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Autoimmune Liver Disease

  • Mikio ZeniyaEmail author
  • Masaki Iwai
  • Arief A. Suriawinata
Chapter

Abstract

Autoimmunity of the human body can be directed toward the hepatocytes or toward the bile ducts. Autoimmune disease affecting the hepatocytes (with elevation of hepatocellular enzymes—AST, ALT) is called autoimmune hepatitis (AIH), whereas the classical example of autoimmune disease affecting small bile ducts is called primary biliary cholangitis (PBC). The latter is associated with elevation of cholestatic liver enzyme (ALP, gamma-GT). The role of autoimmunity in primary sclerosing cholangitis (PSC) affecting the large bile ducts is rather unclear, although in recent years a variant of PSC is certainly caused by IgG4-mediated bile duct injury. Finally, sometimes features of both AIH and PBC or PSC can be present, producing so-called overlap syndrome.

Keyword

Autoimmune hepatitis Primary biliary cholangitis (primary biliary cirrhosis) Primary sclerosing cholangitis Autoantibody Chronic nonsuppurative destructive cholangitis Human leucocyte antigen Overlap syndrome Graft-versus-host reaction 

Abbreviations

AIH

Autoimmune hepatitis

ALP

Alkaline phosphatase

AMA

Anti-mitochondrial antibody

ANA

Antinuclear antibody

ASMA

Anti-smooth muscle antibody

CNSDC

Chronic nonsuppurative destructive cholangitis

ERCP

Endoscopic retrograde cholangiopancreatography

GGTP

Gamma-glutamyltranspeptidase

GOT

Glutamic oxaloacetic transaminase

GPT

Glutamic pyruvic transaminase

GVHD

Graft-versus-host disease

HLA

Human leucocyte antigen

Ig

Immunoglobulin

MRCP

Magnetic resonance cholangiopancreatography

PBC

Primary biliary cholangitis

PSC

Primary sclerosing cholangitis

UDCA

Ursodeoxycholic acid

Notes

Acknowledgments

Prof. Dirk J. van Leeuwen was a coauthor of the first edition of this chapter.

References

  1. 1.
    Zeniya M, Watanabe F, Aizawa Y, Toda G. Genetic background of autoimmune hepatitis in Japan. In: Nishioka M, Toda G, Zeniya M, editors. Autoimmune hepatitis. Amsterdam: Elsevier Science Publishers B.V.; 1994. p. 267–79.Google Scholar
  2. 2.
    DjilaliSaiah I, Fakhfakh A, Louafi H, CaillatZucman S, Debray D, Alvarez F. HLA class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis. J Hepatol. 2006;45:844–50.Google Scholar
  3. 3.
    Johnson PJ, McFarlane IG. Meeting report: international autoimmune hepatitis group. Hepatology. 1993;18:998–1005.PubMedGoogle Scholar
  4. 4.
    Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929–38.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Hennes EM, Zeniya M, Czaja AJ, Parés A, Dalekos GN, Krawitt EL, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48:169–76.PubMedGoogle Scholar
  6. 6.
    Journal of Hepatology 2015 vol. 62 j S100–S111.Google Scholar
  7. 7.
    Krawitt EL. Autoimmune hepatitis. N Engl J Med. 2006;354:54–66.PubMedGoogle Scholar
  8. 8.
    Sherman KE, Narkewicz M, Pinto PC. Cyclosporine in the management of corticosteroid-resistant type 1 autoimmune chronic active hepatitis. J Hepatol. 1994;21:1040–7.PubMedGoogle Scholar
  9. 9.
    Reich DJ, Fiel I, Guarrera JV, Emre S, Guy SR, Schwartz ME, et al. Liver transplantation for autoimmune hepatitis. Hepatology. 2000;32:693–700.PubMedGoogle Scholar
  10. 10.
    Stravits RT, Lelfkowitch JH, Fontana RJ, Gershwin ER, Leung PS, Steerling RK, Manns MP, Norman GL, Lee WM, Acute Liver failure Study Group. Autoimmune acute liver failure: Proposed clinical and histological criteria. Hepatology. 2011;53:517–26.Google Scholar
  11. 11.
    Canh HN, Harada K, Ouchi H, Sato Y, Tsuneyama K, Kage M, Nakano M, Yoshizawa K, Takahashi A, Abe M, Kang J-H, Koike K, Inui A, Fujisawa T, Takaki A, Arinaga-Hino T, Torimura T, Suzuki Y, Fujiwara K, Zeniya M, Ohira H, Tanaka A, Takikawa H, Intractable Liver and Biliary Diseases, Study Group of Japan. Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients. J Clin Pathol. 2017;70:961–9.Google Scholar
  12. 12.
    Crispe IN. The liver as a lymphoid organ. Annu Rev Immunol. 2009;27:147–63.PubMedGoogle Scholar
  13. 13.
    Kubes P, Jenne C. Immune responses in the liver. Annu Rev Immunol. 2018;36:247–77.PubMedGoogle Scholar
  14. 14.
    Te HS, Koukoulis G, Ganger DR. Autoimmune hepatitis: a histological variant associated with prominent centrilobular necrosis. Gut. 1997;41:269–71.PubMedGoogle Scholar
  15. 15.
    Canh HN, Harada K, Ouchi H, et al. Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients. J Clin Pathol. 2017;70:961–9699.Google Scholar
  16. 16.
    Devaney K, Goodman ZD, Ishak KG. Postinfantile giant-cell transformation in hepatitis. Hepatology. 1992;16:327–33.PubMedGoogle Scholar
  17. 17.
    Lau JYN, Koukoulis G, Mieli-Vergani G, Portman BC. Syncytial giant-cell hepatitis—a specific disease entity? J Hepatol. 1992;15:216–9.PubMedGoogle Scholar
  18. 18.
    Philips MJ, Blendis LM, Poucell S, Patterson J, Petric M, Roberts E, et al. Sporadic giant-cell hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features. N Engl J Med. 1991;324:455–60.Google Scholar
  19. 19.
    Hicks J, Barrish J, Zhu SH. Neonatal syncytial giant cell hepatitis with paramyxoviral-like inclusions. Ultrastruct Pathol. 2001;25:65–71.PubMedGoogle Scholar
  20. 20.
    Joshita S, Yoshizawa K, Umemura T, et al. Clinical features of autoimmune hepatitis with acute presentation: a Japanese nationwide survey. J Gastroenterol. 2018;53:1079–88.PubMedGoogle Scholar
  21. 21.
    Lacerda MA, Ludwig J, Dickson ER, Jorgensen RA, Lindor KD. Antimitochondria antibody-negative primary biliary cirrhosis. Am J Gastroenterol. 1995;90:247–9.PubMedGoogle Scholar
  22. 22.
    Czaja AJ, Carpenter H. Autoimmune hepatitis with incidental histologic features of bile duct injury. Hepatology. 2001;34:659–65.PubMedGoogle Scholar
  23. 23.
    Onji M, Zeniya M, Yamamoto K, Tsubouchi H. Autoimmune hepatitis: diagnosis and treatment guide in Japan, 2013. Hep Res. 2014;44:368–70.Google Scholar
  24. 24.
    Misdraji J, Thiim M, Graeme-Cook FM. Autoimmune hepatitis with centrilobular necrosis. Am J Surg Pathol. 2004;28:471–8.PubMedGoogle Scholar
  25. 25.
    Schvarcz R, Glaumann H, Weiland O. Survival and histological resolution of fibrosis in patients with autoimmune chronic active hepatitis. J Hepatol. 1993;18:15–23.PubMedGoogle Scholar
  26. 26.
    Kogan J, Safadi R, Ashur Y, Shouval D, Ilan Y. Prognosis of symptomatic versus asymptomatic autoimmune hepatitis: a study of 68 patients. J Clin Gastroenterol. 2002;35:75–81.PubMedGoogle Scholar
  27. 27.
    Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The revised criteria for the classification of systemic lupus erythematous. Arthritis Rheum. 1982;25:1271–7.CrossRefGoogle Scholar
  28. 28.
    Miller AH, Urowitz MB, Gladman DD, Blendis LM. The liver in systemic lupus erythematosus. Q J Med. 1984;53:401–9.PubMedGoogle Scholar
  29. 29.
    van Hoek B. The spectrum of liver disease in systemic lupus erythematous. Nether J Med. 1996;46:244–53.Google Scholar
  30. 30.
    Matsumoto T, Yoshimine T, Shimouchi K, Shiotsu H, Kuwabara N, Fukuda Y, et al. The liver in systemic lupus erythematosus: pathologic analysis of 52 cases and review of Japanese autopsy registry data. Human Pathol. 1992;23:1151–8.Google Scholar
  31. 31.
    Moriwaki Y, Maebo A, Yamada W, Yamamoto T, Amuro Y, Hada T, et al. Autoimmune hepatitis or hepatic involvement in SLE? A case report. Gastroenterol Jpn. 1987;22:222–7.PubMedGoogle Scholar
  32. 32.
    Kooy A, de Heide LJM, Engelkens HJH, Mulder AH, van Hagen M, Schalm SW. Hepatitis in a patient with SLE: is it autoimmune hepatitis? Nether J Med. 1996;48:128–32.Google Scholar
  33. 33.
    Leggett B, Collins R, Pentice R, Powell LW. CAH or SLE? Hepatology. 1986;6:341–2.PubMedGoogle Scholar
  34. 34.
    Kooy A, de Heide Loek JM, Engelkens HJK, Mulder AH, van Hagen M, Schalm SW. How to diagnose autoimmune hepatitis in systemic lupus erythematosus? Hepatology. 1995;23:936–8.Google Scholar
  35. 35.
    Kojima H, Uemura M, Sakurai S, Ann T, Ishii Y, Imazu H, et al. Clinical features of liver disturbance in rheumatoid diseases: clinicopathological study with special reference to the cause of liver disturbance. J Gastroenterol. 2002;37:617–25.PubMedGoogle Scholar
  36. 36.
    Runyon BA, LaBreque DR, Anuras S. The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature. Am J Med. 1980;69:187–94.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Rubin E, Schaffner F, Popper H. Primary biliary cirrhosis. Chronic non-suppurative destructive cholangitis. Am J Pathol. 1965;46:387–407.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Leung PSC, Coppel RL, Anari A, Munoz S, Gershwin ME. Antimitochondria antibodies in primary biliary cirrhosis. Semin Liver Dis. 1997;17:61–9.PubMedGoogle Scholar
  39. 39.
    Nurata Y, Abe M, Furukawa S, Kuamagai T, Matsui H, Matsuura K, et al. Clinical features of symptomatic primary biliary cirrhosis initially complicated with esophageal varices. Hepatol Res. 2006;12:1220–6.Google Scholar
  40. 40.
    Heathcote J. Primary biliary cirrhosis. Clin Perspect Gastroenterol. 2001;1:39–46.Google Scholar
  41. 41.
    Nakanuma Y, Zen Y, Harada K, et al. Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement. Pathol Int. 2010;60:167–74.PubMedGoogle Scholar
  42. 42.
    Corpechot C, Carrat F, Bahr A, Chretien Y, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis. Gastroenterology. 2005;128:297–303.PubMedGoogle Scholar
  43. 43.
    Lindor KD, Dickson ER, Baldus WP, Jorgensen RA, Ludwig J, Murtaugh PA, et al. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology. 1994;106:1284–90.PubMedGoogle Scholar
  44. 44.
    Heathcote EJ, Cauch-Dudek K, Walker V, Bailey RJ, Blendis LM, Ghent CN, et al. The Canadian multicenter double-blind randomized controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1994;19:1149–56.PubMedGoogle Scholar
  45. 45.
    Corprechot C, Carrat F, Bonnand AM, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology. 2000;32:1196–9.Google Scholar
  46. 46.
    Corprechot C. Promary biliary cirrhosis and bile acids. Clin Res Hepatol Gastroenterol. 2012;36(suppl 1):S12–20.Google Scholar
  47. 47.
    Lens S, Leoz M, Nazal L, Bruguera M, Pares A. Bezafibrate normalizes alkaline phosphatase in primary biliar cirrhosis patients with incomplete response to ursodeoxycholic acid. Liver Int. 2014;34:197–203.PubMedGoogle Scholar
  48. 48.
    Iwasaki S, Ohira H, Nishiguchi S, Zeniya M, Kaneko S, Onji M, et al. The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: a prospective, multicenter study. Hepatol Res. 2008;38:557–64.PubMedGoogle Scholar
  49. 49.
    Zeron PB, Retamozo S, Bove A, Kostov BA, Siso A, Ramos-Casais M. Diagnosis of liver involvement in primary Sjogren syndrome. J Clin Trans Hepatol. 2013;1:94–102.Google Scholar
  50. 50.
    Rabinovitz M, Appasamy R, Finkelstein S. Primary biliary cirrhosis diagnosed during pregnancy. Does it have a different outcome? Dig Dis Sci. 1995;40:571–4.PubMedGoogle Scholar
  51. 51.
    Czaja AJ. Frequency and nature of the variant syndrome of autoimmune liver disease. Hapatology. 1998;28:360–5.Google Scholar
  52. 52.
    Chazouilleres O, Wendum D, Serfatty L, et al. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology. 1998;28:296–301.PubMedGoogle Scholar
  53. 53.
    Heurgue A, Vitry F, Diebold MD, et al. Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis: a retrospective study of 115 cases of autoimmune liver disease. Gastroenterol Clin Biol. 2007;31:17–25.PubMedGoogle Scholar
  54. 54.
    Poupon R, Chauzouilleres O, Corpechot C, Chretien Y. Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis. Hepatology. 2006;44:85–90.PubMedGoogle Scholar
  55. 55.
    Chapman R, Fevery J, Kalloo A, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010;51:660–78.PubMedGoogle Scholar
  56. 56.
    Bjornsson E. Small-duct primary sclerosing cholangitis. Curr Gastroenterol Rep. 2009;11:l37–41.Google Scholar
  57. 57.
    Floreani A, Rizzotto ER, Ferrara F, et al. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol. 2005;100:1516–22.PubMedGoogle Scholar
  58. 58.
    Melum E, Franke A, Schramm C, et al. Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci. Nat Genet. 2011;43:17–9.PubMedGoogle Scholar
  59. 59.
    O’Mahony CA, Vierling JM. Etiopathogenesis of primary sclerosing cholangitis. Semin Liver Dis. 2006;26:3–21.PubMedGoogle Scholar
  60. 60.
    Grant AJ, Lalor PF, Salmi M, Jalkanen S, Adams DH. Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease. Lancet. 2002;359:150–7.PubMedGoogle Scholar
  61. 61.
    Roder F, Coppe JP, Patil CK, et al. Persistent DNA damage signaling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 2009;11:973–9.Google Scholar
  62. 62.
    Tabibian JH, O’Hara SP, Splinter PL, Trussoni CE, LaRusso NF. Cholangiocyte senescence by way of N-ras activation is a characteristic of primary sclerosing cholangitis. Hepatology. 2014;59:2263–75.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Eaton JE, Talwalker JA, Lazaridis KN, Gores GJ, Lindor KD. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology. 2013;145:521–36.PubMedGoogle Scholar
  64. 64.
    Colle I, Van Vlierberghe H. Diagnosis and therapeutic problems of primary sclerosing cholangitis. Acta Gastroenterol Belg. 2003;66:155–9.PubMedGoogle Scholar
  65. 65.
    Fosby B, Karlsen TH, Melum E. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis. World J Gastroenterol. 2012;18:1–15.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Mitchell SA, Bansi DS, Hunt N, Von Bergmann K, Fleming KA, Chapman RW. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology. 2001;121:900–7.PubMedGoogle Scholar
  67. 67.
    Wagner S, Gebel M, Meier P, Trautwein C, Bleck J, Nashan B, et al. Endoscopic management of biliary tract strictures in primary sclerosing cholangitis. Endoscopy. 1996;28:546–51.PubMedGoogle Scholar
  68. 68.
    Chapman WC. Primary sclerosing cholangitis: role of liver transplantation. J Gastrointest Surg. 2008;12:426–8.PubMedGoogle Scholar
  69. 69.
    Yamashiro M, Kouda W, Kono N, Tsuneyama K, Matsui O, Nakanuma Y. Distribution of intrahepatic mast cells in various hepatobiliary disorders. An immunohistochemical study. Virchows Arch. 1998;433:471–9.PubMedGoogle Scholar
  70. 70.
    Farell DJ, Hines JE, Walls AF, Kelly PJ, Bennett MK, Burt AD. Intrahepatic mast cells in chronic liver diseases. Hepatology. 1995;22:1175–81.Google Scholar
  71. 71.
    Armbrust T, Batusic D, Ringe B, Ramadori G. Mast cells distribution in human liver disease and experimental rat liver fibrosis. Indications for mast cell participation in development of liver fibrosis. J Hepatol. 1997;26:1042–54.PubMedGoogle Scholar
  72. 72.
    Nakamura A, Yamazaki K, Suzuki K, Sato S. Increased portal tract infiltration of mast cells and eosinophils in primary biliary cirrhosis. Am J Gastroenterol. 1997;92:2245–9.PubMedGoogle Scholar
  73. 73.
    Matsunaga Y, Kawasaki H, Terada T. Stromal mast cells and nerve fibers in various chronic liver diseases: relevance to hepatic fibrosis. Am J Gastroenterol. 1999;94:1923–32.PubMedGoogle Scholar
  74. 74.
    Bjomsson E, Chari ST, Smyrk TC, et al. IgG4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology. 2007;45:1547–54.Google Scholar
  75. 75.
    Kamisawa T, Okamoto A, Funata N. Clinicopathological features of autoimmune pancreatitis in relation to elevation of serum IgG4. Pancreas. 2005;31:23–31.Google Scholar
  76. 76.
    Bjornsson E, Chari ST, Smyrk TC, Lindor K. Immunoglobulin G4-associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology. 2007;45:1547–54.PubMedGoogle Scholar
  77. 77.
    Kumagi T, Alswat K, Hirschfield GM, Heathcote J. New insights into autoimmune liver diseases. Hepatol Res. 2008;38:745–61.PubMedGoogle Scholar
  78. 78.
    Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003;38:982–4.PubMedGoogle Scholar
  79. 79.
    Deheragoda MG, Church NI, Rodriguez-Justo M, Munson P, Sandanayake N, Seward EW, et al. The use of immunoglobulin g4 immunostaining in diagnosing pancreatic and extrapancreatic involvement in autoimmune pancreatitis. Clin Gastroenterol Hepatol. 2007;5:1229–34.PubMedGoogle Scholar
  80. 80.
    Umemura T, Zen Y, Hamano H, Kawa S, Nakanuma Y, Kiyosawa K. Immunoglobulin G4 hepatopathy: association of immunoglobulin G4-bearing plasma cells in liver with autoimmune pancreatitis. Hepatology. 2007;46:463–71.PubMedGoogle Scholar
  81. 81.
    Chung H, Watanabe T, Kudo M, Maenishi O, Chiba T. Identification and characterization of IgG4-associated autoimmune hepatitis. Liver Int. 2010;30:222–31.PubMedGoogle Scholar
  82. 82.
    Nakazawa T, Ohara H, Sano H, et al. Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis. Gastroinetst Endosc. 2004;60:937–44.Google Scholar
  83. 83.
    Ito T, Nishimori I, Inoue N, Kawabe K, Gibo J, Arita Y, et al. Treatment for autoimmune pancreatitis: consensus on the treatment for patients with autoimmune pancreatitis in Japan. J Gastroenterol. 2007;42(Suppl 18):50–8.PubMedGoogle Scholar
  84. 84.
    Hirano K, Tada M, Isayama H, Yagioka H, Sasaki T, Kogure H, et al. Long-term prognosis of autoimmune pancreatitis with and without corticosteroid treatment. Gut. 2007;56:1719–24.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Umemura T, Zen Y, Hamano H, Ichijyo T, Kawa S, Nakanuma Y, Kiyosawa K. IgG4 associated autoimmune hepatitis: a differential diagnosis for classical autoimmune hepatitis. Gut. 2007;56:1471–2.PubMedPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Mikio Zeniya
    • 1
    Email author
  • Masaki Iwai
    • 2
  • Arief A. Suriawinata
    • 3
  1. 1.TokyoJapan
  2. 2.KyotoJapan
  3. 3.New HampshireUSA

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