Clinicopathological and immunological characteristics and outcome of concomitant coeliac disease and non-alcoholic fatty liver disease in adults: a large prospective longitudinal study

Abstract

Objective: Concomitant non-alcoholic fatty liver disease (NAFLD) and coeliac disease (CD) have not been adequately studied. This study investigated the frequency of CD among NAFLD patients and the clinicopathological and immunological patterns and outcome of concomitant NAFLD and CD.

Design: This prospective longitudinal study screened patients with NAFLD for CD (tissue transglutaminase antibodies (TTGA); anti-TTGA and antiendomysial antibodies (EMA)). Patients with concomitant NAFLD and CD and patients with either NAFLD or CD were enrolled and followed. Duodenal biopsy, transient elastography, tumour necrosis factor (TNF)-alpha, transforming growth factor-beta, interleukins (ILs) 1, 6, 10, 15 and 17, folic acid and vitamins B12 and D were performed at baseline and 1 year after gluten-free diet (GFD).

Results: CD was confirmed in 7.2% of patients with NAFLD. Refractory anaemia and nutritional deficiencies were frequent in patients with concomitant NAFLD and CD who had advanced intestinal and hepatic lesions, higher levels of TNF-α, IL-15 and IL-17 compared with patients with CD and NAFLD. Patients concomittant CD and NAFLD showed clinical response to GFD, but intestinal histological improvement was suboptimal. Combining EMA-IgA or anti-TTGA with either IL-15 or IL-17 enhances the prognostic performance of both tests in predicting histological response to GFD.

Conclusion: Concomitant NAFLD and CD is not uncommon. Recurrent abdominal symptoms, refractory anaemia, nutritional deficiencies in patients with NAFLD warrant screening for CD. The study has important clinical implications since failure in diagnosing CD in patients with NAFLD patients results in marked intestinal and hepatic damage and suboptimal response to GFD that can be alleviated by early diagnosis and initiation of GFD.

Keywords: celiac disease; cytokines; gluten free diet; nonalcoholic steatohepatitis; small intestinal biopsy.

Figure 1

Flow of patients through the trial. CD, coeliac disease; DGP, deamidated gliadin peptide; EMA IgA, endomysial antibody IgA; GIT, gastrointestinal disorders; HLA, human leukocyte antigen; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; TE, transient elastography; TTGA, tissue transglutaminase antibody.

Figure 2

Baseline cytokines in the three groups. (A) Baseline TTGA, TNF-α, IL-15 and IL-17 and (B) IL-6, IL-10 and TGF-β and YKL-40 in patients of the three groups. Group A: concomitant NAFLD and coeliac disease (n=182); group B: NAFLD (n=100); group C: coeliac disease (n=50). In the box plot, the black centre line represents the median for each dataset. The first and third quartiles (IQR) are located at the edges of the box. The points represent outliers. *Significant. **Highly significant. IL, interleukin; NAFLD, non-alcoholic fatty liver disease; TNF-α, tumour necrosis factor-alpha; TGF-β, transforming growth factor beta; TTGA, tissue transglutaminase antibody; YKL-40: chitinase-3-like-1 human cartilage glycoprotein-39.

Figure 3

Correlation between individual cytokines and Modified Marsh classification for coeliac disease that assesses the intraepithelial lymphocytes per 100 enterocytes (IEL/100 enterocytes), crypt hyperplasis and villi. IL, interleukin; TNF-α, tumour necrosis factor-alpha; TTGA, tissue transglutaminase antibody.

Figure 4

Baseline and follow-up transient elastography (TE) in patients with concomitant NAFLD and coeliac disease (n=182; group A), patients with NAFLD (n=100; group B) and patients with coeliac disease alone (n=50; group C). NAFLD, NAFLD, non-alcoholic fatty liver disease.