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Metabolic Disorders in the Liver

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Diagnosis of Liver Disease

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Abstract

Iron overload, or siderosis, is a commonly encountered problem in clinical practice and may be classified as primary (genetic) or secondary to other diseases, such as hereditary anemias (Table 12.1). Dietary iron is absorbed primarily by enterocytes in the duodenum, transported from the intestine to the portal blood stream (where it is bound to apotransferrin), and transported to the liver. It is, therefore, not surprising that excessive deposition of iron in liver is commonly encountered in liver biopsies.

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Abbreviations

AIP:

Acute intermittent porphyria

ALA:

δ-aminolevulinic acid

ALP:

Alkaline phosphatase

ATP7B:

Adenosine triphospholic acid 7B

CTLN2:

Adult-onset type II citrullinemia

EPP:

Erythropoietic protoporphyria

FTTDCD:

Failure to thrive and dyslipidemia caused by citrin deficiency

HH:

Hereditary hemochromatosis

HLA:

Human leukocyte antigen

LSCs:

Liver stellate cells

NADH:

Reduced nicotinamide adenine dinucleotide

NICCD:

Neonatal intrahepatic cholestasis caused by citrin deficiency

PBG:

Porphobilinogen

PCT:

Porphyria cutanea tarda

TfR2:

Transferrin receptor 2

References

  1. Powell LW, Kerr JF. The pathology of the liver in hemochromatosis. Pathobiol Anu. 1975;5:317–37.

    CAS  Google Scholar 

  2. Niederau C, Fischer R, Sonnenberg A, Stremmel W, Trampisch HJ, Strohmeyer G. Survival and causes of death in cirrhotic and noncirrhotic patients with primary hemochromatosis. N Engl J Med. 1985;313:1256–62.

    Article  CAS  PubMed  Google Scholar 

  3. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary hemochromatosis. Nat Genet. 1996;13:399–408.

    Article  CAS  PubMed  Google Scholar 

  4. Pietrangelo A. Non-HFE hemochromatosis. Semin Liver Dis. 2005;25:450–60.

    Article  CAS  PubMed  Google Scholar 

  5. Létocart E, Le Gac G, Majore S, et al. A novel missense mutation in SLC40A1 results in resistance to hepcidin and confirms the existence of two ferroportin-associated iron overload diseases. Br J Haematol. 2009;147:379–85.

    Article  PubMed  CAS  Google Scholar 

  6. Pietrangelo A. Genetics, genetic testing, and management of hemochromatosis. Gastroenterology. 2015;149:1240–51.

    Article  PubMed  Google Scholar 

  7. Hussain SP, Raja K, Amstad PA, Sawyer M, Trudel LJ, Wogan GN, Hofseth LJ, Shields PG, Billiar TR, Trautwein C, Hohler T, Galle PR, Phillips DH, Markin R, Marrogi AJ, Harris CC. Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: oxyradical overload diseases. Proc Natl Acad Sci U S A. 2000;97:12770–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tsui WM, Lam PW, Lee KC, Ma KF, Chan YK, Wong MW, et al. The C282Y mutation of the HFE gene is not found in Chinese haemochromatotic patients: multicentre retrospective study. Hong Kong Med J. 2000;6:153–8.

    CAS  PubMed  Google Scholar 

  9. Wonke B, Hoffbrand AV, Brown D, Dusheiko G. Antibody to hepatitis C virus in multiply transfused patients with thalassaemia major. J Clin Pathol. 1990;43:638–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kaji K, Nakanuma Y, Sasaki M, Unoura M, Kobayashi K, Nonomura A. Hemosiderin deposition in portal endothelial cells: a novel hepatic hemosiderosis frequent in chronic viral hepatitis B and C. Human Pathol. 1995;26:1080–5.

    Article  CAS  Google Scholar 

  11. Kothari T, Swamy AP, Lee JC, Mangla JC, Cestero RV. Hepatic hemosiderosis in maintenance hemodialysis (MHD) patients. Dig Dis Sci. 1980;25:363–8.

    Article  CAS  PubMed  Google Scholar 

  12. Schafer AI, Cheron RG, Dluhy R, Cooper B, Gleason RE, Soeldner JS, et al. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med. 1981;304:319–24.

    Article  CAS  PubMed  Google Scholar 

  13. Ali M, Fayemi AO, Rigolosi R, Frascino J, Marsden T, Malcolm D. Hemosiderosis in hemodialysis patients. An autopsy study of 50 cases. JAMA. 1980;244:343–5.

    Article  CAS  PubMed  Google Scholar 

  14. Carthew P, Dorman BM, Edwards RE, Francis JE, Smith AG. A unique rodent model for both the cardiotoxic and hepatotoxic effects of prolonged iron overload. Lab Investig. 1993;69:217–22.

    CAS  PubMed  Google Scholar 

  15. de Leeuw AM, McCarthy SP, Geerts A, Knook DL. Purified rat liver fat-storing cells in culture divide and contain collagen. Hepatology. 1984;4:392–403.

    Article  PubMed  Google Scholar 

  16. Ramm GA, Li SC, Li L, Britton RS, O’Neill R, Kobayashi Y, et al. Chronic iron overload causes activation of rat lipocytes in vivo. Am J Phys. 1995;268(3 Pt 1):G451–8.

    CAS  Google Scholar 

  17. Akalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G. A monoclonal antibody against α-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 1986;103:2787–96.

    Article  Google Scholar 

  18. Chezmar JL, Nelson RC, Malko JA, Bernardino ME. Hepatic iron overload; diagnosis and quantification by noninvasive imaging. Gastrointest Radiol. 1990;15:27–31.

    Article  CAS  PubMed  Google Scholar 

  19. Howard JM, Ghent CN, Valberg LS. Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload. Gastroenterology. 1983;84:209–15.

    Article  CAS  PubMed  Google Scholar 

  20. Miller FH, Fisher MR, Soper W, Gore RM. MRI of hepatic iron deposition in patients with renal transplant. Gastrointest Radiol. 1991;16:229–33.

    Article  CAS  PubMed  Google Scholar 

  21. Stål P. Iron as a hepatotoxin. Dig Dis Sci. 1995;13:205–22.

    Article  Google Scholar 

  22. Bacon BR, Britton RS. The pathology of hepatic iron overload: a free radical-mediated process? Hepatology. 1990;11:127–37.

    Article  CAS  PubMed  Google Scholar 

  23. Bacon BR, Tavill AS, Brittenham GM, Park CH, Recknagel RP. Hepatic 1ipid peroxidation in vivo in rats with chronic iron overload. J Clin Invest. 1983;71:429–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yokoi Y, Namihisa T, Matsuzaki A, Yamaguchi Y. Distribution of Ito cells in experimental hepatic fibrosis. Liver. 1988;8:48–52.

    Article  CAS  PubMed  Google Scholar 

  25. Enzan H, Himeno H, Iwamura S, Saibara T, Ohnishi S, Yamamoto Y, et al. Sequential changes in human Ito cells and their relation to postnecrotic liver fibrosis in massive and submassive hepatic necrosis. Virchows Arch. 1995;426:95–101.

    Article  CAS  PubMed  Google Scholar 

  26. Schmitt-Graff A, Kruger S, Bochard F, Gabbiani G, Denk H. Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. Am J Pathol. 1991;138:1233–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Britton RS, Ramm GA, Olynyk J, Singh R, O’Neil R, Bacon BR. Pathophysiology of iron toxicity. Adv Exp Med Biol. 1994;356:239–53.

    Article  CAS  PubMed  Google Scholar 

  28. Ludwig JL, Hashimoto E, Porayko MK, Moyer TP, Baldus WP. Hemosiderosis in cirrhosis: a study of 447 native livers. Gastroenterology. 1997;112:882–8.

    Article  CAS  PubMed  Google Scholar 

  29. Grove J, Daly AK, Burt AD, Guzall M, James OF, Bassendine MF, et al. Heterozygotes for HFE mutations have no increased risk of advanced alcoholic liver diseases. Gut. 1998;43:262–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bonkovsky HL, Jawaid Q, Tortorelli K, LeClair P, Cobb J, Lambrecht RW, et al. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol. 1999;31:421–9.

    Article  CAS  PubMed  Google Scholar 

  31. Bugianesi E, Manzini P, D’Antico S, Vanni E, Longo F, Leone N, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology. 2004;39:179–87.

    Article  CAS  PubMed  Google Scholar 

  32. Riordan SM, Williams R. The Wilson’s disease gene and phenotypic diversity. J Hepatol. 2001;34:165–71.

    Article  CAS  PubMed  Google Scholar 

  33. Mehta R, Templeton D, O’Brien PJ. Mitochondrial involvement in genetically determined transition metal toxicity. II. Copper toxicity. Chem Biol Interact. 2006;163:77–85.

    Article  CAS  PubMed  Google Scholar 

  34. Roberts EA, Schilsky ML. A practice guideline on Wilson disease. Hepatology. 2003;37:1475–92.

    Article  PubMed  Google Scholar 

  35. Ala A, Walker AP, Ashkan K, et al. Wilson’s disease. Lancet. 2007;369:397–408.

    Article  CAS  PubMed  Google Scholar 

  36. Roberts EA, Schilky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47:2089–111.

    Article  CAS  PubMed  Google Scholar 

  37. Ferenci P, Caca K, Loudianos G, et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003;23:139–42.

    Article  PubMed  Google Scholar 

  38. Nicastro E, Ranucci G, Vajro P, et al. Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease. Hepatology. 2010;52:1948–56.

    Article  PubMed  Google Scholar 

  39. Hayashi H, Tatsumi Y, Yahata S, et al. Acute hepatic phenotype of Wilson’s disease: clinical features of acute episodes and chronic lesions remaining in survivors. J Clin Transl Hepatol. 2015;3:239–45.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Walshe JM. Diagnosis and treatment of presymptomatic Wilson’s disease. Lancet. 1988;2:435–7.

    Article  CAS  PubMed  Google Scholar 

  41. Scheinberg IH, Sternlieb I. Wilson’s disease. In: Smith Jr LH, editor. Major problems in internal medicine, vol. 23. Philadelphia, PA: WB Saunders; 1984. p. 25–35.

    Google Scholar 

  42. Strohmeyer FW, Ishak KG. Histology of the liver in Wilson’s disease: a study of 34 cases. Am J Clin Pathol. 1980;73:12–24.

    Article  Google Scholar 

  43. Sternlieb I. Evolution of the hepatic lesion in Wilson’s disease (hepatolenticular degeneration). Prog Liver Dis. 1972;4:511–25.

    CAS  PubMed  Google Scholar 

  44. Strand S, Hofmann WJ, Grambihler A, et al. Hepatic failure and liver cell damage in acute Wilson’s disease involve CD95 (APO-1/Fas) mediated apoptosis. Nat Med. 1998;4:588–93.

    Article  CAS  PubMed  Google Scholar 

  45. Korman JD, Volenberg I, Balko J, et al. Pediatric and adult acute liver failure study groups. Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests. Hepatology. 2008;48:1167–74.

    Article  CAS  PubMed  Google Scholar 

  46. Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson’s disease. Lancet. 2007;369:397–408.

    Article  CAS  PubMed  Google Scholar 

  47. Davis W, Chowrimootoo GF, Seymour CA. Defective biliary copper excretion in Wilson’s disease: the role of caeruloplasmin. Eur J Clin Investig. 1996;26:893–901.

    Article  CAS  Google Scholar 

  48. Walshe JM. Treatment of Wilson’s disease with trientine (triethylene tetramine) dihydrochloride. Lancet. 1982;1:643–7.

    Article  CAS  PubMed  Google Scholar 

  49. Dhawan A, Taylor RM, Cheeseman P, et al. Wilson’s disease in children: 37-year experience and revised King’s score for liver transplantation. Liver Transplant. 2005;11:441–8.

    Article  Google Scholar 

  50. Bellary SV, Hassanein T, van Thiel DH. Liver transplantation for Wilson’s disease. J Hepatol. 1995;23:373–81.

    Article  CAS  PubMed  Google Scholar 

  51. Rakela J, Kurtz SB, McCarthy JT, Ludwig J, Ascher NL, Bloomer JR, et al. Fulminant Wilson’s disease treated with postdilution hemofiltration and orthotopic liver transplantation. Gastroenterology. 1986;90:2004–7.

    Article  CAS  PubMed  Google Scholar 

  52. Pankit AN, Bhave SA. Copper metabolic defects and liver disease: environmental aspect. J Gastroenterol Hepatol. 2002;17(Supp. 3):S403–7.

    Article  PubMed  Google Scholar 

  53. Adamson M, Reiner B, Olson JL, et al. Indian child cirrhosis in an American child. Gastroenterology. 1992;102:1771–7.

    Article  CAS  PubMed  Google Scholar 

  54. Joshi VV. Indian child cirrhosis. Perspect Pediatr Pathol. 1987;11:175–92.

    CAS  PubMed  Google Scholar 

  55. Muller T, Langner C, Fuchsbichler A, et al. Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis. Hepatology. 2004;39:963–9.

    Article  PubMed  Google Scholar 

  56. Bawdekar AR, Bhave SA, Pradham AM, et al. Long-term survival in Indian childhood cirrhosis treated with D-penicillamine. Arch Dis Child. 1996;74:32–5.

    Article  Google Scholar 

  57. Muller T, Feichtinger H, Berger H, Muller W. Endemic Tyrolean infantile cirrhosis: an ecogenic disorder. Lancet. 1996;347:877–80.

    Article  CAS  PubMed  Google Scholar 

  58. Muller-Hocker J, Summer KH, Schramel P, Rodeck B. Different pathomorphologic patterns in exogenic infantile copper intoxication of the liver. Pathol Res Pract 1998; 194: HAHN MD.

    Google Scholar 

  59. Hayashi H, Shinohara T, Goto K, et al. Liver structures of a patient with idiopathic copper toxicosis. Med Mol Morphol. 2012;45:105–9.

    Article  PubMed  Google Scholar 

  60. Petris M, Mercer JFB, Culvenor JG, et al. Ligand-regulated transport of the Menkes copper P-type ATPase from the Golgi apparatus to the plasma membrane; a novel mechanism of regulated trafficking. ENBO J. 1996;15:6084–95.

    CAS  Google Scholar 

  61. Montgomery BD, Anderson KE, Bonkovsky HL. Porphyrias. N Engl J Med. 2017;377(9):862–72.

    Article  Google Scholar 

  62. Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute por-phyrias. Ann Intern Med. 2005;142:439–50.

    Article  PubMed  Google Scholar 

  63. Whatley SD, Badminton MN. Acute intermittent porphyria. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews. Seattle: University of Washington; 2013.

    Google Scholar 

  64. Bissell DM, Lai JC, Meister RK, Blanc PD. Role of delta-aminolevulinic acid in the symptoms of acute porphyria. Am J Med. 2015;128:311–7.

    Article  CAS  Google Scholar 

  65. Pischik E, Kauppinen R. An update of clinical management of acute intermittent porphyria. Appl Clin Genet. 2015;8:201–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kappas A, Sassa S, Galbraith RA, Nordman Y. The porphyrias. In: Scriver CR, Beaaudet A, Sly WS, Valle D, editors. The metabolic basis of inherited disease. New York: McGraw-Hill; 1989. p. 1305–65.

    Google Scholar 

  67. Okano J, Horie Y, Kawasaki H, Kondo M. Interferon treatment of porphyria cutanea associated with chronic hepatitis C. Hepato-Gastroenterol. 1997;44:525–8.

    CAS  Google Scholar 

  68. Kondo M, Horie Y, Okano J, et al. High prevalence of hepatitis C virus infection in Japanese patients with porphyria cutanea tarda. Hepatology. 1997;26:246.

    Article  CAS  PubMed  Google Scholar 

  69. Ashwani K, Singal AK, Parker C, Bowden C, Thapar M, Liu L, McGuire BM. Liver transplantation in the Management of Porphyria. Hepatology. 2014;60:1082–9.

    Article  Google Scholar 

  70. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995;32:45–59.

    CAS  PubMed  Google Scholar 

  71. Gertz MA, Kyle RA. Hepatic amyloidosis (primary [AL], immunoglobulin light chain): the natural history in 80 patients. Am J Med. 1988;85:73–80.

    Article  CAS  PubMed  Google Scholar 

  72. Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc. 1983;58:665–83.

    CAS  PubMed  Google Scholar 

  73. Levy M, Fryd CH, Eliakim M. Intrahepatic obstructive jaundice due to amyloidosis of the liver. A case report and review of the literature. Gastroenterology. 1971;61:234–8.

    Article  CAS  PubMed  Google Scholar 

  74. Peters RA, Koukoulis G, Gimson A, Portman B, Westaby D, Williams R. Primary amyloidosis and severe intrahepatic cholestatic jaundice. Gut. 1994;35:1322–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yamamoto T, Maeda N, Kawasaki H. Hepatic failure in a case of multiple myeloma-associated amyloidosis (kappa-AL). J Gastroenterol. 1995;30:393–7.

    Article  CAS  PubMed  Google Scholar 

  76. Dohmen K, Nagano M, Iwakiri M, Yamano Y, Kikuchi Y, Mizoguchi M, et al. A case of prominent hepatic cholestasis developing to hepatic failure in lambda-AL amyloidosis. Gastroenterol Jpn. 1991;26:376–81.

    Article  CAS  PubMed  Google Scholar 

  77. Zeijen RNM, Sels JPJE, Flendrig JA, Arends JW. Portal hypertension and intrahepatic cholestasis in hepatic amyloidosis. Netherland J Med. 1991;38:257–61.

    CAS  Google Scholar 

  78. Hormans Y, Brenard R, Ferrant A, Lagneaux G, Geubel AP. Long-term favorable outcome of portal hypertension complicating primary systemic amyloidosis. Liver. 1995;15:332–4.

    Article  Google Scholar 

  79. Melato M, Manconi R, Magris D, Morassi P, Benussi DG, Tiribelli C. Different morphologic aspects and clinical features in massive hepatic amyloidosis. Digestion. 1984;29:138–45.

    Article  CAS  PubMed  Google Scholar 

  80. Mergo PJ, Ros PR, Buetow PC, Buck JL. Diffuse disease of the liver: radiologic-pathologic correlation. Radiographics. 1994;14:1291–307.

    Article  CAS  PubMed  Google Scholar 

  81. Itescu S. Hepatic amyloidosis. An unusual cause of ascites and portal hypertension. Arch Intern Med. 1984;144:2257–9.

    Article  CAS  PubMed  Google Scholar 

  82. Beck K, Dischler W, Helms M, Kiani B, Sickinger K, Tenner R. Atlas der Laparoskopie. F.K. Schattauer-Verlag: Stuttgart and New York; 1968.

    Google Scholar 

  83. Stauffer MH, Gross JB, Foulk WT, Dahlin DC. Amyloidosis: diagnosis with needle biopsy of the liver in eighteen patients. Gastroenterology. 1961;41:92–6.

    Article  Google Scholar 

  84. Iwata T, Hoshii Y, Kawano H, Gondo T, Takahashi M, Ishihara T, et al. Hepatic amyloidosis in Japan: histological and morphometric analysis based on amyloid proteins. Hum Pathol. 1995;26:1148–53.

    Article  CAS  PubMed  Google Scholar 

  85. Skinner MS, Kattine AA, Spurlock BO. Electron microscope: Pico observations of early amyloidosis in human liver. Gastroenterology. 1966;50:243–7.

    Article  Google Scholar 

  86. Livni N, Behar AJ, Lafair JS. Unusual amyloid bodies in human liver. Ultrastructural and freeze-etching studies. Isr J Med Sci. 1977;13:1163–70.

    CAS  PubMed  Google Scholar 

  87. Finkelstein SD, Fornasier VL, Pruzanski W. Intrahepatic cholestasis with predominant pericentral deposition in systemic amyloidosis. Hum Pathol. 1981;12:470–2.

    Article  CAS  PubMed  Google Scholar 

  88. Mir-Madjlessi SH, Farmer RG, Hawk WA Jr. Cholestatic jaundice associated with primary amyloidosis. Cleve Clin Q. 1972;39:167–75.

    Article  CAS  PubMed  Google Scholar 

  89. Tsukada N, Ackerley CA, Phillips MJ. The structure and organization of bile canalicular cytoskeleton with special reference to actin and actin-binding proteins. Hepatology. 1995;21:1106–13.

    CAS  PubMed  Google Scholar 

  90. Terada T, Hirata K, Hisada Y, Hoshii Y, Nakanuma Y. Obstructive jaundice caused by the deposition of amyloid-like substances in the extrahepatic and large intrahepatic bile ducts in a patient with multiple myeloma. Histopathology. 1994;24:485–7.

    Article  CAS  PubMed  Google Scholar 

  91. Kyle RA, Gerz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan, prednisone, and colchicine. N Engl J Med. 1997;336:1202–7.

    Article  CAS  PubMed  Google Scholar 

  92. Palladini G, Milani P, Foli A, et al. Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long term results of a risk-adapted approach. Hema. 2014;99:743–50.

    CAS  Google Scholar 

  93. Morie AG. Immunoglobulin light chain amyloidosis: 214 up-date on diagnosis, prognosis, and treatment. Am J Hematol. 2014;89:1133–40.

    Google Scholar 

  94. Gertz MA, Landau H, Comenzo RL, et al. First-in-human phase I/II study of NEOD001 in patients with light chain amyloidosis and persistent organ dysfunction. J Clin Oncol. 2016;34:1097–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Rosen E, Bakshi N, Watters A, Rosen HR, Mehler PS. Hepatic complications of anorexia nervosa. Dis Dis Sci. 2017;62:2977–81.

    Article  CAS  Google Scholar 

  96. Rautou PE, Cazals-Hatem D, Moreau R, Francoz C, Feldmann G, Lebrec D, Ogier-Denis E, Bedossa P, Valla D, Durand F. Acute liver cell damage in patients with anorexia nervosa: a possible role of starvation-induced hepatocyte autophagy. Gastroenterology. 2008;135:840–8.

    Article  PubMed  Google Scholar 

  97. Komuta M, Harada M, Ueno T, Uchimura Y, Inada C, Mitsuyama K, Sakisaka S, Sata M, Tanakawa K. Unusual accumulation of glycogen in liver parenchymal cells in a patient with anorexia nervosa. Int Med. 1998;37:678–82.

    Article  CAS  Google Scholar 

  98. Bridet L, Martin JJ, Nuno JL. Acute liver damage and anorexia nervosa: a case report. Turk J Gastroenterol. 2014;25:205–8.

    Article  PubMed  Google Scholar 

  99. von Gierke E. Liver and kidney in glycogen storage disease. Beitr Pathol Anat. 1929;82:497–513.

    Google Scholar 

  100. Labrune P, Trioche P, Duvaltier I, Chevalier P, Odièvre M. Hepatocellular adenomas in glycogen storage disease type I and III: a series of 43 patients and review of the literature. J Pediatr Gastroenterol Nutr. 1997;24:276–9.

    Article  CAS  PubMed  Google Scholar 

  101. Coire CI, Qizilbash AH, Castelli MF. Hepatic adenomata in type Ia glycogen storage disease. Arch Pathol Lab Med. 1987;111:166–9.

    CAS  PubMed  Google Scholar 

  102. Limmer J, Fleig WE, Leupold D, Bittner R, Ditschuneit H, Beger HG. Hepatocellular carcinoma in type I glycogen storage disease. Hepatology. 1988;8:531–7.

    Article  CAS  PubMed  Google Scholar 

  103. Panaro F, Andorno E, Basile G, et al. Simultaneous liver-kidney transplantation for glycogen storage disease type 1A (von Girke’s disease). Tranplant Proc. 2004;36:1483–4.

    Article  CAS  Google Scholar 

  104. Parmieri L, Pardo B, Lasorsa FM, del Arco A, Kobayashi K, Iijima M, Runswick MJ, Walker JE, Saheki T, Satrustegui J, Palmieri F. Citrin and aralar1 are Ca2+−stimulated aspartate/glutamate transporters in mitochondria. EMBO J. 2001;20:5060–9.

    Article  Google Scholar 

  105. Kobayashi K, Sinasac DS, Iijima M, Boright AP, Begum L, Lee JR, et al. The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat Genet. 1999;22:159–63.

    Article  CAS  PubMed  Google Scholar 

  106. Kobayashi K, Saheki T. Aspartate glutamate carrier (Citrin) deficiency. In: Brorer S, Wagner CA, editors. Membrane transporter diseases. New York, NY: Kluwer Academic/Plenum Publishers; 2003. p. 147–60.

    Chapter  Google Scholar 

  107. Saheki T, Kobayashi K. Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type IIcitrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). J Hum Genet. 2002;47:333–41.

    Article  CAS  PubMed  Google Scholar 

  108. Saheki T, Kobayashi K, Iijima M, Horiuchi M, Begum L, Jalil MA, et al. Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle. Mol Genet Metab. 2004;81(Suppl 1):S20–6.

    Article  CAS  PubMed  Google Scholar 

  109. Takagi H, Hagiwara S, Hashizume H, Kanda D, Sato K, Sohara N, et al. Adult onset type II citrullinemia as a cause of non-alcoholic steatohepatitis. J Hepatol. 2006;44:236–9.

    Article  CAS  PubMed  Google Scholar 

  110. Nakamura M, Yazaki M, Kobayashi Y, Fukushima K, Ikeda S, Kobayashi K, Saheki T, Nakaya Y. The characteristics of food intake in patients with type II citrullinemia. J Nutr Sci Vitaminol. 2011;57:239–45.

    Article  CAS  PubMed  Google Scholar 

  111. Todo S, Starzl TE, Tzakis A, Benkov KJ, Kalousek F, Saheki T, et al. Orthotopic liver transplantation for urea cycle enzyme deficiency. Hepatology. 1992;15:419–22.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Emeritus Professor Hisao Hayashi in Aichi Gakuin University School of Pharmacy and Dr. Hironori Mitsuyoshi in Kyoto Chubu Medical Center are acknowledged for their help in editing content of hemochromatosis and Wilson’s or other copper-related diseases.

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Authors and Affiliations

  1. Kyoto, Japan

    Masaki Iwai MD, PhD

  2. Shimane, Japan

    Atsushi Kitamura MD, PhD & Yutaka Horie MD, PhD

  3. Tottori, Japan

    Hajime Isomoto MD, PhD

  4. Hong Kong, China

    Wilson M. S. Tsui MD, FRCPath

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  4. Yutaka Horie MD, PhD
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  5. Wilson M. S. Tsui MD, FRCPath
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Corresponding author

Correspondence to Masaki Iwai MD, PhD .

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Editors and Affiliations

  1. Department of Gastroenterology & Hepatology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan

    Etsuko Hashimoto

  2. Department of Gastroenterology/Hepatology, Stanford University School of Medicine, Palo Alto, CA, USA

    Paul Y. Kwo

  3. Department of Pathology and Laboratory Medicine, Dartmouth–Hitchcock Medical Center, Lebanon, NH, USA

    Arief A. Suriawinata

  4. Department of Pathology, Caritas Medical Center, Kowloon, Hong Kong, China

    Wilson M.S. Tsui

  5. Division of Gastroenterology, Hepatology & Internal Medicine, Iwai Clinic, Kamigyo-ku, Kyoto, Japan

    Masaki Iwai

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Iwai, M., Kitamura, A., Isomoto, H., Horie, Y., Tsui, W.M.S. (2019). Metabolic Disorders in the Liver. In: Hashimoto, E., Kwo, P., Suriawinata, A., Tsui, W., Iwai, M. (eds) Diagnosis of Liver Disease. Springer, Singapore. https://doi.org/10.1007/978-981-13-6806-6_12

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  • DOI: https://doi.org/10.1007/978-981-13-6806-6_12

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  • Online ISBN: 978-981-13-6806-6

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