High Prevalence of Celiac Disease in Autoimmune Hepatitis

Systematic Review and Meta-analysis

Linnea Haggård; Ida Glimberg; Benjamin Lebwohl; Rajani Sharma; Elizabeth C. Verna; Peter H. R. Green; Jonas F. Ludvigsson

Disclosures

Liver International. 2021;44(11):2693-2702. 

In This Article

Abstract and Introduction

Abstract

Background: Previous studies investigating the prevalence of celiac disease (CD) in individuals with autoimmune hepatitis (AIH) have shown highly variable results. We therefore aimed to examine the prevalence of CD in individuals with AIH.

Methods: Two professional librarians searched PubMed, EMBASE, Cochrane and Web of Science Core Collection up until 7 February 2020. The search terms included 'celiac disease', 'celiac', 'transglutaminases', 'gluten', 'gliadin', 'EMA', 'TTG' and 'villous' combined with 'autoimmune', 'hepatitis', 'ANA', 'SMA' and 'LKM'. This search yielded 2419 unique publications. A systematic review based on the PRISMA guidelines resulted in 31 articles eligible for full text review. Fifteen articles were deemed relevant, with 8 being included in our main analysis. A fixed-effect inverse variance-weighted model was used, and heterogeneity was calculated.

Results: Our main analysis included 567 individuals with AIH from eight studies, where biopsy-verified CD (equivalent to Marsh III) was seen in 23 individuals (4.1%). The pooled prevalence of CD in AIH was 3.5% (95% CI = 1.6%-5.3%) (heterogeneity: P = .874; I 2 = 0.0%), which is clearly higher than the 1% CD seen in most general populations. When also including studies where CD had been diagnosed through positive serology without biopsy (15 studies: n = 1817 individuals with AIH), the pooled prevalence of CD was 2.9% (95% CI = 2.1%-3.8%) (heterogeneity: P < .001; I 2 = 66.8%).

Conclusion: Our results demonstrate a higher prevalence of CD in individuals with AIH compared to the general population. CD screening may be considered in patients with AIH.

Introduction

Autoimmune hepatitis (AIH) is a severe chronic and progressive autoimmune liver disorder characterized by immune-mediated inflammation of the liver that may proceed to cirrhosis and liver failure.[1–3] The incidence of AIH ranges between 0.85 and 1.68 per 100 000 person-years, predominantly afflicting women.[4–6] AIH may have a multifactorial pathogenesis, where both genetics, immune response regulation and environmental factors play a crucial role.[2,3,7]

AIH have been linked to several extrahepatic autoimmune disorders, including autoimmune thyroiditis, diabetes, rheumatoid arthritis, inflammatory bowel disease and potentially also to celiac disease (CD).[8] CD is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals and is characterized by circulating celiac-specific autoantibodies and gastrointestinal symptoms including malabsorption caused by small intestinal villous atrophy but also extraintestinal symptoms.[9] In prior studies, the prevalence of CD has ranged from 2% to 20% in children and adults with AIH.[10–12] While the prevalence of CD in AIH individuals seems to be higher than in the general population (~1%),[9] prior studies have been small, mostly single-centre studies resulting in large variability in results and lack of precise estimates.[10–12]

It is known that CD is associated with various types of liver diseases[13] and that the use of a gluten-free diet has been shown to improve liver injury in CD-associated hepatopathy,[14] autoimmune cholangitis[15] and non-alcoholic fatty liver disease (NAFLD).[16] Although the data is more sparse in those who have AIH, there is one report that indicated that, in individuals with AIH, the use of a gluten-free diet for CD improved liver injury, whereas the AIH treatment alone had not been satisfying in liver recovery.[17] However, it remains unknown whether CD worsens AIH activity or causes separate liver injury in addition to AIH.

Because of the highly varying CD prevalence data in AIH in earlier studies, we performed a meta-analysis and investigated the prevalence of CD in AIH.

processing....