Liver transplantation at Hospital Israelita Albert Einstein

179

ORIGINAL ARTICLE

Liver transplantation at Hospital Israelita Albert Einstein Transplante de fígado no Hospital Israelita Albert Einstein Sergio Mies*

ABSTRACT Objective: To present patients and results of liver transplantation performed by the Liver Unit team at the Hospital Israelita Albert Einstein. Methods: The medical records of all patients transplanted by the team at the Liver Unit of the Hospital Israelita Albert Einstein, from January 2002 to June 2005, were analyzed. Results: During this period, 328 transplants were performed and 64.3% were male recipients; 64.9% were performed with cadaveric donor; 31.1% with living donors; and 4.3% were domino liver transplants. The three-year survival rate was 78% with cadaveric donors, 71.1% with living donor and 46.2% with domino liver transplant. The mean severity index according to the Child-Pugh score was 8.7 (Child B–9) and the median was 9 (Child B-9); the mean MELD score was 17.6 and the median 18. Conclusion: The Liver Unit team has the largest number of liver transplantation cases in Latin America with over 850 transplants performed and outcomes similar to the world’s best centers. Keywords: Liver transplantation/history; Liver cirrhosis; Immunosuppression; Graft rejection.

RESUMO Objetivo: Apresentar a casuística e o resultado dos transplantes de fígado realizados pela equipe da Unidade de Fígado no Hospital Israelita Albert Einstein. Métodos: Foram analisados os prontuários de todos os pacientes submetidos a transplante hepático pela equipe da Unidade de Fïgado no período compreendido entre janeiro de 2002 e junho de 2005 no Hospital Israelita Albert Einstein. Resultados: Dos 328 transplantes analisados no período, 64,3% ocorreram em pacientes do sexo masculino; 64,6% na modalidade cadáver, 31,1% na modalidade intervivos, 4,3% na modalidade “repique”. A taxa de sobrevida de três anos foi de 78,0% na modalidade cadáver, 71,1% na modalidade intervivos e 46,2% na modalidade “repique”. No que diz respeito ao índice de gravidade, a média foi de 8,7 na classificação de Child-Pugh (Child-Pugh B9), com mediana de 9 (Child-Pugh B9) e de 17,6 na classificação de MELD, com mediana de 18 pontos. Conclusão: A equipe da Unidade de Fígado tem a maior casuística de transplante de fígado da

América Latina com cerca de 850 transplantes realizados, com resultados comparáveis aos melhores centros mundiais. Descritores: Transplante de fígado/história; Cirrose hepática; Imunossupressão; Rejeição de enxerto

INTRODUCTION The transplantation or the removal of an organ from an organism and its implantation into another has always fascinated Science. Legends of both western and eastern cultures mention transplants. One classic record is found in Homer’s Iliad, which describes the Chimera monster, a creature formed by parts of different animals. The term chimera is now used to describe individuals who possess hybrid characteristics, such as the presence of circulating cells from both donor and recipient after a bone marrow transplantation(1). The first report of liver transplantation was performed in an experiment animal (a dog) in 1955, in Albany, New York (USA)(2). In 1963, the team coordinated by Thomas Starzl performed the first attempt of a liver transplantation in humans but it went unsuccessful. The first prolonged survival in humans was achieved in 1967, by the same team under Starzl(4), in an 18-month-old child with cholangiocarcinoma, who eventually died over a year later in consequence of tumor relapse. The first transplantation attempts in Brazil were made between 1968 and 1972 at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, by two different teams. All patients died within the first month. Similarly to what occurred in other centers, the attempts were interrupted due to negative outcomes(5-6). The biological effects of cyclosporine as an immunosuppressive drug were described in 1976(7). The

Study carried out at Hospital Israelita Albert Einstein – HIAE – São Paulo (SP), Brazil. * Ph.D., Hospital Israelita Albert Einstein - HIAE , São Paulo (SP), Brazil. Corresponding author: Sergio Mies - R. Capepuxis,. 215 - Vila Madalena - CEP 05452030 - São Paulo (SP), Brazil - Tel.: 3747-3573 - e-mail: [email protected] Received on March 30, 2005 – Accepted on June 31, 2005

einstein. 2005; 3(3):179-184

180

Mies S

drug started to be clinically administered by Calne et al., in England(8), and by Starzl et al., in the USA, in 1978 (9) . According to these authors the use of cyclosporine increased the average survival rate of the recipient from 30 to 70% in one year. In 1983, the National Institutes of Health Consensus Development Conference(10) involved different specialists in liver transplantation and established that this transplantation should be considered a therapeutic procedure, indicated to patients with chronic liver disease with no other therapeutic alternatives, which forced the health insurance companies to pay the procedure. As a consequence of this meeting, less than two years later, in 1985, there were 20 liver transplant centers in the USA and 23 in Europe. In Brazil, our group (Liver Unit - LU) performed the first successful transplantation in Latin America, in September 1985 (figure 1). The patient was a 19 year-old female with hepatoblastoma. She died a little more than a year later due to tumor relapse.

Figure 1. First successful liver transplantion performed in Brazil. Photograph took when the organ was introduced in the abdominal cavity. The procedure lasted 23 hours, was initiated on August 31 1985 and concluded on the following day

With the development of better conservation solutions, which allowed the conservation of the graft for a longer period of time (12 to 24 hours), the transplantation became virtually an elective procedure as from 1987(11-12). The evolution and consequent success of the transplantation and the dissemination of specialized teams of both referral and transplantation have contributed to a significant increase of graft demands and the consequent increasing waiting time for an organ. This longer waiting period led to higher mortality on the waiting list, which encouraged our group, then working at the Hospital das Clínicas de São Paulo(13), to perform the first two living donor liver transplantations, in 1988 and 1989. Despite all criticism received at the time, the procedures allowed operating on virtually all children on the waiting list for liver transplants.

einstein. 2005; 3(3):179-184

The first living donor transplantation in adult patients using the right lobe (segments V to VIII), representing 55 to 60% of the liver parenchyma, was registered by Yamaoka et al.(14), in Kyoto, Japan, in 1994. It resulted in a dissemination of the method due to the great shortage of organs, especially in Asia, where the criteria for encephalic death are not accepted by society. More than 500 living donor transplants in adult patients were performed in the United States in 2001(15), a number greatly reduced with the death of a donor in New York. The results are also still lower than those achieved with cadaveric donor due to the technical complexity involved in the procedure(16-18). The establishment of the first center for organ procurement in Sao Paulo in 1991 and the financial support of the Unified Health System (SUS), as of 1992, were essential to encourage this kind of organ transplantation in Brazil. In 1997, a new transplant act was sanctioned by Fernando Henrique Cardoso(19), the Brazilian president at the time. The law provided the presumed donation, which offended the Brazilian popular culture and has never been enforced. Later, a provisional remedy established that a family authorization for carrying out the organ donation was once again compulsory(19). The single waiting list (Technical Register) currently being used was created by the 1997 act. The organ allocation follows the registration of patients in chronological order in a single regional list of recipients (normally of the state), which guarantees the population free and egalitarian access to the procedure, independently from socialeconomic situation. However, this form of organ allocation does not consider the severity of the recipient’s condition, and the only priorities provided by the law being fulminant hepatitis and retransplantations, when indicated up to 30 days after surgery. The LU worked at the Hospital das Clínicas of the Faculdade de Medicina da Universidade de São Paulo until December 2001 and as from January 2nd 2002 at the Hospital Israelita Albert Einstein (HIAE).

OBJECTIVE The object of this work is to present the cases and results of transplantations performed by the LU at the HIAE. METHODS The medical records of all patients submitted to liver transplantations performed by the LU team from January 2nd 2002 to 30th June 2005, at the HIAE, were analyzed. The transplantations with cadaveric donor were performed with organs offered by the Center for Notification, Procurement and Distribution of Organs

Liver transplantation at Hospital Israelita Albert Einstein

of the Secretariat of Health of the State of São Paulo (CNCDO). The transplant referral criteria were those established by the Secretariat of Health and by the National Transplant System of the Ministry of Health (21). There was no specific selection for this allocation, that is, the organ offered by the CNCDO was allocated for the first patient on the Unit’s list by blood group, taking into consideration only the ABO identity and size compatibility between the weights of donor and recipient. Therefore, except for cases of extreme disproportion of weight between them (normally when the donor’s weight is 50% above or 50% below the recipient’s), the patient who received a specific organ was the first on the Unit’s list and so on. The living donor transplantation would not follow this chronological order since the potential candidate followed a very explicit Liver Unit protocol. According to this protocol, the candidate donor should be aged between 18 and 50 years, with body weight up to 20% lower than the dry weight of the recipient BMI< 30kg/ m2; and the recipient candidate should be registered at the Secretariat of Health – CNCDO. The extended referral criteria were accepted for patients with hepatic tumor whose staging exceeded that foreseen by the National Transplantation System. However, if a transplant were necessary, the recipient would not be entitled to this benefit. The order for the transplantation would be carried out if the probable transplant donor had followed through the whole assessment protocol, including medical history, lab exams, chest X-ray, abdominal ultra-sound with portal vein Doppler, pulmonary function test, electrocardiogram, echocardiogram, abdominal MRI with quantification of liver volume and degree of steatosis, cholangio-MRI and hepatic arteriography. These procedures were performed in a definite sequence of four stages. Before each stage an informed consent was obtained. Legal authorization was required for non-related cases (not required up to first degree cousins). All cases were referred to the Public Prosecution Service, according to legal requirement. The domino or sequential transplantation (20) corresponds to the use of the liver of a recipient with familial paramyloidosis (FPA) also known as familial amyloidotic polyneuropathy (FAP) in a recipient with advanced hepatocellular carcinoma and, therefore, not included on the cadaveric donor list of the CNCDO. The candidate to this kind of transplantation also follows a single list according to the order of registration in the program. One variation of this method is the triple procedure transplantation (three simultaneous surgical procedures), in which the patient with FPA receives the right lobe of a living donor. In this study, domino cases comprised both modalities.

181

The patients were assessed and distributed per sex; severity of liver disease according to the Child-Pugh score and the MELD (Model for End-Stage Liver Disease) classification, calculated directly on the UNOS site, in the USA(22); disease that led to transplant and type of transplant based on donor (cadaveric, living donor and domino). The discontinued variables are presented in percentage in relation to the total of cases or in relation to their category. The continuous variables are presented as mean and median. Patients were classified according to the Child-Pugh (A, B or C) severity criteria and to the MELD (