Autoimmune Polyendocrine Syndromes in Adult Italian Celiac Disease Patients.

Celiac disease (CD) is frequently associated with other autoimmune disorders. Different studies have explored the association between CD and single autoimmune endocrine disease (AED), especially autoimmune thyroiditis (AIT) and type-1 diabetes mellitus (T1DM). Data about CD as a component of autoimmune polyendocrine syndrome (APS) are scant. We analyzed a large dataset including prospectively collected data from 920 consecutive adult CD patients diagnosed in a third-level Italian institution in the 2013-2023 period, The prevalence of isolated autoimmune endocrine diseases and APS were collected. A total of 262 (28.5%) CD patients had at least one associated AED, with AIT (n = 223, 24.2%) and T1DM (n = 27, 2.9%) being the most frequent conditions. In most cases (n = 173, 66%), AEDs were diagnosed after CD. Thirteen patients (1.4%) had at least two of the requested three endocrinopathies, satisfying the diagnosis of type 2 APS. APS-2 is a rare but not exceptional occurrence among Italian CD patients, underscoring the intricate and multifaceted nature of autoimmune disorders. Periodic evaluations of thyroid function and glycaemia should be recommended after the diagnosis of CD together with testing for autoantibodies that may be helpful in assessing disease risk before disease onset. Likewise, implementation of a systematic screening for CD amongst T1DM and other autoimmune endocrine diseases are paramount.

Evolution of bone densitometry parameters and risk of fracture in coeliac disease: a 10-year perspective.

BACKGROUND: Metabolic bone disease is frequently found in patients with coeliac disease (CD). Despite its high prevalence, international guidelines are partially discordant about its management due to the lack of long-term data. METHODS: We retrospectively evaluated a large dataset of prospectively collected data of CD patients assessing the variation of DXA parameters and estimated fracture risk according to the FRAX® score in a 10-year follow-up. Incident fractures are reported, and the predictive ability of the FRAX® score is verified. RESULTS: We identified 107 patients with low bone density (BMD) at the diagnosis of CD and a 10-year follow-up. After improving at the first follow-up, T-scores slowly reduced over time but with no clinically relevant differences between the first and last examination (lumbar spine: from - 2.07 to - 2.07, p = 1.000; femoral neck: from - 1.37 to - 1.55, p = 0.006). Patients with osteoporosis at the index measurement had more marked fluctuations than those with osteopenia; the latter group also showed minimal modifications of the FRAX® score over time. Six incident major fragility fractures occurred, with a good predictive ability of the FRAX® (AUC 0.826). CONCLUSION: Adult CD patients with osteopenia and no risk factors had substantially stable DXA parameters and fracture risk during a 10-year follow-up. A dilated interval between follow-up DXA for these patients could be considered to reduce diagnosis-related time and costs, maintaining a 2-year interval for patients with osteoporosis or risk factors.

Hepatic Steatosis in Patients with Celiac Disease: The Role of Packaged Gluten-Free Foods.

Background: An increased risk of nonalcoholic fatty liver disease (NAFLD) in patients with celiac disease (CD) adhering to a gluten-free diet (GFD) was recently reported. The nutritional composition of packaged gluten-free foods (PGFF) has been proposed as a possible cause. This hypothesis has not been investigated further, since a systematic structural nutritional interview for all patients would be problematic in clinical practice. Methods: We administered a simple questionnaire based on a Recency, Frequency, and Monetary value (RFM) analysis (a cornerstone of direct marketing segmentation) to consecutive CD patients on a GFD for >6 months and verified its association with NAFLD. Subgroup analyses were performed to understand whether specific patterns of PGFF consumption were significantly associated with NAFLD. Results: Amongst 147 patients (female 82%, median age 42 years), 45 (30.6%) had NAFLD. Total RFM score (adjusted odds ratio = 1.223, 95% CI: 1.059−1.413, p = 0.006), body mass index, and total cholesterol and triglycerides were independently related to NAFLD, and "Bread and bakery" (p = 0.002), "salty convenience" (p = 0.005), and "sweet convenience" (p = 0.049) products were significantly related with NAFLD. Also, questions about the number of purchased PGFF in the last month (monetary value) and different categories of PGFF consumed in the last week (recency) were particularly able to identify NAFLD patients. Conclusions: The specific GFD dietary habits of CD patients were correlated with the degree of risk of NAFLD. Information was obtained through a questionnaire which could be used in clinical practice to favor a patient-tailored approach and in future studies to verify the reproducibility of our results in different geographical areas.

Risk of Drop-Out from Follow-Up Evaluations for Celiac Disease: Is It Similar for All Patients?

Background: Celiac disease (CD) follow-up is a relatively underevaluated topic. However, correct adherence to follow-up procedures is central to the early recognition of complicated CD and other conditions typically associated with CD. Establishing whether patients at increased risk of complications follow clinicians' recommendations has multiple repercussions. Methods: We retrospectively analyzed the records of patients consecutively diagnosed with CD in our outpatient clinic between January 2004 and October 2017 to investigate the factors associated with drop-out from follow-up procedures. Results: Among the 578 patients analyzed, 40 (6.9%) dropped out during the first six months and 272 (50.6%) during the observation period. The median time to drop-out was 7.4 years (95% confidence interval: 6.8−8.0). No factors were associated with early drop-out. Instead, age at diagnosis >40 years (40−59 years, p < 0.001; ≥60 years, p = 0.048) and classical clinical presentation (p = 0.016) were significantly associated with a lower risk of later drop-out. Conclusions: Patients at increased risk of complicated CD are more compliant with follow-up procedures than patients at lower risk, despite being prescribed the same controls. These results indirectly support the hypothesis of tailored follow-up strategies, differentiated according to the risk of complications.

Current guidelines for the management of celiac disease: A systematic review with comparative analysis.

BACKGROUND: Wheat and other gluten-containing grains are widely consumed, providing approximately 50% of the caloric intake in both industrialised and developing countries. The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence. This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media. However, in recent years, the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease (CD) from obscurity to global prominence. These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD. Different scientific societies, mainly from Europe and America, have proposed guidelines based on CD's most recent evidence. AIM: To identify the most recent scientific guidelines on CD, aiming to find and critically analyse the main differences. METHODS: We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language. PubMed was lastly accessed on 1 March 2021. RESULTS: We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions. Differences were noted in the possibility of a no-biopsy diagnosis, HLA testing, follow-up protocols, and procedures. CONCLUSION: We found a relatively high concordance between the guidelines for CD. Important modifications have occurred in the last years, especially about the possibility of a no-biopsy diagnosis in children. Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.

Prognosis of Single Early-Stage Hepatocellular Carcinoma (HCC) with CEUS Inconclusive Imaging (LI-RADS LR-3 and LR-4) Is No Better than Typical HCC (LR-5).

The American College of Radiology (ACR) released the Liver Imaging Report and Data System (LI-RADS) scheme, which categorizes hepatic nodules in risk classes from LR-1 to LR-5 (according to the degree of risk to be HCC) and LR-M (probable malignancy not specific for HCC). The aim of this study was to test whether HCC with different LR patterns on CEUS have different overall survival (OS) and recurrence-free survival (RFS). We retrospectively enrolled 167 patients with the first definitive diagnosis of single HCC (by using CT/MRI or histological techniques if CT/MRI were inconclusive) for whom CEUS examination was available. The median size of HCC lesions was 2.2 cm (range 1.0-7.2 cm). According to CEUS LI-RADS classification, 28 patients were in LR-3, 48 in LR-4, 83 in LR-5, and 8 in LR-M. Patient liver function and nodule characteristics were not statistically different between CEUS LI-RADS classes. Using univariate analysis, CEUS LI-RADS class was not found to be a predictor of survival (p = 0.347). In conclusion, HCC showing the CEUS LI-RADS classes LR-3 and LR-4 have no better clinical outcome than typical HCC. Such data support the EASL policy, aimed at conclusive diagnostic investigations of indeterminate nodules up to obtaining histological proof to avoid leaving aggressive HCC not timely treated.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; P = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; P = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; P = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; P = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; P = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; P = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; P = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021 Online supplemental material is available for this article.