Maternal gestational hypertension, smoking and pre-eclampsia are associated with metabolic dysfunction-associated fatty liver disease in overweight offspring.

INTRODUCTION: Due to a steep increase in obesity, metabolic dysfunction-associated fatty liver disease (MAFLD) has also become the most common chronic hepatic condition among children and adolescents. Various maternal and pregnancy-related factors have also been implicated in the development of MAFLD, but human studies remain scarce. MATERIAL AND METHODS: Comprehensive data of 460 overweight or obese children aged 2-16 years were collected and combined with data on selected maternal and pregnancy-related factors for a case-control study. MALFD was defined as alanine aminotransferase >2× upper limit of normal. Children with and without MAFLD were compared regarding to the study variables and multivariable regression analysis was utilized. RESULTS: Median age of the study children was 11.8 (quartiles 9.1-14.2) years; 44% were girls and 17.8% had MAFLD. Children with MAFLD were older (12.7 vs. 11.6 years, p = 0.002), while the groups did not differ age-standardized body mass index (BMI-SDS) or gender. Factors associated with MAFLD in a multivariable model considering also the offspring's present BMI-SDS, sex, and maternal prepregnancy overweight, were child's older age (odds ratio [OR] 1.16, 95% confidence interval [CI]: 1.06-1.28), maternal gestational smoking (OR 2.01, 95% CI: 1.16-3.47), gestational hypertension (OR 3.44, 95% CI: 1.08-11.0) and pre-eclampsia (OR 2.93, 95% CI: 1.15-7.45). There was no significant association between MAFLD and maternal BMI, birth anthropometrics or perinatal complications. CONCLUSIONS: Maternal smoking, gestational hypertension and pre-eclampsia were associated with MAFLD among overweight or obese children. Further prospective studies are needed to verify causal relationships.

Measurement practices of alanine aminotransferase in children: Temporal changes and etiology for increased values.

Data on alanine aminotransferase (ALT) measurement practices and diagnoses associated with increased values are limited. We evaluated these issues by collecting ALT measurements from 1- to 16-year-old patients investigated in 1992-2018 in a tertiary center. Diagnoses were gathered in 2008-2018. Altogether 145,092 measurements from 28,118 children were taken 42% undergoing repeated testing. Testing increased from 21/1000 to 81/1000 children and the prevalence of elevated values fluctuated between 18% and 26%. An increase was seen especially in emergency care and departments of rheumatology, gastroenterology, hemato-oncology, and psychiatry. Common acute causes associated with elevated ALT were infections (45%), hemato-oncologic conditions (17%), and external reasons (13%), whereas autoimmune diseases (28%), psychiatric conditions (14%), and metabolic-dysfunction associated steatotic liver disease (10%) were common chronic causes. In conclusion, ALT testing increased 3.9-fold while the proportion of increased values remained stable, indicating that increased testing was justified. However, in some departments the testing efficiency was low.

Alanine aminotransferase cutoffs for the pediatric fatty liver disease: Major impact of the reference population.

OBJECTIVES AND STUDY: The often-recommended alanine aminotransferase (ALT) cutoffs (girls 21 U/l, boys 25 U/l) are based on a NHANES cohort. A novel concept of metabolic dysfunction associated steatotic liver disease (MASLD) emphasizes the role of ALT. We tested the prevalence of increased ALT and MASLD in children with overweight or obesity applying population-based and NHANES-based cut-offs. METHODS: Six- to seventeen-year-old children underwent data collection in a prospective Physical Activity and Nutrition in Children (PANIC) study. ALT 95th percentiles were calculated from 1167 separate measurements considering various confounders. Test cohort comprised 1044 children with overweight/obesity. RESULTS: ALT values increased at puberty onset (p = 0.031) and correlated negatively with age in girls (r = -0.222, p < 0.001). Particularly overall and central obesity increased ALT, whereas underweight or metabolic abnormalities had smaller effect. After applying the tested exclusions, the age-related ALT 95th percentiles were 24-29 U/l for girls and 29-32 U/l for boys. In 6-8-year-old children with overweight/obesity, the prevalence of increased ALT and MASLD were 21.6% and 2.4% with age-specific PANIC cutoffs. In older children, when NHANES-based cutoffs were used, there was a trend for higher prevalence of increased ALT and MASLD in all age groups for both sexes, reaching significance for increased ALT in 12-16-year-old boys (NHANES 63.5%, 95% confidence interval [CI]: 56.4%-70.0% vs. PANIC 47.1%, 95% CI [40.1%-54.2%]) and 9-11-year-old girls (60.0% [49.4%-69.8%] vs. 31.8% [22.8%-42.3%]), respectively. Increased ALT/MASLD were more common in boys than in girls, and in boys these increased with age, whereas in girls these peaked at age 9-12 years. CONCLUSION: A reference population impacts on the prevalence of increased ALT and MASLD. Considering this help optimizing screening while avoiding unnecessary investigations and surveillance. The prospective part of this study is registered in clinicaltrials.gov; identifier NCT01803776.

Celiac Disease Affects 1% of Global Population-Who Will Manage All These Patients? What Are Criteria to Prioritize Along Risk for Complications?

Celiac disease is a common gastrointestinal condition with an estimated global prevalence of up to 1%. Adequate long-term surveillance of patients is imperative to ensure strict adherence to treatment with a gluten-free diet and the ensuing clinical and histologic recovery. Traditionally, this has been accomplished by means of regular on-site attendance at specialist health care facilities, accompanied for most patients by follow-up endoscopic and laboratory tests. However, the rapidly increasing prevalence of celiac disease and the limited health care resources challenge the current centralized and nonindividualized follow-up strategies. The improved noninvasive surveillance tools and online health care services are further changing the landscape of celiac disease management. There is a clear need for more personalized and on-demand follow-up based on early treatment response and patient-related factors associated with long-term prognosis. Additional scientific evidence on the optimal implementation of follow-up for pediatric and adulthood celiac disease is nevertheless called for.

Measured levels of positive transglutaminase 2 antibodies are not associated with presentation or incidental endoscopic findings at celiac disease diagnosis.

OBJECTIVES: It has been suggested that celiac disease could be diagnosed non-invasively in adults with transglutaminase antibody (TGA) levels >10x upper limit of normal (ULN). It is, however, unclear if high values signify more advanced disease and higher risk of co-morbidities. We investigated the association between the TGA levels, clinical characteristics and non-celiac endoscopic findings. METHODS: Medical data on 450 celiac disease patients at diagnosis were collected. They were further divided into those with high positive (>10x ULN, n = 164), moderately positive (1-10x ULN, n = 219), and negative (n = 67) TGA. RESULTS: Median age of patients was 50 years and 60% were women. Patients with negative TGA were older (median age 58 vs. 51 vs. 46 years respectively, p = 0.002) and had more often weight loss (27% vs. 10% vs. 9%, p < 0.001) and abdominal pain or dyspepsia (40% vs 27% vs. 22%, p = 0.017) than did those with moderately positive/high TGA. The groups did not differ in sex, BMI, or other symptoms. Major endoscopic findings included one esophageal adenocarcinoma presenting with dysphagia, six esophagitis, three gastric ulcers, and 39 H. Pylori or other active gastritis. High, moderately positive or negative TGA levels were not associated with these findings in crude or age-adjusted analyses. CONCLUSIONS: Presentation was similar in patients with moderate or high levels of TGA, whereas patients with negative TGA were different. The level of TGA was not associated with incidental endoscopic findings and the only malignancy presented with an alarm symptom atypical to celiac disease.

Trends in the prevalence rates and predictive factors of coeliac disease: A long-term nationwide follow-up study.

BACKGROUND: The prevalence of coeliac disease doubled in Finland from 1980 to 2000. AIMS: To investigate whether this increase is continuing and if there are specific patient-related factors predicting the development of coeliac disease at a population level. METHODS: We elicited comprehensive health data in the nationwide Health 2000 and Health 2011 surveys. Serum samples were taken for the measurement of tissue transglutaminase antibodies (TGA); subjects who were seropositive were tested for endomysial antibodies (EmA). Coeliac disease was defined either as a reported diagnosis or as positive TGA and EmA. The surveys comprised, respectively, 6379 and 4056 individuals, forming representative samples for 2,946,057 and 2,079,438 Finnish adults. Altogether 3254 individuals participating in both surveys comprised a prospective follow-up cohort. RESULTS: Prevalence of coeliac disease was 2.12% in 2000 and 2.40% in 2011 (p = 0.156). In the prospective cohort, 16 out of the 3254 (0.49%) subjects developed coeliac disease during follow-up from 2000 to 2011, with an annual incidence rate of 45 per 100,000 persons. Positive TGA without EmA (OR: 133, 95% CI: 30.3-584), TGA values in the upper normal range (51.1, 16.0-163), and after adjusting for TGA, previous autoimmune co-morbidity (8.39, 4.98-35.9) in 2000 increased the likelihood of subsequent coeliac disease. CONCLUSIONS: The nationwide prevalence of coeliac disease kept on rising from 2.12% in 2000 to 2.40% in 2011 in Finland. Positive TGA without EmA, TGA titres in the upper normal range and a pre-existing autoimmune disease predisposed to coeliac disease during the 10-year follow-up.

Associations of dietary patterns between age 9 and 24 months with risk of celiac disease autoimmunity and celiac disease among children at increased risk.

BACKGROUND: Higher gluten intake in childhood is associated with increased incidence of celiac disease autoimmunity (CDA) and celiac disease. It remains to be studied whether different dietary patterns independent of gluten intake contribute to the incidence. OBJECTIVES: This study aimed to explore associations of dietary patterns by age 2 y with risk of CDA and celiac disease in genetically susceptible children. METHODS: Data was used from 6726 participants at genetic risk of type 1 diabetes and celiac disease enrolled in the observational cohort, The Environmental Determinants of Diabetes in the Young (TEDDY) study. Children were annually screened for tissue transglutaminase autoantibodies (tTGAs) from age 2 y. Principal component analysis extracted dietary patterns, based on intake of 27 food groups assessed by 3-d food records at age 9 to 24 mo. The primary outcome was CDA (i.e., persistently tTGA-positive in at least 2 consecutive samples), and the secondary outcome was celiac disease. During follow-up to mean age 11.0 (standard deviation 3.6) y, 1296 (19.3%) children developed CDA, and 529 (7.9%) were diagnosed with celiac disease. Associations of adherence to dietary patterns (per 5-unit increase) with the study outcomes were estimated by Cox regression models adjusted for risk factors including gluten intake. RESULTS: At age 9 mo, a dietary pattern higher in the food groups vegetable fats and milk was associated with reduced risk of CDA (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79, 0.98; P = 0.02). At 24 mo, a dietary pattern higher in the food groups wheat, vegetable fats, and juices, and lower in milk, meat, and oats at age 24 mo was associated with increased risk of CDA (HR: 1.18; 95% CI: 1.05, 1.33; P < 0.001) and celiac disease (HR: 1.24; 95% CI: 1.03, 1.50; P = 0.03). CONCLUSIONS: Dietary patterns in early childhood are associated with risk of CDA and celiac disease in genetically predisposed children, independent of gluten intake.

Prevalence of vomiting and nausea and associated factors after chronic and acute gluten exposure in celiac disease.

BACKGROUND: Vomiting and nausea seem to be relatively specific symptoms related to gluten ingestion in treated celiac disease. However, the overall prevalence and associated factors of these symptoms after chronic gluten exposure at celiac disease diagnosis and acute re-exposure during gluten challenge remain obscure. METHODS: Medical data on 815 adult celiac disease patients were collected at diagnosis from the medical records and through supplementary interviews. An additional 74 patients underwent a three-day (10 g/day) gluten challenge (wheat, barley, rye or a combination of the three grains) while in remission. Prevalence of vomiting/nausea and associated factors were evaluated in both cohorts. A literature review was conducted to summarize earlier studies. RESULTS: Twenty-eight (3%) patients presented with vomiting at diagnosis. They were less often screen-detected and suffered from extra-intestinal symptoms, and had more often abdominal pain (71% vs. 49%, p = 0.021), diarrhea (61% vs. 40%, p = 0.031), weight loss (36% vs. 17%, p = 0.019) and childhood symptoms (61% vs. 33%, p = 0.002) than those without vomiting (n = 787). The groups were comparable in other clinical-demographic data and in genetic, serological, and histological findings. Short-term gluten challenge provoked vomiting/nausea in 14/74 (19%) patients. They consumed gluten-free oats less often than those without these symptoms (64% vs. 92%, p = 0.017), whereas the groups did not differ in clinical-demographic features at diagnosis, presence of comorbidities, duration of gluten-free diet, or in other symptoms or grain used ingested during the challenge. According to the literature, prevalence of vomiting/nausea at celiac disease diagnosis has varied 3-46% and during gluten challenge 13-61%. CONCLUSIONS: In chronic gluten exposure at celiac disease diagnosis, vomiting was associated with other gastrointestinal symptoms and onset of symptoms already in childhood, whereas regular consumption of oats may increase the tolerance against vomiting/nausea after acute re-exposure in treated celiac disease.

Prevalence and associated factors of metabolic-associated fatty liver disease in overweight Finnish children and adolescents.

Introduction: Data on the prevalence of pediatric fatty liver disease remain limited, partly due to challenges in diagnosis. A novel concept of metabolic-associated fatty liver disease (MAFLD) makes it possible to establish the diagnosis in overweight children with sufficiently elevated alanine aminotransferase (ALT). We investigated the prevalence, risk factors, and metabolic co-morbidities of MAFLD in a large group of overweight children. Methods: Data on 703 patients aged 2-16 years examined due to overweight in different levels of healthcare in 2002-2020 were collected retrospectively from patient records. MAFLD was here defined as ALT >2x reference (>44 U/l in girls and >50 U/l in boys) in overweight children according to recently updated definition. Patients with MAFLD and without it were compared, and subgroup analyses were conducted among boys and girls. Results: Median age was 11.5 years, and 43% were girls. Altogether 11% were overweight, 42% obese and 47% severely obese. Abnormal glucose metabolism was present in 44%, dyslipidemia in 51%, hypertension in 48% and type 2 diabetes (T2D) in 2%. MAFLD prevalence varied between 14-20% in examined years without significant change (p=0.878). The pooled prevalence over the years was 15% (boys 18%, girls 11%; p=0.018), peaking in girls at early puberty and increasing in boys with age and puberty. Associated factors in boys were T2D (OR 7.55, 95% CI 1.23-46.2), postpubertal stage (5.39, 2.26-12.8), increased fasting insulin (3.20, 1.44-7.10), hypertriglyceridemia (2.97, 1.67-5.30), hyperglycemia (2.88, 1.64-5.07), decreased high-density lipoprotein (HDL) cholesterol (2.16, 1.18-3.99), older age (1.28, 1.15-1.42) and higher body-mass-index (1.01, 1.05-1.15), and in girls T2D (18.1, 3.16-103), hypertriglyceridemia (4.28, 1.99-9.21), and decreased HDL (4.06, 1.87-8.79). Conclusion: Prevalence of MAFLD was 15%, with no statistically significant increase in the 2000s. The condition was associated in general with male gender, puberty stage and disturbances in glucose and lipid metabolism, and higher age and BMI in boys.

The role of gluten challenge in the diagnosis of celiac disease: a review.

INTRODUCTION: Duodenal biopsy is the gold standard in the diagnosis of celiac disease, with increasing utilization of serology. A gluten challenge may be required, for example, when dietary gluten reduction precedes appropriate diagnostic evaluations. Evidence on the best challenge protocol is currently sparse. Pharmaceutical trials in recent years may have provided new insights into the challenge and advanced the development of novel sensitive histological and immunological methods. AREAS COVERED: This review outlines the current perspectives on the use of gluten challenge in the diagnosis of celiac disease and explores future directions in this area. EXPERT OPINION: Comprehensive elimination of celiac disease before dietary gluten restriction is essential to avoid diagnostic uncertainties. Gluten challenge continues to have an important role in certain clinical scenarios, although it is important to understand its limitations in the diagnostic evaluation. The evidence so far permits no unequivocal recommendation considering the timing, duration, and amount of gluten used in the challenge. Thus, these decisions should be made on a case-by-case basis. Further studies with more standardized protocols and outcome measures are called for. In the future novel immunological methods may help to shorten or even avoid gluten challenge.

Gluten-free diet adherence in children with screening-detected celiac disease using a prospective birth cohort study.

BACKGROUND: Celiac disease has an increasing incidence worldwide and is treated with lifelong adherence to a gluten-free diet. We aimed to describe gluten-free diet adherence rates in children with screening-identified celiac disease, determine adherence-related factors, and compare adherence to food records in a multinational prospective birth cohort study. METHODS: Children in The Environmental Determinants of Diabetes in the Young study with celiac disease were included. Subjects had at least annual measurement of adherence (parent-report) and completed 3-day food records. Descriptive statistics, t-tests, Kruskal-Wallis tests and multivariable logistic and linear regression were employed. RESULTS: Two hundred ninety (73%) and 199 (67%) of subjects were always adherent to a gluten-free diet at 2 and 5 years post celiac disease diagnosis respectively. The percentage of children with variable adherence increased from 1% at 2 years to 15% at 5 years. Children with a first-degree relative with celiac disease were more likely to be adherent to the gluten-free diet. Gluten intake on food records could not differentiate adherent from nonadherent subjects. Adherent children from the United States had more gluten intake based on food records than European children (P < .001 and P = .007 at 2 and 5 years respectively). CONCLUSION: Approximately three-quarters of children with screening-identified celiac disease remain strictly adherent to a gluten-free diet over time. There are no identifiable features associated with adherence aside from having a first-degree relative with celiac disease. Despite good parent-reported adherence, children from the United States have more gluten intake when assessed by food records. Studies on markers of gluten-free diet adherence, sources of gluten exposure (particularly in the United States), and effects of adherence on mucosal healing are needed.

Incidence of Pediatric Celiac Disease Varies by Region.

INTRODUCTION: The Environmental Determinants of Diabetes in the Young study follows an HLA risk selected birth cohort for celiac disease (CD) development using a uniform protocol. Children under investigation come from 6 different regions within Europe and the United States. Our aim was to identify regional differences in CD autoimmunity and CD cumulative incidence for children born between 2004 and 2010. METHODS: Children (n = 6,628) with DQ2.5 and/or DQ8.1 were enrolled prospectively from birth in Georgia, Washington, Colorado, Finland, Germany, and Sweden. Children underwent periodic study screening for tissue transglutaminase antibodies and then CD evaluation per clinical care. Population-specific estimates were calculated by weighting the study-specific cumulative incidence with the population-specific haplogenotype frequencies obtained from large stem cell registries from each site. RESULTS: Individual haplogenotype risks for CD autoimmunity and CD varied by region and affected the cumulative incidence within that region. The CD incidence by age 10 years was highest in Swedish children at 3%. Within the United States, the incidence by age 10 years in Colorado was 2.4%. In the model adjusted for HLA, sex, and family history, Colorado children had a 2.5-fold higher risk of CD compared to Washington. Likewise, Swedish children had a 1.4-fold and 1.8-fold higher risk of CD compared with those in Finland and Germany, respectively. DISCUSSION: There is high regional variability in cumulative incidence of CD, which suggests differential environmental, genetic, and epigenetic influences even within the United States. The overall high incidence warrants a low threshold for screening and further research on region-specific CD triggers.

Association of concomitant autoimmunity with the disease features and long-term treatment and health outcomes in Celiac disease.

Background: Celiac disease (CeD) is often accompanied by other autoimmune diseases (AID). However, the association of co-existing autoimmunity with the presentation and treatment success in CeD is unclear. We investigated these issues with a large and well-defined cohort of Finnish patients. Methods: Adult CeD patients (n = 806) were collected from multiple heath care sites via nationwide recruitment. They were interviewed, underwent measurement of CeD autoantibodies, and filled out questionnaires to ascertain quality of life (PGWB) and gastrointestinal symptoms (GSRS) after a median of 9.7 years on a gluten-free diet. Data were supplemented retrospectively from patient records. The results were compared between CeD patients with and without a coexisting AID. Results: Altogether 185 patients had CeD+AID and 621 had CeD only. At CeD diagnosis, patients with CeD+AID were older (median 42 vs. 36 years, p = 0.010) and had more joint symptoms (9.1 vs. 4.2%, p = 0.011), whereas the groups were comparable in sex, family history of CeD, other presenting symptoms, proportion of screen-detected subjects, and severity of duodenal lesion. During follow-up on gluten-free diet, CeD+AID patients experienced poorer general health (median score 12 vs. 14, p < 0.001) in PGWB, more overall gastrointestinal symptoms (2.1 vs. 1.9, p = 0.001), and constipation (2.0 vs. 1.7, p < 0.001) in GSRS, whereas there was no difference in histological and serological recovery, dietary adherence, use of gluten-free oats, smoking, and presence of regular follow-up. Conclusions: Co-existing AID was not significantly associated with the baseline features or with most long-term outcomes in CeD. However, the increased prevalence of gastrointestinal symptoms and reduced poorer self-perceived health during treatment indicates these patients' need for special support.

Validation of the X-ray microtomography in the assessment of duodenal morphometry and surface area in celiac disease.

Background: Duodenal histology remains the diagnostic reference standard in celiac disease. However, traditional methods have suboptimal sensitivity and reproducibility for early mucosal changes and research purposes. We validated a recently introduced micro-CT imaging method for an accurate digital evaluation of duodenal histomorphometry and mucosal surface areas. Methods: Endoscopic biopsies from 58 individuals were utilized for the micro-CT imaging, selecting histological changes ranging from normal to severely damaged mucosa. The imaging protocol was optimized for practicability and resolution. The Bland-Altman method was applied to test intra- and interobserver variations in the blinded measurements. Results: The 3D micro-CT reconstructions enabled easy and precise digital cutting with optimal orientation and computer-assisted measurement of the surface area. Intraobserver analysis of morphological measurements showed a mean difference of 0.011 with limits of agreement (LA) from -0.397 to 0.375 and a standard deviation (SD) of 0.197. The corresponding figures for interobserver analysis were 0.080, from -0.719 to 0.537 and 0.320, respectively. The intraclass correlation coefficients (ICC) for the intraobserver and interobserver variations were 0.981 and 0.954, respectively. Intraobserver surface area analysis yielded a mean difference of 0.010, LA from -0.764 to 0.785 and an SD of 0.395, and an interobserver analysis mean difference of 0.028, LA from -0.642 to 0.698 and SD of 0.342. The respective ICCs for the intra- and interobserver variations were 0.963 and 0.972. Conclusions: Micro-CT showed excellent accuracy and reproducibility in the evaluation of mucosal morphometry and surface areas. The improved sensitivity for histological changes is a powerful tool for the diagnosis of celiac disease and for clinical and pharmacological studies.

Differential diagnosis and long-term outcomes of non-atrophic duodenal changes in children.

Objectives and study: Gastrointestinal endoscopy is often performed when investigating abdominal complaints in children. While atrophic changes of the duodenal mucosa are usually caused by celiac disease, the prevalence and clinical significance of non-atrophic duodenal changes are less clear. We studied these issues in a large pediatric endoscopic cohort. Methods: Comprehensive data on clinical features, diagnostic findings and long-term outcomes of children who had undergone upper gastrointestinal endoscopy with systematic duodenal sampling were collected. Study variables were compared between children with non-atrophic changes and normal histology, and between those with non-atrophic changes who did and did not receive a diagnosis. Results: The study comprised 1,170 consecutive children, of whom 51 (4.4%) had non-atrophic and 315 (26.9%) atrophic duodenal changes and 804 (68.7%) normal histology. The most common non-atrophic findings were non-specific inflammation (n = 19) and intraepithelial lymphocytosis (n = 14). Patients with non-atrophic changes presented more often with blood in stools (23.5 vs. 11.3%; p = 0.009), anemia (43.2 vs. 36.5%; p = 0.028) and positive celiac serology (34.3 vs. 12.9%; p < 0.001) than those with a normal duodenum. Twenty-four (44%) of those with non-atrophic changes received an initial diagnosis, the most common of which were inflammatory bowel disease (IBD) (n = 8), Helicobacter pylori infection (n = 3) and food allergy (n = 3). The prevalence of the diagnoses did not differ from those with a normal duodenum. Those who received a diagnosis had more often blood in stools (37.5 vs. 11.1%; p = 0.027), anemia (70.6 vs. 20.0%; p = 0.002) and negative celiac serology (50.0 vs. 7.7%; p = 0.013) than those without diagnosis. During a follow-up of 6.1-13.3 years, five of the 12 initially undiagnosed seropositive patients developed celiac disease, and one patient also developed ulcerative colitis. Conclusion: Non-atrophic duodenal changes are relatively common and associated with anemia, blood in stools, and positive celiac disease serology. Excluding potential celiac disease, those without an initial diagnosis have a favorable long-term prognosis.

Significance of low ferritin without anaemia in screen-detected, adult coeliac disease patients.

BACKGROUND: Low ferritin without anaemia has been linked to adverse health effects. OBJECTIVES: To investigate the prevalence and clinical significance of low ferritin in screen-detected coeliac disease. METHODS: Seventy-six screen-detected coeliac disease patients were enrolled in the prospective collection of comprehensive clinical, laboratory and histological data at diagnosis and after 1-2 years on a gluten-free diet (GFD). All variables were compared between patients with different ferritin levels. RESULTS: At coeliac disease diagnosis, six patients had anaemia. Of the 70 nonanaemic patients, ferritin levels were <15 µg/L in 21%, 15-29 µg/L in 19%, 30-99 µg/L in 36% and ≥100 µg/L in 24%. Those with lower ferritin were more often females, had lower body mass index, haemoglobin and villous height-crypt depth ratio and also had higher intra-epithelial lymphocyte CD3+ levels in duodenal biopsies. The groups did not differ in neurological or gastrointestinal symptoms, health-related quality of life, bone mineral density, liver values, vitamin, albumin or coeliac autoantibody levels or the prevalence of comorbidities. Median ferritin levels increased from 41.5 µg/L to 86.0 µg/L on GFD (p < 0.001). Ferritin remained <30 µg/L in 21% of patients but was not associated with dietary compliance, nor was any correlation between changes in ferritin and quality of life, gastrointestinal symptoms, autoantibody levels or degree of histological damage detected. CONCLUSION: Decreased ferritin is a frequent finding in screen-detected coeliac disease and may not be fully restored on a GFD. However, low ferritin levels are not associated with more severe symptoms or poorer quality of life.

Review article: Systemic consequences of coeliac disease.

BACKGROUND: The best-known symptoms of coeliac disease are related to the gastrointestinal tract, but the disease may also present with various systemic manifestations outside the intestine. Some of these consequences may remain permanent in undiagnosed individuals or if the diagnostic delay is prolonged. However, for many of the systemic manifestations, the scientific evidence remains scant and contradictory. AIMS AND METHODS: We conducted a narrative review of the most thoroughly studied and clinically relevant systemic consequences of coeliac disease, especially those that could be prevented or alleviated by early diagnosis. The review is intended particularly for physicians encountering these patients in daily clinical practice. RESULTS: The possible systemic consequences of coeliac disease extend to multiple organ systems, the best studied of which are related to skeletal, reproductive, cardiovascular and neurological systems. Furthermore, the disease is associated with an elevated risk of psychiatric comorbidities, non-Hodgkin lymphomas and intestinal adenocarcinoma. CONCLUSIONS: The various systemic consequences of coeliac disease play a significant role in the overall health of patients. Early diagnosis and treatment with a gluten-free diet appear to be beneficial for most, but not all of these conditions. The possible negative metabolic and psychosocial effects of the diet should be acknowledged during follow-up.

Persistent symptoms are diverse and associated with health concerns and impaired quality of life in patients with paediatric coeliac disease diagnosis after transition to adulthood.

OBJECTIVE: To investigate the prevalence and associated factors of persistent symptoms despite a strict gluten-free diet in adult patients with coeliac disease diagnosed in childhood. DESIGN: Medical data on 239 currently adult patients with paediatric diagnosis were collected from patient records. Also, patients completed structured study questionnaire. All variables were compared between those with and without persistent symptoms. RESULTS: Altogether 180 patients reported adhering to a strict gluten-free diet. Of these, 18% experienced persistent symptoms, including various gastrointestinal symptoms (73%), arthralgia (39%), fatigue (39%), skin symptoms (12%) and depression (6%). Those reporting persistent symptoms had more often gastrointestinal comorbidities (19% vs 6%, p=0.023), health concerns (30% vs 12%, p=0.006) and experiences of restrictions on daily life (64% vs 43%, p=0.028) than the asymptomatic subjects. The patients with symptoms had poorer general health (median score 13 vs 14, p=0.040) and vitality (15 vs 18, p=0.015) based on a validated Psychological General Well-Being Questionnaire and more severe symptoms on a Gastrointestinal Symptom Rating Scale scale (total score 2.1 vs 1.7, p<0.001). Except for general health, these differences remained significant after adjusting for comorbidities. The groups were comparable in current sociodemographic characteristics. Furthermore, none of the childhood features, including clinical, serological and histological presentation at diagnosis, and adherence and response to the diet after 6-24 months predicted symptom persistence in adulthood. CONCLUSION: Almost one-fifth of adult patients diagnosed in childhood reported persistent symptoms despite a strict gluten-free diet. The ongoing symptoms were associated with health concerns and impaired quality of life.

ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease.

OBJECTIVES: To gather the current evidence and to offer recommendations for follow-up and management. METHODS: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. RESULTS: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. CONCLUSIONS: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.