Non-Alcoholic Steatohepatitis Occurs in Celiac Disease and is Associated with Cellular Stress

Kälsch, Julia; Bechmann, Lars P.; Manka, Paul; Kahraman, Alişan; Schlattjan, Martin; Marth, Thomas; Rehbehn, Kai-Uwe; Baba, Hideo A.; Canbay, Ali

doi:10.1055/s-0032-1330421

Cited by 28 publications

(10 citation statements)

References 26 publications

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“…Some have speculated that cellular stress induced in CD patients may trigger the onset of NAFLD. [32] Intestinal permeability is increased in CD[33] as well as in NAFLD[17, 34], and SIBO, known to be increased both in CD[20] as well as in NAFLD[17, 18], may alter intestinal permeability. [35] Furthermore, increased intestinal permeability has been suggested as a potential trigger for the development of NASH in patients with hepatic steatosis.…”

Section: Discussionmentioning

confidence: 99%

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease

Reilly

Lebwohl

Hultcrantz

et al. 2015

Journal of Hepatology

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Background and Aims Nonalcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of nonalcoholic fatty liver disease in patients with celiac disease. Methods Population-based cohort study. We compared the risk of nonalcoholic fatty liver disease diagnosed from 1997-2009 in individuals with celiac disease (n=26,816) to matched reference individuals (n=130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of nonalcoholic fatty liver disease. Cox regression estimated hazard ratios for nonalcoholic fatty liver disease were determined. Results During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of nonalcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with nonalcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95%CI=2.0-3.8), with the highest risk estimates seen in children (HR=4.6; 95%CI=2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95%CI=3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR=2.5; 95% CI 1.0-5.9). Conclusion Individuals with celiac disease are at increased risk of nonalcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years beyond diagnosis with celiac disease.

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Section: Discussionmentioning

confidence: 99%

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease

Reilly

Lebwohl

Hultcrantz

et al. 2015

Journal of Hepatology

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“…Serum Vit D is also reduced in patients with non-alcoholic fatty liver disease [25]. Surprisingly, there are multiple studies linking non-alcoholic fatty liver disease to CD [26,27,28]. Recently, it has been shown that Vit D acts as an immunomodulating agent and plays important roles in the pathogenesis of AIDs.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Polyautoimmunity among Patients with Celiac Disease: A Cross-Sectional Survey

et al. 2015

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Aim: To define the prevalence of polyautoimmunity (PAI) among celiac disease (CD) patients and to compare clinical and laboratory features of CD patients with or without PAI in order to determine the risk factors for PAI in CD. Material and Method: Patients diagnosed with CD in our clinic between 2007 and 2014 with at least 1 year of follow-up were retrospectively evaluated. Totally 145 patients were included in the study. Information on patient demographics and laboratory data were obtained from patient records. The study participants were divided into 2 groups. Group 1 was the CD-alone group consisting of patients without any other autoimmune diseases (AIDs), while group 2 was the PAI group consisting of patients with accompanying one or more AIDs. Results: The mean age of 145 CD patients (106 female and 39 male) included in the study was 37.2 ± 12.3 years. Of the 145 patients included, 48 (33.1%) were in the PAI group. When two groups were compared with each other in terms of the demographic features and laboratory data, the following were identified as risk factors for PAI: female gender, family history for AIDs, antigliadin IgG positivity, vitamin D deficiency, antinuclear antibody positivity ≥1/80 titer and having any musculoskeletal disease. Conclusion: To the best of our knowledge, this is one of the largest studies in the literature on CD patients for the PAI prevalence and related risk factors. Identification of the risk factors in early stages is important to explore PAI among CD patients. Larger, prospective studies are warranted about the risk factors and autoimmune characteristics of CD.

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“…In overweight (body mass index, BMI = 25–29.9 kg/m 2 ) and obese (BMI ≥ 30 kg/m 2 ) patients weight reduction by 5%–10% results in a 20%–80% decrease in intrahepatic triglyceride content and serum aminotransferase activity [1,7,8,34,35]. The optimal weight loss goal seems to be 0.5–1.0 kg per week (although some authors suggest higher goals), with particular attention to visceral fat reduction [9,36,37]. In patients with NAFLD, reduction of 5% to 7% of the initial body weight is recommended, while in those with suspected or biopsy-proven NASH, the weight loss goal is higher (7% to 10%) [14].…”

Section: Lifestyle Interventionsmentioning

confidence: 99%

“…About 90% of NAFLD patients present at least one feature of the metabolic syndrome, while the fully symptomatic metabolic syndrome (diagnosed in 33% patients) is a significant risk factor for the progression from NAFL into NASH [4]. In addition, co-existence of other medical conditions, such as hypothyroidism, hypogonadism, obstructive sleep apnea, polycystic ovary syndrome, and celiac disease, may associate with or promote the progress of NAFLD into NASH [5,6,7,8,9]. Intestinal barrier damage and intestinal microbiota imbalance (lower concentration of Bacteroidetes and higher concentration of Firmicutes) may also promote the progression of the disease [10].…”

Section: Introductionmentioning

confidence: 99%

Dietary and Pharmacological Treatment of Nonalcoholic Fatty Liver Disease

Jeznach-Steinhagen

Ostrowska

Czerwonogrodzka–Senczyna

et al. 2019

Medicina

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the developed world. Simple hepatic steatosis is mild, but the coexistence of steatohepatitis (NASH) and fibrosis increases the risk of hepatocellular carcinoma. Proper dietary and pharmacological treatment is essential for preventing NAFLD progression. The first-line treatment should include dietary intervention and increased physical activity. The diet should be based on the food pyramid, with a choice of products with low glycemic index, complex carbohydrates in the form of low-processed cereal products, vegetables, and protein-rich products. Usage of insulin-sensitizing substances, pro- and prebiotics, and vitamins should also be considered. Such a therapeutic process is intended to support both liver disease and obesity-related pathologies, including insulin resistance, diabetes, dyslipidemia, and blood hypertension. In the pharmacological treatment of NAFLD, apart from pioglitazone, there are new classes of antidiabetic drugs that are of value, such as glucagon-like peptide 1 analogs and sodium/glucose cotransporter 2 antagonists, while several other compounds that target different pathogenic pathways are currently being tested in clinical trials. Liver biopsies should only be considered when there is a lack of decline in liver enzymes after 6 months of the abovementioned treatment. Dietary intervention is recommended in all patients with NAFLD, while pharmacological treatment is recommended especially for those with NASH and showing significant fibrosis in a biopsy.

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Non-Alcoholic Steatohepatitis Occurs in Celiac Disease and is Associated with Cellular Stress

Abstract: Stress-induced ligands and apoptosis are induced in CD. Prospective studies need to determine the exact role of cellular stress and apoptosis in the gut-liver axis and the clinical implications to screen for NAFLD in CD patients.

Cited by 28 publications

References 26 publications

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease

Risk Factors for Polyautoimmunity among Patients with Celiac Disease: A Cross-Sectional Survey

Dietary and Pharmacological Treatment of Nonalcoholic Fatty Liver Disease

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