Pediatric Liver Transplantation in South America: Incidence and Indications

Introduction

South America currently has approximately 430,485,637 inhabitants, 16.2% of whom are under the age of 18. Brazil is the most populous South American country (213,106,000 people), followed by Colombia and Argentina (48,106,000 and 47,106,000 people, respectively). Economic resources vary widely, with most South Americans having a low or mid-range income. As an example of the disparity, the gross domestic product at purchasing power parity per capita is 3219 billion USD in Brazil but only 68 billion USD in Paraguay.

The first liver transplantation (LT) in South America was performed in 1968 in Brazil on an adult patient. This procedure improved the prospects of patients with highly complex liver diseases. The first living donor LT (LDLT) in the world was performed in 1988 in São Paolo. The following text will describe pediatric LT (PLT) indications and features in several South American countries.

Liver Transplantation and Liver Transplantation Centers in South America

The number of LTs has progressively increased over the past 10 years in most of the countries listed in the Latin American and Caribbean Transplant Registry. LT is now performed in 15 Latin American countries, including 17 centers that have medical facilities fully dedicated to LT. There are currently more than 160 transplantation teams in Latin America, mostly in Brazil (42 centers), followed by Mexico (15 centers), Argentina (12 centers), Colombia (7 centers), and Chile (6 centers). Only eight Latin American countries have official records of PLTs: Brazil, Argentina, Mexico, Chile, Colombia, Peru, Venezuela, and Cuba.

A worldwide list of the 20 countries performing the most LTs per million people (pmp) includes only two Latin American countries (Argentina and Brazil). In Latin America, the mean annual number of effective donations is 8.3 pmp (range, 0 to > 20 pmp). The family refusal rate for organ donation ranges from approximately 30% in Uruguay to 70% in Peru. In Uruguay, Argentina, Cuba, and some parts of Brazil, the number of yearly donations currently exceeds 15 pmp, whereas in other Latin American countries, deceased donor organs are not routinely used.

Despite major economic improvements in South America, its healthcare industry is still underdeveloped. Some South American countries (e.g., Argentina, Brazil, Chile, and Uruguay) provide universal public healthcare with full coverage, including immunosuppressive drugs. Other South American countries offer only partial coverage for medical treatments such as LT. Lack of or inadequate healthcare coverage is considered the main barrier to LT in South America.

Local transplantation-related activities are handled by organizations usually directly linked to the ministry of health in each Latin American country. Most of these countries have organ procurement organizations, with national laws that include the fulfillment of specific criteria for the diagnosis of brain death and the acquisition of informed or presumed consent for organ retrieval. Due to difficulties in obtaining deceased donors for pediatric patients, more than 30 Latin American centers offer LDLTs. LDLTs in Latin America are mainly restricted to pediatric patients, particularly those who would otherwise require deceased donors weighing less than 10 kg. Surgical techniques such as split, domino, and living donor adult and PLT are now routinely performed in several countries.

Liver Transplantation in Various South American Countries

Brazil

Brazil performs the highest number of kidney and LTs in the world. In 2017, the number of effective donors reached 16.6 pmp, with an annual increment rate of 14%. Moreover, the proportion of LTs involving living donors increased to 15.9%, and the percentage of LTs involving deceased donors increased to 11.8%, which corresponds 10.2 pmp. LTs were performed in 12 states and the Federal District by 69 teams, and all organ procurements and retrievals were financed by the Brazilian Public Unified Health System, as were 95% of the LTs.

Because of the great social and economic disparities within Brazil, transplantation-related activities are concentrated in the southeast. Most PLTs, mainly LDLTs, are performed in São Paulo, and most patients in Brazil are referred to São Paolo centers for treatment. The modified pediatric end-stage liver disease (PELD) system, which was established in 2006, prioritizes pediatric candidates. All candidates younger than 12 years old receive a score (the calculated PELD value multiplied by three) at the time of listing. Only those with scores within a specific range are eligible for receiving the transplant. The modified PELD system has not, however, significantly reduced the waiting list mortality rate. For example, Pugliese et al reported a mortality rate of 12% for a group of pediatric patients on a 90-day waiting list. Social and economic disparities in Brazil might explain the delay in referring patients to transplantation centers.

Split LT is an underdeveloped procedure in Latin America because few policies allow its use. It is rarely performed in Brazil and is restricted to cases with ideal donors for the attainment of the best results in both recipients. Another option is domino LT, which uses a related living donor and was developed for children with maple syrup urine disease.

Argentina

In Argentina, the first LT was performed in 1988. Argentina has a single national waiting list, and its national institute for organ allocation and procurement exclusively manages all transplantation-related matters (there are no private procurement agencies). Argentina adopted the model for end-stage liver disease (ESLD) and the PELD system in 2005 as official allocation policies. By 2018, there were more than 33 authorized LT centers in Argentina, which has a population of 47,106,000 and has recorded the second-highest number of PLTs: 1000 LTs since 1986 and 997 LDLTs from 2004 to 2018. Up until 2016, the number of hepatic transplantations performed on adults and children was 8.9 pmp, and the number of living donor hepatic transplantations was 8.5 pmp. Most Argentinean centers perform split LTs, which is an accepted means for expanding the donor pool.

Colombia

In Colombia, the first PLT was performed in 1996, and all PLT-related activities have been entered into the national registry since 2008. According to Colombia’s national database, PLTs represented 20% of all LTs in 2015. Up until 2016, the number of hepatic transplantations was 5.5 pmp, including adults and children. Currently, four centers in Colombia perform PLTs, two of which perform LDLTs.

Chile

In Chile, the first human LT was performed in 1969. LT performance was somewhat sporadic in Chile until 1993, at which time several transplantation programs were inaugurated; since then, over 1500 LTs have been performed. Because LT was not a priority of the Chilean government in the last two decades, most LT centers in Chile were established by private health entities. Consequently, seven of the eight LT programs were established at private clinics, although most organ recipients have publicly provided insurance. Up until 2016, the number of adult and child hepatic transplantations was 4.5 pmp, and the number of living donor hepatic transplantations was 0.4 pmp.

Other Countries

Other South American countries such as Peru, Venezuela, Bolivia, Paraguay, and Ecuador have performed only a few PLTs (< 4.9 pmp). Some LTs may not have been reported.

Indications for Liver Transplantation

In Latin America, the indications for LT in children include malignant and nonmalignant conditions, typically with a bimodal distribution. ESLD because of biliary atresia remains the most common reason for LT. In a Brazilian assessment of 430 consecutive pediatric LDLTs, the indications for liver replacement were as follows: biliary atresia, 66.1%; tyrosinemia, 3.6%; Alagille syndrome, 1.9%; primary liver neoplasms, 3.4%; fulminant liver failure, 2.4%; alpha-1-antitrypsin deficiency, 2.7%; primary sclerosing cholangitis, 2.4%; Budd-Chiari syndrome, 2.7%; cryptogenic cirrhosis, 5.3%; autoimmune hepatitis (AIH), 1.9%; progressive familial intrahepatic cholestasis, 1.5%; chronic cholestasis, 1.5%; other metabolic diseases, 2.9%; and other diseases, 1.7% ( Fig. 42.1 ).