Reproductive functions and pregnancy outcome in female patients with celiac disease.

BACKGROUND AND AIM: Abnormalities in the reproductive functions are often ignored while evaluating a patient with celiac disease (CeD). We evaluated the entire reproductive functions in female patients with CeD. METHODS: In a case control study between 2020 and 2021 using detailed questionnaire, we evaluated reproductive functions (age at menarche, menstrual pattern, fertility, pregnancy outcome and menopause) in biopsy-proven female patients with CeD of age >10 years. The questionnaire was administered either in person or telephonically. Age-matched healthy female controls (twice the number) were also recruited. RESULTS: Of 1086 CeD patients, 470 were females and 288 were included. As compared with controls (n = 586), females with CeD had higher age at menarche (14.6 ± 2.0 vs 13.6 ± 1.5 years; P = 0.001), delayed menarche (30.8% vs 11.4%; P = 0.001), abnormal menstrual pattern (39.7% vs 25.8%; P < 0.001), involuntary delay in conception at > 1 year (33.8% vs 11.8%; P = 0.01), current infertility rate (10.5% vs 5.2%;P = 0.028), and poorer overall pregnancy outcomes (abortion [23.5% vs 12.8%; P = 0.001], pre-term birth [16.3% vs 3.7%; P = 0.001]). CONCLUSIONS: Either one or more aspect of reproductive functions and pregnancy outcome is affected adversely in three-fourth female patients with CeD.

Sieving out non-celiac gluten sensitivity amongst patients with irritable bowel syndrome.

OBJECTIVES: It is challenging to make diagnosis of non-celiac gluten sensitivity/non-celiac wheat sensitivity (NCGS/NCWS) in clinical practice, since there is no biomarker and diagnosis is based on response to gluten-free-diet (GFD). We used anti-gliadin antibody (AGA) for screening patients with IBS for gluten-sensitivity. METHODS: 492 Adult-patients with IBS underwent screening for celiac disease and gluten-sensitivity using IgA anti-tissue transglutaminase antibody and IgA-AGA and IgG-AGA, respectively. Patients with positive AGA (IgA and/or IgG) were invited to follow GFD, those willing were put on GFD for 6-weeks. Responsive patients were given gluten re-challenge. Diagnosis of NCGS was confirmed if they had recurrence of symptoms. RESULTS: Of 492 patients with IBS, AGA was positive in 61(12.4 %), hence suspected to have gluten-sensitivity. Of 31 who agreed to participate and followed GFD for 6-weeks, 17 (54.8 %) had complete (>30 % improvement) and 10(32.2 %) had partial (>20 % improvement) response. All 17 complete-responders were given gluten re-challenge for 6-weeks, symptoms recurred in all and hence were confirmed to have NCGS/NCWS. Significant decrease in AGA levels occurred almost in all GFD-responders. CONCLUSIONS: 12.4 % IBS patients have biological evidence of gluten/wheat-sensitivity. Almost 87 % patients with IBS having AGA responded to GFD. The value of AGA may further be explored as a biomarker for screening for the presence of NCGS, before recommending this test for the clinical practice.

Impact of delay in the diagnosis on the severity of celiac disease.

BACKGROUND AND AIM: Celiac disease (CeD) has now become a global disease with a worldwide prevalence of 0.67%. Despite being a common disease, CeD is often not diagnosed and there is a significant delay in its diagnosis. We reviewed the impact of the delay in the diagnosis on the severity of manifestations of CeD. METHODS: We reviewed clinical records of 726 consecutive patients with CeD from the Celiac Clinic database and the National Celiac Disease Consortium database. We extracted specific data including the demographics, symptoms at presentation, time of onset of symptoms, time to diagnosis from the onset of the symptoms, and relevant clinical data including fold-rise in anti-tissue transglutaminase antibody (IgA anti-tTG Ab) and severity of villous and crypt abnormalities as assessed using modified Marsh classification. RESULTS: The median duration between the onset of symptoms and the diagnosis of CeD was 27 months (interquartile range 12-60 months). A longer delay in the diagnosis of CeD from the onset of symptoms was associated with lower height for age, lower hemoglobin, higher fold rise in IgA Anti tTG titers, and higher severity of villous and crypt abnormalities. About 18% of patients presented with predominantly non-gastrointestinal complaints and had a longer delay in the diagnosis of CeD. CONCLUSIONS: There is a significant delay in the diagnosis of CeD since the onset of its symptoms. The severity of celiac disease increases with increasing delay in its diagnosis. There is a need to keep a low threshold for the diagnosis of CeD in appropriate clinical settings.

Emerging Biomarkers for Screening and Management of Celiac Disease.

Celiac disease (CeD) is a chronic, immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals expressing HLA-DQ2 and/or HLA-DQ8. In the current clinical practice, there are many serologic studies to aid in the diagnosis of CeD which include autoantibodies like IgA antitissue transglutaminase, antiendomysium, and antideamidated forms of gliadin peptide antibodies. Small intestinal biopsy has long been considered an essential step for the diagnosis of CeD. However, in the recent era, researchers have explored the possibility of CeD screening and diagnosis without endoscopy or biopsy. The newer emerging biomarkers of CeD appear promising in diagnostic evaluation and subsequent monitoring of disease. In this review of literature, we have explored the emerging biomarker-based diagnostic evaluation and monitoring of CeD.

Familial Touraine-Solente-Gole syndrome.

Touraine-Solente-Gole syndrome is a rare, autosomal dominant multisystem disorder arising from dysregulated prostaglandin synthesis due to underlying genetic defects. Early symptoms are related to skin and soft tissue involvement (coarse facial features, widening of wrists, etc) and may thus be overlooked unless a careful physical examination is carried out. Secondary causes of pachydermoperiosteitis must always be looked for in such patients. During evaluation, a systemic review of all organ systems should be carried out to identify asymptomatic or subclinical involvement of organ systems and identify means to avoid disease progression. Treatment options are limited to steroids and non-steroidal anti-inflammatory drugs. In the absence of definitive guidelines, clinical decisions are largely case based, with no definite duration of drug therapy or screening of potential malignancies outlined in current literature. Mental health and social rehabilitation of these patients due to their disfiguring deformities are an unmet need.

Pan-Gastrointestinal Tract Mucosal Pathologies in Patients with Celiac Disease with the Demonstration of IgA Anti-Transglutaminase Mucosal Deposits: A Case-Control Study.

BACKGROUND: While celiac disease (CeD) is considered to affect primarily the small intestine, pathological changes in other parts of the gastrointestinal tract (GIT) are also known to occur. IgA anti-tissue transglutaminase-2 antibody (anti-TG2 Ab) deposits at the site of involvement is one of the methods to establish CeD-related tissue pathology. AIMS: To explore the utility of IgA anti-TG2 Ab deposits in pan-gastrointestinal mucosal biopsies as evidence of CeD-related pathologies. METHODS: Forty-two treatment-naive patients with CeD and 45 patients with irritable bowel syndrome were included as cases and controls, respectively. Mucosal biopsies were collected from the esophagus, stomach, duodenum, and rectosigmoid regions at baseline from cases and controls, and additionally after 6-months of gluten-free diet in cases. All biopsies were evaluated for histological changes and subjected to dual-color immunohistochemical staining for identifying IgA anti-TG2 Ab deposits. RESULTS: Significantly higher number of patients with CeD had lymphocytic esophagitis (9.7% vs. 0%, P = 0.05), lymphocytic gastritis (35% vs. 8.8%, P < 0.01) and lymphocytic colitis (17.4% vs. 0%, P < 0.05) than that in controls. IgA anti-TG2 Ab deposits were observed in significantly more numbers in esophagus (30.9% vs. 6%, P < 0.001), stomach (62.2% vs. 9.3%, P < 0.01), duodenum (88.5% vs. 0%, P < 0.001) and rectum (17.4% vs. 0%, P < 0.05) than that in controls. There was a decline, but not statistically significant, in severity of lymphocytosis and intensity of IgA anti-TG2 Ab deposits in follow-up biopsies. CONCLUSION: Significantly higher number of patients with CeD had evidence of lymphocytic infiltration and IgA anti-TG2 deposits along GIT suggesting that CeD affects other parts of GIT.

Spectrum of height in patients with celiac disease.

BACKGROUND: Growth retardation is an important feature of celiac disease (CeD) that can lead to the failure of attainment of potential adult height. There is lack of data on the spectrum of height in treatment-naïve patients with CeD, with normal expected height at one end and short stature at the other. METHODS: We performed a retrospective analysis of a prospectively maintained database at our center, including a total of 583 treatment-naïve patients with CeD: 419 adults (183 [43.7%] males) and 164 adolescents (12-18 years) (72 [43.9%] males). The details extracted from the database included demographic details, height, weight, body mass index, clinical symptoms, biochemical parameters, anti-tissue transglutaminase antibody anti-tTG Ab) titer, and the severity of villous abnormalities (as per modified Marsh grade). The data from Indian National Family Health Survey-4 were used as comparators. RESULTS: Overall, 19.6% of adults and 57.9% of adolescents with CeD had short stature. While mean height of men with CeD was similar, women were taller than population controls. While a higher proportion of men with CeD had short stature as compared to the controls (32.2% vs. 20%, p<0.001), a lower proportion of women with CeD had short stature (9.7% vs. 18.9%, p<0.001). Higher proportion of adolescents with CeD had short stature compared to adults (57.9% vs. 19.6%, p<0.001). On multivariate analysis, adulthood was found to be associated with a lower prevalence of short stature. CONCLUSIONS: Overall, 19.6% of adults and 57.9% of adolescents with CeD had short stature. While the mean height of adult men with CeD was not significantly different from the population controls, women were taller. Adolescents with CeD were significantly shorter than their peers.

Impact of Corona Virus Disease 2019 pandemic on adherence to gluten-free diet in Indian patients with celiac disease.

AIMS: Lockdown and restricted mobility due to the pandemic of corona virus disease  2019 (COVID-19) has severely affected the continuity of healthcare of patients with acute and chronic diseases. We evaluated the impact of COVID-19 on the adherence to gluten-free diet (GFD), symptom control, and quality of life (QOL) in patients with celiac disease (CeD). METHODS: A questionnaire, consisting of both ad-hoc and validated questions, was created after review of literature, group discussions, and expert meetings. Standardized questionnaires namely CeD adherence test (CDAT), celiac symptom index score, and CeD-related QOL were used. The web-based questionnaire was sent to 3130 patients via social media and 452 responses (14.4%) were received. Also, additional 68 patients (not available on any social media application) were interviewed telephonically by a trained dietitian. RESULTS: Overall, 505 patients (females: 318; mean age: 24.1±14.2 years) were included. While only 6.7% (n = 34) had poor compliance to GFD (CDAT > 17) before COVID-19 pandemic, it almost doubled to 12.6% (n = 64) during the COVID-19 pandemic times (p = 0.02). Furthermore, 4.9% (n = 25) of patients were diagnosed contacting  COVID-19. Interestingly, 73.2% (n = 370) patients preferred online appointment than physical appointment. Most common difficulties faced during lockdown period were high delivery charges for getting gluten-free (GF) food at home (54.4%), increased prices of regular GF food (43.1%), and travelling long distance to arrange GF food (44.9%). CONCLUSIONS: The COVID-19 pandemic has substantially affected the adherence, symptom control, and QOL in patients with CeD, attributable to unavailability, shortage of money, and heightened cost of GF food. The pandemic has offered an opportunity to practice teleconsultation approach for patients with CeD.

Real-world re-treatment outcomes of direct-acting antiviral therapy failure in patients with chronic hepatitis C.

Direct-acting antiviral (DAA) drugs are associated with high (>95%) sustained virological response at 12 weeks (SVR12) in chronic hepatitis C (CHC) patients. There is a paucity of data regarding the characteristics and re-treatment outcomes of DAA treatment failure patients. In a retrospective analysis of the prospectively collected database, we assessed the outcomes of re-treatment among patients with previous DAA failure. Patients' characteristics, viral characteristics, including resistance-associated substitutions (RAS) in a subgroup of patients, SVR12, and clinical outcomes were studied. Of 40 patients with DAA failure, among whom 36 were retreated, mean age was 45.7 years, 63.9% (n = 23) were male, 63.9% (n = 23) had a genotype-3 infection and 63.9% (n = 23) were cirrhotic. The re-treatment regimens included a combination of pan-genotypic DAA, mainly sofosbuvir and velpatasvir with or without ribavirin. Three patients who declined retreatment and one who was still on treatment was excluded. For patients who completed re-treatment, SVR12 was 100% irrespective of genotypes. SVR12 among genotype 3 was 75% (15 of 20) when lost to follow-up was considered a treatment failure. Six patients died due to liver-related causes, including five (83.3%) with hepatocellular carcinoma. RAS analysis in 17 randomly selected patients did not reveal any dominant substitutions in NS5A or NS5B region affecting SVR12, though several novel mutations were observed. In conclusion, re-treatment of CHC patients with prior DAA failure using pan-genotypic DAA is associated with high SVR12 rates irrespective of genotype or the presence of RAS.

Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver.

BACKGROUND/AIMS: Gluten-free diet has an excess of fats and simple sugars and puts patients with celiac disease at risk of metabolic complications including metabolic syndrome and fatty liver. We assessed prevalence of metabolic syndrome and fatty liver in two cohorts of celiac disease. METHODS: Study was done in 2 groups. In group 1, 54 treatment naïve patients with celiac disease were recruited. Of them, 44 returned after 1-year of gluten-free diet and were reassessed. In group 2, 130 celiac disease patients on gluten-free diet for ≥1 year were recruited. All patients were assessed for anthropometric and metabolic parameters and fatty liver. Metabolic syndrome was defined as per consensus definition for Asian Indians. Fatty liver was defined as controlled attenuation parameter value >263 decibels by FibroScan. RESULTS: In group 1, of 44 treatment naïve patients with celiac disease, metabolic syndrome was present in 5 patients (11.4%) at baseline and 9 (18.2%) after 1 year of gluten-free diet. Patients having fatty liver increased from 6 patients (14.3%) at baseline to 13 (29.5%) after 1year of gluten-free diet (P=0.002). In group 2, of 130 patients with celiac disease on gluten-free diet for a median duration of 4 years, 30 out of 114 (26.3%) and 30 out of 130 patients (23%) had metabolic syndrome and fatty liver, respectively. CONCLUSIONS: Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver, which increases further with gluten-free diet. These patients should be assessed for nutritional and metabolic features and counseled about balanced diet and physical activity regularly.

FibroScan-aspartate aminotransferase score in an Asian cohort of non-alcoholic fatty liver disease and its utility in predicting histological resolution with bariatric surgery.

BACKGROUND AND AIM: The FibroScan-aspartate aminotransferase (FAST) score was developed for identifying patients with non-alcoholic steatohepatitis, who also have an elevated non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥ 4 and significant fibrosis (F ≥ 2). We aimed to validate it in our NAFLD cohort and assess if it correlates with the histological changes after bariatric surgery. METHODS: Patients with NAFLD, including those undergoing bariatric surgery, were included. The FAST score was calculated using liver stiffness measure, controlled attenuation parameter, and aspartate aminotransferase. Calibration and discrimination of the model were assessed by calibration plots and area under the receiver operating characteristic curve, respectively. Sensitivity and specificity were assessed at the rule-out and rule-in cutoffs (≤0.35 and ≥0.67), respectively. Changes in the NAS and FAST scores were compared in the bariatric cohort 1 year after surgery. RESULTS: The cohort composed of 309 patients, of which 48 patients underwent repeat liver biopsy at 1 year. The model showed good discrimination with area under the receiver operating characteristic curve of 0.79 (0.74-0.84); however, it was not satisfactorily calibrated (Hosmer-Lemeshow test, P = 0.008). The sensitivity and specificity at the rule-out and rule-in cutoffs were 0.90 and 0.84, respectively. A significant correlation was seen between the 1-year reduction in the NAS and FAST scores (r = 0.38, P = 0.009). A significant reduction in the median FAST score was seen in patients who had ≥2-point reduction in NAS after bariatric surgery. CONCLUSION: FibroScan-aspartate aminotransferase score demonstrated good discrimination for fibrotic non-alcoholic steatohepatitis in our cohort. However, a miscalibration resulted in overprediction. The score correlated well with the histological response to interventions for NAFLD.