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Mo rtality rate o n th e w aitin g lis t fo r liv e r trans p lan tatio n M.Vo ic u le s c u , Marian a Mih aila C e n te r o f In te rn al Me d ic in e Fu n d e n i C lin ic al In s titu te B u c h are s t
B ac kg ro u n d - Liv e r tran s p lan tatio n is n o w re c o g n is e d as a h ig h ly e ffe c tiv e fo rm o f tre atm e n t fo r p atie n ts w ith e n d s tag e liv e r d is e as e . - C u rre n tly , o n e an d fiv e y e ar s u rv iv al rate s are in e x c e s s o f 8 0% . - A s a c o n s e q u e n c e o f m an y d e v e lo p m e n ts in all as p e c ts o f tran s p lan tatio n , in d ic atio n s h av e w id e n e d an d c o n train d ic atio n s h av e b e c o m e fe w e r .
B ac kg ro u n d - Th e in c re as e in th e n u m b e r o f p atie n ts re fe rre d fo r tran s p lan tatio n h as n o t b e e n m atc h e d b y an in c re as e in d o n o r rate s . - Th e c o n s e q u e n c e o f th e re lativ e s h o rtag e o f d o n o rs is : - m o re p atie n ts are o n the w aitin g lis t fo r tran s p lan tatio n - th o s e o n th e w aitin g lis t b e c o m e s ic k e r b e fo re th e y re c e iv e a g raft - th e re is the lik e lih o o d o f m o re d e ath s o n th e w aitin g lis t .
O b je c tiv e s To u n d e rs tan d th e c au s e s o f d e ath an d als o to id e n tify m arke rs w h ic h c o u ld d e te rm in e p atie n ts at h ig h ris k o f d y in g o n th e w aitin g lis t, w e u n d e rto o k a re tro s p e c tiv e an aly s is o f all p atie n ts (ad u lts an d c h ild re n ) lis te d b e tw e e n J an u ary 2 0 0 1 an d De c e m b e r 2 0 0 2.
Mate rial and m e th o d (1 ) : • This is a re tro s p e c tiv e s tu d y ; • 10 9 p atie n ts w e re ac c e p te d fo r tran s p lan tatio n .
Mate rial and m e th o d (2 ) : • A g e re p a rtit io n : - ad u lts (>16 y e ars o ld ): m e an ag e 4 7 +/ .3 y e ars -2 - c h ild re n (<16 y e ars o ld ): b e tw e e n 4 m o n th s an d 1 5 y e ars • S e x re pa rt itio n : - 41 fe m ale (37 .6 1 % ) - 66 m ale (62.3 9 % )
Mate rial and m e th o d (3 ) : E tio lo g y o f C h ro nic Liv e r Dis e as e : • c h ro n ic h e p atitis : - HVB : 24 (22.01% ) - HB V+HDV : 15 (17.76% ) - HC V : 30 (27% ) - HB V+HC V : 8 ( 7. 33% ) • alc o h o lic liv e r d is e as e : 9 (8 .2 5 % ) • Wils o n ’s d is e as e : 8 (7 .3 4 % ) • o th e r 1 5 (1 3 .7 6 % ) : - au to im m u n e h e p atitis - p rim ary b iliary c irrho s is - HHC - m e tab o lic liv e r d is e as e - b iliary atre s ia
Re s ults (1) : - C h ild-P u g h s c o re a t a dm is s io n fo r a ll g ro u ps : - A =2 (1 .8 3 % ) - B =76 (6 9 .7 2 % ) - C =31 (2 8 .4 4 % ) - C h ild-P u g h s c o re a t a dm is s io n in pa tie n ts w h o die d: - A =0
Re s ults (2) : • Mo rta lity ra te : - 16 p atie n ts in 2 4 m o n th s (9 .7 8 % / e ar) y • E tio lo g y o f c h ro n ic liv e r dis e a s e in de c e a s e d pa tie n ts do e s n o t s e e m to in flu e n c e the m o rta lity ra te : - h e p atitis v iru s 1 0 (1 2 .9 8 % ) - alc o h o l 2 (22 .2 2 % ) - Wils o n ’s d is e as e 1 (1 2 ,5 % ) - o th e rs 3 (20% )
Re s ults (3) : C a us es of death were the following: - liv e r failu re 9 (5 6 .2 2 % ) - h e p ato re n al s y n d ro m e 4 (2 5 % ) - u p p e r d ig e s tiv e b le e d in g 3 (1 8 .7 8 % )
Dis c us s io ns : - a ne w s c o re is us e d fo r im p ro v in g the m o rtality rate in the liv e r tran s p lantatio n w aitin g lis t: the ME LD s c o re (m o d e l fo r e nd s tag e liv e r d is e as e ) - th e ME LD s c o re is hig h ly p re d ic tiv e fo r e v aluating th e ris k o f d e ath in p atie nts o n th e w aiting lis t ME LD s c o re = [0.957 x lo g e c r (m g / l) + 0.37 x lo g e b il d (m g / l) + 1.120 x lo g e (INR) + 0.643] x 10 d
Dis c us s io ns : Waitin g lis t d ata fo r liv e r trans p lantatio n in th e UK 1990 1991 1992 1993 1994 1995 1996 1997 360 4439 504 577 629 675 872 696 N e w pts re g is te re d T ra n s pla n t s 358 421 508 534 620 669 640 671 Die d o n 37 30 42 57 51 56 59 66 a c tiv e lis t R e m o v e d fro m 19 38 35 41 40 41 47 81 UKTS aA tiv e lis t S c
Dis c us s io ns : B lo o d T y pe Year 1995 1996 1997 1998 1999 2000 2001 T o ta l P a tie n t s 10475 12734 14947 17807 21063 23561 25746 De a t h s 829 998 1187 1421 1821 1763 1978 Ra te 1 7 7 ,4 1 5 6 ,4 1 4 3 ,8 1 3 7 ,0 1 4 1 ,9 1 1 7 ,2 1 1 4 ,7 O P a tie n t s 5083 6226 7340 8782 10358 11572 12598 De a t h s 437 513 621 751 915 919 1 ,0 1 4 Ra te 1 8 0 ,6 1 5 3 ,3 1 4 6 ,0 1 4 0 ,8 1 3 9 ,6 1 1 9 ,8 1 1 6 ,6 A P a tie n t s 3744 4635 5366 6370 7549 8533 9273 De a t h s 254 336 384 488 645 589 661 Ra te 1 6 2 ,4 1 5 4 ,5 1 3 3 ,2 1 3 5 ,4 1 4 4 ,5 1 1 1 ,7 1 1 1 ,8 B P a tie n t s 1272 1423 1702 2066 2473 2735 3047 De a t h s 111 116 143 139 208 199 228 Ra te 2 0 2 ,0 1 7 4 ,1 1 6 2 ,3 1 2 1 ,7 1 4 3 ,3 1 1 8 ,0 1 1 5 ,8
Dis c us s io ns : Re p o rte d d e ath s an d an n u al d e ath rate s p e r 1 00 0 p atie n t y e ars G e n de r Year 1995 1996 1997 1998 1999 2000 2001 T o ta l P a t ie n t s 10475 12734 14947 17807 21063 23561 25746 De a t hs 829 998 1187 1421 1821 1763 1978 Ra te 1 7 7 ,4 1 5 6 ,4 1 4 3 ,8 1 3 7 ,0 1 4 1 ,9 1 1 7 ,2 1 1 4 ,7 F e m a le P a t ie n t s 4728 5584 6440 7498 8827 9830 10686 De a t hs 356 420 486 601 742 701 830 Ra te 1 6 3 ,2 1 4 5 ,4 1 3 4 ,0 1 3 4 ,2 1 3 5 ,1 1 0 9 ,2 1 1 3 ,1 Ma le O PTN/ RTR S P a t ie n t s 5747 7150 8507 10309 12236 13731 15060
Dis c us s io ns : Patient status Year 1995 1996 1997 1998 1999 2000 2001 Total 5572 7352 9452 11782 14258 16565 18505 1 28 29 15 7 14 14 13 2 103 113 - - - - - 2A - - 17 31 45 63 132 2B - - 136 1952 2656 3027 3032 3 2746 3979 7522 7944 9573 11157 12101 4 1854 2236 - - - - - Temporarily 841 995 1762 1848 1970 2304 3227 inactive Total (%) 100% 100% 100% 100% 100% 100% 100% 1 0,5% 0,4% 0,2% 0,1% 0,1% 0,1% 0,1% 2 1,8% 1,5% - - - - - 2A - - 0,2% 0,3% 0,3% 0,4% 0,7% 2B - - 1,4% 16,6% 18,6% 18,3% 16,4% 3 49,3% 54,1% 79,6% 67,4% 87,1% 67,4% 65,4% 4 33,3% 30,4% - - - - - Temporarily 15,1% 13,5% 18,6% 15,7% 13,6% 13,9% 17,4% inactive
C o n c lus io ns (1) : - th e annu al m o rtality rate (9.78% ) is s im ilar to d ata fro m the lite rature (5-12% )
C o n c lus io ns (1) : - th e m o rtality rate is NO T in flu e n c e d b y e tio lo g y o f c h ro n ic liv e r d is e as e - th e m o rtality rate is in flu e n c e d b y th e s e v e rity o f th e d is e as e at ad m is s io n to th e w aitin g lis t
C o n c lus io ns (2) : - th e m ain c au s e s o f d e ath are re p re s e n te d b y liv e r failu re , fo llo w e d b y h e p ato -re n al s y n d ro m e an d u p p e r d ig e s tiv e b le e d in g - im p ro v e m e n t o f th e m o rtality rate c o u ld b e o b tain e d th ro u g h a b e tte r c o n tro l o f th e c au s e s o f d e ath , b e c au s e th e n u m b e r o f d o n o rs c an n o t b e in flu e n c e d - th e p re c o c io u s d iag n o s is o f h e p ato -re n al s y n d ro m e an d p re v e n tio n o f u p p e r d ig e s tiv e b le e d in g m ay b e th e o n ly m e as u re s th at c an b e tak e n fo r re d u c in g m o rtality , b e c au s e liv e r failu re c an n o t b e p re v e n te d b y m e d ic al m e as u re s
C o n c lus io ns (3) : - d e s p ite th e in n o v ativ e u s e o f te c h n iq u e s to m ake fu lle s t u s e o f th e d o n o r p o o l, s u c h as s p littin g o f liv e rs an d in c re as in g u s e o f m arg in al liv e rs (th o s e liv e rs w h e re th e re is d o u b t as to in itial g raft fu n c tio n ), th e d e m an d fo r tran s p lan tatio n is failin g to m e e t th e s u p p ly - m o rtality o n th e w aitin g lis t is a s ig n ific an t p ro b le m an d is like ly to ris e fu rth e r u n til d o n o r s h o rtag e c an b e re v e rs e d o r alte rn ativ e s trate g ie s c an b e in tro d u c e d - tim in g o f re fe rral fo r c o n s id e ratio n o f tran s p lan tatio n re m ain s p ro b le m atic
C o n c lus io ns (4) : - if p atie n ts are re fe rre d an d lis te d e arly fo r tran s p lan tatio n th e n , b e c au s e o f th e p e rio p e rativ e ris k an d s m all e arly m o rtality , th e re is a ris k th e p atie n t’s life m ig h t b e s h o rte n e d - th e tran s p lan t c lin ic ian s n e e d to e s tab lis h g u id e lin e s to d e te rm in e w h e n th e p atie n t’s c h an c e s o f s u rv iv al are s o lo w th at tran s p lan tatio n b e c o m e s n o lo n g e r in d ic ate d

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  • 1. Mo rtality rate o n th e w aitin g lis t fo r liv e r trans p lan tatio n M.Vo ic u le s c u , Marian a Mih aila C e n te r o f In te rn al Me d ic in e Fu n d e n i C lin ic al In s titu te B u c h are s t
  • 2. B ac kg ro u n d - Liv e r tran s p lan tatio n is n o w re c o g n is e d as a h ig h ly e ffe c tiv e fo rm o f tre atm e n t fo r p atie n ts w ith e n d s tag e liv e r d is e as e . - C u rre n tly , o n e an d fiv e y e ar s u rv iv al rate s are in e x c e s s o f 8 0% . - A s a c o n s e q u e n c e o f m an y d e v e lo p m e n ts in all as p e c ts o f tran s p lan tatio n , in d ic atio n s h av e w id e n e d an d c o n train d ic atio n s h av e b e c o m e fe w e r .
  • 3. B ac kg ro u n d - Th e in c re as e in th e n u m b e r o f p atie n ts re fe rre d fo r tran s p lan tatio n h as n o t b e e n m atc h e d b y an in c re as e in d o n o r rate s . - Th e c o n s e q u e n c e o f th e re lativ e s h o rtag e o f d o n o rs is : - m o re p atie n ts are o n the w aitin g lis t fo r tran s p lan tatio n - th o s e o n th e w aitin g lis t b e c o m e s ic k e r b e fo re th e y re c e iv e a g raft - th e re is the lik e lih o o d o f m o re d e ath s o n th e w aitin g lis t .
  • 4. O b je c tiv e s To u n d e rs tan d th e c au s e s o f d e ath an d als o to id e n tify m arke rs w h ic h c o u ld d e te rm in e p atie n ts at h ig h ris k o f d y in g o n th e w aitin g lis t, w e u n d e rto o k a re tro s p e c tiv e an aly s is o f all p atie n ts (ad u lts an d c h ild re n ) lis te d b e tw e e n J an u ary 2 0 0 1 an d De c e m b e r 2 0 0 2.
  • 5. Mate rial and m e th o d (1 ) : • This is a re tro s p e c tiv e s tu d y ; • 10 9 p atie n ts w e re ac c e p te d fo r tran s p lan tatio n .
  • 6. Mate rial and m e th o d (2 ) : • A g e re p a rtit io n : - ad u lts (>16 y e ars o ld ): m e an ag e 4 7 +/ .3 y e ars -2 - c h ild re n (<16 y e ars o ld ): b e tw e e n 4 m o n th s an d 1 5 y e ars • S e x re pa rt itio n : - 41 fe m ale (37 .6 1 % ) - 66 m ale (62.3 9 % )
  • 7. Mate rial and m e th o d (3 ) : E tio lo g y o f C h ro nic Liv e r Dis e as e : • c h ro n ic h e p atitis : - HVB : 24 (22.01% ) - HB V+HDV : 15 (17.76% ) - HC V : 30 (27% ) - HB V+HC V : 8 ( 7. 33% ) • alc o h o lic liv e r d is e as e : 9 (8 .2 5 % ) • Wils o n ’s d is e as e : 8 (7 .3 4 % ) • o th e r 1 5 (1 3 .7 6 % ) : - au to im m u n e h e p atitis - p rim ary b iliary c irrho s is - HHC - m e tab o lic liv e r d is e as e - b iliary atre s ia
  • 8. Re s ults (1) : - C h ild-P u g h s c o re a t a dm is s io n fo r a ll g ro u ps : - A =2 (1 .8 3 % ) - B =76 (6 9 .7 2 % ) - C =31 (2 8 .4 4 % ) - C h ild-P u g h s c o re a t a dm is s io n in pa tie n ts w h o die d: - A =0
  • 9. Re s ults (2) : • Mo rta lity ra te : - 16 p atie n ts in 2 4 m o n th s (9 .7 8 % / e ar) y • E tio lo g y o f c h ro n ic liv e r dis e a s e in de c e a s e d pa tie n ts do e s n o t s e e m to in flu e n c e the m o rta lity ra te : - h e p atitis v iru s 1 0 (1 2 .9 8 % ) - alc o h o l 2 (22 .2 2 % ) - Wils o n ’s d is e as e 1 (1 2 ,5 % ) - o th e rs 3 (20% )
  • 10. Re s ults (3) : C a us es of death were the following: - liv e r failu re 9 (5 6 .2 2 % ) - h e p ato re n al s y n d ro m e 4 (2 5 % ) - u p p e r d ig e s tiv e b le e d in g 3 (1 8 .7 8 % )
  • 11. Dis c us s io ns : - a ne w s c o re is us e d fo r im p ro v in g the m o rtality rate in the liv e r tran s p lantatio n w aitin g lis t: the ME LD s c o re (m o d e l fo r e nd s tag e liv e r d is e as e ) - th e ME LD s c o re is hig h ly p re d ic tiv e fo r e v aluating th e ris k o f d e ath in p atie nts o n th e w aiting lis t ME LD s c o re = [0.957 x lo g e c r (m g / l) + 0.37 x lo g e b il d (m g / l) + 1.120 x lo g e (INR) + 0.643] x 10 d
  • 12. Dis c us s io ns : Waitin g lis t d ata fo r liv e r trans p lantatio n in th e UK 1990 1991 1992 1993 1994 1995 1996 1997 360 4439 504 577 629 675 872 696 N e w pts re g is te re d T ra n s pla n t s 358 421 508 534 620 669 640 671 Die d o n 37 30 42 57 51 56 59 66 a c tiv e lis t R e m o v e d fro m 19 38 35 41 40 41 47 81 UKTS aA tiv e lis t S c
  • 13. Dis c us s io ns : B lo o d T y pe Year 1995 1996 1997 1998 1999 2000 2001 T o ta l P a tie n t s 10475 12734 14947 17807 21063 23561 25746 De a t h s 829 998 1187 1421 1821 1763 1978 Ra te 1 7 7 ,4 1 5 6 ,4 1 4 3 ,8 1 3 7 ,0 1 4 1 ,9 1 1 7 ,2 1 1 4 ,7 O P a tie n t s 5083 6226 7340 8782 10358 11572 12598 De a t h s 437 513 621 751 915 919 1 ,0 1 4 Ra te 1 8 0 ,6 1 5 3 ,3 1 4 6 ,0 1 4 0 ,8 1 3 9 ,6 1 1 9 ,8 1 1 6 ,6 A P a tie n t s 3744 4635 5366 6370 7549 8533 9273 De a t h s 254 336 384 488 645 589 661 Ra te 1 6 2 ,4 1 5 4 ,5 1 3 3 ,2 1 3 5 ,4 1 4 4 ,5 1 1 1 ,7 1 1 1 ,8 B P a tie n t s 1272 1423 1702 2066 2473 2735 3047 De a t h s 111 116 143 139 208 199 228 Ra te 2 0 2 ,0 1 7 4 ,1 1 6 2 ,3 1 2 1 ,7 1 4 3 ,3 1 1 8 ,0 1 1 5 ,8
  • 14. Dis c us s io ns : Re p o rte d d e ath s an d an n u al d e ath rate s p e r 1 00 0 p atie n t y e ars G e n de r Year 1995 1996 1997 1998 1999 2000 2001 T o ta l P a t ie n t s 10475 12734 14947 17807 21063 23561 25746 De a t hs 829 998 1187 1421 1821 1763 1978 Ra te 1 7 7 ,4 1 5 6 ,4 1 4 3 ,8 1 3 7 ,0 1 4 1 ,9 1 1 7 ,2 1 1 4 ,7 F e m a le P a t ie n t s 4728 5584 6440 7498 8827 9830 10686 De a t hs 356 420 486 601 742 701 830 Ra te 1 6 3 ,2 1 4 5 ,4 1 3 4 ,0 1 3 4 ,2 1 3 5 ,1 1 0 9 ,2 1 1 3 ,1 Ma le O PTN/ RTR S P a t ie n t s 5747 7150 8507 10309 12236 13731 15060
  • 15. Dis c us s io ns : Patient status Year 1995 1996 1997 1998 1999 2000 2001 Total 5572 7352 9452 11782 14258 16565 18505 1 28 29 15 7 14 14 13 2 103 113 - - - - - 2A - - 17 31 45 63 132 2B - - 136 1952 2656 3027 3032 3 2746 3979 7522 7944 9573 11157 12101 4 1854 2236 - - - - - Temporarily 841 995 1762 1848 1970 2304 3227 inactive Total (%) 100% 100% 100% 100% 100% 100% 100% 1 0,5% 0,4% 0,2% 0,1% 0,1% 0,1% 0,1% 2 1,8% 1,5% - - - - - 2A - - 0,2% 0,3% 0,3% 0,4% 0,7% 2B - - 1,4% 16,6% 18,6% 18,3% 16,4% 3 49,3% 54,1% 79,6% 67,4% 87,1% 67,4% 65,4% 4 33,3% 30,4% - - - - - Temporarily 15,1% 13,5% 18,6% 15,7% 13,6% 13,9% 17,4% inactive
  • 16. C o n c lus io ns (1) : - th e annu al m o rtality rate (9.78% ) is s im ilar to d ata fro m the lite rature (5-12% )
  • 17. C o n c lus io ns (1) : - th e m o rtality rate is NO T in flu e n c e d b y e tio lo g y o f c h ro n ic liv e r d is e as e - th e m o rtality rate is in flu e n c e d b y th e s e v e rity o f th e d is e as e at ad m is s io n to th e w aitin g lis t
  • 18. C o n c lus io ns (2) : - th e m ain c au s e s o f d e ath are re p re s e n te d b y liv e r failu re , fo llo w e d b y h e p ato -re n al s y n d ro m e an d u p p e r d ig e s tiv e b le e d in g - im p ro v e m e n t o f th e m o rtality rate c o u ld b e o b tain e d th ro u g h a b e tte r c o n tro l o f th e c au s e s o f d e ath , b e c au s e th e n u m b e r o f d o n o rs c an n o t b e in flu e n c e d - th e p re c o c io u s d iag n o s is o f h e p ato -re n al s y n d ro m e an d p re v e n tio n o f u p p e r d ig e s tiv e b le e d in g m ay b e th e o n ly m e as u re s th at c an b e tak e n fo r re d u c in g m o rtality , b e c au s e liv e r failu re c an n o t b e p re v e n te d b y m e d ic al m e as u re s
  • 19. C o n c lus io ns (3) : - d e s p ite th e in n o v ativ e u s e o f te c h n iq u e s to m ake fu lle s t u s e o f th e d o n o r p o o l, s u c h as s p littin g o f liv e rs an d in c re as in g u s e o f m arg in al liv e rs (th o s e liv e rs w h e re th e re is d o u b t as to in itial g raft fu n c tio n ), th e d e m an d fo r tran s p lan tatio n is failin g to m e e t th e s u p p ly - m o rtality o n th e w aitin g lis t is a s ig n ific an t p ro b le m an d is like ly to ris e fu rth e r u n til d o n o r s h o rtag e c an b e re v e rs e d o r alte rn ativ e s trate g ie s c an b e in tro d u c e d - tim in g o f re fe rral fo r c o n s id e ratio n o f tran s p lan tatio n re m ain s p ro b le m atic
  • 20. C o n c lus io ns (4) : - if p atie n ts are re fe rre d an d lis te d e arly fo r tran s p lan tatio n th e n , b e c au s e o f th e p e rio p e rativ e ris k an d s m all e arly m o rtality , th e re is a ris k th e p atie n t’s life m ig h t b e s h o rte n e d - th e tran s p lan t c lin ic ian s n e e d to e s tab lis h g u id e lin e s to d e te rm in e w h e n th e p atie n t’s c h an c e s o f s u rv iv al are s o lo w th at tran s p lan tatio n b e c o m e s n o lo n g e r in d ic ate d