The Liver in Systemic Illness

  • Melanie Schranz
  • Maria Grazia Lucà
  • Lorenzo D’Antiga
  • Stefano FagiuoliEmail author


The size of an organ does not always reflect its relevance, but in the case of the liver, this assumption may be true. The liver plays a central role in all metabolic processes in the body. Apart from processing fat, carbohydrates, and proteins to supply energy, the liver is responsible for detoxification and protects the organism from pathogens. Moreover, storage of vitamins and minerals, in particular iron and copper, occurs in the liver, rendering possible their provision in times of deprivation. It is therefore not surprising that during the course of many systemic diseases, the liver gets involved and may be injured. In general, mechanisms that may cause liver damage can be of metabolic, toxic, vascular, or immunologic origin. Despite the large variation of pathogens that affect the liver, the final result is hepato- and/or cholangio-cellular injury that may either end in cirrhosis when the injury is chronic or liver failure in the case of acute severe damage. Since the first step of treatment is the correct diagnosis of liver involvement in a systemic disease, we aim to give an overview of paediatric illnesses that do not primarily affect the liver but may still cause more or less severe liver injury. Treatment of the underlying disease and thereby terminating the pathophysiological mechanism lead to resolution of the liver disease in most of the cases; nevertheless specific interventions ranging from pure observation to avoidance of certain liver toxic medications or even maximal therapy as liver transplantation may sometimes be required.


Systemic illness Liver involvement Paediatric disease Systemic disease Cirrhosis 


  1. 1.
    Khemichian S, Fong TL. Hepatic dysfunction in hyperthyroidism. Gastroenterol Hepatol. 2011;7(5):337–9.Google Scholar
  2. 2.
    Segni M. Disorders of the thyroid gland in infancy, childhood and adolescence. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext. South Dartmouth, MA:, Inc; 2000.Google Scholar
  3. 3.
    Wassner AJ, Brown RS. Congenital hypothyroidism: recent advances. Curr Opin Endocrinol Diabetes Obes. 2015;22(5):407–12.PubMedCrossRefGoogle Scholar
  4. 4.
    Hanley P, Lord K, Bauer AJ. Thyroid disorders in children and adolescents: a review. JAMA Pediatr. 2016;170(10):1008–19.PubMedCrossRefGoogle Scholar
  5. 5.
    Akangire G, Cuna A, Lachica C, Fischer R, Raman S, Sampath V. Neonatal Graves’ disease with maternal hypothyroidism. AJP Rep. 2017;7(3):e181–4.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Leger J, Carel JC. Hyperthyroidism in childhood: causes, when and how to treat. J Clin Res Pediatr Endocrinol. 2013;5(Suppl 1):50–6.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Hasosah M, Alsaleem K, Qurashi M, Alzaben A. Neonatal hyperthyroidism with fulminant liver failure: a case report. J Clin Diagn Res. 2017;11(4):SD01–2.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Foley TP Jr. Maternally transferred thyroid disease in the infant: recognition and treatment. Adv Exp Med Biol. 1991;299:209–26.PubMedCrossRefGoogle Scholar
  9. 9.
    Rastogi MV, Lafranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis. 2010;5:17.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Nebesio TD, Mckenna MP, Nabhan ZM, Eugster EA. Newborn screening results in children with central hypothyroidism. J Pediatr. 2010;156(6):990–3.PubMedCrossRefGoogle Scholar
  11. 11.
    Karnsakul W, Sawathiparnich P, Nimkarn S, Likitmaskul S, Santiprabhob J, Aanpreung P. Anterior pituitary hormone effects on hepatic functions in infants with congenital hypopituitarism. Ann Hepatol. 2007;6(2):97–103.PubMedGoogle Scholar
  12. 12.
    Malik R, Hodgson H. The relationship between the thyroid gland and the liver. QJM. 2002;95(9):559–69.PubMedCrossRefGoogle Scholar
  13. 13.
    Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab. 2003;88(6):2438–44.PubMedCrossRefGoogle Scholar
  14. 14.
    Bakker SJ, Ter Maaten JC, Popp-Snijders C, Slaets JP, Heine RJ, Gans RO. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J Clin Endocrinol Metab. 2001;86(3):1206–11.PubMedGoogle Scholar
  15. 15.
    Saxena NK, Ikeda K, Rockey DC, Friedman SL, Anania FA. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology. 2002;35(4):762–71.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Kaltenbach TE, Graeter T, Oeztuerk S, et al. Thyroid dysfunction and hepatic steatosis in overweight children and adolescents. Pediatr Obes. 2017;12(1):67–74.PubMedCrossRefGoogle Scholar
  17. 17.
    Denzer C, Karges B, Nake A, et al. Subclinical hypothyroidism and dyslipidemia in children and adolescents with type 1 diabetes mellitus. Eur J Endocrinol. 2013;168(4):601–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Lodish M. Cushing’s syndrome in childhood: update on genetics, treatment, and outcomes. Curr Opin Endocrinol Diabetes Obes. 2015;22(1):48–54.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    More J, Young J, Reznik Y, et al. Ectopic ACTH syndrome in children and adolescents. J Clin Endocrinol Metab. 2011;96(5):1213–22.PubMedCrossRefGoogle Scholar
  20. 20.
    Pivonello R, De Leo M, Vitale P, et al. Pathophysiology of diabetes mellitus in Cushing’s syndrome. Neuroendocrinology. 2010;92(Suppl 1):77–81.PubMedCrossRefGoogle Scholar
  21. 21.
    Tarantino G, Finelli C. Pathogenesis of hepatic steatosis: the link between hypercortisolism and non-alcoholic fatty liver disease. World J Gastroenterol. 2013;19(40):6735–43.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Dowman JK, Hopkins LJ, Reynolds GM, et al. Loss of 5alpha-reductase type 1 accelerates the development of hepatic steatosis but protects against hepatocellular carcinoma in male mice. Endocrinology. 2013;154(12):4536–47.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Marino L, Jornayvaz FR. Endocrine causes of nonalcoholic fatty liver disease. World J Gastroenterol. 2015;21(39):11053–76.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014;383(9935):2152–67.PubMedCrossRefGoogle Scholar
  25. 25.
    Boulton R, Hamilton MI, Dhillon AP, Kinloch JD, Burroughs AK. Subclinical Addison’s disease: a cause of persistent abnormalities in transaminase values. Gastroenterology. 1995;109(4):1324–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Vafaeimanesh J, Bagherzadeh M, Parham M. Adrenal insufficiency as a cause of acute liver failure: a case report. Case Rep Endocrinol. 2013;2013:487189.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Font J, Cervera R, Espinosa G, et al. Systemic lupus erythematosus (SLE) in childhood: analysis of clinical and immunological findings in 34 patients and comparison with SLE characteristics in adults. Ann Rheum Dis. 1998;57(8):456–9.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Mina R, Brunner HI. Pediatric lupus—are there differences in presentation, genetics, response to therapy, and damage accrual compared with adult lupus? Rheum Dis Clin North Am. 2010;36(1):53–80., vii-viii.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Thakral A, Klein-Gitelman MS. An update on treatment and management of pediatric systemic lupus erythematosus. Rheumatol Ther. 2016;3(2):209–19.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Irving KS, Sen D, Tahir H, Pilkington C, Isenberg DA. A comparison of autoimmune liver disease in juvenile and adult populations with systemic lupus erythematosus—a retrospective review of cases. Rheumatology (Oxford). 2007;46(7):1171–3.CrossRefGoogle Scholar
  31. 31.
    Bessone F, Poles N, Roma MG. Challenge of liver disease in systemic lupus erythematosus: clues for diagnosis and hints for pathogenesis. World J Hepatol. 2014;6(6):394–409.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Berzigotti A, Frigato M, Manfredini E, et al. Liver hemangioma and vascular liver diseases in patients with systemic lupus erythematosus. World J Gastroenterol. 2011;17(40):4503–8.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Shizuma T. Clinical characteristics of concomitant systemic lupus erythematosus and primary biliary cirrhosis: a literature review. J Immunol Res. 2015;2015:713728.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Piga M, Vacca A, Porru G, Cauli A, Mathieu A. Liver involvement in systemic lupus erythematosus: incidence, clinical course and outcome of lupus hepatitis. Clin Exp Rheumatol. 2010;28(4):504–10.PubMedGoogle Scholar
  35. 35.
    Koshy JM, John M. Autoimmune hepatitis—SLE overlap syndrome. J Assoc Physicians India. 2012;60:59–60.PubMedGoogle Scholar
  36. 36.
    Deen ME, Porta G, Fiorot FJ, Campos LM, Sallum AM, Silva CA. Autoimmune hepatitis and juvenile systemic lupus erythematosus. Lupus. 2009;18(8):747–51.PubMedCrossRefGoogle Scholar
  37. 37.
    Gatselis NK, Zachou K, Koukoulis GK, Dalekos GN. Autoimmune hepatitis, one disease with many faces: etiopathogenetic, clinico-laboratory and histological characteristics. World J Gastroenterol. 2015;21(1):60–83.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Di Giorgio A, Bravi M, Bonanomi E, et al. Fulminant hepatic failure of autoimmune aetiology in children. J Pediatr Gastroenterol Nutr. 2015;60(2):159–64.PubMedCrossRefGoogle Scholar
  39. 39.
    Takahashi A, Abe K, Saito R, et al. Liver dysfunction in patients with systemic lupus erythematosus. Intern Med. 2013;52(13):1461–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Czaja AJ, Morshed SA, Parveen S, Nishioka M. Antibodies to single-stranded and double-stranded DNA in antinuclear antibody-positive type 1-autoimmune hepatitis. Hepatology. 1997;26(3):567–72.PubMedCrossRefGoogle Scholar
  41. 41.
    Shahian M, Khosravi A, Anbardar MH. Early cholestasis in neonatal lupus erythematosus. Ann Saudi Med. 2011;31(1):80–2.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Lin SC, Shyur SD, Huang LH, Wu JY, Chuo HT, Lee HC. Neonatal lupus erythematosus with cholestatic hepatitis. J Microbiol Immunol Infect. 2004;37(2):131–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Timpane S, Brandling-Bennett H, Kristjansson AK. Autoimmune collagen vascular diseases: Kids are not just little people. Clin Dermatol. 2016;34(6):678–89.PubMedCrossRefGoogle Scholar
  44. 44.
    Arkin LM, Ansell L, Rademaker A, et al. The natural history of pediatric-onset discoid lupus erythematosus. J Am Acad Dermatol. 2015;72(4):628–33.PubMedCrossRefGoogle Scholar
  45. 45.
    Sampaio MC, De Oliveira ZN, Machado MC, Dos Reis VM, Vilela MA. Discoid lupus erythematosus in children—a retrospective study of 34 patients. Pediatr Dermatol. 2008;25(2):163–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Modesto C, Anton J, Rodriguez B, et al. Incidence and prevalence of juvenile idiopathic arthritis in Catalonia (Spain). Scand J Rheumatol. 2010;39(6):472–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Behrens EM, Beukelman T, Gallo L, et al. Evaluation of the presentation of systemic onset juvenile rheumatoid arthritis: data from the Pennsylvania Systemic Onset Juvenile Arthritis Registry (PASOJAR). J Rheumatol. 2008;35(2):343–8.PubMedGoogle Scholar
  48. 48.
    Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2.PubMedGoogle Scholar
  49. 49.
    Gurion R, Lehman TJ, Moorthy LN. Systemic arthritis in children: a review of clinical presentation and treatment. Int J Inflam. 2012;2012:271569.PubMedCrossRefGoogle Scholar
  50. 50.
    Schneider R, Laxer RM. Systemic onset juvenile rheumatoid arthritis. Baillieres Clin Rhesumatol. 1998;12(2):245–71.CrossRefGoogle Scholar
  51. 51.
    Schaller J, Beckwith B, Wedgwood RJ. Hepatic involvement in juvenile rheumatoid arthritis. J Pediatr. 1970;77(2):203–10.PubMedCrossRefGoogle Scholar
  52. 52.
    Stephan JL, Zeller J, Hubert P, Herbelin C, Dayer JM, Prieur AM. Macrophage activation syndrome and rheumatic disease in childhood: a report of four new cases. Clin Exp Rheumatol. 1993;11(4):451–6.PubMedGoogle Scholar
  53. 53.
    Grom AA, Passo M. Macrophage activation syndrome in systemic juvenile rheumatoid arthritis. J Pediatr. 1996;129(5):630–2.PubMedCrossRefGoogle Scholar
  54. 54.
    Minoia F, Davi S, Horne A, et al. Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients. Arthritis Rheumatol. 2014;66(11):3160–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Ramanan AV, Schneider R. Macrophage activation syndrome—what’s in a name! J Rheumatol. 2003;30(12):2513–6.PubMedGoogle Scholar
  56. 56.
    Gorelik M, Fall N, Altaye M, et al. Follistatin-like protein 1 and the ferritin/erythrocyte sedimentation rate ratio are potential biomarkers for dysregulated gene expression and macrophage activation syndrome in systemic juvenile idiopathic arthritis. J Rheumatol. 2013;40(7):1191–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Ravelli A, Minoia F, Davi S, et al. 2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol. 2016;68(3):566–76.PubMedCrossRefGoogle Scholar
  58. 58.
    Boom V, Anton J, Lahdenne P, et al. Evidence-based diagnosis and treatment of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2015;13:55.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Patwardhan A, Rennebohm R, Dvorchik I, Spencer CH. Is juvenile dermatomyositis a different disease in children up to three years of age at onset than in children above three years at onset? A retrospective review of 23 years of a single center’s experience. Pediatr Rheumatol Online J. 2012;10(1):34.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD. Liver involvement in patients with systemic autoimmune diseases. Maedica (Buchar). 2013;8(4):394–7.Google Scholar
  61. 61.
    Russo RA, Katsicas MM, Davila M, Ciocca M, Zelazko M. Cholestasis in juvenile dermatomyositis: report of three cases. Arthritis Rheum. 2001;44(5):1139–42.PubMedCrossRefGoogle Scholar
  62. 62.
    Chwalinska-Sadowska H, Maldykowa H. Polymyositis-dermatomyositis: 25 years of follow-up of 50 patients disease course, treatment, prognostic factors. Mater Med Pol. 1990;22(3):213–8.PubMedGoogle Scholar
  63. 63.
    Mayes MD, Lacey JV Jr, Beebe-Dimmer J, et al. Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum. 2003;48(8):2246–55.PubMedCrossRefGoogle Scholar
  64. 64.
    Shah AA, Wigley FM. My approach to the treatment of scleroderma. Mayo Clin Proc. 2013;88(4):377–93.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Assassi S, Fritzler MJ, Arnett FC, et al. Primary biliary cirrhosis (PBC), PBC autoantibodies, and hepatic parameter abnormalities in a large population of systemic sclerosis patients. J Rheumatol. 2009;36(10):2250–6.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Rigamonti C, Shand LM, Feudjo M, et al. Clinical features and prognosis of primary biliary cirrhosis associated with systemic sclerosis. Gut. 2006;55(3):388–94.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Swart JF, Wulffraat NM. Diagnostic workup for mixed connective tissue disease in childhood. Isr Med Assoc J. 2008;10(8-9):650–2.PubMedGoogle Scholar
  68. 68.
    Berard RA, Laxer RM. Pediatric mixed connective tissue disease. Curr Rheumatol Rep. 2016;18(5):28.PubMedCrossRefGoogle Scholar
  69. 69.
    Sedej K, Toplak N, Praprotnik M, Luzar B, Brecelj J, Avcin T. Autoimmune hepatitis as a presenting manifestation of mixed connective tissue disease in a child. Case report and review of the literature. Pediatr Rheumatol Online J. 2015;13(1):47.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Civilibal M, Canpolat N, Yurt A, et al. A child with primary Sjogren syndrome and a review of the literature. Clin Pediatr (Phila). 2007;46(8):738–42.CrossRefGoogle Scholar
  71. 71.
    Cimaz R, Casadei A, Rose C, et al. Primary Sjogren syndrome in the paediatric age: a multicentre survey. Eur J Pediatr. 2003;162(10):661–5.PubMedCrossRefGoogle Scholar
  72. 72.
    Longhi BS, Appenzeller S, Centeville M, Gusmao RJ, Marini R. Primary Sjogren’s syndrome in children: is a family approach indicated? Clinics (Sao Paulo). 2011;66(11):1991–3.CrossRefGoogle Scholar
  73. 73.
    Zeron PB, Retamozo S, Bove A, Kostov BA, Siso A, Ramos-Casals M. Diagnosis of liver involvement in primary Sjogren syndrome. J Clin Transl Hepatol. 2013;1(2):94–102.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8–26.PubMedCrossRefGoogle Scholar
  75. 75.
    Fikree A, Chelimsky G, Collins H, Kovacic K, Aziz Q. Gastrointestinal involvement in the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):181–7.PubMedCrossRefGoogle Scholar
  76. 76.
    Mossberg M, Segelmark M, Kahn R, Englund M, Mohammad AJ. Epidemiology of primary systemic vasculitis in children: a population-based study from southern Sweden. Scand J Rheumatol. 2018;47(4):295–302. Scholar
  77. 77.
    Weiss PF. Pediatric vasculitis. Pediatr Clin North Am. 2012;59(2):407–23.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Weiss PF, Klink AJ, Luan X, Feudtner C. Temporal association of Streptococcus, Staphylococcus, and parainfluenza pediatric hospitalizations and hospitalized cases of Henoch-Schonlein purpura. J Rheumatol. 2010;37(12):2587–94.PubMedCrossRefGoogle Scholar
  79. 79.
    Chao HC, Kong MS, Lin SJ. Hepatobiliary involvement of Henoch-Schonlein purpura in children. Acta Paediatr Taiwan. 2000;41(2):63–8.PubMedGoogle Scholar
  80. 80.
    Rosti G, Milani GP, Laicini EA, Fossali EF, Bianchetti MG. Liver chemistry in new-onset Henoch-Schonlein syndrome. Ital J Pediatr. 2017;43(1):85.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    O’Connor N, Dargan PI, Jones AL. Hepatocellular damage from non-steroidal anti-inflammatory drugs. QJM. 2003;96(11):787–91.PubMedCrossRefGoogle Scholar
  82. 82.
    Eladawy M, Dominguez SR, Anderson MS, Glode MP. Abnormal liver panel in acute Kawasaki disease. Pediatr Infect Dis J. 2011;30(2):141–4.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Pawlowska J, Naorniakowska M, Liber A. Liver involvement in children with collagen vascular diseases. Clin Exp Hepatol. 2015;1(3):117–9.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2004;110(17):2747–71.PubMedCrossRefGoogle Scholar
  85. 85.
    Yi DY, Kim JY, Choi EY, Choi JY, Yang HR. Hepatobiliary risk factors for clinical outcome of Kawasaki disease in children. BMC Pediatr. 2014;14:51.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Matsumoto T, Kobayashi S, Shimizu H, et al. The liver in collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver. Liver. 2000;20(5):366–73.PubMedCrossRefGoogle Scholar
  87. 87.
    Selmi C, De Santis M, Gershwin ME. Liver involvement in subjects with rheumatic disease. Arthritis Res Ther. 2011;13(3):226.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Oguzkurt P, Akcoren Z, Kale G, Tanyel FC. Polyarteritis nodosa involving the hepatobiliary system in an eight-year-old girl with a previous diagnosis of familial Mediterranean fever. Eur J Pediatr Surg. 2000;10(2):145–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Park HJ, Choi YJ, Kim JE, Ye YM, Park HS, Suh CH. Successful treatment of pediatric systemic polyarteritis nodosa with cholestatic hepatitis. Clin Rheumatol. 2007;26(1):122–4.PubMedCrossRefGoogle Scholar
  90. 90.
    Baysun S, Demircin G, Erdodan O, Bulbul M, Yildiz YT, Oner A. Multiple visceral hematomas in a child with familial Mediterranean fever: polyarteritis nodosa. Pediatr Nephrol. 2008;23(8):1233., 1235-1237.PubMedCrossRefGoogle Scholar
  91. 91.
    Cakar N, Yalcinkaya F, Duzova A, et al. Takayasu arteritis in children. J Rheumatol. 2008;35(5):913–9.PubMedGoogle Scholar
  92. 92.
    Herrera CN, Tomala-Haz JE. Portal hypertension: an uncommon clinical manifestation of Takayasu arteritis in a 9-year-old child. Open Access Rheumatol. 2016;8:115–8.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Durant C, Martin J, Hervier B, Gournay J, Hamidou M. Takayasu arteritis associated with hepatic sinusoidal dilatation. Ann Hepatol. 2011;10(4):559–61.PubMedGoogle Scholar
  94. 94.
    Yotsuyanagi H, Chikatsu N, Kaneko Y, Kurokawa K. Takayasu’s arteritis in prepulseless stage manifesting lymph node swelling and hepatosplenomegaly. Intern Med. 1995;34(5):455–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Karincaoglu Y, Borlu M, Toker SC, et al. Demographic and clinical properties of juvenile-onset Behcet’s disease: a controlled multicenter study. J Am Acad Dermatol. 2008;58(4):579–84.PubMedCrossRefGoogle Scholar
  96. 96.
    Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1–11.PubMedCrossRefGoogle Scholar
  97. 97.
    Kone-Paut I. Behcet’s disease in children, an overview. Pediatr Rheumatol Online J. 2016;14(1):10.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behcet’s disease: a review. World J Gastroenterol. 2015;21(13):3801–12.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Calamia KT, Schirmer M, Melikoglu M. Major vessel involvement in Behcet’s disease: an update. Curr Opin Rheumatol. 2011;23(1):24–31.PubMedCrossRefGoogle Scholar
  100. 100.
    Orloff LA, Orloff MJ. Budd-Chiari syndrome caused by Behcet’s disease: treatment by side-to-side portacaval shunt. J Am Coll Surg. 1999;188(4):396–407.PubMedCrossRefGoogle Scholar
  101. 101.
    Cabral DA, Canter DL, Muscal E, et al. Comparing presenting clinical features in 48 children with microscopic polyangiitis to 183 children who have granulomatosis with polyangiitis (Wegener’s): an ARChiVe cohort study. Arthritis Rheumatol. 2016;68(10):2514–26.PubMedCrossRefGoogle Scholar
  102. 102.
    Calatroni M, Oliva E, Gianfreda D, et al. ANCA-associated vasculitis in childhood: recent advances. Ital J Pediatr. 2017;43(1):46.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Alberici F, Martorana D, Vaglio A. Genetic aspects of anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrol Dial Transplant. 2015;30(Suppl 1):i37–45.PubMedGoogle Scholar
  104. 104.
    Iudici M, Quartier P, Terrier B, Mouthon L, Guillevin L, Puechal X. Childhood-onset granulomatosis with polyangiitis and microscopic polyangiitis: systematic review and meta-analysis. Orphanet J Rare Dis. 2016;11(1):141.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Zwerina J, Eger G, Englbrecht M, Manger B, Schett G. Churg-Strauss syndrome in childhood: a systematic literature review and clinical comparison with adult patients. Semin Arthritis Rheum. 2009;39(2):108–15.PubMedCrossRefGoogle Scholar
  106. 106.
    Singh R, Singh D, Abdou N. Churg-Strauss syndrome presenting as acute abdomen: are gastrointestinal manifestations an indicator of poor prognosis? Int J Rheum Dis. 2009;12(2):161–5.PubMedCrossRefGoogle Scholar
  107. 107.
    Childhood Hodgkin Lymphoma Treatment (PDQ(R)). Health Professional Version. In PDQ Cancer Information Summaries, Bethesda, MD; 2002.Google Scholar
  108. 108.
    Pileri SA, Ascani S, Leoncini L, et al. Hodgkin’s lymphoma: the pathologist’s viewpoint. J Clin Pathol. 2002;55(3):162–76.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Kennedy-Nasser AA, Hanley P, Bollard CM. Hodgkin disease and the role of the immune system. Pediatr Hematol Oncol. 2011;28(3):176–86.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Pourtsidis A, Doganis D, Baka M, et al. Differences between younger and older patients with childhood Hodgkin lymphoma. Pediatr Hematol Oncol. 2013;30(6):532–6.PubMedCrossRefGoogle Scholar
  111. 111.
    Yusuf MA, Elias E, Hubscher SG. Jaundice caused by the vanishing bile duct syndrome in a child with Hodgkin lymphoma. J Pediatr Hematol Oncol. 2000;22(2):154–7.PubMedCrossRefGoogle Scholar
  112. 112.
    Vardareli E, Dundar E, Aslan V, Gulbas Z. Acute liver failure due to Hodgkin’s lymphoma. Med Princ Pract. 2004;13(6):372–4.PubMedCrossRefGoogle Scholar
  113. 113.
    Murakami J, Shimizu Y. Hepatic manifestations in hematological disorders. Int J Hepatol. 2013;2013:484903.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Smith MA, Altekruse SF, Adamson PC, Reaman GH, Seibel NL. Declining childhood and adolescent cancer mortality. Cancer. 2014;120(16):2497–506.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Childhood Non-Hodgkin Lymphoma Treatment (PDQ(R)). Health Professional Version. In PDQ Cancer Information Summaries, Bethesda, MD; 2002.Google Scholar
  116. 116.
    Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med. 1996;334(19):1238–48.PubMedCrossRefGoogle Scholar
  117. 117.
    Hong FS, Smith CL, Angus PW, Crowley P, Ho WK. Hodgkin lymphoma and fulminant hepatic failure. Leuk Lymphoma. 2010;51(5):947–51.PubMedCrossRefGoogle Scholar
  118. 118.
    Ghosh I, Bakhshi S. Jaundice as a presenting manifestation of pediatric non-Hodgkin lymphoma: etiology, management, and outcome. J Pediatr Hematol Oncol. 2010;32(4):e131–5.PubMedCrossRefGoogle Scholar
  119. 119.
    Civardi G, Vallisa D, Berte R, Lazzaro A, Moroni CF, Cavanna L. Focal liver lesions in non-Hodgkin’s lymphoma: investigation of their prevalence, clinical significance and the role of Hepatitis C virus infection. Eur J Cancer. 2002;38(18):2382–7.PubMedCrossRefGoogle Scholar
  120. 120.
    Karaosmanoglu D, Karcaaltincaba M, Oguz B, Akata D, Ozmen M, Akhan O. CT findings of lymphoma with peritoneal, omental and mesenteric involvement: peritoneal lymphomatosis. Eur J Radiol. 2009;71(2):313–7.PubMedCrossRefGoogle Scholar
  121. 121.
    Miller ST, Wollner N, Meyers PA, Exelby P, Jereb B, Miller DR. Primary hepatic or hepatosplenic non-Hodgkin’s lymphoma in children. Cancer. 1983;52(12):2285–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Masood A, Kairouz S, Hudhud KH, Hegazi AZ, Banu A, Gupta NC. Primary non-Hodgkin lymphoma of liver. Curr Oncol. 2009;16(4):74–7.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Kikuma K, Watanabe J, Oshiro Y, et al. Etiological factors in primary hepatic B-cell lymphoma. Virchows Arch. 2012;460(4):379–87.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Cameron AM, Truty J, Truell J, et al. Fulminant hepatic failure from primary hepatic lymphoma: successful treatment with orthotopic liver transplantation and chemotherapy. Transplantation. 2005;80(7):993–6.PubMedCrossRefGoogle Scholar
  125. 125.
    Guo X, Li Q, Zhu YP. Childhood hepatosplenic T-cell lymphoma with skin involvement. Indian Pediatr. 2015;52(5):427–8.PubMedCrossRefGoogle Scholar
  126. 126.
    Beigel F, Jurgens M, Tillack C, et al. Hepatosplenic T-cell lymphoma in a patient with Crohn’s disease. Nat Rev Gastroenterol Hepatol. 2009;6(7):433–6.PubMedCrossRefGoogle Scholar
  127. 127.
    De Rooij JD, Zwaan CM, Van Den Heuvel-Eibrink M. Pediatric AML: from biology to clinical management. J Clin Forensic Med. 2015;4(1):127–49.Google Scholar
  128. 128.
    Smith MA, Seibel NL, Altekruse SF, et al. Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol. 2010;28(15):2625–34.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer. 2008;112(2):416–32.PubMedCrossRefGoogle Scholar
  130. 130.
    Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373(16):1541–52.PubMedCrossRefGoogle Scholar
  131. 131.
    Segal I, Rassekh SR, Bond MC, Senger C, Schreiber RA. Abnormal liver transaminases and conjugated hyperbilirubinemia at presentation of acute lymphoblastic leukemia. Pediatr Blood Cancer. 2010;55(3):434–9.PubMedCrossRefGoogle Scholar
  132. 132.
    Rivet C, Leverger G, Jacquemin E, Bernard O. Acute leukemia presenting as acute hepatitis without liver failure. J Pediatr Gastroenterol Nutr. 2014;59(5):640–1.PubMedCrossRefGoogle Scholar
  133. 133.
    Reddi DM, Barbas AS, Castleberry AW, et al. Liver transplantation in an adolescent with acute liver failure from acute lymphoblastic leukemia. Pediatr Transplant. 2014;18(2):E57–63.PubMedCrossRefGoogle Scholar
  134. 134.
    Grimwade D, Ivey A, Huntly BJ. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood. 2016;127(1):29–41.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Nakano Y, Yamasaki K, Otsuka Y, et al. Acute myeloid leukemia with RBM15-MKL1 presenting as severe hepatic failure. Glob Pediatr Health. 2017;4:2333794X16689011.PubMedPubMedCentralGoogle Scholar
  136. 136.
    Hofmann I. Myeloproliferative neoplasms in children. J Hematop. 2015;8(3):143–57.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Hoekstra J, Bresser EL, Smalberg JH, Spaander MC, Leebeek FW, Janssen HL. Long-term follow-up of patients with portal vein thrombosis and myeloproliferative neoplasms. J Thromb Haemost. 2011;9(11):2208–14.PubMedCrossRefGoogle Scholar
  138. 138.
    Ferri PM, Rodrigues Ferreira A, Fagundes ED, et al. Evaluation of the presence of hereditary and acquired thrombophilias in Brazilian children and adolescents with diagnoses of portal vein thrombosis. J Pediatr Gastroenterol Nutr. 2012;55(5):599–604.PubMedCrossRefGoogle Scholar
  139. 139.
    Bertrand A, Heissat S, Caron N, et al. Deep vein thrombosis revealing myeloproliferative syndrome in two adolescents. Arch Pediatr. 2014;21(5):497–500.PubMedCrossRefGoogle Scholar
  140. 140.
    Valla D, Casadevall N, Lacombe C, et al. Primary myeloproliferative disorder and hepatic vein thrombosis. A prospective study of erythroid colony formation in vitro in 20 patients with Budd-Chiari syndrome. Ann Intern Med. 1985;103(3):329–34.PubMedCrossRefGoogle Scholar
  141. 141.
    Coskun ME, Height S, Dhawan A, Hadzic N. Ruxolitinib treatment in an infant with JAK2+ polycythaemia vera-associated Budd-Chiari syndrome. BMJ Case Rep. 2017;2017.Google Scholar
  142. 142.
    Randi ML, Putti MC, Scapin M, et al. Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative. Blood. 2006;108(10):3600–2.PubMedCrossRefGoogle Scholar
  143. 143.
    Giona F, Teofili L, Moleti ML, et al. Thrombocythemia and polycythemia in patients younger than 20 years at diagnosis: clinical and biologic features, treatment, and long-term outcome. Blood. 2012;119(10):2219–27.PubMedCrossRefGoogle Scholar
  144. 144.
    Hasle H. Incidence of essential thrombocythaemia in children. Br J Haematol. 2000;110(3):751.PubMedCrossRefGoogle Scholar
  145. 145.
    Saksena A, Arora P, Khurana N, Sethi GR, Singh T. Paediatric idiopathic myelofibrosis. Indian J Hematol Blood Transfus. 2014;30(Suppl 1):363–5.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    An W, Wan Y, Guo Y, et al. CALR mutation screening in pediatric primary myelofibrosis. Pediatr Blood Cancer. 2014;61(12):2256–62.PubMedCrossRefGoogle Scholar
  147. 147.
    Druker BJ, Guilhot F, O'brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408–17.PubMedCrossRefGoogle Scholar
  148. 148.
    De La Fuente J, Baruchel A, Biondi A, et al. Managing children with chronic myeloid leukaemia (CML): recommendations for the management of CML in children and young people up to the age of 18 years. Br J Haematol. 2014;167(1):33–47.PubMedCrossRefGoogle Scholar
  149. 149.
    Loh ML. Recent advances in the pathogenesis and treatment of juvenile myelomonocytic leukaemia. Br J Haematol. 2011;152(6):677–87.PubMedCrossRefGoogle Scholar
  150. 150.
    Sakashita K, Matsuda K, Koike K. Diagnosis and treatment of juvenile myelomonocytic leukemia. Pediatr Int. 2016;58(8):681–90.PubMedCrossRefGoogle Scholar
  151. 151.
    Emanuel PD. Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. Leukemia. 2008;22(7):1335–42.PubMedCrossRefGoogle Scholar
  152. 152.
    Allen CE, Kelly KM, Bollard CM. Pediatric lymphomas and histiocytic disorders of childhood. Pediatr Clin North Am. 2015;62(1):139–65.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013;121(25):5006–14.PubMedCrossRefGoogle Scholar
  154. 154.
    Stalemark H, Laurencikas E, Karis J, Gavhed D, Fadeel B, Henter JI. Incidence of Langerhans cell histiocytosis in children: a population-based study. Pediatr Blood Cancer. 2008;51(1):76–81.PubMedCrossRefGoogle Scholar
  155. 155.
    Yi X, Han T, Zai H, Long X, Wang X, Li W. Liver involvement of Langerhans’ cell histiocytosis in children. Int J Clin Exp Med. 2015;8(5):7098–106.PubMedPubMedCentralGoogle Scholar
  156. 156.
    Tang Y, Zhang Z, Chen M, et al. Severe sclerosing cholangitis after Langerhans cell histiocytosis treated by liver transplantation: An adult case report. Medicine (Baltimore). 2017;96(9):e5994.CrossRefGoogle Scholar
  157. 157.
    Braier J, Ciocca M, Latella A, De Davila MG, Drajer M, Imventarza O. Cholestasis, sclerosing cholangitis, and liver transplantation in Langerhans cell Histiocytosis. Med Pediatr Oncol. 2002;38(3):178–82.PubMedCrossRefGoogle Scholar
  158. 158.
    Kaplan KJ, Goodman ZD, Ishak KG. Liver involvement in Langerhans’ cell histiocytosis: a study of nine cases. Mod Pathol. 1999;12(4):370–8.PubMedGoogle Scholar
  159. 159.
    Jaffe R. Liver involvement in the histiocytic disorders of childhood. Pediatr Dev Pathol. 2004;7(3):214–25.PubMedCrossRefGoogle Scholar
  160. 160.
    Meeths M, Chiang SC, Lofstedt A, et al. Pathophysiology and spectrum of diseases caused by defects in lymphocyte cytotoxicity. Exp Cell Res. 2014;325(1):10–7.PubMedCrossRefGoogle Scholar
  161. 161.
    Creput C, Galicier L, Buyse S, Azoulay E. Understanding organ dysfunction in hemophagocytic lymphohistiocytosis. Intensive Care Med. 2008;34(7):1177–87.PubMedCrossRefGoogle Scholar
  162. 162.
    Ishii E. Hemophagocytic lymphohistiocytosis in children: pathogenesis and treatment. Front Pediatr. 2016;4:47.PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Amin N, Shah I, Bhatnagar S. Hemophagocytic lymphohistiocytosis (HLH) in children presenting as liver disease. J Clin Exp Hepatol. 2014;4(2):175–7.PubMedCrossRefGoogle Scholar
  164. 164.
    Larroche C, Ziol M, Zidi S, Dhote R, Roulot D. Liver involvement in hemophagocytic syndrome. Gastroenterol Clin Biol. 2007;31(11):959–66.PubMedCrossRefGoogle Scholar
  165. 165.
    Favara BE. Histopathology of the liver in histiocytosis syndromes. Pediatr Pathol Lab Med. 1996;16(3):413–33.PubMedCrossRefGoogle Scholar
  166. 166.
    Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046–60.PubMedCrossRefGoogle Scholar
  167. 167.
    Pilbeam KL, Lund TC. Pediatric multiple myeloma. Blood. 2017;129(3):395.PubMedCrossRefGoogle Scholar
  168. 168.
    Corbacioglu S, Carreras E, Ansari M, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European society for blood and marrow transplantation. Bone Marrow Transplant. 2018;53(2):138–45.PubMedCrossRefGoogle Scholar
  169. 169.
    Fan CQ, Crawford JM. Sinusoidal obstruction syndrome (hepatic veno-occlusive disease). J Clin Exp Hepatol. 2014;4(4):332–46.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Deleve LD, Shulman HM, Mcdonald GB. Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Semin Liver Dis. 2002;22(1):27–42.PubMedCrossRefGoogle Scholar
  171. 171.
    Sakamoto S, Nakazawa A, Shigeta T, et al. Devastating outflow obstruction after pediatric split liver transplantation. Pediatr Transplant. 2013;17(1):E25–8.PubMedCrossRefGoogle Scholar
  172. 172.
    Cesaro S, Pillon M, Talenti E, et al. A prospective survey on incidence, risk factors and therapy of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. Haematologica. 2005;90(10):1396–404.PubMedGoogle Scholar
  173. 173.
    Schulz AS, Classen CF, Mihatsch WA, et al. HLA-haploidentical blood progenitor cell transplantation in osteopetrosis. Blood. 2002;99(9):3458–60.PubMedCrossRefGoogle Scholar
  174. 174.
    Cheuk DK, Wang P, Lee TL, et al. Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007;40(10):935–44.PubMedCrossRefGoogle Scholar
  175. 175.
    Coppell JA, Richardson PG, Soiffer R, et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2010;16(2):157–68.PubMedCrossRefGoogle Scholar
  176. 176.
    Mohty M, Malard F, Abecassis M, et al. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2015;50(6):781–9.PubMedPubMedCentralCrossRefGoogle Scholar
  177. 177.
    Palomo M, Mir E, Rovira M, Escolar G, Carreras E, Diaz-Ricart M. What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance. Blood. 2016;127(13):1719–27.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Corbacioglu S, Greil J, Peters C, et al. Defibrotide in the treatment of children with veno-occlusive disease (VOD): a retrospective multicentre study demonstrates therapeutic efficacy upon early intervention. Bone Marrow Transplant. 2004;33(2):189–95.PubMedCrossRefGoogle Scholar
  179. 179.
    Dalle JH, Giralt SA. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification, prophylaxis, and treatment. Biol Blood Marrow Transplant. 2016;22(3):400–9.PubMedCrossRefGoogle Scholar
  180. 180.
    Corbacioglu S, Richardson PG. Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation. Expert Rev Gastroenterol Hepatol. 2017;11(10):885–98.PubMedCrossRefGoogle Scholar
  181. 181.
    Flinn AM, Gennery AR. Treatment of pediatric acute graft-versus-host disease-lessons from primary immunodeficiency? Front Immunol. 2017;8:328.PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    Carpenter PA, Macmillan ML. Management of acute graft-versus-host disease in children. Pediatr Clin North Am. 2010;57(1):273–95.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389–401 e381.PubMedCrossRefGoogle Scholar
  184. 184.
    Baird K, Cooke K, Schultz KR. Chronic graft-versus-host disease (GVHD) in children. Pediatr Clin North Am. 2010;57(1):297–322.PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Melin-Aldana H, Thormann K, Duerst R, Kletzel M, Jacobsohn DA. Hepatitic pattern of graft versus host disease in children. Pediatr Blood Cancer. 2007;49(5):727–30.PubMedCrossRefGoogle Scholar
  186. 186.
    Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med. 2005;353(11):1135–46.PubMedCrossRefGoogle Scholar
  187. 187.
    Muncie HL Jr, Campbell J. Alpha and beta thalassemia. Am Fam Physician. 2009;80(4):339–44.PubMedGoogle Scholar
  188. 188.
    Galanello R, Cao A. Gene test review. Alpha-thalassemia. Genet Med. 2011;13(2):83–8.PubMedCrossRefGoogle Scholar
  189. 189.
    Modell B, Khan M, Darlison M. Survival in beta-thalassaemia major in the UK: data from the UK Thalassaemia Register. Lancet. 2000;355(9220):2051–2.PubMedCrossRefGoogle Scholar
  190. 190.
    Lucarelli G, Andreani M, Angelucci E. The cure of thalassemia by bone marrow transplantation. Blood Rev. 2002;16(2):81–5.PubMedCrossRefGoogle Scholar
  191. 191.
    Ghavamzadeh A, Mirzania M, Kamalian N, Sedighi N, Azimi P. Hepatic iron overload and fibrosis in patients with beta thalassemia major after hematopoietic stem cell transplantation: a pilot study. Int J Hematol Oncol Stem Cell Res. 2015;9(2):55–9.PubMedPubMedCentralGoogle Scholar
  192. 192.
    Aguilar Martinez P, Angastiniotis M, Eleftheriou A, et al. Haemoglobinopathies in Europe: health & migration policy perspectives. Orphanet J Rare Dis. 2014;9:97.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Ahn H, Li CS, Wang W. Sickle cell hepatopathy: clinical presentation, treatment, and outcome in pediatric and adult patients. Pediatr Blood Cancer. 2005;45(2):184–90.PubMedCrossRefGoogle Scholar
  194. 194.
    Johnson CS, Omata M, Tong MJ, Simmons JF Jr, Weiner J, Tatter D. Liver involvement in sickle cell disease. Medicine (Baltimore). 1985;64(5):349–56.CrossRefGoogle Scholar
  195. 195.
    Jitraruch S, Fitzpatrick E, Deheragoda M, et al. Autoimmune liver disease in children with Sickle cell disease. J Pediatr. 2017;189:79–85.e2.PubMedCrossRefGoogle Scholar
  196. 196.
    Dhaliwal G, Cornett PA, Tierney LM Jr. Hemolytic anemia. Am Fam Physician. 2004;69(11):2599–606.PubMedGoogle Scholar
  197. 197.
    Aladjidi N, Leverger G, Leblanc T, et al. New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children. Haematologica. 2011;96(5):655–63.PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Hill QA, Stamps R, Massey E, et al. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol. 2017;176(3):395–411.PubMedCrossRefGoogle Scholar
  199. 199.
    Maggiore G, Sciveres M, Fabre M, et al. Giant cell hepatitis with autoimmune hemolytic anemia in early childhood: long-term outcome in 16 children. J Pediatr. 2011;159(1):127–132.e121.PubMedCrossRefGoogle Scholar
  200. 200.
    Paganelli M, Patey N, Bass LM, Alvarez F. Anti-CD20 treatment of giant cell hepatitis with autoimmune hemolytic anemia. Pediatrics. 2014;134(4):e1206–10.PubMedCrossRefGoogle Scholar
  201. 201.
    Rovelli A, Corti P, Beretta C, Bovo G, Conter V, Mieli-Vergani G. Alemtuzumab for giant cell hepatitis with autoimmune hemolytic anemia. J Pediatr Gastroenterol Nutr. 2007;45(5):596–9.PubMedCrossRefGoogle Scholar
  202. 202.
    Bouguila J, Mabrouk S, Tilouche S, et al. Giant cell hepatitis with autoimmune hemolytic anemia in a nine month old infant. World J Hepatol. 2013;5(4):226–9.PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Ware RE, Hall SE, Rosse WF. Paroxysmal nocturnal hemoglobinuria with onset in childhood and adolescence. N Engl J Med. 1991;325(14):991–6.PubMedCrossRefGoogle Scholar
  204. 204.
    Mercuri A, Farruggia P, Timeus F, et al. A retrospective study of paroxysmal nocturnal hemoglobinuria in pediatric and adolescent patients. Blood Cells Mol Dis. 2017;64:45–50.PubMedCrossRefGoogle Scholar
  205. 205.
    Hall C, Richards S, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood. 2003;102(10):3587–91.PubMedCrossRefGoogle Scholar
  206. 206.
    Van Den Heuvel-Eibrink MM, Bredius RG, Te Winkel ML, et al. Childhood paroxysmal nocturnal haemoglobinuria (PNH), a report of 11 cases in the Netherlands. Br J Haematol. 2005;128(4):571–7.PubMedCrossRefGoogle Scholar
  207. 207.
    Rajagopal R, Thachil J, Monagle P. Disseminated intravascular coagulation in paediatrics. Arch Dis Child. 2017;102(2):187–93.PubMedCrossRefGoogle Scholar
  208. 208.
    Wada H, Matsumoto T, Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines. J Intensive Care. 2014;2(1):15.PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Bakhshi S, Arya LS. Diagnosis and treatment of disseminated intravascular coagulation. Indian Pediatr. 2003;40(8):721–30.PubMedGoogle Scholar
  210. 210.
    Stevens SM, Woller SC, Bauer KA, et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis. 2016;41(1):154–64.PubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Raffini L, Thornburg C. Testing children for inherited thrombophilia: more questions than answers. Br J Haematol. 2009;147(3):277–88.PubMedCrossRefGoogle Scholar
  212. 212.
    Tanaka M, Wanless IR. Pathology of the liver in Budd-Chiari syndrome: portal vein thrombosis and the histogenesis of veno-centric cirrhosis, veno-portal cirrhosis, and large regenerative nodules. Hepatology. 1998;27(2):488–96.PubMedCrossRefGoogle Scholar
  213. 213.
    Tripodi A, Anstee QM, Sogaard KK, Primignani M, Valla DC. Hypercoagulability in cirrhosis: causes and consequences. J Thromb Haemost. 2011;9(9):1713–23.PubMedCrossRefGoogle Scholar
  214. 214.
    Mann DA, Marra F. Fibrogenic signalling in hepatic stellate cells. J Hepatol. 2010;52(6):949–50.PubMedCrossRefGoogle Scholar
  215. 215.
    Schouten JN, Verheij J, Seijo S. Idiopathic non-cirrhotic portal hypertension: a review. Orphanet J Rare Dis. 2015;10:67.PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Fasano A, Catassi C. Clinical practice. Celiac disease. N Engl J Med. 2012;367(25):2419–26.PubMedCrossRefGoogle Scholar
  217. 217.
    Tack GJ, Verbeek WH, Schreurs MW, Mulder CJ. The spectrum of celiac disease: epidemiology, clinical aspects and treatment. Nat Rev Gastroenterol Hepatol. 2010;7(4):204–13.PubMedCrossRefGoogle Scholar
  218. 218.
    Newton KP, Singer SA. Celiac disease in children and adolescents: special considerations. Semin Immunopathol. 2012;34(4):479–96.PubMedCrossRefGoogle Scholar
  219. 219.
    Husby S, Koletzko S, Korponay-Szabo IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136–60.PubMedCrossRefGoogle Scholar
  220. 220.
    Bonamico M, Pitzalis G, Culasso F, et al. Hepatic damage in celiac disease in children. Minerva Pediatr. 1986;38(21):959–62.PubMedGoogle Scholar
  221. 221.
    Volta U, De Franceschi L, Lari F, Molinaro N, Zoli M, Bianchi FB. Coeliac disease hidden by cryptogenic hypertransaminasaemia. Lancet. 1998;352(9121):26–9.PubMedCrossRefGoogle Scholar
  222. 222.
    Vajro P, Fontanella A, Mayer M, et al. Elevated serum aminotransferase activity as an early manifestation of gluten-sensitive enteropathy. J Pediatr. 1993;122(3):416–9.PubMedCrossRefGoogle Scholar
  223. 223.
    Anania C, De Luca E, De Castro G, Chiesa C, Pacifico L. Liver involvement in pediatric celiac disease. World J Gastroenterol. 2015;21(19):5813–22.PubMedPubMedCentralCrossRefGoogle Scholar
  224. 224.
    Caprai S, Vajro P, Ventura A, Sciveres M, Maggiore G. Disease SSGFaLDIC. Autoimmune liver disease associated with celiac disease in childhood: a multicenter study. Clin Gastroenterol Hepatol. 2008;6(7):803–6.PubMedCrossRefGoogle Scholar
  225. 225.
    Di Biase AR, Colecchia A, Scaioli E, et al. Autoimmune liver diseases in a paediatric population with coeliac disease—a 10-year single-centre experience. Aliment Pharmacol Ther. 2010;31(2):253–60.PubMedGoogle Scholar
  226. 226.
    Ventura A, Magazzu G, Greco L. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for autoimmune disorders in celiac disease. Gastroenterology. 1999;117(2):297–303.PubMedCrossRefGoogle Scholar
  227. 227.
    Lacaille F, Canioni D, Bernard O, Fabre M, Brousse N, Schmitz J. Celiac disease, inflammatory colitis, and primary sclerosing cholangitis in a girl with Turner's syndrome. J Pediatr Gastroenterol Nutr. 1995;21(4):463–7.PubMedCrossRefGoogle Scholar
  228. 228.
    Reilly NR, Lebwohl B, Hultcrantz R, Green PH, Ludvigsson JF. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease. J Hepatol. 2015;62(6):1405–11.PubMedPubMedCentralCrossRefGoogle Scholar
  229. 229.
    Miele L, Marrone G, Lauritano C, et al. Gut-liver axis and microbiota in NAFLD: insight pathophysiology for novel therapeutic target. Curr Pharm Des. 2013;19(29):5314–24.PubMedCrossRefGoogle Scholar
  230. 230.
    Rowe K, Pankow J, Nehme F, Salyers W. Gastrointestinal amyloidosis: review of the literature. Cureus. 2017;9(5):e1228.PubMedPubMedCentralGoogle Scholar
  231. 231.
    Cowan AJ, Skinner M, Seldin DC, et al. Amyloidosis of the gastrointestinal tract: a 13-year, single-center, referral experience. Haematologica. 2013;98(1):141–6.PubMedPubMedCentralCrossRefGoogle Scholar
  232. 232.
    Beneteau-Burnat B, Baudin B, Morgant G, Baumann FC, Giboudeau J. Serum angiotensin-converting enzyme in healthy and sarcoidotic children: comparison with the reference interval for adults. Clin Chem. 1990;36(2):344–6.PubMedGoogle Scholar
  233. 233.
    Coash M, Forouhar F, Wu CH, Wu GY. Granulomatous liver diseases: a review. J Formos Med Assoc. 2012;111(1):3–13.PubMedCrossRefGoogle Scholar
  234. 234.
    Wahl SM. Hepatic granuloma as a model of inflammation and repair: an overview. Methods Enzymol. 1988;163:605–22.PubMedCrossRefGoogle Scholar
  235. 235.
    Hams E, Aviello G, Fallon PG. The schistosoma granuloma: friend or foe? Front Immunol. 2013;4:89.PubMedPubMedCentralCrossRefGoogle Scholar
  236. 236.
    Geramizadeh B, Jahangiri R, Moradi E. Causes of hepatic granuloma: a 12-year single center experience from southern Iran. Arch Iran Med. 2011;14(4):288–9.PubMedGoogle Scholar
  237. 237.
    Collins MH, Jiang B, Croffie JM, Chong SK, Lee CH. Hepatic granulomas in children. A clinicopathologic analysis of 23 cases including polymerase chain reaction for histoplasma. Am J Surg Pathol. 1996;20(3):332–8.PubMedCrossRefGoogle Scholar
  238. 238.
    Lagana SM, Moreira RK, Lefkowitch JH. Hepatic granulomas: pathogenesis and differential diagnosis. Clin Liver Dis. 2010;14(4):605–17.PubMedCrossRefGoogle Scholar
  239. 239.
    Shetty AK, Gedalia A. Childhood sarcoidosis: a rare but fascinating disorder. Pediatr Rheumatol Online J. 2008;6:16.PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    Dahlan Y, Smith L, Simmonds D, et al. Pediatric-onset primary biliary cirrhosis. Gastroenterology. 2003;125(5):1476–9.PubMedCrossRefGoogle Scholar
  241. 241.
    Murano I, Yoshii H, Kurashige H, Sugio Y, Tsukahara M. Giant hepatic granuloma caused by Bartonella henselae. Pediatr Infect Dis J. 2001;20(3):319–20.PubMedCrossRefGoogle Scholar
  242. 242.
    Teixeira AB, Lana AM, Lamounier JA, Pereira Da Silva O, Eloi-Santos SM. Neonatal listeriosis: the importance of placenta histological examination-a case report. AJP Rep. 2011;1(1):3–6.PubMedPubMedCentralCrossRefGoogle Scholar
  243. 243.
    Ozkan TB, Mistik R, Dikici B, Nazlioglu HO. Antiviral therapy in neonatal cholestatic cytomegalovirus hepatitis. BMC Gastroenterol. 2007;7:9.PubMedPubMedCentralCrossRefGoogle Scholar
  244. 244.
    Bolis V, Karadedos C, Chiotis I, Chaliasos N, Tsabouri S. Atypical manifestations of Epstein-Barr virus in children: a diagnostic challenge. J Pediatr (Rio J). 2016;92(2):113–21.CrossRefGoogle Scholar
  245. 245.
    Egritas O, Sari S, Dalgic B, Vural C, Akyol G. Granulomatous hepatitis, perihepatic lymphadenopathies, and autoantibody positivity: an unusual association in a child with hepatitis C. Eur J Pediatr. 2009;168(3):275–9.PubMedCrossRefGoogle Scholar
  246. 246.
    Elbaz T, Esmat G. Hepatic and intestinal schistosomiasis: review. J Adv Res. 2013;4(5):445–52.PubMedPubMedCentralCrossRefGoogle Scholar
  247. 247.
    Amin MD, Harpavat S, Leung DH. Drug-induced liver injury in children. Curr Opin Pediatr. 2015;27(5):625–33.PubMedCrossRefGoogle Scholar
  248. 248.
    Tajima Y, Takagi R, Nakajima T, Kominato Y. An infant with asymptomatic hepatic granuloma probably caused by bacillus Calmette-Guerin (BCG) vaccination found incidentally at autopsy: a case report. Cases J. 2008;1(1):337.PubMedPubMedCentralCrossRefGoogle Scholar
  249. 249.
    Levine S, Smith VV, Malone M, Sebire NJ. Histopathological features of chronic granulomatous disease (CGD) in childhood. Histopathology. 2005;47(5):508–16.PubMedCrossRefGoogle Scholar
  250. 250.
    Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42(3):641–9.PubMedCrossRefGoogle Scholar
  251. 251.
    Shoenfeld Y. Systemic antiphospholipid syndrome. Lupus. 2003;12(7):497–8.PubMedCrossRefGoogle Scholar
  252. 252.
    Avcin T, Cimaz R, Rozman B, Ped-APS Registry Collaborative Group. The Ped-APS Registry: the antiphospholipid syndrome in childhood. Lupus. 2009;18(10):894–9.PubMedCrossRefGoogle Scholar
  253. 253.
    Cervera R, Piette JC, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):1019–27.PubMedCrossRefGoogle Scholar
  254. 254.
    Avcin T, Cimaz R, Silverman ED, et al. Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics. 2008;122(5):e1100–7.PubMedCrossRefGoogle Scholar
  255. 255.
    Groot N, De Graeff N, Avcin T, et al. European evidence-based recommendations for diagnosis and treatment of paediatric antiphospholipid syndrome: the SHARE initiative. Ann Rheum Dis. 2017;76(10):1637–41.PubMedCrossRefGoogle Scholar
  256. 256.
    Berkun Y, Padeh S, Barash J, et al. Antiphospholipid syndrome and recurrent thrombosis in children. Arthritis Rheum. 2006;55(6):850–5.PubMedCrossRefGoogle Scholar
  257. 257.
    Deleve LD, Valla DC, Garcia-Tsao G. American Association for the Study Liver D. Vascular disorders of the liver. Hepatology. 2009;49(5):1729–64.PubMedCrossRefGoogle Scholar
  258. 258.
    Boudhina T, Ghram N, Ben Becher S, et al. Budd-Chiari syndrome in children. Apropos of 7 cases. Arch Fr Pediatr. 1991;48(4):243–8.PubMedGoogle Scholar
  259. 259.
    Khubchandani RP, D’souza S. Antiphospholipid antibody syndrome as a cause of Budd-Chiari syndrome. Indian Pediatr. 2003;40(9):907–8.PubMedGoogle Scholar
  260. 260.
    Ravelli A, Martini A. Antiphospholipid syndrome. Pediatr Clin North Am. 2005;52(2):469–91., vi.PubMedCrossRefGoogle Scholar
  261. 261.
    Saca LF, Szer IS, Henar E, Nanjundiah P, Haddad ZH, Quismorio FP Jr. Budd-Chiari syndrome associated with antiphospholipid antibodies in a child: report of a case and review of the literature. J Rheumatol. 1994;21(3):545–8.Google Scholar
  262. 262.
    Karim F, Loeffen J, Bramer W, et al. IgG4-related disease: a systematic review of this unrecognized disease in pediatrics. Pediatr Rheumatol Online J. 2016;14(1):18.PubMedPubMedCentralCrossRefGoogle Scholar
  263. 263.
    Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25(9):1181–92.PubMedCrossRefGoogle Scholar
  264. 264.
    Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015;385(9976):1460–71.PubMedCrossRefGoogle Scholar
  265. 265.
    Khosroshahi A, Wallace ZS, Crowe JL, et al. International Consensus Guidance Statement on the management and treatment of IgG4-related disease. Arthritis Rheumatol. 2015;67(7):1688–99.PubMedCrossRefGoogle Scholar
  266. 266.
    Hubers LM, Maillette De Buy Wenniger LJ, Doorenspleet ME, et al. IgG4-associated cholangitis: a comprehensive review. Clin Rev Allergy Immunol. 2015;48(2-3):198–206.PubMedCrossRefGoogle Scholar
  267. 267.
    Nakazawa T, Naitoh I, Hayashi K, Miyabe K, Simizu S, Joh T. Diagnosis of IgG4-related sclerosing cholangitis. World J Gastroenterol. 2013;19(43):7661–70.PubMedPubMedCentralCrossRefGoogle Scholar
  268. 268.
    Kawakami H, Zen Y, Kuwatani M, et al. IgG4-related sclerosing cholangitis and autoimmune pancreatitis: histological assessment of biopsies from Vater’s ampulla and the bile duct. J Gastroenterol Hepatol. 2010;25(10):1648–55.PubMedCrossRefGoogle Scholar
  269. 269.
    Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol. 2006;4(8):1010–6.; quiz 1934.PubMedCrossRefGoogle Scholar
  270. 270.
    Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40(3):352–8.PubMedCrossRefGoogle Scholar
  271. 271.
    Rosen D, Thung S, Sheflin-Findling S, et al. IgG4-sclerosing cholangitis in a pediatric patient. Semin Liver Dis. 2015;35(1):89–94.PubMedCrossRefGoogle Scholar
  272. 272.
    Ibrahim SH, Zhang L, Freese DK. A 3-year-old with immunoglobulin G4-associated cholangitis. J Pediatr Gastroenterol Nutr. 2011;53(1):109–11.PubMedCrossRefGoogle Scholar
  273. 273.
    Nada R, Gupta A, Kang M, et al. Hepatic mass and coagulopathy in a ten-year-old boy with fever. Arthritis Rheumatol. 2015;67(7):1977.PubMedCrossRefGoogle Scholar
  274. 274.
    Zen Y. The pathology of IgG4-related disease in the bile duct and pancreas. Semin Liver Dis. 2016;36(3):242–56.PubMedCrossRefGoogle Scholar
  275. 275.
    Safran AP, Schaffner F. Chronic passive congestion of the liver in man. Electron microscopic study of cell atrophy and intralobular fibrosis. Am J Pathol. 1967;50(3):447–63.PubMedPubMedCentralGoogle Scholar
  276. 276.
    Moller S, Bernardi M. Interactions of the heart and the liver. Eur Heart J. 2013;34(36):2804–11.PubMedCrossRefGoogle Scholar
  277. 277.
    Wanless IR, Liu JJ, Butany J. Role of thrombosis in the pathogenesis of congestive hepatic fibrosis (cardiac cirrhosis). Hepatology. 1995;21(5):1232–7.PubMedGoogle Scholar
  278. 278.
    Alvarez AM, Mukherjee D. Liver abnormalities in cardiac diseases and heart failure. Int J Angiol. 2011;20(3):135–42.PubMedPubMedCentralCrossRefGoogle Scholar
  279. 279.
    Asrani SK, Asrani NS, Freese DK, et al. Congenital heart disease and the liver. Hepatology. 2012;56(3):1160–9.PubMedCrossRefGoogle Scholar
  280. 280.
    Runyon BA, Committee APG. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49(6):2087–107.PubMedCrossRefGoogle Scholar
  281. 281.
    Birgens HS, Henriksen J, Matzen P, Poulsen H. The shock liver. Clinical and biochemical findings in patients with centrilobular liver necrosis following cardiogenic shock. Acta Med Scand. 1978;204(5):417–21.PubMedGoogle Scholar
  282. 282.
    Cassidy WM, Reynolds TB. Serum lactic dehydrogenase in the differential diagnosis of acute hepatocellular injury. J Clin Gastroenterol. 1994;19(2):118–21.PubMedCrossRefGoogle Scholar
  283. 283.
    Van Der Linde D, Konings EE, Slager MA, et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58(21):2241–7.PubMedCrossRefGoogle Scholar
  284. 284.
    Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39(12):1890–900.PubMedCrossRefGoogle Scholar
  285. 285.
    Massin MM, Astadicko I, Dessy H. Epidemiology of heart failure in a tertiary pediatric center. Clin Cardiol. 2008;31(8):388–91.PubMedCrossRefGoogle Scholar
  286. 286.
    Sommers C, Nagel BH, Neudorf U, Schmaltz AA. Congestive heart failure in childhood. An epidemiologic study. Herz. 2005;30(7):652–62.PubMedCrossRefGoogle Scholar
  287. 287.
    Masarone D, Valente F, Rubino M, et al. Pediatric heart failure: a practical guide to diagnosis and management. Pediatr Neonatol. 2017;58(4):303–12.PubMedCrossRefGoogle Scholar
  288. 288.
    Ginde S, Lam J, Hill GD, et al. Long-term outcomes after surgical repair of complete atrioventricular septal defect. J Thorac Cardiovasc Surg. 2015;150(2):369–74.PubMedCrossRefGoogle Scholar
  289. 289.
    O'laughlin MP, Slack MC, Grifka RG, Perry SB, Lock JE, Mullins CE. Implantation and intermediate-term follow-up of stents in congenital heart disease. Circulation. 1993;88(2):605–14.PubMedCrossRefGoogle Scholar
  290. 290.
    Becker AE, Connor M, Anderson RH. Tetralogy of Fallot: a morphometric and geometric study. Am J Cardiol. 1975;35(3):402–12.PubMedCrossRefGoogle Scholar
  291. 291.
    Dearani JA, Danielson GK. Surgical management of Ebstein’s anomaly in the adult. Semin Thorac Cardiovasc Surg. 2005;17(2):148–54.PubMedCrossRefGoogle Scholar
  292. 292.
    Nihoyannopoulos P, Mckenna WJ, Smith G, Foale R. Echocardiographic assessment of the right ventricle in Ebstein’s anomaly: relation to clinical outcome. J Am Coll Cardiol. 1986;8(3):627–35.PubMedCrossRefGoogle Scholar
  293. 293.
    Yuan SM. Ebstein’s Anomaly: Genetics, Clinical Manifestations, and Management. Pediatr Neonatol. 2017;58(3):211–5.PubMedCrossRefGoogle Scholar
  294. 294.
    Samanek M. Congenital heart malformations: prevalence, severity, survival, and quality of life. Cardiol Young. 2000;10(3):179–85.PubMedCrossRefGoogle Scholar
  295. 295.
    Jatene AD, Fontes VF, Paulista PP, et al. Anatomic correction of transposition of the great vessels. J Thorac Cardiovasc Surg. 1976;72(3):364–70.PubMedGoogle Scholar
  296. 296.
    Devabhaktuni SR, Chakfeh E, Malik AO, Pengson JA, Rana J, Ahsan CH. Subvalvular aortic stenosis: a review of current literature. Clin Cardiol. 2018;41(1):131–6.PubMedCrossRefGoogle Scholar
  297. 297.
    Etnel JR, Takkenberg JJ, Spaans LG, Bogers AJ, Helbing WA. Paediatric subvalvular aortic stenosis: a systematic review and meta-analysis of natural history and surgical outcome. Eur J Cardiothorac Surg. 2015;48(2):212–20.PubMedCrossRefGoogle Scholar
  298. 298.
    Kim DH, Park SJ, Jung JW, Kim NK, Choi JY. The comparison between the echocardiographic data to the cardiac catheterization data on the diagnosis, treatment, and follow-up in patients diagnosed as pulmonary valve stenosis. J Cardiovasc Ultrasound. 2013;21(1):18–22.PubMedPubMedCentralCrossRefGoogle Scholar
  299. 299.
    Norwood WI, Lang P, Hansen DD. Physiologic repair of aortic atresia-hypoplastic left heart syndrome. N Engl J Med. 1983;308(1):23–6.PubMedCrossRefGoogle Scholar
  300. 300.
    Agnoletti G, Ferraro G, Bordese R, et al. Fontan circulation causes early, severe liver damage. Should we offer patients a tailored strategy? Int J Cardiol. 2016;209:60–5.PubMedCrossRefGoogle Scholar
  301. 301.
    Camposilvan S, Milanesi O, Stellin G, Pettenazzo A, Zancan L, D'antiga L. Liver and cardiac function in the long term after Fontan operation. Ann Thorac Surg. 2008;86(1):177–82.PubMedCrossRefGoogle Scholar
  302. 302.
    Fidai A, Dallaire F, Alvarez N, et al. Non-invasive investigations for the diagnosis of Fontan-associated liver disease in pediatric and adult Fontan patients. Front Cardiovasc Med. 2017;4:15.PubMedPubMedCentralCrossRefGoogle Scholar
  303. 303.
    Lee TM, Hsu DT, Kantor P, et al. Pediatric cardiomyopathies. Circ Res. 2017;121(7):855–73.PubMedPubMedCentralCrossRefGoogle Scholar
  304. 304.
    Hollander SA, Addonizio LJ, Chin C, et al. Abdominal complaints as a common first presentation of heart failure in adolescents with dilated cardiomyopathy. Am J Emerg Med. 2013;31(4):684–6.PubMedCrossRefGoogle Scholar
  305. 305.
    Rossano JW, Shaddy RE. Heart failure in children: etiology and treatment. J Pediatr. 2014;165(2):228–33.PubMedCrossRefGoogle Scholar
  306. 306.
    Juneja R, Tandon R. Rheumatic carditis: a reappraisal. Indian Heart J. 2004;56(3):252–5.PubMedGoogle Scholar
  307. 307.
    De Rosa G, Pardeo M, Stabile A, Rigante D. Rheumatic heart disease in children: from clinical assessment to therapeutical management. Eur Rev Med Pharmacol Sci. 2006;10(3):107–10.PubMedGoogle Scholar
  308. 308.
    Zuhlke LJ, Beaton A, Engel ME, et al. Group A Streptococcus, acute rheumatic fever and rheumatic heart disease: epidemiology and clinical considerations. Curr Treat Options Cardiovasc Med. 2017;19(2):15.PubMedPubMedCentralCrossRefGoogle Scholar
  309. 309.
    Tandon R, Sharma M, Chandrashekhar Y, Kotb M, Yacoub MH, Narula J. Revisiting the pathogenesis of rheumatic fever and carditis. Nat Rev Cardiol. 2013;10(3):171–7.PubMedCrossRefGoogle Scholar
  310. 310.
    Perlmutter DH, Shepherd RW. Extrahepatic biliary atresia: a disease or a phenotype? Hepatology. 2002;35(6):1297–304.PubMedCrossRefGoogle Scholar
  311. 311.
    Silveira TR, Salzano FM, Howard ER, Mowat AP. Congenital structural abnormalities in biliary atresia: evidence for etiopathogenic heterogeneity and therapeutic implications. Acta Paediatr Scand. 1991;80(12):1192–9.PubMedCrossRefGoogle Scholar
  312. 312.
    Nizery L, Chardot C, Sissaoui S, et al. Biliary atresia: clinical advances and perspectives. Clin Res Hepatol Gastroenterol. 2016;40(3):281–7.PubMedCrossRefGoogle Scholar
  313. 313.
    De La Villeon B, Le Goudeveze S, Goudard Y, Fondin M, Vauchaussade De Chaumont A, Duverger V. Polysplenia syndrome. J Visc Surg. 2011;148(5):e395–6.Google Scholar
  314. 314.
    Davenport M, Tizzard SA, Underhill J, Mieli-Vergani G, Portmann B, Hadzic N. The biliary atresia splenic malformation syndrome: a 28-year single-center retrospective study. J Pediatr. 2006;149(3):393–400.PubMedPubMedCentralCrossRefGoogle Scholar
  315. 315.
    Bridy-Pappas AE, Margolis MB, Center KJ, Isaacman DJ. Streptococcus pneumoniae: description of the pathogen, disease epidemiology, treatment, and prevention. Pharmacotherapy. 2005;25(9):1193–212.PubMedCrossRefGoogle Scholar
  316. 316.
    Minemura M, Tajiri K, Shimizu Y. Liver involvement in systemic infection. World J Hepatol. 2014;6(9):632–42.PubMedPubMedCentralCrossRefGoogle Scholar
  317. 317.
    Defilippi A, Silvestri M, Tacchella A, et al. Epidemiology and clinical features of mycoplasma pneumoniae infection in children. Respir Med. 2008;102(12):1762–8.PubMedCrossRefGoogle Scholar
  318. 318.
    Kim KW, Sung JJ, Tchah H, et al. Hepatitis associated with mycoplasma pneumoniae infection in Korean children: a prospective study. Korean J Pediatr. 2015;58(6):211–7.PubMedPubMedCentralCrossRefGoogle Scholar
  319. 319.
    Suzuyama Y, Iwasaki H, Izumikawa K, Hara K. Clinical complications of mycoplasma pneumoniae disease—other organs. Yale J Biol Med. 1983;56(5-6):487–91.PubMedPubMedCentralGoogle Scholar
  320. 320.
    Morgenstern R, Hayes PC. The liver in typhoid fever: always affected, not just a complication. Am J Gastroenterol. 1991;86(9):1235–9.PubMedGoogle Scholar
  321. 321.
    Karoli R, Fatima J, Chandra A, Singh G. Salmonella hepatitis: an uncommon complication of a common disease. J Family Med Prim Care. 2012;1(2):160–2.PubMedPubMedCentralCrossRefGoogle Scholar
  322. 322.
    El-Newihi HM, Alamy ME, Reynolds TB. Salmonella hepatitis: analysis of 27 cases and comparison with acute viral hepatitis. Hepatology. 1996;24(3):516–9.PubMedCrossRefGoogle Scholar
  323. 323.
    Balasubramanian S, Kaarthigeyan K, Srinivas S, Rajeswari R. Serum ALT: LDH ratio in typhoid fever and acute viral hepatitis. Indian Pediatr. 2010;47(4):339–41.PubMedCrossRefGoogle Scholar
  324. 324.
    Maher D, Harries A. Pitfalls in the diagnosis and management of the jaundiced patient in the tropics. Trop Doct. 1994;24(3):128–30.PubMedCrossRefGoogle Scholar
  325. 325.
    Talwani R, Gilliam BL, Howell C. Infectious diseases and the liver. Clin Liver Dis. 2011;15(1):111–30.PubMedPubMedCentralCrossRefGoogle Scholar
  326. 326.
    Chaudhary P. Hepatobiliary tuberculosis. Ann Gastroenterol. 2014;27(3):207–11.PubMedPubMedCentralGoogle Scholar
  327. 327.
    Oliva A, Duarte B, Jonasson O, Nadimpalli V. The nodular form of local hepatic tuberculosis. A review. J Clin Gastroenterol. 1990;12(2):166–73.PubMedCrossRefGoogle Scholar
  328. 328.
    Essop AR, Posen JA, Savitch I, Levin J, Kew MC. Radiocolloid liver imaging in tuberculous hepatitis. Clin Nucl Med. 1984;9(2):81–4.PubMedCrossRefGoogle Scholar
  329. 329.
    Maartens G, Willcox PA, Benatar SR. Miliary tuberculosis: rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. Am J Med. 1990;89(3):291–6.PubMedCrossRefGoogle Scholar
  330. 330.
    Kok KY, Yapp SK. Tuberculosis of the bile duct: a rare cause of obstructive jaundice. J Clin Gastroenterol. 1999;29(2):161–4.PubMedCrossRefGoogle Scholar
  331. 331.
    Chu JH, Feudtner C, Heydon K, Walsh TJ, Zaoutis TE. Hospitalizations for endemic mycoses: a population-based national study. Clin Infect Dis. 2006;42(6):822–5.PubMedCrossRefGoogle Scholar
  332. 332.
    Lewis JH, Patel HR, Zimmerman HJ. The spectrum of hepatic candidiasis. Hepatology. 1982;2(4):479–87.PubMedCrossRefGoogle Scholar
  333. 333.
    Steinbach WJ. Pediatric invasive candidiasis: epidemiology and diagnosis in children. J Fungi (Basel). 2016;2(1).PubMedCentralCrossRefGoogle Scholar
  334. 334.
    Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis. 2005;41(9):1232–9.PubMedCrossRefGoogle Scholar
  335. 335.
    Chitsulo L, Loverde P, Engels D. Schistosomiasis. Nat Rev Microbiol. 2004;2(1):12–3.PubMedCrossRefGoogle Scholar
  336. 336.
    Gryseels B, Polman K, Clerinx J, Kestens L. Human schistosomiasis. Lancet. 2006;368(9541):1106–18.PubMedCrossRefGoogle Scholar
  337. 337.
    Osakunor DNM, Woolhouse MEJ, Mutapi F. Paediatric schistosomiasis: what we know and what we need to know. PLoS Negl Trop Dis. 2018;12(2):e0006144.PubMedPubMedCentralCrossRefGoogle Scholar
  338. 338.
    Ladhani S, Aibara RJ, Riordan FA, Shingadia D. Imported malaria in children: a review of clinical studies. Lancet Infect Dis. 2007;7(5):349–57.PubMedCrossRefGoogle Scholar
  339. 339.
    Schumacher RF, Spinelli E. Malaria in children. Mediterr J Hematol Infect Dis. 2012;4(1):e2012073.PubMedPubMedCentralCrossRefGoogle Scholar
  340. 340.
    Anand AC, Puri P. Jaundice in malaria. J Gastroenterol Hepatol. 2005;20(9):1322–32.PubMedCrossRefGoogle Scholar
  341. 341.
    Rupani AB, Amarapurkar AD. Hepatic changes in fatal malaria: an emerging problem. Ann Trop Med Parasitol. 2009;103(2):119–27.PubMedCrossRefGoogle Scholar
  342. 342.
    Kawasaki T. Update on pediatric sepsis: a review. J Intensive Care. 2017;5:47.PubMedPubMedCentralCrossRefGoogle Scholar
  343. 343.
    Weiss SL, Fitzgerald JC, Pappachan J, et al. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015;191(10):1147–57.PubMedPubMedCentralCrossRefGoogle Scholar
  344. 344.
    Wolfler A, Silvani P, Musicco M, Antonelli M, Salvo I, Italian Pediatric Sepsis Study Group. Incidence of and mortality due to sepsis, severe sepsis and septic shock in Italian Pediatric Intensive Care Units: a prospective national survey. Intensive Care Med. 2008;34(9):1690–7.PubMedCrossRefGoogle Scholar
  345. 345.
    Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589–96.PubMedCrossRefGoogle Scholar
  346. 346.
    Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Crit Care Med. 2014;42(11):2409–17.PubMedPubMedCentralCrossRefGoogle Scholar
  347. 347.
    Kramer L, Jordan B, Druml W, Bauer P, Metnitz PG. Austrian Epidemiologic Study on Intensive Care ASG. Incidence and prognosis of early hepatic dysfunction in critically ill patients—a prospective multicenter study. Crit Care Med. 2007;35(4):1099–104.PubMedCrossRefGoogle Scholar
  348. 348.
    Yan J, Li S, Li S. The role of the liver in sepsis. Int Rev Immunol. 2014;33(6):498–510.PubMedPubMedCentralCrossRefGoogle Scholar
  349. 349.
    Koskinas J, Gomatos IP, Tiniakos DG, et al. Liver histology in ICU patients dying from sepsis: a clinico-pathological study. World J Gastroenterol. 2008;14(9):1389–93.PubMedPubMedCentralCrossRefGoogle Scholar
  350. 350.
    Muftuoglu MA, Aktekin A, Ozdemir NC, Saglam A. Liver injury in sepsis and abdominal compartment syndrome in rats. Surg Today. 2006;36(6):519–24.PubMedCrossRefGoogle Scholar
  351. 351.
    Deng M, Scott MJ, Loughran P, et al. Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis. J Immunol. 2013;190(10):5152–60.PubMedPubMedCentralCrossRefGoogle Scholar
  352. 352.
    Wasmuth HE, Kunz D, Yagmur E, et al. Patients with acute on chronic liver failure display “sepsis-like” immune paralysis. J Hepatol. 2005;42(2):195–201.PubMedCrossRefGoogle Scholar
  353. 353.
    Dhainaut JF, Marin N, Mignon A, Vinsonneau C. Hepatic response to sepsis: interaction between coagulation and inflammatory processes. Crit Care Med. 2001;29(7 Suppl):S42–7.PubMedCrossRefGoogle Scholar
  354. 354.
    Siore AM, Parker RE, Stecenko AA, et al. Endotoxin-induced acute lung injury requires interaction with the liver. Am J Physiol Lung Cell Mol Physiol. 2005;289(5):L769–76.PubMedCrossRefGoogle Scholar
  355. 355.
    Gustot T, Durand F, Lebrec D, Vincent JL, Moreau R. Severe sepsis in cirrhosis. Hepatology. 2009;50(6):2022–33.PubMedCrossRefGoogle Scholar
  356. 356.
    Li F, Tian Z. The liver works as a school to educate regulatory immune cells. Cell Mol Immunol. 2013;10(4):292–302.PubMedPubMedCentralCrossRefGoogle Scholar
  357. 357.
    Ren D, Bi Q, Li L, et al. Myeloid-derived suppressor cells accumulate in the liver site after sepsis to induce immunosuppression. Cell Immunol. 2012;279(1):12–20.PubMedCrossRefGoogle Scholar
  358. 358.
    Uetrecht J, Naisbitt DJ. Idiosyncratic adverse drug reactions: current concepts. Pharmacol Rev. 2013;65(2):779–808.PubMedPubMedCentralCrossRefGoogle Scholar
  359. 359.
    Aithal GP, Rawlins MD, Day CP. Clinical diagnostic scale: a useful tool in the evaluation of suspected hepatotoxic adverse drug reactions. J Hepatol. 2000;33(6):949–52.PubMedCrossRefGoogle Scholar
  360. 360.
    Shi Q, Yang X, Greenhaw JJ, Salminen AT, Russotti GM, Salminen WF. Drug-induced liver injury in children: clinical observations, animal models, and regulatory status. Int J Toxicol. 2017;36(5):365–79.PubMedCrossRefGoogle Scholar
  361. 361.
    Chalasani N, Fontana RJ, Bonkovsky HL, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135(6):1924–34.PubMedPubMedCentralCrossRefGoogle Scholar
  362. 362.
    Molleston JP, Fontana RJ, Lopez MJ, et al. Characteristics of idiosyncratic drug-induced liver injury in children: results from the DILIN prospective study. J Pediatr Gastroenterol Nutr. 2011;53(2):182–9.PubMedPubMedCentralCrossRefGoogle Scholar
  363. 363.
    Devarbhavi H, Karanth D, Prasanna KS, Adarsh CK, Patil M. Drug-induced liver injury with hypersensitivity features has a better outcome: a single-center experience of 39 children and adolescents. Hepatology. 2011;54(4):1344–50.PubMedCrossRefGoogle Scholar
  364. 364.
    Ocete-Hita E, Salmeron-Fernandez M, Urrutia-Maldonado E, et al. Analysis of immunogenetic factors in idiosyncratic drug-induced liver injury in the pediatric population. J Pediatr Gastroenterol Nutr. 2017;64(5):742–7.PubMedCrossRefGoogle Scholar
  365. 365.
    Bjornsson E, Talwalkar J, Treeprasertsuk S, et al. Drug-induced autoimmune hepatitis: clinical characteristics and prognosis. Hepatology. 2010;51(6):2040–8.PubMedCrossRefGoogle Scholar
  366. 366.
    Orman ES, Conjeevaram HS, Vuppalanchi R, et al. Clinical and histopathologic features of fluoroquinolone-induced liver injury. Clin Gastroenterol Hepatol. 2011;9(6):517–523.e513.PubMedPubMedCentralCrossRefGoogle Scholar
  367. 367.
    Temple R. Hy’s law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf. 2006;15(4):241–3.PubMedCrossRefGoogle Scholar
  368. 368.
    Chen YT, Trzoss L, Yang D, Yan B. Ontogenic expression of human carboxylesterase-2 and cytochrome P450 3A4 in liver and duodenum: postnatal surge and organ-dependent regulation. Toxicology. 2015;330:55–61.PubMedPubMedCentralCrossRefGoogle Scholar
  369. 369.
    Allegaert K, Van Den Anker JN, Naulaers G, De Hoon J. Determinants of drug metabolism in early neonatal life. Curr Clin Pharmacol. 2007;2(1):23–9.PubMedCrossRefGoogle Scholar
  370. 370.
    Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology—drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–67.CrossRefPubMedGoogle Scholar
  371. 371.
    Brouwer KL, Aleksunes LM, Brandys B, et al. Human ontogeny of drug transporters: review and recommendations of the Pediatric Transporter Working Group. Clin Pharmacol Ther. 2015;98(3):266–87.PubMedPubMedCentralCrossRefGoogle Scholar
  372. 372.
    Bartelink IH, Rademaker CM, Schobben AF, Van Den Anker JN. Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin Pharmacokinet. 2006;45(11):1077–97.PubMedCrossRefGoogle Scholar
  373. 373.
    Mahmood I. Prediction of drug clearance in children: a review of different methodologies. Expert Opin Drug Metab Toxicol. 2015;11(4):573–87.PubMedCrossRefGoogle Scholar
  374. 374.
    Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990;11(2):272–6.PubMedCrossRefGoogle Scholar
  375. 375.
    Devarbhavi H, Patil M, Reddy VV, Singh R, Joseph T, Ganga D. Drug-induced acute liver failure in children and adults: results of a single-centre study of 128 patients. Liver Int. 2018;38(7):1322–9. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Melanie Schranz
    • 1
  • Maria Grazia Lucà
    • 1
  • Lorenzo D’Antiga
    • 2
  • Stefano Fagiuoli
    • 1
    Email author
  1. 1.Gastroenterology, Hepatology and TransplantationHospital Papa Giovanni XXIIIBergamoItaly
  2. 2.Paediatric Hepatology, Gastroenterology and TransplantationHospital Papa Giovanni XXIIIBergamoItaly

Personalised recommendations