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Pediatric Living Donor Liver Transplant in Indonesia’s National Referral Hospital

Oswari, Hanifah MD, PhD1; Rahayatri, Tri Hening MD2; Soedibyo, Sastiono MD2

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doi: 10.1097/TP.0000000000003154
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Indonesia has a population of ~270 million, representing the world’s fourth most populated country; 30.5% of the country’s population are <18 y.1 Pediatric liver transplantation (LT) was initiated in Indonesia in 2006. Supported by a Japanese collaboration, the program excelled in the last 4 y. The Indonesian LT program provides hope for those in need of LT. Deceased donor LT is currently not performed in the country.

PEDIATRIC LIVER TRANSPLANT PROGRAMS

Five hospitals have performed pediatric LT in Indonesia and 2 are presently active. Dr Cipto Mangunkusumo Hospital (CMH) is one of the 2 active centers performing pediatric and adult LT. The other pediatric liver transplant center is Dr Sardjito General Hospital, which started its program in November 2015 with 4 pediatric LT performed thus far.

CMH is a national referral hospital located in Jakarta. The institution has performed its first pediatric living donor liver transplant (LDLT) in December 2010, in collaboration with Zhejiang University, Hangzhou, China, a partnership that lasted for 2 y. Transplant activities thereafter continued in collaboration with the National University Hospital Singapore. Progress had been slow during that time (2010–2014), with a total of 3 transplants. One of the various reasons for the slow progress had been a strict recipient selection; during that period we only accepted recipients weighing >10 kg.

In 2015, CMH started a collaboration with the National Centre for Child Health and Development, Japan, led by Prof Mureo Kasahara, MD, PhD. A rapid increase in the number of LT has been observed onwards (37 LTs have been performed since 2015). In April 2018, CMH pediatric LT team conducted its first independent LT surgery.

Between 2010 and 2018, CMH had performed 45 pediatric LDLT (25 male and 20 female recipients, Table 1) with biliary atresia as the most common indication. Liver transplant recipients have been referred to from across the entire country (Figure 1).

TABLE 1.
TABLE 1.:
Diagnosis, PELD, complications, and cooperations
FIGURE 1.
FIGURE 1.:
Indonesia, patient referrals (gray area) to CMH, and location of 2 active LT centers. CMH, Dr Cipto Mangunkusumo Hospital; LT, liver transplantation.

TRANSPLANT DETAILS AND OUTCOMES

All donors at CMH have been relatives, in most cases parents. Potential donors undergo thorough psychiatric and psychosocial assessment; we also seek advice from an independent patient advocate who determines whether or not to proceed with the medical/surgical evaluation.

Next, an extensive past medical history, physical examination and laboratory examination, abdominal ultrasonography, computed tomography/angiography, magnetic resonance cholangiopancreatography, and a liver biopsy of the donor are obtained. If both donor and recipient have been approved, the CMH Medical Ethics Committee assesses the final phase.

SIGNIFICANT ACHIEVEMENTS AND CHALLENGES

The 1-y graft survival rate in 2018 has been 88.9%, and this number is compared favorably to outcomes reported by the Japan Transplantation Society (88.3%) and data reported from the United States by Venick et al (86%).2,3 Sepsis had been the leading cause of mortality post-LDLT (66.7%) with an overall sepsis-related mortality rate of 8.9%, which is slightly lower than rates reported from other countries.4

The incidence of acute cellular rejections during the first year at CMH was 31%, compared with rates between <20% and 50% reported worldwide.5 The 1-y chronic rejection rate declined from 50% in 2013 to 22% in 2018, mostly based on improved management of acute cellular rejection. Nevertheless, chronic rejection rates have remained high compared with those reported from the United States and India (8% and 2.5%, respectively).6,7 The diagnosis is confirmed histopathologically and characterized by degenerative changes in small bile ducts, loss of hepatic arterioles, and inflammation and fibrosis in the hepatic venules, hepatocytes, and the perihilar hepatic arteries or bile ducts.8 We have not been able to perform retransplants due to the inability to obtain a second living donor.

There has not been any major donor complication. One donor developed postoperative wound infection that was treated with a debridement procedure.

Delay in referral remains a significant problem, and many patients arrive at an already advanced stage, severely malnourished with preexisting infections (urinary tract infection, cytomegalovirus, Epstein-Barr virus, and others), all of which are associated with poor prognosis.

Tailored immunosuppression remains challenging, with limitations of available immunosuppressants in the country.

REGULATORY AND ECONOMIC ASPECTS

Liver transplant is a high-cost procedure. The cost of transplantation is approximately USD 42 000 (1 USD = IDR. 14 196.6) and does not include donor screening; costs are partially covered by Indonesian National Health Insurance. The remaining costs are settled by CMH (76%), the recipient’s parents’ employment company (16%), local government (2%), and other sources of funding (6%). The cost of donor screening is paid out of pocket.

An initiative of LT regulation has been submitted by the CMH team to the Indonesian Ministry of Health in 2016. This initiative has resulted in the ratification of the Decree of Ministry of Health No. 38, on the management of Organ Transplants (2016). Recently, the CMH Solid Organ Transplantation Team has started an initiative with the Ministry of Health working on regulations for deceased donors.

SUMMARY

In conclusion, pediatric LDLT has made great strides in Indonesia. Most recently, CMH, the national referral center, has performed the procedure independently. The program continues to improve surgical skills and medical management. A deceased donor program will be necessary to overcome the scarcity of donors.

ACKNOWLEDGMENTS

We are grateful to Prof Mureo Kasahara from National Centre for Child Health and Development, Japan for the assistance in building a strong foundation for our LT team. We also wish to express our gratitude to Prof Prabhakaran Krishnan from NUH-Singapore and Prof Shusen Zheng from The First Affiliated Hospital, School of Medicine, Zhejiang University, China for their support in initiating the pediatric LT program at CMH.

REFERENCES

1. Indonesia SIndonesia Population Projection. 2013JakartaBadan Pusat Statistik
2. Kasahara M, Umeshita K, Inomata Y, et al.; Japanese Liver Transplantation SocietyLong-term outcomes of pediatric living donor liver transplantation in Japan: an analysis of more than 2200 cases listed in the registry of the Japanese Liver Transplantation Society. Am J Transplant. 2013; 13:1830–1839
3. Venick RS, Farmer DG, Soto JR, et al. One thousand pediatric liver transplants during thirty years: lessons learned. J Am Coll Surg. 2018; 226:355–366
4. Pouladfar G, Jafarpour Z, Malek Hosseini SA, et al. Bacterial infections in pediatric patients during early post liver transplant period: a prospective study in Iran. Transpl Infect Dis. 2019; 21:e13001
5. Dehghani SM, Shahramian I, Afshari M, et al. Acute hepatic allograft rejection in pediatric recipients: independent factors. Int J Organ Transplant Med. 2017; 8:203–206
6. Mohan N, Karkra S, Rastogi A, et al. Outcome of 200 pediatric living donor liver transplantations in India. Indian Pediatr. 2017; 54:913–918
7. Yilmaz F, Aydin U, Nart D, et al. The incidence and management of acute and chronic rejection after living donor liver transplantation. Transplant Proc. 2006; 38:1435–1437
8. Demetris AJ, Bellamy C, Hübscher SG, et al. 2016 comprehensive update of the Banff working group on liver allograft pathology: introduction of antibody-mediated rejection. Am J Transplant. 2016; 16:2816–2835
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