New Pediatric Liver Transplant Program Gives Cuban Children New Lease on Life
Text & Photos by Hope Bastian

April 25, 2008 - As the son of a surgeon father and a pediatrician mother, it should be no surprise that Ramón Villamil grew up to become Dr Villamil. Today, he is chief surgeon and coordinator of the interdisciplinary team at William Soler Pediatric Teaching Hospital’s Clinical Hepatology, Hepato-Biliar Surgery and Liver Transplant Program. Since 2006, the center has been home to Cuba’s new pediatric liver transplant program; children from all over Cuba are referred to this national reference center in Havana for early diagnosis and treatment of liver disorders and diseases. Cuba Health Reports spoke with Dr Villamil last month in his office at William Soler to learn more about the program.

Young liver transplant recipient and mother wait for checkup.

History of Liver Transplantation
Liver transplants are the most complicated of organ transplants and a relatively new advance in medicine. The first human liver transplant was performed in 1963 by a US surgeon Thomas Starzl. His patient, a three-year-old boy, did not survive the transplant. Until 1970, only 30% of transplant recipients lived longer than a year post-transplant [1] It wasn’t until 1983 that the US National Institutes of Health’s Consensus Conference declared liver transplants a valid therapy for end-stage liver disease [2]. In the 40 years since Dr Starzl’s first failed transplant, advances in surgical techniques, intensive care and the development of new immunosuppressive drugs to prevent rejection have improved the prognosis for these patients and made liver transplantation a viable option for patients with end-stage liver disease [3].

The history of liver transplantation in Cuba began on July 17, 1987 when the first adult transplant took place at the Hermanos Ameijeiras Hospital in Havana [4]. In July of 1999, Cuba’s Ministry of Public Health began developing a liver transplant group at Havana’s Center for Medical-Surgical Research (CIMEQ) in cooperation with Virgen del Rocío Hospital in Spain. Since the first transplant on Cuban soil two decades ago, more than 100 liver transplants have been performed in Cuba [5]. 

The Beginning of Cuba’s Pediatric Liver Transplant Program
The pediatric liver program that Dr Villamil heads today dates back to 2002. Just three years after Cuba’s adult liver transplant group was founded, the Ministry of Public Health began exploring the possibilities of forming a group to coordinate the treatment of pediatric liver and biliary disorders and diseases nationwide. In Cuba, 20 to 30 children require transplants each year as a result of congenital liver conditions. To better treat these children, the Ministry of Public Health (MINSAP) began to build an interdisciplinary team to design the program. The first team consisted of three surgeons, a hepatologist, a pediatrician with training in gastroenterology, an anesthesiologist, an intensive care specialist and various nurses with specialized training in surgery and intensive care [6].

As a member of this pioneering team, Dr Villamil was sent for additional training at La Paz Children's Hospital in Madrid, Spain, a hospital with a long record of successful pediatric transplantation. La Paz Children’s Hospital has performed more than 400 liver transplants since 1986 with an eight-year survival rate of 96% [7]. A second member of the team was sent to another specialized hospital in Madrid for training.

When the doctors returned to Cuba they began to perform experimental transplants in animals, and worked under the tutelage of the adult liver transplant teams at the Hermanos Ameijeiras Hospital, assisting in adult transplants. The configuration of the original interdisciplinary team was expanded and now includes: two surgeons, two hepatologists, two anesthesiologists, four intensive care specialists, three pediatricians (with subspecialties in nutrition, infectology and hematology), two nurses with coordination responsibilities, four surgical nurses, eight intensive care nurses, a pathologist, a radiologist, a perfusion technician, a social worker, and a psychologist. After operating theaters, ICU units and patient facilitates at William Soler Pediatric Teaching Hospital were remodeled, the facility was certified as a transplant hospital by Cuba’s National Transplant Organization and MINSAP.

Establishing a national pediatric liver transplant program is no easy task, especially for a nation of the Global South. In addition to the complexities of the procedure itself, requiring highly trained medical professionals and specialized equipment, liver transplantation and the long-term follow-up care are expensive. In the United States, a liver transplant for a child costs approximately $150,000 to $200,000, and immunosuppressive medications can cost an additional $20,000 a year [8]. In Cuba the national health system picks up the tab.

Cuba’s program is still in the first stage, a period of development that usually lasts from three to ten years, in which a new transplant team gradually takes on more complicated cases and surgical procedures. In the short time the Clinical Hepatology, Hepato-Biliar Surgery and Liver Transplant Service has operated as a national reference center, it has already begun to change the way that children with liver disorders are treated in Cuba. 

Before the program, children with liver problems were treated in regular clinical-surgical hospitals throughout the island. There was no main coordinating body and data about outcomes were not centralized. Since there was no pediatric liver transplant program in Cuba, children with end-stage liver disease and acute liver failure usually died without access to life-saving transplants. Less than 3% of Cuban children who needed transplants were able to receive them.

The few children who did receive transplants did so through the collaboration of La Paz Children’s Hospital, which since 2002 has offered Cuba a limited number of transplants free of charge. Although the hospital does not charge, transplantation abroad is still costly in both time and money. Cuba must assume the costs of visas, travel, room and board, for the patient and caretaker, plus medications. With international transplants there is also a risk that in the time it takes to arrange visas, the patient’s condition could deteriorate to such a point that it is too late for transplant. Despite the difficulties, 16 Cuban patients have been transplanted in Spain since 2002 and Cuba’s smallest patients continue to be treated there [9].

Transplant Surgeons, Pastor Thomas Olivares, César Silverio García and Ramón Villamil, with young liver transplant recipients at William Soler Pediatric Teaching Hospital's Liver Care Center.

“Any child in Cuba who presents symptoms of jaundice or cholestasis that cause the doctors to suspect biliary atresia or a liver disorder are sent to our program. Doctors in the national networks of gastroenterologists, pediatricians, and pediatric surgery make the preliminary diagnosis,” explains Dr Villamil. “No matter how remote the patient’s home is, if the doctor suspects one of these illnesses, or simply if the child is jaundiced and has dark urine and white stools, he is sent to our center for evaluation by our interdisciplinary team.”

Early diagnosis and treatment can in many cases improve a child’s condition to such a degree that a transplant can be postponed or avoided altogether. One of the most common congenital liver disorders in Cuba is biliary atresia: 12 new cases are diagnosed annually. In patients with biliary atresia, bile does not drain normally from the small bile ducts within the liver into the larger bile ducts that connect to the gall bladder and small intestine. The longer the bile accumulates, the more damage is done to the liver. In the treatment of biliary atresia, time is critical.

“When biliary atresia is suspected in a patient our protocol establishes that a complete patient workup is completed within 24 to 48 hours. If surgery is needed, it is usually done within seven days,” said Dr Villamil.

If left untreated, biliary atresia will eventually destroy the liver, but if a surgery called the Kasai procedure, or a hepatoportojejunostomy is performed within 30 days, 60% to 85% of children see improvement in their liver’s ability to drain bile [10]. In about 25% of the patients, the operation will completely fix the problem. Another third will be helped by the procedure enough to remain in good health for several years and face an eventual transplant in better health, while the last third will need a liver transplant sooner.

Since 2005, the team has performed 27 Kasai procedures on children with biliary atresia with a 100% survival rate. Sixty-five percent of those operations were successful in recuperating bile drainage from the liver to the intestine.

Cuba Sees New “Firsts” In Treatment of Cuban Pediatric Liver Patients
History was made on October 7, 2005 when five-year-old Frank Hernandez, suffering from cryptogenic liver cirrhosis, received Cuba’s first pediatric liver transplant. In a 13- hour operation at Havana’s Hermanos Ameijeiras Hospital, the boy from the province of Sancti Spíritus received a reduced size liver transplant [11]. After this first success, the team went on to perform a second transplant that December in a five-year-old girl with fulminant liver failure who received a reduced size liver transplant (left lateral segment) [12]. The next transplant took place at the pediatric transplant center in the William Soler Pediatric Teaching Hospital in June of 2006.

Since these first transplants in older children with liver cirrhosis, the team has slowly begun incorporating more complex conditions, technology and procedures, and reducing the age of the receptors. They have now performed 14 transplants in 13 patients. The majority of the transplants were done to treat children with liver cirrhosis (eight), and acute liver failure (four) [13].

The Transplant Process
At the William Soler Pediatric Teaching Hospital, an interdisciplinary liver transplant committee meets weekly to evaluate patients for transplantation. Once they decide that a transplant is appropriate, the national transplant coordinator puts the patient on the donor organ waiting list. Cuba’s system is based on internationally standard criteria to rank patients on the list [14].

Since Cuba’s pediatric liver transplant program began, 45 patients have been evaluated, and 18 put on the donor organ waiting list [15]. Of those, 13 were ultimately transplanted, one was removed from the list, and four died waiting for a liver match[16].

According to Dr Villamil, since the program is still in its infancy, they have not yet faced the scarcity of organs that is common in more established programs. In fact, Cuba’s overall organ donation rate has increased over the last two years from 11 to 18.2 donors per million population, a rate which puts Cuba above the European average of 17.8 donors per million [17].

Once listed, the wait begins for a suitable match. In Cuba, the average wait time for pediatric liver recipients with the most common blood types is 20 to 30 days. However, locating an organ match is a complicated calculation, taking additional factors into account, such as age (donor must be younger than 35 years old), enzyme levels, time the donor spent in ICU (less than three days), cold ischemia time (less than eight hours), and blood pressure. In Cuba, as in the rest of the world, the majority of cadaveric donors come from brain-dead cadavers. Since brain death is rare in children, adult organs must be used in pediatric transplants. The mismatches in size between the donor organ and the recipient have led to new techniques in which only a portion of a donor organ is used.

In Cuba, all surgical hospitals are part of the national system of organ and tissue donation. When an organ becomes available, it is listed and if it is identified as a possible match, the team contacts the hospital’s organ donor coordinator. Some team members then travel to the hospital to extract and evaluate the organ. If they decide it is a match, the second step of surgery begins at William Soler to prepare to extract the organ from the sick child. Once again, time is of the essence. The whole process from extraction to transplantation can take 10 to 16 hours.

After the transplant is complete, the child will stay in ICU for two to five days until he/she has recovered enough to eat and eliminate wastes unassisted. From the moment the child is moved from the operating room to ICU, the parents room-in with the child, something that the team has found helps speed recovery.

After leaving ICU, the patient will usually spend about a month in the recovery room. During this time, both patient and graft functioning are closely monitored for signs of vascular, infectious or surgical complications. In Cuba, graft failure is the most common surgical complication, having occurred in two patients. The most common medical complications are arterial hypertension- 43% of transplants, acute rejection-36%, bacterial infections-31%, and viral infections-15% [18]. After the first month, surgical complications are rare; after the first year, the danger of medical complications has largely passed; but rejection can come at any time. The current one-year survival rate in Cuba’s pediatric liver transplant program is 52% [19].

During the month-long in-patient period, immunosuppressive drugs are administered to help prevent graft rejection. The family and child are also educated about home-based follow-up, proper diet, and medication schedules, and how to recognize symptoms of rejection or complications.

“Once the patient returns home from our center, care is continued in the hands of the child’s local family doctor and the gastroenterologist in their area, who coordinatewith us. One of the advantages of our system is that if they need to be readmitted to the hospital or need further evaluation, we are in constant communication by email and phone, with the child’s primary care physician in the community,” explained Dr Villamil. 

In addition, after hospital discharge, the child will return to William Soler for regular monthly checkups in the first year and three-to-six month checkups after the first year, to monitor the functioning of their new liver. 

“We consider a transplant successful when the child can go home from the hospital with a liver that is functioning well and producing bile like it should,” said Dr Villamil.

After concluding our interview, Dr Villamil took me to see patients on the ward. In the hallway, a group of children were playing hide-and-go-seek. The youngest was clearly the leader of the group, reinventing the rules as the game preceded and bossing around the older kids. All three children were liver transplant recipients back at the hospital for their post-transplant checkups. Watching them play, run, laugh and squeal it was hard to imagine them the way they were when Dr Villamil first met them, jaundiced and sick. The transformation in their bodies and their lives was proof positive that Cuba’s new pediatric liver transplant program, though still in its first stage of development, is already making a difference.

Notes and References

[1] De la Osa J. Cuba*100 Trasplantes Hepático en el CIMEQ. Granma. 2005 Jun 10 [cited 2008 Apr 10] Available from: http://www.tinet.org/~mgm/2005/05amigos176.htm [2] For a discussion of the history of pediatric liver transplantation and the factors that improved outcomes of liver transplants and history of pediatric liver homepages transplants see Carter BA, Murat K, Karpen S, Goss J. History of Pediatric Liver Transplantation. In: eMedicine, WebMD. [database on the Internet]. New York: WebMD;1996- [last updated 2006 Jun 13; cited 2008 Apr 16].[about 17 screens]. Available from: http://www.emedicine.com/PED/topic2840.htm [3] Ibid. [4] González I, Abdo AA, López O, Hernández C, Samada M, Cepero M, et al. First 100 Liver Transplants at the Medico-Surgical Research Center (CIMEQ). Transplant Proc. 2006 Oct; 38(8):2473-4. [5] De la Osa J. Cuba*100 Trasplantes Hepático en el CIMEQ. Granma. 2005 Jun 10 [cited 2008 Apr 10] Available from: http://www.tinet.org/~mgm/2005/05amigos176.htm [6] Abdo Cuza A. Primer trasplante hepático en el Hospital Pediátrico William Soler [homepage on the Internet]. Havana: Infomed Red Telemática de Salud [cited 22 Apr 2008]. [about 2 screens]. Available from: http://www.sld.cu/sitios/trasplante/temas.php?idv=10264 [7] Un equipo de La Paz consigue por primera vez reparar la vía biliar destruida de un bebé con cirugía mínimamente invasive. Solo Ciencia. 2005 Nov 3 [cited 16 Apr 2008] Available from: http://www.solociencia.com/noticias/0511/03134311.htm [8] Financing a Liver Transplant. [Internet] Cincinnati (OH): Cincinnati Children's Hospital Medical Center, Liver Care Center; c1997-2007 [updated 2005 Jun; cited 2008 Apr 18] Available from: http://www.cincinnatichildrens.org/svc/alpha/l/liver/transplant/finance.htm [9] Personal Communication, Dr Ramón Villamil, 2008 Apr 18. Cuba continues to send the smallest children to Spain for transplants because the program does not yet have the capacity to operate on children under 15kg. Dr Villamil estimates that by the end of 2008- beginning 2009 the equipment will be in place at William Soler to perform these procedures in Cuba. [10] Without biliary drainage, the three year survival is less than 10%. See Lefkowitch JH. Biliary Atresia. Ludwig Symposium on Biliary Disorders. Mayo Clin Proc [Internet]. 1998 [cited 2008 Apr 18]; 73:90-95. Available from: http://www.mayoclinicproceedings.com/inside.asp?AID=2828&UID= Kasai Procedure. Pittsburgh (PA): Children's Hospital of Pittsburg. [updated 2007 Dec 6; cited Apr 18] Available from: http://www.chp.edu/centers/03x_lit_procedure_4.php [11] Borrego ML. Primer trasplante de hígado en la pediatría cubana. Escambry. 2007 Sep 18 [cited 2008 Apr 16] Available from: http://www.escambray.cu/Esp/ss/Etrasplante060802355.htm [12] Ibid. [13] Silverio García CE. Transplante Hepático Pediátrico. [Power Point Presentation] Slide 2. [14] More information about how available organs are distributed and the ranking system Cuba uses are available online here in the document: Trasplante Hepático: Criterios de distribución [PDF document on the Internet]. Havana: Infomed Red Telemática de Salud [cited 2008 Apr 21] Available from: http://www.sld.cu/galerias/pdf/sitios/trasplante/criterios_de_distribucion_1_.pdf [15] Silverio García CE. Transplante Hepático Pediátrico. [Power Point Presentation] Slide 5. [16] Ibid. [17] España ha formado a 150 profesionales sanitarios iberoamericanos en esta legislatura para extender en Iberoamérica [press release] Madrid: Presidencia del Gobierno, Servicios de Prensa. [posted 2008 Mar 28; cited 2008 Apr 18] Available from: http://www.la-moncloa.es/ServiciosdePrensa/NotasPrensa/MSC/_2008/ntpr20080328_trasplantes.htm  [18] Silverio García CE. Transplante Hepático Pediátrico. [Power Point Presentation] Slides 10-12. [19] Ibid.