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Pathogenesis and Clinical Significance of Liver Injury in Celiac Disease

Clinical Reviews in Allergy & Immunology volume 36, pages 62–70 (2009)Cite this article

Abstract

Abnormalities of liver function are one of the manifold extraintestinal manifestations of celiac disease. Although the spectrum of liver manifestations associated with celiac disease is particularly wide, two main forms of liver damage namely, cryptogenic and autoimmune, appear to be strictly related to gluten-sensitive enteropathy. The most frequent finding is represented by a cryptogenic hypertransaminasemia, observed in about a half of untreated celiac patients, as an expression of a mild liver dysfunction with a histological picture of nonspecific reactive hepatitis (celiac hepatitis) reverting to normal after 6–12 months of a strict gluten-free diet. In a few cases, when celiac disease is diagnosed, a more severe liver injury, characterized by a cryptogenic chronic hepatitis or liver cirrhosis, is present. In these patients, liver damage can still improve after a gluten-free diet institution. Moreover, a close association between celiac disease and autoimmune liver disorders has been widely demonstrated. Indeed, celiac disease has been found in 3–7% of patients with primary biliary cirrhosis, in 3–6% with autoimmune hepatitis, and in 2–3% with primary sclerosing cholangitis. Differently from cryptogenic liver injury, autoimmune liver dysfunction, found in celiac disease, does not usually improve after a gluten-free diet. Presently, it is difficult to establish if the two main kinds of liver injury found in celiac disease (cryptogenic and autoimmune) are discrete entities with a different pathogenesis or if they are an expression of the same disorder where genetic factors and the duration of gluten exposure may determine the severity and the pattern of liver injury.

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References

  1. Farrell RJ, Kelly CP (2002) N Eng J Med 346:180–188

    CAS  Google Scholar 

  2. Maki M, Mustalahti K, Kokkonen J et al (2003) N Engl J Med 348:2517–2524

    PubMed  Google Scholar 

  3. Volta U, Bellentani S, Bianchi FB et al (2001) Dig Dis Sci 46:1500–1505

    PubMed  CAS  Google Scholar 

  4. Schuppan D (2000) Gastroenterology 119:234–242

    PubMed  CAS  Google Scholar 

  5. Dieterich W, Ehnis T, Bauer M et al (1997) Nat Med 3:797–801

    PubMed  CAS  Google Scholar 

  6. Schuppan D, Ciccocioppo R (2002) Dig Liver Dis 34:13–15

    PubMed  CAS  Google Scholar 

  7. Corazza GR, Martucci S (2002) Gastroenterology 122:2072–2075

    PubMed  Google Scholar 

  8. Abenavoli L, Leggio L, Ferrulli A et al (2006) World J Gastroenterol 12:843–852

    PubMed  CAS  Google Scholar 

  9. Volta U, Ravaglia G, Granito A (2001) Digestion 64:61–65

    PubMed  CAS  Google Scholar 

  10. Rensch MJ, Merenich JA, Lieberman M, Long BD, Davis DR, Mcnally PR (1996) Ann Intern Med 124:564–567

    PubMed  CAS  Google Scholar 

  11. Curione M, Barbato M, De Biase L, Viola F, Lo Russo L, Cardi E (1999) Lancet 354:222–223

    PubMed  CAS  Google Scholar 

  12. Maki M, Hallstrom O, Verronen P et al (1988) Lancet 1:479–480

    PubMed  CAS  Google Scholar 

  13. Ludvigsson JF, Michaelsson K, Ekbom A, Montgomery SM (2007) Aliment Pharmacol Ther 25:273–285

    PubMed  CAS  Google Scholar 

  14. Sher KS, Jayanthy V, Probert CS, Stewart CR, Mayberry JF (1994) Dig Dis 12:186–190

    PubMed  Article  CAS  Google Scholar 

  15. Meloni GF, Dessole S, Vargiu N, Tomasi PA, Musumeci S (1999) Hum Reprod 14:2759–2761

    PubMed  CAS  Google Scholar 

  16. Volta U, De Giorgio R, Petrolini N et al (2002) Scand J Gastroenterol 37:1276–1281

    PubMed  CAS  Google Scholar 

  17. Davison S (2002) Arch Dis Child 87:293–296

    PubMed  CAS  Google Scholar 

  18. Maggiore G, Caprai S (2003) J Pediatr Gastroenterol Nutr 37:117–119

    PubMed  Google Scholar 

  19. Thevenot T, Mathurin P, Di Martino V et al (2003) Gastroenterol Clin Biol 27:28–42

    PubMed  Google Scholar 

  20. Stevens FM, McLoughlin RM (2005) Eur J Gastroenterol Hepatol 17:1015–1017

    PubMed  Google Scholar 

  21. Duggan JM, Duggan AE (2005) Aliment Pharmacol Ther 21:515–518

    PubMed  CAS  Google Scholar 

  22. Freeman HJ (2006) World J Gastroenterol 12:1503–1508

    PubMed  CAS  Google Scholar 

  23. Pollock DJ (1977) Histopathology 1:421–430

    PubMed  CAS  Google Scholar 

  24. Hagander B, Berg NO, Brandt L et al (1977) Lancet 2:270–272

    PubMed  CAS  Google Scholar 

  25. Lindberg T, Berg NO, Borulf S (1978) Lancet 1:390–391

    PubMed  CAS  Google Scholar 

  26. Jacobsen MB, Fausa O, Elgio K et al (1990) Scand J Gastroenterol 25:656–662

    PubMed  CAS  Google Scholar 

  27. Volta U, De Franceschi L, Molinaro N et al (1998) Dig Dis Sci 43:2190–2195

    PubMed  CAS  Google Scholar 

  28. Volta U, Rodrigo L, Granito A et al (2002) Am J Gastroenterol 97:2609–2613

    PubMed  Google Scholar 

  29. Villalta D, Girolami D, Bidoli E et al (2005) J Clin Lab Anal 19:6–10

    PubMed  CAS  Google Scholar 

  30. Abdo A, Meddings J, Swain M (2004) Clin Gastroenterol Hepatol 2:107–112

    PubMed  Google Scholar 

  31. Bardella MT, Fraquelli M, Quatrini M et al (1995) Hepatology 22:833–836

    PubMed  CAS  Google Scholar 

  32. Molinaro N, De Franceshi L, Tetta C (1996) Ital J Gastroenterol 28:534

    Google Scholar 

  33. Novacek G, Mieshler W, Wrba F et al (1999) Eur J Gastroenterol Hepatol 11:283–288

    PubMed  CAS  Google Scholar 

  34. Farre C, Esteve M, Curcoy A et al (2002) Am J Gastroenterol 97:3176–3181

    PubMed  CAS  Google Scholar 

  35. Bonamico M, Pitzalis G, Culasso F et al (1986) Minerva Pediatr 38:959–962

    PubMed  CAS  Google Scholar 

  36. Arslan N, Buyukgebiz B, Ozturk Y et al (2005) Acta Gastro-enterol Belg 68:424–427

    CAS  Google Scholar 

  37. Corazza GR, Valentini RA, Andreani ML et al (1995) Scand J Gastroenterol 30:153–156

    PubMed  CAS  Google Scholar 

  38. Olszwezka M, Sulej J, Kotowski B (2006) Acta Derm Venereol 86:332–334

    Google Scholar 

  39. Collin P, Reunala T, Pukkala E, Laippala P, Keirilainen O, Pasternack A (1995) Gut 35:1215–1218

    Google Scholar 

  40. Cacciari E, Salardi S, Volta U (1985) Lancet 1:1469–1471

    PubMed  CAS  Google Scholar 

  41. Wierink CD, van Diermen DE, Aartman DH, Heymans HS (2007) Int J Paediatr Dent 17:163–168

    PubMed  Google Scholar 

  42. Volta U, De Franceshi L, Lari F et al (1998) Lancet 352:26–29

    PubMed  CAS  Google Scholar 

  43. Volta U, Granito A, De Franceschi L et al (2001) Dig Liver Dis 33:420–425

    PubMed  CAS  Google Scholar 

  44. Bardella MT, Vecchi M, Conte D et al (1999) Hepatology 29:654–657

    PubMed  CAS  Google Scholar 

  45. Vajro P, Fontanella A, Mayer M et al (1993) J Pediatr 122:416–419

    PubMed  CAS  Google Scholar 

  46. Selcuk H, Kanbay M, Murat K et al (2006) Dig Dis Sci 51:213–214

    PubMed  Google Scholar 

  47. Kaukinen K, Halme L, Collin P et al (2002) Gastroenterology 122:881–888

    PubMed  Google Scholar 

  48. Ojetty V, Fini L, Zileri Dal Verme L et al (2005) Eur J Gastroenetrol Hepatol 17:1119–1121

    Google Scholar 

  49. Demir H, Yuce A, Caglar M et al (2005) J Clin Gastroenterol 39:630–633

    PubMed  Google Scholar 

  50. Logan RFA, Ferguson A, Finlayson NDC, Weir DG (1978) Lancet 1:230–233

    PubMed  CAS  Google Scholar 

  51. Kingham JGC, Parker DR (1998) Gut 42:120–122

    PubMed  CAS  Google Scholar 

  52. Sorensen HT, Thulstrup AM, Blomqwist P, Norgaard B, Fonager K, Ekbom A (1999) Gut 44:736–738

    PubMed  CAS  Google Scholar 

  53. Dickey W, McMillan SA, Callender ME (1997) J Clin Gastroenterol 25:328–329

    PubMed  CAS  Google Scholar 

  54. Gillett HR, Cauch-Dudek K, Jenny E, Heathcote EJ, Freeman HJ (2000) Can J Gastroenterol 14:672–675

    PubMed  CAS  Google Scholar 

  55. Volta U, Rodrigo L, Granito A et al (2002) Am J Gastroenterol 97:2609–2613

    PubMed  Google Scholar 

  56. Lee FI, Murray SM, Norfolk D, Vasudev KS (1978) Lancet 1:713

    Google Scholar 

  57. Craxì A, Pinzello G, Oliva L, Pagliaro L (1978) Lancet 1:713–714

    Google Scholar 

  58. Iliffe GD, Owen DA (1979) Dig Dis Sci 24:802–806

    PubMed  CAS  Google Scholar 

  59. Shanahan F, O’Regan PF, Crowe JP (1983) Ir Med J 76:282

    PubMed  CAS  Google Scholar 

  60. Schrijver G, Berge Heneugouwen GP, Bronkhorst FB (1984) Neth J Med 27:218–221

    PubMed  CAS  Google Scholar 

  61. Lofgren J, Jarnerot G, Danielsson D, Hendal I (1985) Scand J Gastroenterol 20:647–650

    PubMed  CAS  Google Scholar 

  62. Gabrielsen TO, Hoel PS (1985) Dermatologica 170:31–34

    PubMed  CAS  Article  Google Scholar 

  63. Behr W, Barnet J (1986) Am J Gastroenterol 81:796–799

    PubMed  CAS  Google Scholar 

  64. Lohr M, Lotterer E, Hahn EG, Fleig WE (1994) Eur J Gastroenterol Hepatol 6:263–267

    Google Scholar 

  65. Galvez C, Garrigues V, Ponce J (1994) Eur J Gastroenterol Hepatol 6:847

    Google Scholar 

  66. Lawson A, West J, Aithal GP, Logan RFA (2005) Aliment Pharmacol Ther 21:401–405

    PubMed  CAS  Google Scholar 

  67. Ludvigsson JF, Elfstrom P, Broome U, Ekbom A, Montgomery MS (2007) Clin Gastroenterol Hepatol 5:63–69

    PubMed  Google Scholar 

  68. Bardella MT, Quatrini M, Zuin M et al (1997) Am J Gastroenterol 92:1524–1526

    PubMed  CAS  Google Scholar 

  69. Habior A, Lewartowska A, Ortowska J et al (2003) Eur J Gastroenterol Hepatol 15:159–164

    PubMed  Google Scholar 

  70. Hay JE, Wiesner RH, Shorter RG, LaRusso NF, Baldus WP (1988) Ann Intern Med 109:713–717

    PubMed  CAS  Google Scholar 

  71. Tysk C (1994) J Clin Gastroenterol 18:241–242

    PubMed  CAS  Google Scholar 

  72. Brazier F, Delcenserie R, Sevestre H, Delamarre J, Capron JP (1994) Eur J Gastroenterol Hepatol 6:183–186

    Google Scholar 

  73. Lacaille F, Canioni D, Bernard O, Fabre M, Brousse N, Schmitz J (1995) J Pediatr Gastroenterol Nutr 21:463–467

    PubMed  CAS  Article  Google Scholar 

  74. Fracassetti O, Delvecchio G, Tambini R, Lorenzi N, Gavazzeni G (1996) J Clin Gastroenterol 22:71–72

    PubMed  CAS  Google Scholar 

  75. Venturini I, Cosenza R, Miglioli L et al (1998) Hepatogastroenterology 45:2344–2347

    PubMed  CAS  Google Scholar 

  76. Schrumpf E, Abdelnoor M, Fausa O, Elgjo K, Jenssen E, Kolmannskog F (1994) J Hepatol 21:1061–1066

    PubMed  CAS  Google Scholar 

  77. Lindberg J, Ahren C, Iwarson S (1979) Scand J Gastroenterol 14:1015–1018

    PubMed  CAS  Google Scholar 

  78. Swarbrick ET, Fairclough PD, Campbell PJ, Levison DA, Greenwood RH, Baker LR (1980) Lancet 2:1984–1985

    Google Scholar 

  79. Lindberg J, Ahren C, Jonsson J (1982) Hepatogastroenterology 29:52–54

    PubMed  CAS  Google Scholar 

  80. Ollson R, Kagevi I, Rydberg L (1982) Scand J Gastroenterol 17:625–628

    Article  Google Scholar 

  81. Ventura A, Magazzù G, Greco L (1999) Gastroenterology 117:297–303

    PubMed  CAS  Google Scholar 

  82. Maggiore G, Massei F, Ventura A et al (2001) J Pediatr Gastroenterol Nutr 32:387

    Google Scholar 

  83. Gogos CA, Nikolopoulou V, Zolota V et al (1999) J Hepatol 30:321–324

    PubMed  CAS  Google Scholar 

  84. Sedlack RE, Smyrk TC, Czaja AJ, Talwalkar JA (2002) Am J Gastroenterol 97:3196–3198

    PubMed  Google Scholar 

  85. Bardella MT, Valenti L, Pagliari C et al (2004) Dig Liver Dis 36:333–336

    PubMed  CAS  Google Scholar 

  86. Nehra V, Angulo P, Buchman AL, Lindor KD (2001) Dig Dis Sci 46:2347–2352

    PubMed  CAS  Google Scholar 

  87. Angulo P (2002) N Engl J Med 346:1221–1231

    PubMed  CAS  Google Scholar 

  88. Fine KD, Ogunji F, Saloum Y, Beharry S, Crippin J, Weistein J (2001) Am J Gastroenterol 96:138–145

    PubMed  CAS  Google Scholar 

  89. Thevenot T, Boruchowicz A, Henrion J, Nalet B, Moindrot H, ANGH (2007) Dig Dis Sci 52:1310–1313

    PubMed  Google Scholar 

  90. Martins EV Jr, Gaburi AK (2004) Arq Gastroenterol 41:132–133

    PubMed  Google Scholar 

  91. Cammarota G, Cuoco L, Cianci R, Fedeli G, Gasbarrini G (2000) Lancet 356:1494–1495

    PubMed  CAS  Google Scholar 

  92. Adinolfi LE, Durante Mangoni E, Andreana A (2001) Am J Gastroenterol 96:607–608

    PubMed  CAS  Google Scholar 

  93. Bourliere M, Oules V, Perrier H, Mengotti C (2001) Lancet 357:803–804

    PubMed  CAS  Google Scholar 

  94. Lindberg T, Berg NO, Borulf S, Jakobsson I (1978) Lancet 1:390–391

    PubMed  CAS  Google Scholar 

  95. Pelaez-Luna M, Schmulson M, Robles-Diaz G (2005) Med Hypotheses 65:937–941

    PubMed  CAS  Google Scholar 

  96. Spiller RC, Lee YC, Edge C et al (1987) Gut 28:1275–1282

    PubMed  CAS  Google Scholar 

  97. Nunes DP, Kelly CP, Nolan NP, O’Connor MP, Weir DG (1991) Eur J Gastroenterol Hepatol 3:313–319

    Google Scholar 

  98. Korponay-Szabo IR, Halttunen T, Szalai Z et al (2004) Gut 53:641–648

    PubMed  CAS  Google Scholar 

  99. Sollid LM, Thorsby E (1993) Gatroenterology 105:910–922

    CAS  Google Scholar 

  100. Czaja AJ, Doherthy DG, Donaldson PT (2002) Dig Dis Sci 47:2139–2150

    PubMed  CAS  Google Scholar 

  101. Wiencke K, Karlsen TH, Thorsby E et al (2007) Tissue Antigens 69:161–169

    PubMed  CAS  Google Scholar 

  102. Mullarkey ME, Stevens AM, McDonnell WM et al (2005) Tissue Antigens 65:199–205

    PubMed  CAS  Google Scholar 

  103. Volta U, Granito A, Fiorini E et al (2008) Dig Dis Sci 53:1582–1588

    PubMed  CAS  Google Scholar 

  104. Vecchi M, Folli C, Donato MF, Formenti S, Arosio E, de Franchis R (2003) Scand J Gastroenterol 38:50–54

    PubMed  CAS  Google Scholar 

  105. Lo Iacono O, Petta S, Venezia G et al (2005) Am J Gastroenterol 100:2472–2477

    PubMed  Google Scholar 

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Acknowledgments

The Author thanks Dr. Liliana Lattanzio for revising the manuscript.

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  1. Department of Gastroenterology and Internal Medicine, University of Bologna, S. Orsola Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy

    Umberto Volta

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Volta, U. Pathogenesis and Clinical Significance of Liver Injury in Celiac Disease. Clinic Rev Allerg Immunol 36, 62–70 (2009). https://doi.org/10.1007/s12016-008-8086-x

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Keywords

  • Celiac disease
  • Liver injury
  • Gluten-sensitive enteropathy