Abstract

Aim: To determine the prevalence of patients with hepatic injury related to celiac disease.

Method: Retrospective analysis of patients’ records from Hepatology Outpatient Clinic in the period of 18 months was done. Data regarding referral and final diagnosis as well as hepatic injury profile were analysed.

Results: There were 1207 exams performed in 684 patients, and only 446 of them with initial diagnosis suggesting liver disease. Elevated liver enzymes had 299/446 patients (67%), and only in 30% of them (89/299) proper screening for metabolic, viral, and autoimmune diseases was done. None of referred (0%) patients was screened for celiac disease. Finally, in 248 patients diagnosis of either viral hepatitis, NAFLD/NASH, ALD, haemochromatosis, autoimmune liver disease, Gilbert syndrome, toxic liver injury and even primary aceruloplasminemia, was established. In five patients celiac disease was already established, but additional liver disease was suspected and confirmed, but there were still 52 patients with no diagnosis. In 9 of those 52 patients (17%), celiac disease was diagnosed with positive tissue transglutaminase antibodies and confirmed with duodenal mucosa biopsy.

Conclusion: Our data suggest that the prevalence of celiac disease in adult population with hepatic injury is up to 17%. Celiac disease can be the sole cause of hepatic injury, meaning celiac hepatitis, but can also be combined with other autoimmune diseases of the liver as well as with steatohepatitis. High level of suspicion is necessary to recognize disease early, and that is the reason why serology testing for celiac disease should be positioned high in the algorithm of liver injury workup.

Keywords: Celiac Disease; Celiac Hepatitis; Screening; Liver Injury Workup

References

1. Bai JC and Ciacci C. “WGO Global Guidelines. Celiac Disease”. Journal of Clinical Gastroenterology9 (2017): 755-768.
2. Tack GJ., et al. “The spectrum of celiac disease: epidemiology, clinical aspects and treatment”. Nature Reviews Gastroenterology and Hepatology4 (2010): 204-213.
3. Lauret E and Rodrigo L. “Celiac disease and autoimmune-associated conditions”. BioMed Research International (2013): 127-589.
4. Van Belzen MJ., et al. “Defining the contribution of the HLA region to cisDQ2-positive coeliac disease patients”. Genes and Immunity 5 (2004): 215-220.
5. Karell K., et al. “HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease”. Human Immunology 64 (2003): 469-477.
6. Rostami-Nejad M., et al. “Allele and haplotype frequencies for HLA-DQ in Iranian celiac disease patients”. World Journal of Gastroenterology20 (2014): 6302-6308.
7. Al-Toma A., et al. “European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders”. United European Gastroenterology Journal5 (2019): 583-613.
8. Ludvigsson JF., et al. “Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology”. Gut8 (2014): 1210-1228.
9. Rubio-Tapia A., et al. “American College of Gastroenterology. ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease”. The American Journal of Gastroenterology5 (2013): 656-676.
10. Leffler DA and Schuppan D. “Update on serologic testing in celiac disease”. The American Journal of Gastroenterology12 (2010): 2520-2524.
11. Werkstetter KJ., et al. “Accuracy in diagnosis of celiac disease without biopsies in clinical practice”. Gastroenterology4 (2017): 924-935.
12. Leffler D., et al. “Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease”. Gut 7 (2013): 996-1004.
13. Ludvigsson JF., et al. “The Oslo definitions for coeliac disease and related terms”. Gut 1 (2013): 43-52.
14. Sainsbury A., et al. “Meta-analysis: coeliac disease and hypertransaminasaemia”. Alimentary Pharmacology and Therapeutics 1 (2011): 33-40.
15. Hagander B., et al. “Hepatic injury in adult coeliac disease”. Lancet 8032 (1977): 270-272.
16. Bardella MT., et al. “Prevalence of hypertransaminasemia in adult celiac patients and effect of gluten-free diet”. Hepatology3 (1995): 833-836.
17. Volta U., et al. “Coeliac disease hidden by cryptogenic hypertransaminasaemia”. Lancet 9121 (1998): 26-29.
18. Ludvigsson JF., et al. “Celiac disease and risk of liver disease: a general population-based study”. Clinical Gastroenterology and Hepatology 1 (2007): 63-69.
19. Rubio-Tapia A and Murray JA. “The liver and Celiac Disease”. Clinical Liver Disease2 (2019): 167-176.
20. Marciano F., et al. “Celiac disease-related hepatic injury: Insights into associated conditions and underlying pathomechanisms”. Digestive and Liver Disease2 (2016): 112-119.
21. Narciso-Schiavon JL and Schiavon LL. “To screen or not to screen? Celiac antibodies in liver diseases”. World Journal of Gastroenterology5 (2017): 776-791.
22. Catassi C and Fasano A. “Coeliac disease. The debate on coeliac disease screening - are we there yet?” Nature Reviews Gastroenterology and Hepatology8 (2014): 457-458.
23. Dowd B and Walker-Smith J. “Samuel Gee, Aretaeus, and the Coeliac Affection”. British Medical Journal 2 (1974): 45-47.
24. Čuković-Čavka S., et al. Medicus2 (2012): 179-186.
25. Farrell RJ and Kelly CP. “Celiac sprue”. The New England Journal of Medicine3 (2002): 180-188.
26. Santonicola A., et al. “From menarche to menopause: the fertile life span of celiac women”. Menopause10 (2011): 1125-1130.
27. Aarela L., et al. “Prevalence and associated factors of abnormal liver values in children with celiac disease”. Digestive and Liver Disease 48 (2016): 1023-1029.
28. Anania C., et al. “Liver involvement in pediatric celiac disease”. World Journal of Gastroenterology 21 (2015): 5813-5822.
29. Lee GJ., et al. “Hypertransaminasemia in newly diagnosed pediatric patients with celiac disease”. Journal of Pediatric Gastroenterology and Nutrition 63 (2016): 340-343.
30. Korpimäki S., et al. “Gluten-sensitive hypertransaminasemia in celiac disease: an infrequent and often subclinical finding”. The American Journal of Gastroenterology9 (2011): 1689-1696.
31. Kaukinen K., et al. “Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure”. Gastroenterology 122 (2002): 881-888.
32. Hoffmanová I., et al. “Review Celiac Disease and Liver Disorders: From Putative Pathogenesis to Clinical Implications”. Nutrients 10 (2018): 892.
33. Husby S and Bai JC. “Follow-up of Celiac Disease”. Gastroenterology Clinics of North America 1 (2019): 127-136.
34. Hagander B., et al. “Hepatic injury in adult coeliac disease”. Lancet 2 (1977): 270-272.
35. Koning F., et al. “Pathomechanisms in celiac disease. Best practice and research”. Clinical Gastroenterology3 (2005): 373-387.