Review Article
Living Related Liver Transplantation for Metabolic Liver Diseases in Children
Vikrant Sood,
James E. Squires,
George V. Mazariegos,
Jerry Vockley,
Patrick J. McKiernan,
Vikrant Sood
Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
Search for more papers by this authorJames E. Squires
Division of Gastroenterology, Hepatology and Nutrition, Hillman Center for Pediatric Transplantation, Pittsburgh, PA
Search for more papers by this authorGeorge V. Mazariegos
Division of Pediatric Transplantation, Hillman Center for Pediatric Transplantation, Pittsburgh, PA
Search for more papers by this authorJerry Vockley
Center for Rare Disease Therapy, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorCorresponding Author
Patrick J. McKiernan
Division of Gastroenterology, Hepatology and Nutrition, Hillman Center for Pediatric Transplantation, Pittsburgh, PA
Address correspondence and reprint requests to Patrick J. McKiernan, Division of Gastroenterology, Hepatology and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA (e-mail: [email protected]).Search for more papers by this authorVikrant Sood,
James E. Squires,
George V. Mazariegos,
Jerry Vockley,
Patrick J. McKiernan,
Vikrant Sood
Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
Search for more papers by this authorJames E. Squires
Division of Gastroenterology, Hepatology and Nutrition, Hillman Center for Pediatric Transplantation, Pittsburgh, PA
Search for more papers by this authorGeorge V. Mazariegos
Division of Pediatric Transplantation, Hillman Center for Pediatric Transplantation, Pittsburgh, PA
Search for more papers by this authorJerry Vockley
Center for Rare Disease Therapy, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorCorresponding Author
Patrick J. McKiernan
Division of Gastroenterology, Hepatology and Nutrition, Hillman Center for Pediatric Transplantation, Pittsburgh, PA
Address correspondence and reprint requests to Patrick J. McKiernan, Division of Gastroenterology, Hepatology and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA (e-mail: [email protected]).Search for more papers by this authorConflicts of interest: None
Funding: None
ABSTRACT
Metabolic liver diseases (MLDs) are a heterogeneous group of inherited conditions for which liver transplantation can provide definitive treatment. The limited availability of deceased donor organs means some who could benefit from transplant do not have this option. Living related liver transplant (LrLT) using relatives as donors has emerged as one solution to this problem. This technique is established worldwide, especially in Asian countries, with shorter waiting times and patient and graft survival rates equivalent to deceased donor liver transplantation. However, living donors are underutilized for MLDs in many western countries, possibly due to the fear of limited efficacy using heterozygous donors. We have reviewed the published literature and shown that the use of heterozygous donors for liver transplantation is safe for the majority of MLDs with excellent metabolic correction. The use of LrLT should be encouraged to complement deceased donor liver transplantation (DDLT) for treatment of MLDs.
REFERENCES
- 1.McKiernan PJ, Ganoza A, Squires JE, et al. Evolving trends in liver transplant for metabolic liver disease in the United States. Liver Transpl 2019; 25: 911–921.
- 2.Kwong A, Kim WR, Lake JR, et al. OPTN/SRTR 2018 annual data report: liver. Am J Transplant 2020; 20: 193–299.
- 3.Pham TA, Enns GM, Esquivel CO. Living donor liver transplantation for inborn errors of metabolism - an underutilized resource in the United States. Pediatr Transplant 2016; 20: 770–773.
- 4.Kasahara M, Sakamoto S, Horikawa R, et al. Living donor liver transplantation for pediatric patients with metabolic disorders: the Japanese multicenter registry. Pediatr Transplant 2014; 18: 6–15.
- 5.Ali MA, Elshobari MM, Salah T, et al. Impact of donor-recipient genetic relationship on outcome of living donor liver transplantation. Liver Transpl 2017; 23: 43–49.
- 6.EASL Clinical Practice Guidelines: Wilson's disease. J Hepatol 2012; 56: 671–685.
- 7.Cheng F, Li GQ, Zhang F, et al. Outcomes of living-related liver transplantation for Wilson's disease: a single-center experience in China. Transplantation 2009; 87: 751–757.
- 8.Asonuma K, Inomata Y, Kasahara M, et al. Living related liver transplantation from heterozygote genetic carriers to children with Wilson's disease. Pediatr Transplant 1999; 3: 201–205.
- 9.Komatsu H, Fujisawa T, Inui A, et al. Hepatic copper concentration in children undergoing living related liver transplantation due to Wilsonian fulminant hepatic failure. Clin Transplant 2002; 16: 227–232.
- 10.Suzuki S, Sato Y, Ichida T, et al. Recovery of severe neurologic manifestations of Wilson's disease after living-related liver transplantation: a case report. Transplant Proc 2003; 35: 385–386.
- 11.Wang XH, Cheng F, Zhang F, et al. Copper metabolism after living related liver transplantation for Wilson's disease. World J Gastroenterol 2003; 9: 2836–2838.
- 12.Tamura S, Sugawara Y, Kishi Y, et al. Living-related liver transplantation for Wilson's disease. Clin Transplant 2005; 19: 483–486.
- 13.Yoshitoshi EY, Takada Y, Oike F, et al. Long-term outcomes for 32 cases of Wilson's disease after living-donor liver transplantation. Transplantation 2009; 87: 261–267.
- 14.Kim JS, Kim KM, Oh SH, et al. Liver transplantation for metabolic liver disease: experience at a living donor dominant liver transplantation center. Pediatr Gastroenterol Hepatol Nutr 2015; 18: 48–54.
- 15.Huang Y, Takatsuki M, Soyama A, et al. Living donor liver transplantation for Wilson's disease associated with fulminant hepatic failure: a case report. Am J Case Rep 2018; 19: 304–308.
- 16.Haberle J, Burlina A, Chakrapani A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision. J Inherit Metab Dis 2019; 42: 1192–1230.
- 17.Kasahara M, Sakamoto S, Shigeta T, et al. Living-donor liver transplantation for carbamoyl phosphate synthetase 1 deficiency. Pediatr Transplant 2010; 14: 1036–1040.
- 18.Kim IK, Niemi AK, Krueger C, et al. Liver transplantation for urea cycle disorders in pediatric patients: a single-center experience. Pediatr Transplant 2013; 17: 158–167.
- 19.Shanmugam NP, Valamparampil JJ, Reddy MS, et al. Auxiliary partial orthotopic liver transplantation for monogenic metabolic liver diseases: single-centre experience. JIMD Rep 2019; 45: 29–36.
- 20.Kasahara M, Ohwada S, Takeichi T, et al. Living-related liver transplantation for type II citrullinemia using a graft from heterozygote donor. Transplantation 2001; 71: 157–159.
- 21.Ikeda S, Yazaki M, Takei Y, et al. Type II (adult onset) citrullinaemia: clinical pictures and the therapeutic effect of liver transplantation. J Neurol Neurosurg Psychiatry 2001; 71: 663–670.
- 22.Takagi H, Hagiwara S, Hashizume H, et al. Adult onset type II citrullinemia as a cause of non-alcoholic steatohepatitis. J Hepatol 2006; 44: 236–239.
- 23.Ban K, Sugiyama N, Sugiyama K, et al. A pediatric patient with classical citrullinemia who underwent living-related partial liver transplantation. Transplantation 2001; 71: 1495–1497.
- 24.Tamamori A, Okano Y, Ozaki H, et al. Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation. Eur J Pediatr 2002; 161: 609–613.
- 25.Mazariegos GV, Morton DH, Sindhi R, et al. Liver transplantation for classical maple syrup urine disease: long-term follow-up in 37 patients and comparative United Network for Organ Sharing experience. J Pediatr 2012; 160: 116–121.
- 26.Feier FH, Miura IK, Fonseca EA, et al. Successful domino liver transplantation in maple syrup urine disease using a related living donor. Braz J Med Biol Res 2014; 47: 522–526.
- 27.Kadohisa M, Matsumoto S, Sawada H, et al. Living donor liver transplantation from a heterozygous parent for classical maple syrup urine disease. Pediatr Transplant 2015; 19: E66–E69.
- 28.Patel N, Loveland J, Zuckerman M, et al. Heterozygote to homozygote related living donor liver transplantation in maple syrup urine disease: a case report. Pediatr Transplant 2015; 19: E62–E65.
- 29.Al-Shamsi A, Baker A, Dhawan A, et al. Acute metabolic crises in maple syrup urine disease after liver transplantation from a related heterozygous living donor. JIMD Rep 2016; 30: 59–62.
- 30.Mohan N, Karkra S, Rastogi A, et al. Living donor liver transplantation in maple syrup urine disease - case series and world's youngest domino liver donor and recipient. Pediatr Transplant 2016; 20: 395–400.
- 31.Feier F, Schwartz IV, Benkert AR, et al. Living related versus deceased donor liver transplantation for maple syrup urine disease. Mol Genet Metab 2016; 117: 336–343.
- 32.Basturk A, Keceli M, Erbis H, et al. Liver transplantation from a live donor to a patient with maple syrup urine disease: two case reports. Turk Pediatri Ars 2018; 53: 113–116.
- 33.Herden U, Grabhorn E, Santer R, et al. Surgical aspects of liver transplantation and domino liver transplantation in maple syrup urine disease: analysis of 15 donor-recipient pairs. Liver Transpl 2019; 25: 889–900.
- 34.Celik N, Kelly B, Soltys K, et al. Technique and outcome of domino liver transplantation from patients with maple syrup urine disease: expanding the donor pool for live donor liver transplantation. Clin Transplant 2019; 33: e13721.
- 35.de Laet C, Dionisi-Vici C, Leonard JV, et al. Recommendations for the management of tyrosinaemia type 1. Orphanet J Rare Dis 2013; 8: 8.
- 36.Dalgic A, Ozcay F, Arslan G, et al. Living-related liver transplantation in pediatric patients. Transplant Proc 2005; 37: 3133–3136.
- 37.Arikan C, Kilic M, Nart D, et al. Hepatocellular carcinoma in children and effect of living-donor liver transplantation on outcome. Pediatr Transplant 2006; 10: 42–47.
- 38.Ozcay F, Canan O, Bilezikci B, et al. Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma. Clin Transplant 2006; 20: 776–782.
- 39.Jitraruch S, Treepongkaruna S, Teeraratkul S, et al. Long-term outcome of living donor liver transplantation in a Thai boy with hereditary tyrosinemia type I: a case report. J Med Assoc Thai 2011; 94: 1276–1280.
- 40.Palaniappan K, Borkar VV, Safwan M, et al. Pediatric hepatocellular carcinoma in a developing country: is the etiology changing? Pediatr Transplant 2016; 20: 898–903.
- 41.Strauss KA, Ahlfors CE, Soltys K, et al. Crigler-Najjar syndrome type 1: pathophysiology, natural history, and therapeutic frontier. Hepatology 2020; 71: 1923–1939.
- 42.Ozcay F, Alehan F, Sevmis S, et al. Living related liver transplantation in Crigler-Najjar syndrome type 1. Transplant Proc 2009; 41: 2875–2877.
- 43.Al Shurafa H, Wali S, Chehab MS, et al. Living-related liver transplantation for Crigler-Najjar syndrome in Saudi Arabia. Clin Transplant 2002; 16: 222–226.
- 44.Cochat P, Hulton SA, Acquaviva C, et al. Primary hyperoxaluria type 1: indications for screening and guidance for diagnosis and treatment. Nephrol Dial Transplant 2012; 27: 1729–1736.
- 45.Narasimhan G, Govil S, Rajalingam R, et al. Preserving double equipoise in living donor liver-kidney transplantation for primary hyperoxaluria type 1. Liver Transpl 2015; 21: 1324–1326.
- 46.Sasaki K, Sakamoto S, Uchida H, et al. Two-step transplantation for primary hyperoxaluria: a winning strategy to prevent progression of systemic oxalosis in early onset renal insufficiency cases. Pediatr Transplant 2015; 19: E1–E6.
- 47.Nakamura M, Fuchinoue S, Nakajima I, et al. Three cases of sequential liver-kidney transplantation from living-related donors. Nephrol Dial Transplant 2001; 16: 166–168.
- 48.Shapiro R, Weismann I, Mandel H, et al. Primary hyperoxaluria type 1: improved outcome with timely liver transplantation: a single-center report of 36 children. Transplantation 2001; 72: 428–432.
- 49.Unek T, Egeli T, Ozbilgin M, et al. Long-term results of living donors in simultaneous kidney and liver transplantations. Transplant Proc 2017; 49: 403–406.
- 50.Sato S, Fuchinoue S, Kimikawa M, et al. Sequential liver-kidney transplantation from a living-related donor in primary hyperoxaluria type 1 (oxalosis). Transplant Proc 2003; 35: 373–374.
- 51.Motoyoshil Y, Hattori M, Chikamoto H, et al. [Sequential combined liver-kidney transplantation for a one-year-old boy with infantile primary hyperoxaluria type 1]. Nihon Jinzo Gakkai Shi 2006; 48: 22–28.
- 52.Rosenblatt GS, Jenkins RD, Barry JM. Treatment of primary hyperoxaluria type 1 with sequential liver and kidney transplants from the same living donor. Urology 2006; 68: 427e7–427e8.
- 53.Brinkert F, Ganschow R, Helmke K, et al. Transplantation procedures in children with primary hyperoxaluria type 1: outcome and longitudinal growth. Transplantation 2009; 87: 1415–1421.
- 54.Hori T, Egawa H, Kaido T, et al. Liver transplantation for primary hyperoxaluria type 1: a single-center experience during two decades in Japan. World J Surg 2013; 37: 688–693.
- 55.Boers SJ, Visser G, Smit PG, et al. Liver transplantation in glycogen storage disease type I. Orphanet J Rare Dis 2014; 9: 47.
- 56.Liu PP, de Villa VH, Chen YS, et al. Outcome of living donor liver transplantation for glycogen storage disease. Transplant Proc 2003; 35: 366–368.
- 57.Karaki C, Kasahara M, Sakamoto S, et al. Glycemic management in living donor liver transplantation for patients with glycogen storage disease type 1b. Pediatr Transplant 2012; 16: 465–470.
- 58.Adachi M, Shinkai M, Ohhama Y, et al. Improved neutrophil function in a glycogen storage disease type 1b patient after liver transplantation. Eur J Pediatr 2004; 163: 202–206.
- 59.Iyer SG, Chen CL, Wang CC, et al. Long-term results of living donor liver transplantation for glycogen storage disorders in children. Liver Transpl 2007; 13: 848–852.
- 60.Kaihara S, Ushigome H, Sakai K, et al. Preemptive living donor liver transplantation in glycogen storage disease Ia: case report. Transplant Proc 2008; 40: 2815–2817.
- 61.Kasahara M, Horikawa R, Sakamoto S, et al. Living donor liver transplantation for glycogen storage disease type Ib. Liver Transpl 2009; 15: 1867–1871.
- 62.Critelli K, McKiernan P, Vockley J, et al. Liver transplantation for propionic acidemia and methylmalonic acidemia: perioperative management and clinical outcomes. Liver Transpl 2018; 24: 1260–1270.
- 63.Hsui JY, Chien YH, Chu SY, et al. Living-related liver transplantation for methylmalonic acidemia: report of one case. Acta Paediatr Taiwan 2003; 44: 171–173.
- 64.Morioka D, Kasahara M, Horikawa R, et al. Efficacy of living donor liver transplantation for patients with methylmalonic acidemia. Am J Transplant 2007; 7: 2782–2787.
- 65.Chen PW, Hwu WL, Ho MC, et al. Stabilization of blood methylmalonic acid level in methylmalonic acidemia after liver transplantation. Pediatr Transplant 2010; 14: 337–341.
- 66.Kamei K, Ito S, Shigeta T, et al. Preoperative dialysis for liver transplantation in methylmalonic acidemia. Ther Apher Dial 2011; 15: 488–492.
- 67.Sakamoto R, Nakamura K, Kido J, et al. Improvement in the prognosis and development of patients with methylmalonic acidemia after living donor liver transplant. Pediatr Transplant 2016; 20: 1081–1086.
- 68.Yorifuji T, Kawai M, Mamada M, et al. Living-donor liver transplantation for propionic acidaemia. J Inherit Metab Dis 2004; 27: 205–210.
- 69.Sato S, Kasahara M, Fukuda A, et al. Liver transplantation in a patient with propionic acidemia requiring extra corporeal membrane oxygenation during severe metabolic decompensation. Pediatr Transplant 2009; 13: 790–793.
- 70.Kasahara M, Sakamoto S, Kanazawa H, et al. Living-donor liver transplantation for propionic acidemia. Pediatr Transplant 2012; 16: 230–234.
- 71.Nagao M, Tanaka T, Morii M, et al. Improved neurologic prognosis for a patient with propionic acidemia who received early living donor liver transplantation. Mol Genet Metab 2013; 108: 25–29.
- 72.Ryu J, Shin YH, Ko JS, et al. Intractable metabolic acidosis in a child with propionic acidemia undergoing liver transplantation -a case report. Korean J Anesthesiol 2013; 65: 257–261.
- 73.Rajakumar A, Kaliamoorthy I, Reddy MS, et al. Anaesthetic considerations for liver transplantation in propionic acidemia. Indian J Anaesth 2016; 60: 50–54.
- 74.Honda M, Sakamoto S, Sakamoto R, et al. Antibody-mediated rejection after ABO-incompatible pediatric living donor liver transplantation for propionic acidemia: a case report. Pediatr Transplant 2016; 20: 840–845.
- 75.Quintero J, Molera C, Juamperez J, et al. The role of liver transplantation in propionic acidemia. Liver Transpl 2018; 24: 1736–1745.
- 76.Alexopoulos SP, Matsuoka L, Hafberg E, et al. Liver transplantation for propionic acidemia: a multicenter-linked database analysis. J Pediatr Gastroenterol Nutr 2020; 70: 178–182.
- 77.Curnock R, Heaton ND, Vilca-Melendez H, et al. Liver transplantation in children with propionic acidemia: medium-term outcomes. Liver Transpl 2020; 26: 419–430.
- 78.Mendizabal M, Reddy KR, Cassuto J, et al. Liver transplantation in patients with cystic fibrosis: analysis of United Network for Organ Sharing data. Liver Transpl 2011; 17: 243–250.
- 79.Choi SY, Kang B, Choe JY, et al. A case of glycogen storage disease IV with rare homozygous mutations in the glycogen branching enzyme gene. Pediatr Gastroenterol Hepatol Nutr 2018; 21: 365–368.
- 80.Ban HR, Kim KM, Jang JY, et al. Living donor liver transplantation in a Korean child with glycogen storage disease type IV and a GBE1 mutation. Gut Liver 2009; 3: 60–63.
- 81.Sokal EM, Van Hoof F, Alberti D, et al. Progressive cardiac failure following orthotopic liver transplantation for type IV glycogenosis. Eur J Pediatr 1992; 151: 200–203.
- 82.Troisi RI, Elsheikh YM, Shagrani MA, et al. First fully laparoscopic donor hepatectomy for pediatric liver transplantation using the indocyanine green near-infrared fluorescence imaging in the Middle East: a case report. Ann Saudi Med 2014; 34: 354–357.
- 83.Darwish AA, McKiernan P, Chardot C. Paediatric liver transplantation for metabolic disorders. Part 2: metabolic disorders with liver lesions. Clin Res Hepatol Gastroenterol 2011; 35: 271–280.
- 84.Dubern B, Broue P, Dubuisson C, et al. Orthotopic liver transplantation for mitochondrial respiratory chain disorders: a study of 5 children. Transplantation 2001; 71: 633–637.
- 85.Sasaki K, Sakamoto S, Uchida H, et al. Liver transplantation for mitochondrial respiratory chain disorder: a single-center experience and excellent marker of differential diagnosis. Transplant Proc 2017; 49: 1097–1102.
- 86.Iwama I, Baba Y, Kagimoto S, et al. Case report of a successful liver transplantation for acute liver failure due to mitochondrial respiratory chain complex III deficiency. Transplant Proc 2011; 43: 4025–4028.
- 87.Scheers I, Bachy V, Stephenne X, et al. Risk of hepatocellular carcinoma in liver mitochondrial respiratory chain disorders. J Pediatr 2005; 146: 414–417.
- 88.Hughes MG Jr, Khan KM, Gruessner AC, et al. Long-term outcome in 42 pediatric liver transplant patients with alpha 1-antitrypsin deficiency: a single-center experience. Clin Transplant 2011; 25: 731–736.
- 89.Khorsandi SE, Thompson R, Vilca-Melendez H, et al. Massive ascites and the heterozygous alpha 1 antitrypsin (alpha1 AT) living related donor liver in the homozygous child. Pediatr Transplant 2018; 22:.
- 90.Doshi SD, Wood L, Abt PL, et al. Outcomes of living donor liver transplantation using grafts heterozygous for alpha-1 antitrypsin gene mutations. Transplantation 2018; 103: 1175–1180.
- 91.Roelandt P, Dobbels P, Komuta M, et al. Heterozygous alpha1-antitrypsin Z allele mutation in presumed healthy donor livers used for transplantation. Eur J Gastroenterol Hepatol 2013; 25: 1335–1339.
- 92.Lee SM, Speeg KV, Pollack MS, et al. Progression of morphological changes after transplantation of a liver with heterozygous alpha-1 antitrypsin deficiency. Hum Pathol 2012; 43: 753–756.
- 93.Pungpapong S, Krishna M, Abraham SC, et al. Clinicopathologic findings and outcomes of liver transplantation using grafts from donors with unrecognized and unusual diseases. Liver Transpl 2006; 12: 310–315.
- 94.Maiorana A, Nobili V, Calandra S, et al. Preemptive liver transplantation in a child with familial hypercholesterolemia. Pediatr Transplant 2011; 15: E25–E29.
- 95.Khalifeh M, Faraj W, Heaton N, et al. Successful living-related liver transplantation for familial hypercholesterolemia in the Middle East. Transpl Int 2005; 17: 735–739.
- 96.Shirahata Y, Ohkohchi N, Kawagishi N, et al. Living-donor liver transplantation for homozygous familial hypercholesterolemia from a donor with heterozygous hypercholesterolemia. Transpl Int 2003; 16: 276–279.
- 97.Kawagishi N, Satoh K, Akamatsu Y, et al. Long-term outcome after living donor liver transplantation for two cases of homozygous familial hypercholesterolemia from a heterozygous donor. J Atheroscler Thromb 2007; 14: 94–98.
- 98.Nagasaka H, Yorifuji T, Egawa H, et al. Successful living-donor liver transplantation from an asymptomatic carrier mother in ornithine transcarbamylase deficiency. J Pediatr 2001; 138: 432–434.
- 99.Wakiya T, Sanada Y, Urahashi T, et al. Living donor liver transplantation from an asymptomatic mother who was a carrier for ornithine transcarbamylase deficiency. Pediatr Transplant 2012; 16: E196–E200.
- 100.Morioka D, Kasahara M, Takada Y, et al. Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University. Liver Transpl 2005; 11: 1332–1342.
- 101.Rahayatri TH, Uchida H, Sasaki K, et al. Hyperammonemia in ornithine transcarbamylase-deficient recipients following living donor liver transplantation from heterozygous carrier donors. Pediatr Transplant 2017; 21: e12848.
- 102.Kasahara M, Kiuchi T, Uryuhara K, et al. Treatment of ornithine transcarbamylase deficiency in girls by auxiliary liver transplantation: conceptual changes in a living-donor program. J Pediatr Surg 1998; 33: 1753–1756.
- 103.Sze YK, Dhawan A, Taylor RM, et al. Pediatric liver transplantation for metabolic liver disease: experience at King's College Hospital. Transplantation 2009; 87: 87–93.
- 104.Kasahara M, Takada Y, Egawa H, et al. Auxiliary partial orthotopic living donor liver transplantation: Kyoto University experience. Am J Transplant 2005; 5: 558–565.
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