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Original research
Liver involvement in patients with coeliac disease: proof of causality using IgA/anti-TG2 colocalisation techniques
  1. Rimlee Dutta1,
  2. Asif Iqbal2,
  3. Prasenjit Das1,
  4. Jayanth Kumar Palanichamy3,
  5. Alka Singh2,
  6. Wajiha Mehtab2,
  7. Ashish Chauhan2,
  8. Ashish Aggarwal2,
  9. Vishnubhatla Sreenivas4,
  10. Vineet Ahuja2,
  11. Siddhartha Datta Gupta1,
  12. Govind K Makharia2
  1. 1 Pathology, All India Institute of Medical Sciences, New Delhi, Delhi, India
  2. 2 Gastroenetrology & Human Nutritions, All India Institute of Medical Sciences, New Delhi, Delhi, India
  3. 3 Biochemistry, All India Institute of Medical Sciences, New Delhi, Delhi, India
  4. 4 Biostatistics, All India Instituteof Medical Sciences, New Delhi, Delhi, India
  1. Correspondence to Dr Prasenjit Das, Pathology, All India Institute of Medical Sciences, New Delhi, DL 110029, India; prasenaiims{at}gmail.com

Abstract

Aims Despite clinical evidence of liver involvement in patients with coeliac disease (CeD), there is a lack of a method to prove this association.

Methods Of 146 treatment-naive patients with CeD, 26 had liver dysfunction. Liver biopsies and corresponding small intestinal biopsies were obtained from these 26 patients. Multicolour immunohistochemical and immunofluorescence confocal microscopic studies were performed on paraffin-embedded tissue to detect the IgA/anti-TG2 deposits. Follow-up liver biopsies were taken after a gluten-free diet.

Results Twenty-six out of the 146 patients (17.8%) with suspected coeliac-associated liver disease on histological examination revealed irregular sinusoidal dilatation in 15 (57.6%), steatohepatitis in 4 (15.3%), non-specific chronic hepatitis in 3 (11.5%), autoimmune hepatitis in 2 (7.6%) biopsies, including cirrhosis in one of them, irregular perisinusoidal fibrosis and changes of non-cirrhotic portal fibrosis in one biopsy each (3.8%). IgA/anti-tTG deposits were observed in 22 (84.6%) liver biopsies by dual immunohistochemistry technique, and in 24 (92.3%) by confocal immunofluorescence technique and in all corresponding duodenal biopsies (100%). Overall, IgA/anti-tTG deposits showed 100% sensitivity, 77% specificity and 85% positive predictive value for establishing an association of extraintestinal pathology and CeD using archived tissues. Follow-up liver biopsies could be obtained in five patients; four of them showed not only resolution of the histological lesions but disappearance of IgA/anti-tTG co-localisation.

Conclusions Data of the present study adds to the body of evidence that liver lesions in patients with CeD are disease related and may have been caused by a similar pathogenic mechanism that causes intestinal changes.

  • coeliac disease
  • diagnostic techniques and procedures
  • intestine
  • small
  • liver diseases
  • microscopy
  • fluorescence

Data availability statement

Data are available on reasonable request.

https://doi.org/10.1136/jclinpath-2020-206735

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    Data availability statement

    Data are available on reasonable request.

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    Footnotes

    • Handling editor Dhirendra Govender.

    • Twitter @PRSENJ13259721

    • RD and AI contributed equally.

    • Correction notice The article has been corrected since it was published online first. Incorrect version of figure 4 was published which has been replaced with the correct one. Author names of Jayanth Kumar Palanichamy, Ashish Chauhan and Ashish Aggarwal have also been corrected.

    • Contributors RD and AI were involved in patient screening, recruitment, follow-up, patients’ management and performing all techniques applied in this article. PD, SDG, VA and GKM conceived and planned the study and supervised the whole process. JKP was responsible for supervising the confocal microscopy work. AS, WM, AC and AA were responsible for acquiring patient’s data and counseling them. They were also responsible for scheduling patients’ follow-up visits. VS was responsible for statistical analyses. PD is the overall guarantor of this article.

    • Funding The study was supported by the Intramural Research Grant of the All India Institute of Medical Sciences, New Delhi, India [A641, 2018].

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.