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Pediatric Liver Transplantation in Asia
Introduction
The history of surgery begins with traditional medicine in India (Ayurveda since 2000 BCE) and China (Yin-Yang since 3000 BCE). Surgery began with the first attempt to control bleeding from a vessel. A compelling body of evidence indicates that Sushruta (600 BCE), a surgeon in ancient India, first performed ligation of blood vessels. Sushruta was the first surgeon of antiquity, and his monumental treatise was the first surgical textbook. Although the original manuscript has been lost, several translations from Sanskrit have survived until the present time.
The Chinese surgeon Hua Tuo (145–220 CE) first performed surgery under general anesthesia using a formula made from herbal extracts. In the modern era, as the first reliable documentation of an operation performed under general anesthesia using the same herbal formula as Hua Tuo, Hanaoka Seishu (1760–1835), a Japanese surgeon, performed the first mastectomy for breast cancer in 1804. The technology of general anesthesia and surgery spread in Asian countries through the Second World War. Regarding the Asian history of liver transplantation (LT), deceased donor LT (DDLT) was first performed by Nakayama in 1964 for a 5-month-old patient with biliary atresia. However, the first successful DDLT operation was performed by CL Chen in Taiwan in 1984.
According to the United Nations, there are 48 countries in Asia today. The population of Asia is 4.5 billion, which constitutes approximately 60% of the world’s population. Although Asia is the fastest-growing economic region in the world, there are huge economic and religious disparities ( Fig. 41.1 ).
Major religions have their origins in Asia. The majority of Asian people hold onto the strong cultural belief that the body should go to the grave without any part missing and are therefore reluctant to donate their organs. The religions of Asia include Buddhism, Taoism, Confucianism, Shintoism, Islam, and Hinduism; traditionally, most of these religious groups do not encourage deceased donor organ donation; however, as awareness of donation has increased, modern religious views have changed to encourage donation in the context of a “selfless act” or “an act of righteousness” ( Table 41.1 ).
Table 41.1
Asian Religions: Their Tenets and Views on Transplantation
(From Chen CL, Kabiling CS, Concejero AM. Why does living donor liver transplantation flourish in Asia? Nat Rev Gastroenterol Hepatol. 2013:10;746-751; De Villa VH, Lo CM, Chen CL. Ethics and rationale of living-donor liver transplantation in Asia. Transplantation. 2003;75:S2-S5.)
| Religion | Tenets | Views on Transplantation |
|---|---|---|
| Buddhism | “Spiritual consciousness” remains in the body for days after the last breath; its departure is the actual moment of death; during this time, the body must not be disturbed because it might adversely affect the person’s next rebirth; selfless giving | Opposes deceased organ donation; individual's decision |
| Confucianism | One is born with complete body and should end the same way Modern Confucians: Jen and righteousness are valued more than preserving the integrity of the dead body |
Unfilial and disrespectful; approves deceased organ donation |
| Shintoism | The body after death is impure, dangerous, and powerful; interfering with a corpse brings bad luck and might injure the relationship between dead and bereft | Opposes deceased organ donation; individual's decision |
| Taoism | Naturalness, vitality, peace, and nonaction (to flow of nature) Modern Taoist: body is only shelter to more important parts of life |
Seen as attempt to change natural process; opposes deceased organ donation Approves deceased organ donation |
| Islam | Violating human body (living or dead) is forbidden; customary to bury dead within 24 h. Necessity overrides prohibition | Opposes deceased organ donation Uncertainties: seek advice of local imam |
| Hinduism | Selfless giving, physical integrity of body is not crucial for reincarnation | Approves deceased organ donation |
| Sikhism | Physical body is not crucial for cycle of rebirth | Approves deceased organ donation |
| Christianity | Act of selflessness | Approves deceased organ donation |
Conversely, this strong creed might also be the reason for the success of living donor LT (LDLT) in Asia. The first successful pediatric LDLT operation was performed in 1989 by Russel Y Strong and colleagues in Australia and brought new light to the field of LT, particularly in Asia. This technical innovation was soon implemented for the treatment of pediatric patients with end-stage liver disease in Japan (1989), Hong Kong (1993), Taiwan (1994), South Korea (1994), and mainland China (1995) because of the lack of DDLT. Asian pediatric liver transplant (PLT) physicians have made great innovations—from the initial adult-pediatric LDLT to young adult LDLT, and from using a left lateral segment graft to left/right lobe and a monosegment graft for small babies. Furthermore, donation by hepatitis B core antibody-positive and ABO-incompatible donors can be safely performed with perioperative anti-hepatitis B virus treatment and desensitization of antibodies.
Liver Transplantation in Japan
Organ Allocation System in Japan
When a patient is registered in the Japan Organ Transplant Network (JOT), the patient’s clinical and laboratory data, including the Child-Pugh score, model for end-stage liver disease (MELD) score, and pediatric end-stage liver disease (PELD) score or disease-oriented prognostic score (such as primary sclerosing cholangitis, Wilson disease, and acute liver failure), are revised. Each candidate is allocated a clinical priority score by the National Assessment Committee of Indication for Liver Transplantation according to the MELD/PELD system.
Split LT has been considered by transplant centers for donors under 50 years of age without significant steatosis of the graft liver. In addition, each transplant center in the municipality may decide to perform a split LT according to the recipient’s medical condition, the characteristics of the deceased donor, the estimated ischemic time, and other factors.
The pediatric DDLT waiting list mortality in Japan is almost 3.0% with the backup of LDLT, which is significantly low in comparison with Western countries. LDLT has been implemented as a lifesaving procedure for end-stage liver disease patients, although various ethical considerations and potential constraints remain because of the short duration available for the psychological evaluation and the emotional stress of the potential donor candidate and family.
Pediatric Liver Transplantation in Japan
The first LT operation in Japan was conducted in 1964 from a non-heart-beating donor. Subsequently, LT from a non-heart-beating donor was only performed in one case until 1989 when adult-to-child LDLT was first performed.
In 1997, the Organ Transplantation Law was established in Japan. At that time, DDLT became legally available. However, the demand of patients waiting for organ transplantation has not been sufficiently satisfied. Given this lack of significant progression in DDLT, LT in Japan has largely been centered on LDLT using partial liver grafts from healthy relative donors.
The first LDLT operation in Japan was performed for a pediatric patient with biliary atresia in 1989. In the 28-year period from November 1989 to December 2017, LT has been performed in 8347 cases ( Fig. 41.2 ). Currently, 350–400 LDLTs and 50–60 DDLTs are performed each year in 15 major centers. Overall, 3173 LDLTs were performed in children of under 18 years of age over the same period, which accounts for 36.8% of all living donor transplant procedures. In the United States, PLT cases accounted for 7.3% of the total LT volume. Of note, the proactive performance of pediatric LDLT in Japan has led to such enormous differences in comparison to most Western countries, including the United States and Europe. One reason for this might be the somewhat limited access of adults, who may benefit from LT, throughout Japan.
In Japan, the annual number of LDLT cases has decreased since 2005. Donor deaths caused by adult-to-adult LDLT with an extended right lobe graft were, for example, reported in May 2003. This was paralleled by an overall 50% increase in deceased liver donation since the revision of the organ transplant law in 2010. Maximal efforts have been made to reduce living donor morbidity/mortality and to increase the number of deceased donors in Japan. Indeed, during the same period, DDLT was indicated in 447 cases, 63 (14.1%) of which were pediatric cases.
Regarding the indication of PLT in Japan, cholestatic liver diseases—represented by biliary atresia—account for 64.0% of cases, followed by metabolic liver disease in 9.0% (urea cycle disorders, 50%; organic acidemia, 19%; Wilson disease, 10%; glycogen storage disease, 9%; etc.) and acute liver failure in 9.0% ( Fig. 41.3 ).
PLT in Japan can be considered a successful procedure with an excellent 1-year patient survival rate of 89.9%, a 5-year survival rate of 87.2%, a 10-year survival rate of 84.8%, and a 20-year survival rate of 81.0% ( Fig. 41.4 ). PLT can therefore be considered an established medical treatment in Japan.
Pediatric Liver Transplantation in Other Asian Countries
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