Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation

Celiac disease (CD), also known as gluten-sensitive enteropathy or celiac sprue, is a common, chronic disease of the small intestine caused by an inappropriate immune response to ingested wheat gluten proteins and related proteins in barley and rye (1). Celiac disease is strongly associated with the human leucocyte antigen (HLA) molecules DQ2, encoded by DQA1*05/DQB1*02, and DQ8, encoded by DQA1*03/DQB1*0302 (2, 3). The clinical presentations associated with CD are numerous and include classical, atypical, silent and latent forms (4). Most patients with CD remain undiagnosed because symptom-free subjects (latent and silent forms) and those with atypical clinical presentations may remain without a diagnosis (4, 5). The immunoglobulin (Ig) A-class endomysial antibody (EMA) and IgA tissue transglutaminase antibody (tTGA) have high sensitivities (> 93% for both) and specificities (> 99 and > 95% respectively) for the diagnosis of classical CD, and can be used for screening or to determine the prevalence of CD in at-risk populations (5–9). Human tissue transglutaminase performs much better than guinea-pig tissue transglutaminase (7, 8). The EMA test has greater specificity than the tTGA tests, whether human umbilicus or monkey oesophagus is used (5–8). Variable rates of false-positive results have been reported by using guinea-pig or human recombinant tissue transglutaminase in chronic liver disease of various aetiologies (10, 11). However, the EMA test that is performed by an immunofluorescence technique has a specificity of almost 100% for CD (compared with small bowel biopsy) in patients with chronic liver disease, and the presence on serum of this antibody has a high positive predictive value for CD (12, 13). Liver abnormalities are frequent in patients with CD. Isolated hypertransaminasaemia with non-specific histological changes on the liver biopsy is the commonest ‘hepatic’ presentation of CD, occurring in 40% of adults and in 54% of children with untreated CD (14, 15). Conversely, CD has been found in as many as 9% of patients with chronic unexplained hypertransaminasaemia (16, 17). Moreover, the association between CD and autoimmune liver disorders such as primary biliary cirrhosis (PBC) (18–21), primary sclerosing cholangitis (PSC) (22, 23) and autoimmune hepatitis (AH) (24, 25) is well documented. However, data on the prevalence of CD in end-stage autoimmune liver disease (ESALD) are scarce (26). The impact of liver transplantation on the kinetics of the tTGAs and EMAs and clinical outcome of those with untreated CD is unknown. It can be hypothesized that the correction of the complex structural/functional abnormalities (i.e. increased intestinal permeability) related to cirrhosis after liver transplantation and the use of immunosuppression may have a synergistic effect towards the induction of a decrease in tTGA and EMA levels on a normal gluten-containing diet. Immunosuppression might control the clinical manifestations of CD. The aims of this study are (i) to determine the prevalence of tTGAs and EMAs in patients with ESALD and compare with the prevalence found in a group of patients with non-autoimmune end-stage liver disease; (ii) to evaluate the importance of the HLA-class II DQ2 or -DQ8 haplotypes on the prevalence of antibodies associated with CD and (iii) to evaluate the impact of liver transplantation/immunosuppression on the titre of the tTGAs and EMAs and clinical manifestations of those subjects with CD on a normal gluten-containing diet.