Karaciğer Parankim Hasarı ile Seyreden Kalıtımsal Metabolik Hastalıklarda Pediatrik Karaciğer Nakli

Yıl 2021, Cilt: 15 Sayı: 5, 408 - 414, 23.09.2021

Neslihan Çelik , Remzi Emiroglu

https://doi.org/10.12956/tchd.979822

Öz

Amaç: Çeşitli enzim eksiklikleriyle seyreden doğumsal metabolik hastalıklar, karaciğer parankim hasarının varlığından bağımsız olarak karaciğer nakli ile tedavi edilebilirler ve bu endikasyonlarda karaciğer nakli, cerrahi bir enzim replasman tedavisidir. Tek merkezli bu çalışmanın amacı, karaciğer parankim hasarı ile seyreden metabolik hastalıklı çocuklarda karaciğer nakil endikasyonlarını ve nakil sonrası sonuçları incelemek; tedavinin yararlarını ve başarı oranlarını artırmak için bu süreçte yaşanılan zorlukları ortaya koymaktır.

Gereç ve Yöntemler: Ocak 2015 ve Haziran 2021 tarihleri arasında karaciğer parankim hasarı ile seyreden doğumsal metabolik hastalık tanısıyla karaciğer nakli yapılan 19 yaş altı hastalar, retrospektif olarak incelendi. Hasta ve greft sağ kalım oranları, transplantasyon endikasyonları, immünsupresif protokoller, nakil sonrası erken ve geç dönemdeki cerrahi ve medikal komplikasyonlar incelendi. 

Bulgular: Progresif familial intrahepatik kolestaz (n=8), Alagille sendromu (n=3), tirozinemi tip-1 (n=1), ailevi neonatal hepatit (n=1) ve glikojen depo hastaligi tip-1 (n=1) tanılarıyla, 14 hastaya sol lateral segment (n=10), sağ lob (n=2), küçültülmüş sol lateral segment (n=1) ve monosegment (n=1) greftlerle canlı vericili karaciğer nakli gerçekleştirildi. Ortanca yaşı 42.3 ay (6.9-215.5 ay) olan 5 erkek ve 9 kız hastadan, familial neonatal hepatit tanılı hasta takipten çıktığı için verilerine ulaşılamadı. Ortanca takip süresi 12.7 ay (0.4-53.4 ay) olarak hesaplandı. Sepsis nedeniyle 4 hasta kaybedildi ve akut selüler rejeksiyon ve enfeksiyonlar en sık postoperatif komplikasyonlar olarak belirlendi.

Sonuç: Karaciğer nakli, genetik geçişli metabolik hastalıklarda mevcut medikal ve cerrahi tedavi olanaklarına rağmen karaciğer yetmezliği, malignensi gelişimi ve ilişkili komplikasyonların oluşması durumunda hayat kurtarıcı bir prosedürdür. 

Anahtar Kelimeler

Çocuk, Karaciğer nakli, Metabolik hastalık

Pediatric Liver Transplantation For Hereditary Metabolic Disorders With Structural Liver Damage

Öz

Objective: Variety of inherited metabolic diseases with or without liver parenchymal injury can be cured by liver transplantation and this process is actually a surgical enzyme replacement therapy for the defective protein. The aim of this single center study was to analyze the liver transplantation indications, post-transplantation outcomes with benefits of the procedure, and also identification of the problems encountered during the process to improve the success rate in pediatric metabolic diseases with liver parenchymal damage.

Material and Methods: We retrospectively reviewed the records of children who underwent liver transplantation because of metabolic disorders with liver parenchymal damage from January 2015 to June 2021. Data collected included patient and donor demographics, operative techniques, patient and graft survivals, post-transplant surgical and medical complications, and immunosuppressive protocols.

Results: Fourteen children with progressive familial intrahepatic cholestasis (n = 8), Alagille syndrome (n = 3), tyrosinemia type-I (n=1), familial neonatal hepatitis (FNH, n=1) and glycogen storage disease type-I (GSD-I, n = 1) received left lateral segment (n=10), right lobe (n=2), reduced size left lateral segment (n=1), and mono-segment (n=1) allografts from living donors. The median age of 5 boys and 9 girls at time of transplantation was 42.3 months (range 6.9-215.5 months). One patient with FNH was lost to follow and excluded from the study. The median follow-up time was 12.7 months (range 0.4-53.4 months) and we lost four patients because of sepsis. Most common post-transplant complications were acute cellular rejection and infections.

Conclusion: Liver transplantation is a lifesaving treatment for patients with metabolic disorders comprising liver failure, malignancies, and associated complications despite several medical and surgical treatment modalities.

Anahtar Kelimeler

liver transplantation, metabolic disease, Child

Kaynakça

• 1- Darwish AA, McKiernan P, Chardot C. Paediatric liver transplantation for metabolic disorders. Part 2: Metabolic disorders with liver lesions. Clin Res Hepatol Gastroenterol 2011; 35:271-80.
• 2- Darwish AA, McKiernan P, Chardot C. Paediatric liver transplantation for metabolic disorders. Part 1: Liver-based metabolic disorders without liver lesions. Clin Res Hepatol Gastroenterol 2011; 35:194-203.
• 3- Mazariegos G, Shneider B, Burton B, Fox IJ, Hadzic N, Kishnani P, et al. Liver transplantation for pediatric metabolic disease. Mol Genet Metab 2014; 111:418-27.
• 4- Hansen K, Horslen S. Metabolic liver disease in children. Liver Transpl 2008;14: 713–33.
• 5- Kayler LK, Merion RM, Lee S, Sung RS, Punch JD, Rudich SM, et al. Long-term survival after liver transplantation in children with metabolic disorders. Pediatr Transplant 2002;6: 295–300.
• 6- Kayler LK, Rasmussen CS, Dykstra DM, Punch JD, Rudich SM, Magee JC, et al. Liver transplantation in children with metabolic disorders in the United States. Am J Transplant 2003; 3:334–9.
• 7- Stevenson T, Millan MT, Wayman K, Berquist WE, Sarwal M, Johnston EE, et al. Long-term outcome following pediatric liver transplantation for metabolic disorders. Pediatr Transplant 2010;14: 268–75.
• 8- Mehl A, Bohorquez H, Serrano MS, Galliano G, Reichman TW. Liver transplantation and the management of progressive familial intrahepatic cholestasis in children. World J Transplant 2016;24: 6: 278-90.
• 9- Englert C, Grabhorn E, Richter A, Rogiers X, Burdelski M, Ganschow R. Liver transplantation in children with progressive familial intrahepatic cholestasis. Transplantation 2007; 84: 1361-3.
• 10- Hori T, Egawa H, Miyagawa-Hayashino A, Yorifuji T, Yonekawa Y, Nguyen JH, et al. Living-donor liver transplantation for progressive familial intrahepatic cholestasis. World J Surg 2011;35: 393-402.
• 11- Hori T, Egawa H, Takada Y, Ueda M, Oike F, Ogura Y, et al. Progressive familial intrahepatic cholestasis: a single-center experience of living-donor liver transplantation during two decades in Japan. Clin Transplant 2011;25: 776-785.
• 12- Lykavieris P, van Mil S, Cresteil D, Fabre M, Hadchouel M, Klomp L, et al. Progressive familial intrahepatic cholestasis type 1 and extrahepatic features: no catchup of stature growth, exacerbation of diarrhea, and appearance of liver steatosis after liver transplantation. J Hepatol 2003; 39: 447-52.
• 13- Egawa H, Yorifuji T, Sumazaki R, Kimura A, Hasegawa M, Tanaka K. Intractable diarrhea after liver transplantation for Byler’s disease: successful treatment with bile adsorptive resin. Liver Transpl 2002; 8: 714-6.
• 14- Miyagawa-Hayashino A, Egawa H, Yorifuji T, Hasegawa M, Haga H, Tsuruyama T, et al. Allograft steatohepatitis in progressive familial intrahepatic cholestasis type 1 after living donor liver transplantation. Liver Transpl 2009; 15: 610-8.
• 15- Nicastro E, Stephenne X, Smets F, Fusaro F, de Magnée C, Reding R, et al. Recovery of graft steatosis and protein-losing enteropathy after biliary diversion in a PFIC 1 liver transplanted child. Pediatr Transplant 2012; 16: E177-E182.
• 16- Usui M, Isaji S, Das BC, Kobayashi M, Osawa I, Iida T, et al. Liver Retransplantation with external biliary diversion for progressive familial intrahepatic cholestasis type 1: a case report. Pediatr Transplant 2009; 13: 611-4.
• 17- Deutsch GH, Sokol RJ, Stathos TH, Knisely AS. Proliferation to paucity: evolution of bile duct abnormalities in a case of Alagille syndrome. Pediatr Dev Pathol 2001; 4:559-63.
• 18- Emerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA. Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology 1999; 29:822-9.
• 19- Hoffenberg EJ, Narkewicz MR, Sondheimer JM, Smith DJ, Silverman A, Sokol RJ. Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy. J Pediatr 1995; 127:220-4.
• 20- Kamath BM, Schwarz KB, Hadzić N. Alagille syndrome and liver transplantation. J Pediatr Gastroenterol Nutr 2010;50:11-5.
• 21- Englert C, Grabhorn E, Burdelski M, Ganschow R. Liver transplantation in children with Alagille syndrome: indications and outcome. Pediatr Transplant 2006; 10:154-8.
• 22- Kasahara M, Kiuchi T, Inomata Y, Uryuhara K, Seakamoto S, Ito T, et al. Living-related liver transplantation for Alagille syndrome. Transplantation 2003; 75:2147–50.
• 23- Kamath BM, Bason L, Piccoli DA, Krantz ID, Spinner NB. Consequences of JAG1 mutations. J Med Genet 2003; 40:891-5.
• 24- Lindblad B, Lindstedt S, Steen G. On the enzymic defects in hereditary tyrosinemia. Proc Natl Acad Sci U S A 1977; 74:4641-5.
• 25- McKiernan P. Liver Transplantation for Hereditary Tyrosinaemia Type 1 in the United Kingdom Adv Exp Med Biol 2017; 959:85-91.
• 26- Liu Y, Luo Y, Xia L, Qiu BJ, Zhou T, Feng MX, et al. Living-donor liver transplantation for children with tyrosinemia type I. J Dig Dis 2020; 21:189-94.
• 27- Chinsky JM, Singh R, Ficicioglu C, van Karnebeek CDM, Grompe M, Mitchell G, et al. Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med 2017; 19:12.
• 28- Kishnani PS, Austin SL, Arn P, Bali DS, Boney A, Case LE, et al. Glycogen storage disease type III diagnosis and management guidelines. Genet Med 2010;12: 446-63.
• 29- Koeberl DD, Kishnani PS, Chen YT. Glycogen storage disease types I and II: treatment updates. J Inherit Metab Dis 2007;30: 159-64.
• 30- Hicks J, Wartchow E, Mierau G. Glycogen storage diseases: a brief review and update on clinical features, genetic abnormalities, pathologic features, and treatment. Ultrastruct Pathol 2011;35: 183-96.
• 31- Baertling F, Mayatepek E, Gerner P, Baba HA, Franzel J, Schlune A, et al. Liver cirrhosis in glycogen storage disease Ib. Mol Genet Metab 2013;108: 198-200.
• 32- Manzia TM, Angelico R, Toti L, Cillis A, Ciano P, Orlando G, et al. Glycogen storage disease type Ia and VI associated with hepatocellular carcinoma: two case report. Transplant Proc 2011;43: 1181-3.
• 33- Kido J, Nakamura K, Matsumoto S, Mitsubuchi S, Ohura T, Shigematsu Y, et al. Current status of hepatic glycogen storage disease in Japan: clinical manifestations, treatments and long-term outcomes. J Hum Genet 2013;58: 285-92.
• 34- Maheshwari A, Rankin R, Segev DL, Thuluvath PJ, Outcomes of liver transplantation for glycogen storage disease: a matched-control study and a review of literature, Clin Transplant 2012;26: 432-6.
• 35- McKiernan PJ, Ganoza A, Squires JE, Squires RH, Vockley J, Mazariegos G, et al. Evolving Trends in Liver Transplant for Metabolic Liver Disease in the United States. Liver Transpl 2019;25:911-21.
• 36- Mater D, Starzl TE, Arnaout W, Barnard J, Bynon JS, Dhawan A, et al. Liver transplantation for glycogen storage disease types I, III, and IV. Eur J Pediatr 1999;158 (Suppl 2):43-8.
• 37- Iyer SG, Chen CL, Wang CC, Wang SH, Concejero AM, Liu YW, et al. Long-Term Results of Living Donor Liver Transplantation for Glycogen Storage Disorders in Children. Liver Transplantation 2007; 13:848-52.