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The Liver in Systemic Illness

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Pediatric Hepatology and Liver Transplantation

Abstract

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.

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References

  1. Khemichian S, Fong TL. Hepatic dysfunction in hyperthyroidism. Gastroenterol Hepatol. 2011;7(5):337–9.

    Google Scholar 

  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: MDText.com, Inc; 2000.

    Google Scholar 

  3. Wassner AJ, Brown RS. Congenital hypothyroidism: recent advances. Curr Opin Endocrinol Diabetes Obes. 2015;22(5):407–12.

    Article  CAS  PubMed  Google Scholar 

  4. Hanley P, Lord K, Bauer AJ. Thyroid disorders in children and adolescents: a review. JAMA Pediatr. 2016;170(10):1008–19.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  8. Foley TP Jr. Maternally transferred thyroid disease in the infant: recognition and treatment. Adv Exp Med Biol. 1991;299:209–26.

    Article  PubMed  Google Scholar 

  9. Rastogi MV, Lafranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis. 2010;5:17.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Nebesio TD, Mckenna MP, Nabhan ZM, Eugster EA. Newborn screening results in children with central hypothyroidism. J Pediatr. 2010;156(6):990–3.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  12. Malik R, Hodgson H. The relationship between the thyroid gland and the liver. QJM. 2002;95(9):559–69.

    Article  CAS  PubMed  Google Scholar 

  13. Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab. 2003;88(6):2438–44.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  18. Lodish M. Cushing’s syndrome in childhood: update on genetics, treatment, and outcomes. Curr Opin Endocrinol Diabetes Obes. 2015;22(1):48–54.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Marino L, Jornayvaz FR. Endocrine causes of nonalcoholic fatty liver disease. World J Gastroenterol. 2015;21(39):11053–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014;383(9935):2152–67.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Thakral A, Klein-Gitelman MS. An update on treatment and management of pediatric systemic lupus erythematosus. Rheumatol Ther. 2016;3(2):209–19.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Shizuma T. Clinical characteristics of concomitant systemic lupus erythematosus and primary biliary cirrhosis: a literature review. J Immunol Res. 2015;2015:713728.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  35. Koshy JM, John M. Autoimmune hepatitis—SLE overlap syndrome. J Assoc Physicians India. 2012;60:59–60.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  39. Takahashi A, Abe K, Saito R, et al. Liver dysfunction in patients with systemic lupus erythematosus. Intern Med. 2013;52(13):1461–5.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  41. Shahian M, Khosravi A, Anbardar MH. Early cholestasis in neonatal lupus erythematosus. Ann Saudi Med. 2011;31(1):80–2.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  49. Gurion R, Lehman TJ, Moorthy LN. Systemic arthritis in children: a review of clinical presentation and treatment. Int J Inflam. 2012;2012:271569.

    Article  CAS  PubMed  Google Scholar 

  50. Schneider R, Laxer RM. Systemic onset juvenile rheumatoid arthritis. Baillieres Clin Rhesumatol. 1998;12(2):245–71.

    Article  CAS  Google Scholar 

  51. Schaller J, Beckwith B, Wedgwood RJ. Hepatic involvement in juvenile rheumatoid arthritis. J Pediatr. 1970;77(2):203–10.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  53. Grom AA, Passo M. Macrophage activation syndrome in systemic juvenile rheumatoid arthritis. J Pediatr. 1996;129(5):630–2.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  55. Ramanan AV, Schneider R. Macrophage activation syndrome—what’s in a name! J Rheumatol. 2003;30(12):2513–6.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  64. Shah AA, Wigley FM. My approach to the treatment of scleroderma. Mayo Clin Proc. 2013;88(4):377–93.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Swart JF, Wulffraat NM. Diagnostic workup for mixed connective tissue disease in childhood. Isr Med Assoc J. 2008;10(8-9):650–2.

    PubMed  Google Scholar 

  68. Berard RA, Laxer RM. Pediatric mixed connective tissue disease. Curr Rheumatol Rep. 2016;18(5):28.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1080/03009742.2017.1412497.

    Article  CAS  PubMed  Google Scholar 

  77. Weiss PF. Pediatric vasculitis. Pediatr Clin North Am. 2012;59(2):407–23.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  79. Chao HC, Kong MS, Lin SJ. Hepatobiliary involvement of Henoch-Schonlein purpura in children. Acta Paediatr Taiwan. 2000;41(2):63–8.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  81. O’Connor N, Dargan PI, Jones AL. Hepatocellular damage from non-steroidal anti-inflammatory drugs. QJM. 2003;96(11):787–91.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Pawlowska J, Naorniakowska M, Liber A. Liver involvement in children with collagen vascular diseases. Clin Exp Hepatol. 2015;1(3):117–9.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  87. Selmi C, De Santis M, Gershwin ME. Liver involvement in subjects with rheumatic disease. Arthritis Res Ther. 2011;13(3):226.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  91. Cakar N, Yalcinkaya F, Duzova A, et al. Takayasu arteritis in children. J Rheumatol. 2008;35(5):913–9.

    PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  97. Kone-Paut I. Behcet’s disease in children, an overview. Pediatr Rheumatol Online J. 2016;14(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behcet’s disease: a review. World J Gastroenterol. 2015;21(13):3801–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Calamia KT, Schirmer M, Melikoglu M. Major vessel involvement in Behcet’s disease: an update. Curr Opin Rheumatol. 2011;23(1):24–31.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  102. Calatroni M, Oliva E, Gianfreda D, et al. ANCA-associated vasculitis in childhood: recent advances. Ital J Pediatr. 2017;43(1):46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  107. Childhood Hodgkin Lymphoma Treatment (PDQ(R)). Health Professional Version. In PDQ Cancer Information Summaries, Bethesda, MD; 2002.

    Google Scholar 

  108. Pileri SA, Ascani S, Leoncini L, et al. Hodgkin’s lymphoma: the pathologist’s viewpoint. J Clin Pathol. 2002;55(3):162–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  113. Murakami J, Shimizu Y. Hepatic manifestations in hematological disorders. Int J Hepatol. 2013;2013:484903.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Smith MA, Altekruse SF, Adamson PC, Reaman GH, Seibel NL. Declining childhood and adolescent cancer mortality. Cancer. 2014;120(16):2497–506.

    Article  PubMed  Google Scholar 

  115. Childhood Non-Hodgkin Lymphoma Treatment (PDQ(R)). Health Professional Version. In PDQ Cancer Information Summaries, Bethesda, MD; 2002.

    Google Scholar 

  116. Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med. 1996;334(19):1238–48.

    Article  CAS  PubMed  Google Scholar 

  117. Hong FS, Smith CL, Angus PW, Crowley P, Ho WK. Hodgkin lymphoma and fulminant hepatic failure. Leuk Lymphoma. 2010;51(5):947–51.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Kikuma K, Watanabe J, Oshiro Y, et al. Etiological factors in primary hepatic B-cell lymphoma. Virchows Arch. 2012;460(4):379–87.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  125. Guo X, Li Q, Zhu YP. Childhood hepatosplenic T-cell lymphoma with skin involvement. Indian Pediatr. 2015;52(5):427–8.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer. 2008;112(2):416–32.

    Article  PubMed  Google Scholar 

  130. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373(16):1541–52.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  136. Hofmann I. Myeloproliferative neoplasms in children. J Hematop. 2015;8(3):143–57.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  144. Hasle H. Incidence of essential thrombocythaemia in children. Br J Haematol. 2000;110(3):751.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  146. An W, Wan Y, Guo Y, et al. CALR mutation screening in pediatric primary myelofibrosis. Pediatr Blood Cancer. 2014;61(12):2256–62.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  149. Loh ML. Recent advances in the pathogenesis and treatment of juvenile myelomonocytic leukaemia. Br J Haematol. 2011;152(6):677–87.

    Article  CAS  PubMed  Google Scholar 

  150. Sakashita K, Matsuda K, Koike K. Diagnosis and treatment of juvenile myelomonocytic leukemia. Pediatr Int. 2016;58(8):681–90.

    Article  PubMed  Google Scholar 

  151. Emanuel PD. Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. Leukemia. 2008;22(7):1335–42.

    Article  CAS  PubMed  Google Scholar 

  152. Allen CE, Kelly KM, Bollard CM. Pediatric lymphomas and histiocytic disorders of childhood. Pediatr Clin North Am. 2015;62(1):139–65.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013;121(25):5006–14.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  159. Jaffe R. Liver involvement in the histiocytic disorders of childhood. Pediatr Dev Pathol. 2004;7(3):214–25.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  161. Creput C, Galicier L, Buyse S, Azoulay E. Understanding organ dysfunction in hemophagocytic lymphohistiocytosis. Intensive Care Med. 2008;34(7):1177–87.

    Article  CAS  PubMed  Google Scholar 

  162. Ishii E. Hemophagocytic lymphohistiocytosis in children: pathogenesis and treatment. Front Pediatr. 2016;4:47.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  164. Larroche C, Ziol M, Zidi S, Dhote R, Roulot D. Liver involvement in hemophagocytic syndrome. Gastroenterol Clin Biol. 2007;31(11):959–66.

    Article  PubMed  Google Scholar 

  165. Favara BE. Histopathology of the liver in histiocytosis syndromes. Pediatr Pathol Lab Med. 1996;16(3):413–33.

    Article  CAS  PubMed  Google Scholar 

  166. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046–60.

    Article  CAS  PubMed  Google Scholar 

  167. Pilbeam KL, Lund TC. Pediatric multiple myeloma. Blood. 2017;129(3):395.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  169. Fan CQ, Crawford JM. Sinusoidal obstruction syndrome (hepatic veno-occlusive disease). J Clin Exp Hepatol. 2014;4(4):332–46.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  171. Sakamoto S, Nakazawa A, Shigeta T, et al. Devastating outflow obstruction after pediatric split liver transplantation. Pediatr Transplant. 2013;17(1):E25–8.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  173. Schulz AS, Classen CF, Mihatsch WA, et al. HLA-haploidentical blood progenitor cell transplantation in osteopetrosis. Blood. 2002;99(9):3458–60.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  181. Flinn AM, Gennery AR. Treatment of pediatric acute graft-versus-host disease-lessons from primary immunodeficiency? Front Immunol. 2017;8:328.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Carpenter PA, Macmillan ML. Management of acute graft-versus-host disease in children. Pediatr Clin North Am. 2010;57(1):273–95.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  184. Baird K, Cooke K, Schultz KR. Chronic graft-versus-host disease (GVHD) in children. Pediatr Clin North Am. 2010;57(1):297–322.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  186. Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med. 2005;353(11):1135–46.

    Article  CAS  PubMed  Google Scholar 

  187. Muncie HL Jr, Campbell J. Alpha and beta thalassemia. Am Fam Physician. 2009;80(4):339–44.

    PubMed  Google Scholar 

  188. Galanello R, Cao A. Gene test review. Alpha-thalassemia. Genet Med. 2011;13(2):83–8.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  190. Lucarelli G, Andreani M, Angelucci E. The cure of thalassemia by bone marrow transplantation. Blood Rev. 2002;16(2):81–5.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  192. Aguilar Martinez P, Angastiniotis M, Eleftheriou A, et al. Haemoglobinopathies in Europe: health & migration policy perspectives. Orphanet J Rare Dis. 2014;9:97.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  196. Dhaliwal G, Cornett PA, Tierney LM Jr. Hemolytic anemia. Am Fam Physician. 2004;69(11):2599–606.

    PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  205. Hall C, Richards S, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood. 2003;102(10):3587–91.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  207. Rajagopal R, Thachil J, Monagle P. Disseminated intravascular coagulation in paediatrics. Arch Dis Child. 2017;102(2):187–93.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  209. Bakhshi S, Arya LS. Diagnosis and treatment of disseminated intravascular coagulation. Indian Pediatr. 2003;40(8):721–30.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Raffini L, Thornburg C. Testing children for inherited thrombophilia: more questions than answers. Br J Haematol. 2009;147(3):277–88.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  214. Mann DA, Marra F. Fibrogenic signalling in hepatic stellate cells. J Hepatol. 2010;52(6):949–50.

    Article  PubMed  Google Scholar 

  215. Schouten JN, Verheij J, Seijo S. Idiopathic non-cirrhotic portal hypertension: a review. Orphanet J Rare Dis. 2015;10:67.

    Article  PubMed  PubMed Central  Google Scholar 

  216. Fasano A, Catassi C. Clinical practice. Celiac disease. N Engl J Med. 2012;367(25):2419–26.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  218. Newton KP, Singer SA. Celiac disease in children and adolescents: special considerations. Semin Immunopathol. 2012;34(4):479–96.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  220. Bonamico M, Pitzalis G, Culasso F, et al. Hepatic damage in celiac disease in children. Minerva Pediatr. 1986;38(21):959–62.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  230. Rowe K, Pankow J, Nehme F, Salyers W. Gastrointestinal amyloidosis: review of the literature. Cureus. 2017;9(5):e1228.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  233. Coash M, Forouhar F, Wu CH, Wu GY. Granulomatous liver diseases: a review. J Formos Med Assoc. 2012;111(1):3–13.

    Article  PubMed  Google Scholar 

  234. Wahl SM. Hepatic granuloma as a model of inflammation and repair: an overview. Methods Enzymol. 1988;163:605–22.

    Article  CAS  PubMed  Google Scholar 

  235. Hams E, Aviello G, Fallon PG. The schistosoma granuloma: friend or foe? Front Immunol. 2013;4:89.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  238. Lagana SM, Moreira RK, Lefkowitch JH. Hepatic granulomas: pathogenesis and differential diagnosis. Clin Liver Dis. 2010;14(4):605–17.

    Article  PubMed  Google Scholar 

  239. Shetty AK, Gedalia A. Childhood sarcoidosis: a rare but fascinating disorder. Pediatr Rheumatol Online J. 2008;6:16.

    Article  PubMed  PubMed Central  Google Scholar 

  240. Dahlan Y, Smith L, Simmonds D, et al. Pediatric-onset primary biliary cirrhosis. Gastroenterology. 2003;125(5):1476–9.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  243. Ozkan TB, Mistik R, Dikici B, Nazlioglu HO. Antiviral therapy in neonatal cholestatic cytomegalovirus hepatitis. BMC Gastroenterol. 2007;7:9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  246. Elbaz T, Esmat G. Hepatic and intestinal schistosomiasis: review. J Adv Res. 2013;4(5):445–52.

    Article  PubMed  PubMed Central  Google Scholar 

  247. Amin MD, Harpavat S, Leung DH. Drug-induced liver injury in children. Curr Opin Pediatr. 2015;27(5):625–33.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  249. Levine S, Smith VV, Malone M, Sebire NJ. Histopathological features of chronic granulomatous disease (CGD) in childhood. Histopathology. 2005;47(5):508–16.

    Article  CAS  PubMed  Google Scholar 

  250. Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42(3):641–9.

    Article  PubMed  Google Scholar 

  251. Shoenfeld Y. Systemic antiphospholipid syndrome. Lupus. 2003;12(7):497–8.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  256. Berkun Y, Padeh S, Barash J, et al. Antiphospholipid syndrome and recurrent thrombosis in children. Arthritis Rheum. 2006;55(6):850–5.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  259. Khubchandani RP, D’souza S. Antiphospholipid antibody syndrome as a cause of Budd-Chiari syndrome. Indian Pediatr. 2003;40(9):907–8.

    CAS  PubMed  Google Scholar 

  260. Ravelli A, Martini A. Antiphospholipid syndrome. Pediatr Clin North Am. 2005;52(2):469–91., vi.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  264. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015;385(9976):1460–71.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  274. Zen Y. The pathology of IgG4-related disease in the bile duct and pancreas. Semin Liver Dis. 2016;36(3):242–56.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  276. Moller S, Bernardi M. Interactions of the heart and the liver. Eur Heart J. 2013;34(36):2804–11.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  278. Alvarez AM, Mukherjee D. Liver abnormalities in cardiac diseases and heart failure. Int J Angiol. 2011;20(3):135–42.

    Article  PubMed  PubMed Central  Google Scholar 

  279. Asrani SK, Asrani NS, Freese DK, et al. Congenital heart disease and the liver. Hepatology. 2012;56(3):1160–9.

    Article  PubMed  Google Scholar 

  280. Runyon BA, Committee APG. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49(6):2087–107.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  282. Cassidy WM, Reynolds TB. Serum lactic dehydrogenase in the differential diagnosis of acute hepatocellular injury. J Clin Gastroenterol. 1994;19(2):118–21.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  284. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39(12):1890–900.

    Article  PubMed  Google Scholar 

  285. Massin MM, Astadicko I, Dessy H. Epidemiology of heart failure in a tertiary pediatric center. Clin Cardiol. 2008;31(8):388–91.

    Article  PubMed  PubMed Central  Google Scholar 

  286. Sommers C, Nagel BH, Neudorf U, Schmaltz AA. Congestive heart failure in childhood. An epidemiologic study. Herz. 2005;30(7):652–62.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  290. Becker AE, Connor M, Anderson RH. Tetralogy of Fallot: a morphometric and geometric study. Am J Cardiol. 1975;35(3):402–12.

    Article  CAS  PubMed  Google Scholar 

  291. Dearani JA, Danielson GK. Surgical management of Ebstein’s anomaly in the adult. Semin Thorac Cardiovasc Surg. 2005;17(2):148–54.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  293. Yuan SM. Ebstein’s Anomaly: Genetics, Clinical Manifestations, and Management. Pediatr Neonatol. 2017;58(3):211–5.

    Article  PubMed  Google Scholar 

  294. Samanek M. Congenital heart malformations: prevalence, severity, survival, and quality of life. Cardiol Young. 2000;10(3):179–85.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  303. Lee TM, Hsu DT, Kantor P, et al. Pediatric cardiomyopathies. Circ Res. 2017;121(7):855–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  305. Rossano JW, Shaddy RE. Heart failure in children: etiology and treatment. J Pediatr. 2014;165(2):228–33.

    Article  PubMed  Google Scholar 

  306. Juneja R, Tandon R. Rheumatic carditis: a reappraisal. Indian Heart J. 2004;56(3):252–5.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  310. Perlmutter DH, Shepherd RW. Extrahepatic biliary atresia: a disease or a phenotype? Hepatology. 2002;35(6):1297–304.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  312. Nizery L, Chardot C, Sissaoui S, et al. Biliary atresia: clinical advances and perspectives. Clin Res Hepatol Gastroenterol. 2016;40(3):281–7.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  316. Minemura M, Tajiri K, Shimizu Y. Liver involvement in systemic infection. World J Hepatol. 2014;6(9):632–42.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  320. Morgenstern R, Hayes PC. The liver in typhoid fever: always affected, not just a complication. Am J Gastroenterol. 1991;86(9):1235–9.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  325. Talwani R, Gilliam BL, Howell C. Infectious diseases and the liver. Clin Liver Dis. 2011;15(1):111–30.

    Article  PubMed  PubMed Central  Google Scholar 

  326. Chaudhary P. Hepatobiliary tuberculosis. Ann Gastroenterol. 2014;27(3):207–11.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  330. Kok KY, Yapp SK. Tuberculosis of the bile duct: a rare cause of obstructive jaundice. J Clin Gastroenterol. 1999;29(2):161–4.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  332. Lewis JH, Patel HR, Zimmerman HJ. The spectrum of hepatic candidiasis. Hepatology. 1982;2(4):479–87.

    Article  CAS  PubMed  Google Scholar 

  333. Steinbach WJ. Pediatric invasive candidiasis: epidemiology and diagnosis in children. J Fungi (Basel). 2016;2(1).

    Article  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  335. Chitsulo L, Loverde P, Engels D. Schistosomiasis. Nat Rev Microbiol. 2004;2(1):12–3.

    Article  CAS  PubMed  Google Scholar 

  336. Gryseels B, Polman K, Clerinx J, Kestens L. Human schistosomiasis. Lancet. 2006;368(9541):1106–18.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  339. Schumacher RF, Spinelli E. Malaria in children. Mediterr J Hematol Infect Dis. 2012;4(1):e2012073.

    Article  PubMed  PubMed Central  Google Scholar 

  340. Anand AC, Puri P. Jaundice in malaria. J Gastroenterol Hepatol. 2005;20(9):1322–32.

    Article  PubMed  Google Scholar 

  341. Rupani AB, Amarapurkar AD. Hepatic changes in fatal malaria: an emerging problem. Ann Trop Med Parasitol. 2009;103(2):119–27.

    Article  CAS  PubMed  Google Scholar 

  342. Kawasaki T. Update on pediatric sepsis: a review. J Intensive Care. 2017;5:47.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  348. Yan J, Li S, Li S. The role of the liver in sepsis. Int Rev Immunol. 2014;33(6):498–510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  355. Gustot T, Durand F, Lebrec D, Vincent JL, Moreau R. Severe sepsis in cirrhosis. Hepatology. 2009;50(6):2022–33.

    Article  CAS  PubMed  Google Scholar 

  356. Li F, Tian Z. The liver works as a school to educate regulatory immune cells. Cell Mol Immunol. 2013;10(4):292–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  358. Uetrecht J, Naisbitt DJ. Idiosyncratic adverse drug reactions: current concepts. Pharmacol Rev. 2013;65(2):779–808.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  365. Bjornsson E, Talwalkar J, Treeprasertsuk S, et al. Drug-induced autoimmune hepatitis: clinical characteristics and prognosis. Hepatology. 2010;51(6):2040–8.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  367. Temple R. Hy’s law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf. 2006;15(4):241–3.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  373. Mahmood I. Prediction of drug clearance in children: a review of different methodologies. Expert Opin Drug Metab Toxicol. 2015;11(4):573–87.

    Article  PubMed  Google Scholar 

  374. Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990;11(2):272–6.

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1111/liv.13662.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Gastroenterology, Hepatology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy

    Melanie Schranz, Maria Grazia Lucà & Stefano Fagiuoli

  2. Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy

    Lorenzo D’Antiga

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  1. Melanie Schranz
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  2. Maria Grazia Lucà
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  3. Lorenzo D’Antiga
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  4. Stefano Fagiuoli
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Correspondence to Stefano Fagiuoli .

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  1. Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Bergamo, Italy

    Lorenzo D'Antiga

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Schranz, M., Lucà, M.G., D’Antiga, L., Fagiuoli, S. (2019). The Liver in Systemic Illness. In: D'Antiga, L. (eds) Pediatric Hepatology and Liver Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-96400-3_22

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