Gut-liver axis and disease infidelity: A subject worth exploring

Abstract

The spectrum of gluten-related disorders is widening and varies from celiac disease (CeD) to non-celiac gluten sensitivity [1]. While small intestine was thought to be the only organ involved in patients with CeD, it is now recognized that the hypersensitivity to gluten is not limited to the small intestine alone and may affect other organs such as skin, brain, and bones independent of intestinal involvement [2][3][4][5]. Dermatitis herpetiformis and gluten ataxia are the best example of such phenomena.In a study published in this issue of the Journal, Maiwall et al. [6] have reported small intestinal changes in 61 patients with cryptogenic chronic liver disease (cryptogenic chronic liver disease 47 and 14 biopsy proven noncirrhotic idiopathic portal hypertension) and 59 patients with hepatitis B or hepatitis C virus related cirrhosis as controls. All of them were screened for CeD using anti-tissue transglutaminase antibody (anti-tTG Ab) and patients having a positive screening test were invited for upper gastrointestinal endoscopy and duodenal biopsies were obtained from them. CeD was diagnosed on the basis of combination of a positive serology and presence of villous abnormalities. An unexpectedly high number of both study subjects (40, 66 %) and controls (17, 29 %) were detected to have a positive anti-tTG Ab. Of them, 37 in the study group and 11 in control group underwent duodenal biopsies, respectively. Overall, six patients fulfilled the criteria for the diagnosis of CeD (including two patients with noncirrhotic intrahepatic portal hypertension [NCIPH]) as compared to none in controls.Additionally, a significant number of both study subject controls also had villous abnormalities (various grade of villous atrophy, crypt hyperplasia, and chronic inflammatory cells in the lamina propria, these changes however were not accompanied by rise in intraepithelial lymphocytes. Such changes were seen more often in cryptogenic cirrhosis than those with cirrhosis due to hepatitis B virus or hepatitis C virus-related cirrhosis. Of patients with negative anti-tTG antibody who underwent duodenal biopsies, 4/16 (25 %) of cases and 4/22 (18 %) of controls also showed the presence of villous abnormalities. Furthermore, after observing a high anti-tTG Ab positive in both study group (cryptogenic cirrhosis) and controls (cirrhosis due to HBV or HCV), the authors retested the serum samples by two different ELISA kits procured from two different manufacturers and showed also remarkable variability in the performance of ELISA kits. The anti-tTG antibody was positive in 16 (31 %) cases and in 15 (38 %) controls by a kit obtained from Euroimmune and in 12 (23 %) cases and 8 (20 %) controls using kits obtained from Inova.While Maiwall et al. in the present study have shown that approximately 10 % of cryptogenic cirrhosis have coexistent CeD, more importantly, they raise an important question. Is there a causal relationship between CeD and liver damage, and if so, then how? They also highlighted two another issues. Firstly, that man...

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