AIM: To study the coincidence of celiac disease, we tested its serological markers in patients with various liver diseases. METHODS: Large-scale screening of serum antibodies against tissue transglutaminase (tTG), and deamidated gliadin using enzyme-linked immunosorbent assay and serum antibodies against endomysium using immunohistochemistry, in patients with various liver diseases (n = 962) and patients who underwent liver transplantation (OLTx, n = 523) was performed. The expression of tTG in liver tissue samples of patients simultaneously suffering from celiac disease and from various liver diseases using immunohistochemistry was carried out. The final diagnosis of celiac disease was confirmed by histological analysis of small-intestinal biopsy. RESULTS: We found that 29 of 962 patients (3%) with liver diseases and 5 of 523 patients (0.8%) who underwent OLTx were seropositive for IgA and IgG anti-tTG antibodies. However, celiac disease was biopsy-diagnosed in 16 patients: 4 with autoimmune hepatitis type I, 3 with Wilson's disease, 3 with celiac hepatitis, 2 with primary sclerosing cholangitis, 1 with primary biliary cirrhosis, 1 with Budd-Chiari syndrome, 1 with toxic hepatitis, and 1 with non-alcoholic steatohepatitis. Unexpectedly, the highest prevalence of celiac disease was found in patients with Wilson's disease (9.7%), with which it is only rarely associated. On the other hand, no OLTx patients were diagnosed with celiac disease in our study. A pilot study of the expression of tTG in liver tissue using immunohistochemistry documented the overexpression of this molecule in endothelial cells and periportal hepatocytes of patients simultaneously suffering from celiac disease and toxic hepatitis, primary sclerosing cholangitis or autoimmune hepatitis type I. CONCLUSION: We suggest that screening for celiac disease may be beneficial not only in patients with associated liver diseases, but also in patients with Wilson's disease.

Department of Hepatogastroenterology Institute for Clinical and Experimental Medicine 14021 Prague Czech Republic

Zobrazit více v PubMed

Lochman I, Martis P, Burlingame RW, Lochmanová A. Multiplex assays to diagnose celiac disease. Ann N Y Acad Sci. 2007;1109:330–337. PubMed

McGowan KE, Lyon ME, Loken SD, Butzner JD. Celiac disease: are endomysial antibody test results being used appropriately? Clin Chem. 2007;53:1775–1781. PubMed

Rodrigo L, Fuentes D, Riestra S, Niño P, Alvarez N, López-Vázquez A, López-Larrea C. [Increased prevalence of celiac disease in first and second-grade relatives. A report of a family with 19 studied members] Rev Esp Enferm Dig. 2007;99:149–155. PubMed

Volta U. Pathogenesis and clinical significance of liver injury in celiac disease. Clin Rev Allergy Immunol. 2009;36:62–70. PubMed

Czaja AJ. Cryptogenic chronic hepatitis and its changing guise in adults. Dig Dis Sci. 2011;56:3421–3438. PubMed

Rubio-Tapia A, Murray JA. The liver in celiac disease. Hepatology. 2007;46:1650–1658. PubMed

Sifford M, Koch A, Lee E, Peña LR. Abnormal liver tests as an initial presentation of celiac disease. Dig Dis Sci. 2007;52:3016–3018. PubMed

Freeman HJ, Chopra A, Clandinin MT, Thomson AB. Recent advances in celiac disease. World J Gastroenterol. 2011;17:2259–2272. PubMed PMC

Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’) Gastroenterology. 1992;102:330–354. PubMed

Meresse B, Ripoche J, Heyman M, Cerf-Bensussan N. Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis. Mucosal Immunol. 2009;2:8–23. PubMed

Lo Iacono O, Petta S, Venezia G, Di Marco V, Tarantino G, Barbaria F, Mineo C, De Lisi S, Almasio PL, Craxì A. Anti-tissue transglutaminase antibodies in patients with abnormal liver tests: is it always coeliac disease? Am J Gastroenterol. 2005;100:2472–2477. PubMed

Leonardi S, Pavone P, Rotolo N, Spina M, La Rosa M. Autoimmune hepatitis associated with celiac disease in childhood: report of two cases. J Gastroenterol Hepatol. 2003;18:1324–1327. PubMed

Al-toma A, Verbeek WH, Mulder CJ. The management of complicated celiac disease. Dig Dis. 2007;25:230–236. PubMed

Tack GJ, Verbeek WH, Al-Toma A, Kuik DJ, Schreurs MW, Visser O, Mulder CJ. Evaluation of Cladribine treatment in refractory celiac disease type II. World J Gastroenterol. 2011;17:506–513. PubMed PMC

Prasad KK, Sharma AK, Nain CK, Singh K. Commentary on: Are hepatitis B virus and celiac disease linked?: HBV and Celiac Disease. Hepat Mon. 2011;11:44–45. PubMed PMC

Manns MP, Strassburg CP. Autoimmune hepatitis: clinical challenges. Gastroenterology. 2001;120:1502–1517. PubMed

Kodama H, Fujisawa C, Bhadhprasit W. Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment. Curr Drug Metab. 2012;13:237–250. PubMed PMC

Fox MA, Fox JA, Davies MH. Budd-Chiari syndrome--a review of the diagnosis and management. Acute Med. 2011;10:5–9. PubMed

Elli L, Bergamini CM, Bardella MT, Schuppan D. Transglutaminases in inflammation and fibrosis of the gastrointestinal tract and the liver. Dig Liver Dis. 2009;41:541–550. PubMed

Casswall TH, Papadogiannakis N, Ghazi S, Németh A. Severe liver damage associated with celiac disease: findings in six toddler-aged girls. Eur J Gastroenterol Hepatol. 2009;21:452–459. PubMed

Sánchez D, Tucková L, Sebo P, Michalak M, Whelan A, Sterzl I, Jelínková L, Havrdová E, Imramovská M, Benes Z, et al. Occurrence of IgA and IgG autoantibodies to calreticulin in coeliac disease and various autoimmune diseases. J Autoimmun. 2000;15:441–449. PubMed

Sánchez D, Tucková L, Mothes T, Kreisel W, Benes Z, Tlaskalová-Hogenová H. Epitopes of calreticulin recognised by IgA autoantibodies from patients with hepatic and coeliac disease. J Autoimmun. 2003;21:383–392. PubMed

Hernandez L, Johnson TC, Naiyer AJ, Kryszak D, Ciaccio EJ, Min A, Bodenheimer HC, Brown RS, Fasano A, Green PH. Chronic hepatitis C virus and celiac disease, is there an association? Dig Dis Sci. 2008;53:256–261. PubMed

Leonardi S, La Rosa M. Are hepatitis B virus and celiac disease linked? Hepat Mon. 2010;10:173–175. PubMed PMC

Kaukinen K, Halme L, Collin P, Färkkilä M, Mäki M, Vehmanen P, Partanen J, Höckerstedt K. Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure. Gastroenterology. 2002;122:881–888. PubMed

Mirzaagha F, Azali SH, Islami F, Zamani F, Khalilipour E, Khatibian M, Malekzadeh R. Coeliac disease in autoimmune liver disease: a cross-sectional study and a systematic review. Dig Liver Dis. 2010;42:620–623. PubMed

Volta U. Liver dysfunction in celiac disease. Minerva Med. 2008;99:619–629. PubMed

Mounajjed T, Oxentenko A, Shmidt E, Smyrk T. The liver in celiac disease: clinical manifestations, histologic features, and response to gluten-free diet in 30 patients. Am J Clin Pathol. 2011;136:128–137. PubMed

Vanciková Z, Chlumecký V, Sokol D, Horáková D, Hamsíková E, Fucíková T, Janatková I, Ulcová-Gallová Z, Stĕpán J, Límanová Z, et al. The serologic screening for celiac disease in the general population (blood donors) and in some high-risk groups of adults (patients with autoimmune diseases, osteoporosis and infertility) in the Czech republic. Folia Microbiol (Praha) 2002;47:753–758. PubMed

Dahmani Z, Jemaa Y, Moussa A, Benhammouda I, Debbeche R, Najjar T. [Celiac disease associated to Wilson disease] Tunis Med. 2008;86:940–941. PubMed

Ince AT, Kayadibi H, Soylu A, Ovunç O, Gültepe M, Toros AB, Yaşar B, Kendir T, Abut E. Serum copper, ceruloplasmin and 24-h urine copper evaluations in celiac patients. Dig Dis Sci. 2008;53:1564–1572. PubMed

Goyens P, Brasseur D, Cadranel S. Copper deficiency in infants with active celiac disease. J Pediatr Gastroenterol Nutr. 1985;4:677–680. PubMed

Lurie Y, Landau DA, Pfeffer J, Oren R. Celiac disease diagnosed in the elderly. J Clin Gastroenterol. 2008;42:59–61. PubMed

Rubio-Tapia A, Abdulkarim AS, Wiesner RH, Moore SB, Krause PK, Murray JA. Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation. Liver Int. 2008;28:467–476. PubMed PMC

Celiac Disease and Liver Disorders: From Putative Pathogenesis to Clinical Implications