MAFLD and Celiac Disease in Children

Abstract

Celiac disease (CD) is an immune-mediated systemic disorder elicited by the ingestion of gluten whose clinical presentation ranges from the asymptomatic form to clinical patterns characterized by multiple systemic involvement. Although CD is a disease more frequently diagnosed in patients with symptoms of malabsorption such as diarrhea, steatorrhea, weight loss, or failure to thrive, the raised rate of overweight and obesity among general pediatric and adult populations has increased the possibility to diagnose celiac disease in obese patients as well. Consequently, it is not difficult to also find obesity-related disorders in patients with CD, including “metabolic associated fatty liver disease” (MAFLD). The exact mechanisms linking these two conditions are not yet known. The going assumption is that a gluten-free diet (GFD) plays a pivotal role in determining an altered metabolic profile because of the elevated content of sugars, proteins, saturated fats, and complex carbohydrates, and the higher glycemic index of gluten-free products than gluten-contained foods, predisposing individuals to the development of insulin resistance. However, recent evidence supports the hypothesis that alterations in one of the components of the so-called “gut–liver axis” might contribute to the increased afflux of toxic substances to the liver triggering the liver fat accumulation and to the subsequent hepatocellular damage. The aim of this paper was to describe the actual knowledge about the factors implicated in the pathogenesis of hepatic steatosis in pediatric patients with CD. The presented review allows us to conclude that the serological evaluations for CD with anti-transglutaminase antibodies, should be a part of the general workup in the asymptomatic patients with “non-alcoholic fatty liver disease” (NAFLD) when metabolic risk factors are not evident, and in the patients with steatohepatitis when other causes of liver disease are excluded.

Celiac disease - a pluripathological model in pediatric practice

“…These occur mainly due to the alteration of intestinal permeability that allows their passage into the portal circulation, inducing inflammation with liver lesions. Besides this, the involvement of immune factors cannot be neglected either, an aspect certified by the objectification of liver deposits of anti-tTG antibodies ( 80 , 102 ). Also, in agreement with what was stated previously, the initiation of GFD can predispose to weight gain, especially in the first years.…”

Celiac Disease, Gluten-Free Diet and Metabolic Dysfunction-Associated Steatotic Liver Disease

“…The stocked triglycerides can cause lipotoxicity, thus leading to hepatocyte injury, inflammation, and activation of stellate cells, which contribute to liver fibrosis. High-glycemic index foods consumed within a GFD can cause rapid increases in plasma glucose levels, triggering hyperinsulinemia, promoting liver lipogenesis, and inhibiting fatty acid oxidation [16,80]. Insulin resistance involves both the peripheral tissue and the liver, which leads to increased hepatic fat accumulation and inflammation, two critical features of MASLD [81].…”

“…This response then causes progressive liver injury and fibrosis by activating the hepatic stellate cells [87,88]. Mechanisms like the decreased production of short-chain fatty acids (SCFA), an altered bile acid pool, and a decreased activation of the farnesoid X receptor (FXR) in the distal small intestine by bile acids seem to be associated with impaired intestinal barrier function [80,89]. In CD, protective bacteria such as Bifidobacteria, Firmicutes, Lactobacilli, and Streptococceae are found in lower amounts compared to healthy controls, while harmful Gram-negative bacteria such as Bacteroides, Bacterioidetes, Bacteroides fragilis, Prevotella, E. coli, Proteobacteria, Haemophilus, Serratia, and Klebsiella are more prevalent [90][91][92].…”

Nutritional Status and Metabolism in Celiac Disease: Narrative Review

“…The crucial factors here are gluten-free products with a high sugar content, including glucose syrup, starch, and flour derived from rice. This results in a high glycemic index, predisposing individuals on a GFD to the development of insulin resistance [55]. Tortora compared the metabolic status of patients at diagnosis and after 1 year on a GFD [56].…”