Introduction

Non-alcoholic fatty liver disease (NAFLD) is a common liver condition, and liver biopsy is considered the gold standard to diagnose and stage the disease [1]. However, the risks associated with the invasive procedure limit its widespread use, making noninvasive methods for assessing the severity and progression of fibrosis essential in pediatric NAFLD cohorts [2].

Aims & Methods

To investigate the levels of transforming growth factor-beta 1 (TGF-β1) and glycosaminoglycans (GAGs) in obese children with NAFLD and assess their diagnostic accuracy.
94 children aged 9 to 17 years (average age 12.15 ± 2.51 years) were examined. According to the transient elastography data (FibroScan®502touch, Echosence, France) and body mass index, children were divided into four groups:1 group - 27 obese NAFLD children with fibrosis ≥F1, group 2 - 35 obese NAFLD children without fibrosis, group 3 - 18 obese children without NAFLD and fibrosis. Group 4 (control) comprised 14 children with normal weight without NAFLD and liver fibrosis. Serum transforming growth factor-beta 1 (TGF-β1) levels were evaluated by enzyme-linked immunosorbent assay (ELISA) using the IBL International (Germany) test system, and glycosaminoglycans (GAG) levels were determined spectrophotometrically. ROC analysis was performed for cut-off values calculation.

Results

The highest level of TGF-β1 was found in 1 group children –up to 153.4 (99.7; 189.1) pg/ml, which was significantly higher than in 2 group- 72.4 (53.1; 111.3) pg/ml (p˂0,05), 3 group - 74.0 (50.6; 99.4) pg/ml (p˂0,05) and 4 group - 56.1 (46.0; 77.4) pg/ml (p˂0,05). Moreover, 1 group of children demonstrated increased GAG content up to 4.50 (3.21; 4.60) mmol/L (p˂0,05). ROC analysis revealed that cut-off serum TGF-β1 96.8 pg/ml predicted liver fibrosis in NAFLD children. The area under the curve (AUROC) was 0.787 (p<0.001), the sensitivity of the test was 80.0%, and the specificity was 65.7%. The threshold GAG value for fibrosis was 4.24 mmol/L (sensitivity 70.6%, specificity 69.6%, AUROC 0.743 (p<0.01)).

Conclusion

TGF-β1 and GAG are reliable noninvasive fibrosis markers in children with NAFLD, allowing for their use in liver fibrosis screening.

References

1. Gawrieh S, Harlow KE, Pike F, et al. Relationship of Enhanced Liver Fibrosis Score with Pediatric Nonalcoholic Fatty Liver Disease Histology and Response to Vitamin E or Metformin. J Pediatr. 2021;239:161-167.e5. doi:10.1016/j.jpeds.2021.08.012.
2. Draijer L, Benninga M, Koot B. Pediatric NAFLD: an overview and recent developments in diagnostics and treatment. Expert Rev Gastroenterol Hepatol. 2019;13(5):447-461. doi:10.1080/17474124.2019.1595589

Introduction

Fatigue, defined as “an overwhelming sense of tiredness, lack of energy and feeling of exhaustion” [1] is a frequent complaint in celiac disease. A strict, lifelong gluten free diet is the only established treatment for celiac disease, however its long-term effect on fatigue is unknown.

Aims & Methods

Our aims were to investigate the course of fatigue severity and prevalence in celiac patients from diagnosis to five to seven years on a gluten free diet, and to investigate whether diet adherence, disease activity and selected biochemical markers are associated with fatigue.
We conducted a single-center prospective study in 45 patients with newly diagnosed celiac disease. The primary endpoints were fatigue severity, as measured by the Fatigue Severity Scale (FSS) [2], the fatigue Visual Analog Scale (fVAS) [3], and the Vitality subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36vs) [4]. SF-36vs scores were inverted (100 – SF-36vs = inverted SF-36vs) to ease comparison between the other scales, so that higher scores indicate more fatigue. Clinically relevant fatigue was defined by an FSS score of ≥4, a fVAS score of ≥50, and an inverted SF-36vs score of ≥65. Study visits were performed at the time of diagnosis (Visit 1), after adhering to a gluten free diet for one year (Visit 2) and for five to seven years (Visit 3). Diet adherence was evaluated through urinary gluten immunogenic peptides (GIP) and the Celiac Diet Adherence test (CDAT) [5]. Disease activity was assessed through Celiac Symptom Index (CSI) [6], celiac autoantibodies (anti tissue transglutaminase IgA and deamidated gliadin peptide IgG) and histologic evaluation (Marsh score). Nutritional status was assessed through BMI, hemoglobin, 25-hydroxy vitamin D, cobalamin, ferritin and folic acid levels.

Results

Fatigue severity was significantly reduced from time of diagnosis, for all three instruments (Table 1). Fatigue prevalence rates were significantly decreased from Visit 1 (40-53%) to Visit 3 (27-31%). Fatigue was significantly lower in patients with good adherence compared to patients with poor adherence according to CDAT scores (For FSS p=0.022, fVAS p=0.017, and for inverted SF-36vs p=0.033). There was however no difference in fatigue severity between adherent and nonadherent patients when evaluating adherence through urinary GIP. Fatigue was lower in patients in clinical remission according to CSI scores (for FSS p=0.002, fVAS p=0.004, and for inverted SF-36vs p=0.002), but not associated with autoantibodies or nutritional status. In multiple linear regression analysis, depression was the only independent variable significantly associated with all three fatigue measures at Visit 3, whereas pain was positively associated with inverted SF-36vs scores.

Table 1.

Conclusion

Fatigue remains a frequent complaint in celiac disease even after five to seven years on a gluten free diet. However, fatigue severity is reduced from time of diagnosis. Fatigue was associated with dietary adherence as assessed by CDAT. Disease activity according to CSI was associated with fatigue, whereas nutritional status, autoantibodies and histologic changes were not.

References

1. Krupp, L.B. and D.A. Pollina, Mechanisms and management of fatigue in progressive neurological disorders. Curr Opin Neurol, 1996. 9(6): p. 456-60.
2. Krupp, L.B., et al., The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol, 1989. 46(10): p. 1121-3.
3. Wolfe, F., Michaud K, Pincus T, Preliminary evaluation of a visual analog function scale for use in rheumatoid arthritis. J Rheumatol, 2005. 32(7): p. 1261-6.
4. Ware, J.E., Jr. and C.D. Sherbourne, The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care, 1992. 30(6): p. 473-83.
5. Leffler, D.A., et al., A simple validated gluten-free diet adherence survey for adults with celiac disease. Clin Gastroenterol Hepatol, 2009. 7(5): p. 530-6, 536.e1-2.
6. Leffler, D.A., et al., A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol, 2009. 7(12): p. 1328-34, 1334.e1-3.

Disclosure

Berit Mære Skjellerudsveen: Received lecture honoraria from Takeda for lectures on IBD and pregnancy. This study is partly funded by a grant from the patient organization “The Norwegian Coeliac Society”.

Introduction

Coeliac disease (CeD) is a chronic immune-mediated enteropathy driven by dietary gluten proteins. Previous studies have indicated an increased risk of cardiovascular disease (CVD) in individuals with CeD [1-3]. However, results are inconsistent and specific guidelines on the management of CVD risk and comorbidities for individuals with CeD do not exist. In this study, we aimed to compare the distribution of traditional CVD risk factors in CeD patients and non-CeD controls from a population-based cohort.

Aims & Methods

We performed a CeD screening of 54,541 serum samples by anti-transglutaminase 2 immunoglobulin A and G serology from in total 56,042 adult participants in the fourth wave of the Norwegian Trøndelag Health Study (HUNT4) [4]. All seropositive participants were invited to upper endoscopy with duodenal biopsies to confirm a CeD diagnosis. Seronegative participants with previously diagnosed CeD were identified by linkage to hospital records and the Norwegian Patient Registry. We calculated SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD [5, 6]. The groups “no CeD”, previously diagnosed CeD (“known CeD”) and CeD diagnosed in HUNT4 (“new CeD”), as well as “CeD” (known + new cases) were examined in this study. To compare group characteristics, we used the Wilcoxon rank sum test. Associations between groups and SCORE2(-OP) were assessed using ordinal logistic regression analysis.

Results

468 (0.80%) individuals received a CeD diagnosis in HUNT4, while 309 (0.57%) seronegative individuals had known CeD. Individuals with newly diagnosed CeD were younger, better educated, and had lower blood lipids compared to controls. Individuals with CeD smoked significantly less, had lower BMI and waist-hip-ratio, glycated hemoglobin levels, serum creatinine, and hsCRP levels compared to controls without CeD (n=52,438; p<0.05 for all variables mentioned, see table). We found a significantly lower SCORE2 for CeD cases (n=589) compared to controls (n=39,747; p<0.05). Adjustment for alcohol consumption did not affect group characteristics. A significantly lower SCORE2 was observed in CeD cases also after adjustment for level of education (OR .84, 95% CI .72-.98), high sensitivity C-reactive protein (hsCRP) and serum creatinine (OR .85, 95% CI .78-.99), but not for the combination of all three variables (OR .90, 95% CI .76-1.05).

Conclusion

Individuals with CeD appear to have a lower cardiovascular risk based on traditional risk factors like smoking habits, body fat, diabetes, renal function and inflammation compared to control individuals without CeD. In line with that, SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD were lower in individuals with CeD.

References

1. Bathrellou, E., M.D. Kontogianni, and D.B. Panagiotakos, Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review. Maturitas, 2018. 112: p. 29-33.
2. Ludvigsson, J.F., et al., Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation, 2011. 123(5): p. 483-90.
3. Figtree, G.A., et al., Mortality in STEMI patients without standard modifiable risk factors: a sex-disaggregated analysis of SWEDEHEART registry data. Lancet, 2021. 397(10279): p. 1085-1094.
4. Asvold, B.O., et al., Cohort Profile Update: The HUNT Study, Norway. Int J Epidemiol, 2023. 52(1): p. e80-e91.
5. SCORE2 working group and ESC Cardiovascular risk collaboration, SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J, 2021. 42(25): p. 2439-2454.
6. SCORE2-OP working group and ESC Cardiovascular risk collaboration, SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions. European Heart Journal, 2021. 42(25): p. 2455-2467.

Disclosure

None.

Introduction

Individuals with coeliac disease (CeD) commonly complain of persistent symptoms despite adhering to a gluten free diet (GFD). We analysed baseline data from the prospective pseudonymized German CeD Registry to identify factors associated with ongoing complaints.

Aims & Methods

​​​​​​After written informed consent, participants self-reported demographic, clinical and healthcare related information at baseline and yearly thereafter. Symptoms before diagnosis and during the four weeks prior to completing the baseline questionnaire were retrospectively assessed. Factors associated with symptoms after at least one year of gluten-free diet (GFD) were evaluated by multivariate logistic regression.

Results

From 11/2019 to 10/2021, 2164 participants provided baseline data: 78% were female, median age 36 years (range 1.1 to 93.2), median time since diagnosis 6.3 years (0 to 58.7), and median diagnostic delay (time from first symptom to diagnosis) 2.2 years (0 to 64.8). Most common symptoms before diagnosis included abdominal pain (83%), bloating (82%), fatigue (78%), and diarrhoea (71%). Individuals diagnosed in adulthood were more symptomatic compared to paediatric patients. Although 93.4% of participants reported improvement after diagnosis, a substantial proportion of those keeping a GFD >1year (n=1861, 86% of cohort) had ongoing symptoms. Factors associated with regularly experiencing above symptoms included female gender, having the same symptom before diagnosis, feeling insufficiently informed by their physician about CeD and implications for their daily life, and age at diagnosis (per decade), but not time since diagnosis (table).

Conclusion

Our findings revealed deficits in awareness, the diagnostic process, and post-diagnostic care. In this large cohort of patients with CeD we identified factors associated with persistence of symptoms despite keeping a GFD for at least one years. Early diagnosis, providing comprehensive education after confirmed diagnosis, and ensuring strict dietary adherence are pivotal for symptom resolution. A population-based mass-screening for CeD in childhood should be further explored. Implementing a multifaceted approach will enhance care for individuals with CeD and ultimately improve long-term health and well-being.

Introduction

The part of NAFLD children has a progressive sub-phenotype known as nonalcoholic steatohepatitis (NASH), characterized by the ability to develop advanced fibrosis, cirrhosis, and end-stage liver disease [1]. Given the high prevalence of NAFLD and invasiveness of the liver biopsy, there is an essential need to find safe non-invasive modalities to determine liver fibrosis in children [2].

Aims & Methods

To investigate serum fibrosis markers in obese children with non-alcoholic fatty liver disease (NAFLD) depending on the presence of liver fibrosis.
94 children aged 9 to 17 years (average age 12.15 ± 2.51 years) were included in the study. According to the transient elastography data (FibroScan®502touch, Echosence, France) and body mass index, children were divided into four groups: group 1 - 27 obese NAFLD children with fibrosis ≥F1, group 2 - 35 obese NAFLD children without fibrosis, group 3 - 18 obese children without NAFLD and fibrosis. Group 4 (control) consisted of 14 children with normal weight without NAFLD and liver fibrosis. The serum levels of vascular endothelial growth factor (VEGF) (Wuhan Fine Biotech Co Ltd, China), transforming growth factor-beta 1 (TGF-β1) (IBL International, Germany), cytokeratin-18 (CK-18) (IDL Biotech AB, Sweden) were determined by enzyme-linked immunosorbent assay (ELISA). Serum content of hydroxyproline free (HPf) and hydroxyproline protein-bound (HPp/b) according to Osadchuk and glycosaminoglycans (GAG) according to Rimington were evaluated.

Results

In 1 group children, a significant increase in the median level of CK-18 (in 2.2 times, p<0.05), VEGF (in 2.4 times, p<0.05), and TGF-β1 (in 2.7 times, p<0.05) was found compared to 4 group children. Moreover, CK-18 level was significantly higher in 1 group of patients compared to 2 group (in 1.4 times, p<0.05) and 3 group (in 1.8 times, p<0.05). In all group children, an increase in the serum HPp/b content was found: in 1 group - in 1.2 times (p<0.01), in 2 group - in 1.2 times (p<0.05), in 3 group - in 1.3 times (p<0.05) compared to 4 group. The changes in the content of hydroxyproline led to an increase in the HPp/b/HPf ratio in all groups: 1.4 times (p<0.01) in 1 and 2 groups, in 1.3 times (p<0.01) in 3 group. Also, in 1 group of children median GAG level was increased by 1.3 times (p<0.001).
In children with NAFLD HPf content negatively correlated with CAP (r= - 0.408; p<0.01), CK-18 (r=-0.469; p<0.01), the ratio HPp/b/HPf positively correlated with CAP (r=0.307; p<0.05). CK-18 positively correlated with fibrosis degree (according to METAVIR) (r=0.468; p=0.008) and liver steatosis degree (r=0.357; p=0.048). A positive correlation was also found between VEGF levels and the degree of liver fibrosis (r=0.372, p=0.036).

Conclusion

Serum levels of VEGF, TGF-β1, HPp/b, and GAG were significantly elevated in children with non-alcoholic fatty liver fibrosis. Assessment of these parameters may be useful for early diagnosis of liver fibrosis in children with NAFLD.

References

1. Schwimmer JB, Johnson JS, Angeles JE, et al. Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019;157(4):1109-1122. doi:10.1053/j.gastro.2019.06.028.
2. Alkhouri N. Putting it all together: Noninvasive diagnosis of fibrosis in nonalcoholic fatty liver disease in adults and children. Clin Liver Dis (Hoboken). 2017;9(6):134-137. Published 2017 Jun 29. doi:10.1002/cld.636

Introduction

Celiac disease is an autoimmune disorder where the intake of gluten (a protein found in wheat, barley, and rye) causes damage to the small intestine and impairs nutrient absorption. Studies have shown that individuals with celiac disease have reduced quality of life and higher levels of anxiety and depression. However, this has not been studied in the general population, among individuals with newly discovered, untreated celiac disease.

Aims & Methods

The aim of this study was to investigate anxiety, depression, mental health, and subjective well-being in individuals with newly diagnosed and untreated celiac disease, compared with the general population. This study used data from the fourth Trøndelag health study (HUNT4), conducted between 2017 and 2019 with over 56,000 adult participants from 20 years of age. Previously undiagnosed celiac disease was identified among the participants by analyses of blood samples from all participants and confirmed with endoscopy and duodenal biopsies. The participants in HUNT4 also answered questionnaires measuring levels of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS), mental distress using the Cohort of Norway Medical Health Index (Conor-MHI), and subjective well-being using a three-part questionnaire. Differences in mental health among individuals with newly diagnosed celiac disease and the remaining HUNT4 participants were compared.

Results

Celiac disease was diagnosed in 454 HUNT4 participants by March 2022. The celiac group had a lower median age (53 vs. 56 years) compared to the remaining HUNT4 population. The celiac group had significantly lower mean scores on the HADS anxiety subscale (4.0 vs. 4.4), depression subscale (2.8 vs. 3.3), and total scale (6.8 vs. 7.7) compared to the reference population. On the CONOR-MHI scale, the celiac disease group had a lower total mean score (1.4 vs. 1.5) with lower scores in the categories of "secure and calm", "irritable", "happy and optimistic", "sad/depressed", and "lonely" compared to the reference population. Finally, the celiac disease group had a lower mean score on the question “Do you feel mostly strong and clear, or tired and fatigued?” (3.3 vs. 3.4) and a higher mean score on the question “How is your health now?” (3.0 vs. 2.9) compared to the reference population. No significant difference was observed in the HADS or CONOR-MHI scores by Marsh grades at diagnosis among the celiac disease group.

Conclusion

The study suggests that individuals with undiagnosed celiac disease have lower levels of anxiety, depression, and mental distress compared to the general population, while also reporting slightly better subjective well-being. These findings contradict other studies on psychological health in celiac disease.

Disclosure

No con