV DNA (in episomal configuration in case #1). In addition, in situ hybridization with a digoxiganin-labelled EBV large internal repeat probe showed a strong nuclear signal in the neoplastic cells. Finally, PCR amplification of DNA microsatellites at three different genetic loci detected alleles of donor origin in both tumor samples, suggesting that neoplastic B cells were of donor origin. EBV-infected donor B lymphocytes may thus be responsible for intragraft PTLD in OLTx recipients. Since 20 to 30% post-transplant lymphomas involve the graft itself, donor-derived PTLD may be a relatively frequent phenomenon and prospective studies should be planned to identify possible risk factors.