Results of the first Liver transplantation program in Lozenets Hospital, Bulgaria. Lubomir Spassov, V.Pashev, G.Mutafov, M.Vassilev Milen Vassilev Резултати от първата трансплантационната програма в Болница Лозенец. Любомир Спасов, Вили Пъшев, Георги Мутафов, Милен Василев.

1. Abstract
Fig 1. Evolution of Liver Transplantations in Europe.
Source:www.eltr.org
Biliary
atresia
59%
Alagile
Syndrome
4%
PFIC3
4%
PFIC1
13%
Congenit
al defects
8%
ALF
8%
Wilson's
4% PBC
15%
PSC
15%
AIH
5%
HCV
HBV 10%
10%
ALD
15%
HCC
5%
Congenit
al fibrosis
5%
Cryptoge
nic
5%
NASH
5%
ALF
10%
Liver transplantation (Ltx) at Lozenets Hospital (LH) started with living donor transplantation (LDLT) in 2004 and orthotopic liver
transplantation (OLT) in 2005. Until 2007 it was the only Ltx program in Bulgaria and was offered only 19.17% of the available organs by
the EAT – the national organ procurement organization, for the 9 year period 23.4% of the available organs were allocated for LH. The
average waiting time for adults was 187±254 SD days, and for pediatric recipients 60± 97.25 SD. In the pediatric group, 24 LDLT and 1
cadaveric, split-liver transplantations were performed. The indications included: Biliary atresia 14, Alagyle syndrome –1, PFIC3 -1, PFIC1-
3, congenital defects 2, acute liver failure(ALF) – 2, Wilsons’s disease -1. In the adult group, 24 cadaveric OLT were performed, one of
which spilt-liver. The indications in the chronic liver disease (CLD) group were of PBC-3, PSC-3, AIH-1, HCV-2, HBV-2, HBV+HDV+HCC -
1, alcohol and cryptogenic cirrhosis -4, inborn fibrosis - 1, NASH-1, acute liver failure -2. Six patients with acute liver failure (ALF) were
referred and 4 were transplanted, 2 children and 2 adults. The rate of complications was low with 15 bleeding events, 6 requiring surgery, 4
episodes of acute rejection, 9 chronic rejection, 13 sepsis, 14 lung infections, 7 yeasts infection, 6 viral, mainly CMV&EBV. In the pediatric
group, the first month survival rate was 81%, one year survival rate was survival was 70%, including the ALF cases. The mean PELD score
of the survivors group was 18±13.1 and non survivors 23.28±13.1. The reasons for early patient loss were primary graft dysfunction,
sepsis and multi-organ failure. In the CLD group, one month survival rate was 90%, one year survival 85%, and currently 80% of the Вшй
patients are alive and employed. The reasons for early graft & patient loss were: primary graft dysfunction, fibrocholestatic hepatitis,
uncontrollable bleeding, and sepsis. In the ALF group one of the four transplanted patients survived. The reasons for the deaths were brain
edema, donor related infection, and too sick to transplant recipient with acute on chronic liver failure. The results of Lozenets Hospital liver
transplant program are similar to the unadjusted survival rate reported for UNOS (Goh A. Clin Transpl. 2008:19-34).
Трансплантациите на черен дроб в Болница Лозенец (БЛ) започнаха с трансплантация на жив донор през 2004 г. и от трупен
донор през 2005г. До 2007г. година трансплантационната програма на БЛ беше единствената за страната. За това време
Изпълнителната агенция по трансплантации (ИАТ) предостави 19,17% от наличните органи, а за целия период 23,4%. Средното
време на пребиваване на болните в листата на чакащите за трансплантация беше 187±254 SD дни за възрастните пациенти и
60± 97.25 SD за педиатричните пациенти. В педиатричната група бяха извършени двадесет трансплантации от жив донор и една
split-liver, със следните индикации: билиарна атрезия -14, синдром на Alagyle -1, PFIC-3 -1, PFIC- 3, вродени заболявания -2, остра
чернодробна недостатъчност -2, болест на Уилсън -1. В групата на възрастните бяха направени 20 ортотопни чернодробни
трансплантации и една split-liver. Показанията в тази група включваха: PBC-3, PSC-3, AIH-1, HCV-4, HBV-1, HBV+HDV+HCC -1,
алкохолна и криптогенна цироза -4, вродена фиброза - 1, НАСХ -1, фулминантен хепатит -2. Към БЛ бяха насочени и 6 пациенти с
остра чернодробна недостатъчност, от тях бяха трансплантирани 4, две деца и двама възрастни. Честотата на усложненията
беше ниска с 15 случая на кървене, от които при 6 случая се наложи хирургическо лечение, 4 епизода на остро отхвърляне, 9
случая на хронично отхвърляне, 13 епизода на сепсис, 14 белодробни инфекции, 7 гъбични инфекции, 6 вирусни, ЦМВ и ЕБВ, 3
епизода на депресия. При децата преживяемостта на първия месец беше 81%, а на първата година 70%, включително и при
случаите с ОЧН. Средният PELD скор на преживелите беше 18±13.1 а на загиналите 23.28±13.1. Причините за ранната загуба
на болни бяха първична дисфункция на графта, сепсис и мултиорганна недостатъчност. В групата с възрастните, преживяемостта
на първия месец беше 90%, на първата година 85% и в момента 80% са живи и работоспособни. Причината за ранната загуба на
графта и пациента бяха първична дисфункция на графта, тежка холестаза, неподдаващо се на контрол кървене и сепсис. При
пациентите с остра чернодробна недостатъчност причините за загубата бяха мозъчен оток, тежка ‘остра върху хронична
чернодробна недостатъчност (too sick to transplant) и пренесена с донорския органи инфекция (Pseudomonas). Резултатите в
преживяемостта на пациентите в трансплантационната програма на БЛ са сходни на неажустираните резултати за
преживяемостта съобщени в UNOS (Goh A. Clin Transpl. 2008:19-34).
Background
Patients
Fig. 9 Complications (No of cases)
Conclusion
Biliary stenosis
Biliary leakage
HAT*
Depression
Acute rejection
EBV CMV infections
BE**+ surgery
Micotic Infections
Chronic rejection
Bacterial infections
Pneumonia
Using less than 25% of available donors we did
~ 60% of liver transplants in Bulgaria.
Survival rates in the adult CLD group are
similar to the reported for the EU (4) and
US(5,7) and better than Brazil(6).
Survival rates in the pediatric group are similar
or better to the published unadjusted survival
rates in UNOS and ELTR(4-5, 7)
All surviving patients in the adult group are
currently employed.
Трансплантация на черен дроб в Болница Лозенец 2004-2013
Liver Transplantation in Lozenets Hospital 2004-2013
L.Spassov, V.Pashev, G.Mutafov, M.Vassilev
Lozenets Hospital, Medical Faculty, Sofia University Saint Kliment Ohridski
References
Results
The structure and characteristics of the patient population are shown in fig.4 and tab.1.
Template by:
44 Liver
Transplants
in Lozenets
Hospital
Fig4. Cause of the liver disease in the transplanted patient population
Pediatric group No = 24 Adult group No = 20
Liver transplantation (Ltx) was started by Calne&Williams in UK (1) and Starzl in US(2) late 1960. Living donor related liver transplantation
in children was established and published by Broelsh in 1991 (3). Currently ~6000 Ltx are performed every year in EU Fig.1-2, (4)
Liver transplantation (Ltx) at Lozenets Hospital (LH) started with
living donor transplantation (LDLT) in 2004 due to lack of
established system for donor identification and reporting. The first
orthotopic liver transplantation from cadaveric donor (OLT) was
performed in 2005 on a patient with PBC-AIH overlap syndrome
and hepatorenal syndrome.
Until 2007 it was the only Ltx program in Bulgaria, despite that we
received only a small fraction of the available donor organs, Fig. 3.
Cadaveric livers offered to Lozenets Hospital by EAT
18.18%
0.00%
(Executive Angency for Transplantation)
47.37%
20.00%
11.11%
28.57%
18.18%
50.00%
25.00%
14.29%
60.00%
50.00%
40.00%
30.00%
25.00%
20.00%
10.00%
0.00%
100
90
80
70
60
50
40
30
20
10
0
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 total
Lozenets - OLT Donors % offered to LH
Fig 2. Liver Transplantations in Bulgaria.
Source:www.eltr.org
Fig 3. Available Organ Donations in Bulgaria 2004-2013.
Source:http://bgtransplant.bg/
0 2 4 6 8 10 12 14 16
Bleeding events
Pediatric Adult
mean±SD Range mean±SD Range
Waiting time (days) 60±97.25 1-386 187±254 1-925 days
MELD score 24.6±9.8 1-36 20.5±9.0 6-43
Donor Age (years) 28.8±9.14 7-46 20.5±11.77 17-63 years
Recipient Height (cm) 91.4±39.9 52-166 174.5±11.77 60-180 cm
Recipient Weight (kg) 18.13±18.68 5.2-70 78.6±17.37 52-120 kg
Child score 8.8±1.9 5-13 8.6±2.01 6-12
Ascites*
(grade 1-3)
1.6±0.5 1-3 1.8±0.7 1-3
Encephalopathy **
(grade 1-3)
1.5±0.6 1-3 1.5±0.7 1-3
Bilirubin (mmol/l) 389±318 19-1008 123±141 18-241
Blood group
A
B
O
AB
9
7
8
0
5
6
8
1
Table 1. Clinical Characteristics of the Transplanted Patients
ascites
Fig. 5 Survival rate in the Pediatric group
all etiologies
Fig. 6 Survival rate in the Adults OLT for CLD
all etiologies
1 0 0
80
5 0
0
P e rc e n t s u rv iv a l
1 y 5 y 9 y 0 1 0 0 0 2 0 0 0 3 0 0 0
Y e a rs a f te r L tx
1 00 %
P e rc e n t s u rv iv a l
72%
Fig. 7 Survival rates in the pediatric group
according to the disease severity scores
D a y s a f te r L tx
Fig. 8 Reported Survival Rates in Liver
transplantation from ref. 3
Table 2 Causes of graft and/or patient loss
Pediatric Adult CLD ALF
Primary graft dysfunction 1 1 1
Sepsis 1 1 1
MOF* 3
Bleeding 1
Donor related Infection 1 1 1
Too sick to transplant 1 1 2
Fibrocholestatic Hepatitis 1 1
Total 7 4 5 3
* MOF - Multi Organ Failure
Complication
*HAT=hepatic artery thrombosis
** Bleeding event, requiring surgery
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1970;170:251-258.
3. Liver transplantation in children from living related donors. Surgical techniques and results.
Broelsch CE, Whitington PF, Emond JC, Heffron TG, Thistlethwaite JR, Stevens L, Piper J,
Whitington SH, Lichtor JL. Ann Surg. 1991;214(4):428-37.
4. European Liver Transplant Registry: www.eltr.org
5. Long-term Outcomes for Whole and Segmental Liver Grafts in Adult and Pediatric Liver
Transplant Recipients: A 10-Year Comparative Analysis of 2,988 JC. Hong et al, Cases Journal
of the American College of Surgeons 2009 Volume 208, Issue 5, 2009, Pages 682–689
6. The MELD system and liver transplant waiting-list mortality in developing countries: lessons
learned from São Paulo, Brazil Einstein (São Paulo) 2012 vol.10 no.3 2012 http://goo.gl/5h6pSC
Paolo Salvalaggio et al.,
7. An analysis of liver transplant survival rates from the UNOS registry. Goh A. Au Clin Transpl.
2008:19-34.
The survival rate of the paediatric and adult group are shown in fig. 5-7 and the
causes of graft and/or patient loss and the complications in tab.2 and fig. 9.
Y e a rs a f te r L tx
P e rc e n t s u rv iv a l
P H D +M E LD < 3 0
P H D +M E LD > 3 0
90%
70%
1 y 5 y 9 y
80%
P H D - p e d ia t r ic d e p e n d c y s c o re