ISSN: 2008-2258

Review Article

Neurological Manifestation of Coeliac Disease with particular Emphasis on Gluten Ataxia and Immunological injury, a Review Article.

Dina Osman, Seemeen Seemeen , Humayun Muhammad, Esmaeil Nikfekr, Kamran Rostami, Sauid Ishaq

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021

Coeliac disease (CD) is a gluten induced enteropathy affecting 1% of the population and has extra intestinal manifestations. One of such expression involves nervous system and CD may present as gluten ataxia (GA), peripheral neuropathy and epileptiform disorder among others. Considerable controversy exists on the exact pathophysiological mechanism of gluten leading to ataxia. It is however, clear that in intestinal axis tissue transglutaminase 2 (tTG2) is the primary target but in nervous system tTG6 may be the causative antigen although its exact role is not clear. Furthermore, it has also been postulated that anti-gangliodise antibodies may be playing some role in causation of central pathology if not the key contender. Moreover, the association of neurological injury with non-coeliac gluten sensitivity (NCGS), a related but pathologically different condition points towards an independent mechanism of neuronal injury by gluten in the absence of CD. This review will touch on the salient features of CD and nervous system and will highlight current controversies in relation to gluten and GA.







Original Article

An algorithm for differentiating food antigen related gastrointestinal symptoms

Kamran Rostami, Justine Bold, Jafer Ismail Ali, Alison Parr, Walburga Dieterich, Yurdagül Zopf, Aung Htoo, Mohammad Rostami-Nejad, Mihai Danciu

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021

Background: A large number of food related gastro-intestinal disorders have been attributed to Irritable Bowel Syndrome (IBS) for decades. Discovery of food sensitivities and a high rate of symptomatic response to a low FODMAP diet (fermentable oligo-, di-, monosaccharides and polyols) has revolutionized the treatment of IBS. The aim of this clinical audit was to assess patient reported outcomes on the effect of dietary intervention in managing this group of patients to enhance our understanding of possible treatment options in IBS. Methods: Patient reported outcomes from the records of 149 IBS patients treated at secondary and tertiary Gastroenterology outpatients in two UK hospitals between January 2014 and July 2016 were audited. Patients all presented with symptoms fulfilling Rome III-IV criteria for IBS, had negative coeliac serology and did not have other gastrointestinal(GI) conditions. A modified version of a low FODMAP diet had been recommended (gluten and lactose free diet (G/LFD)) and was implemented for 6 weeks. Outcomes and dietary adherence were recorded during outpatient’s consultations. Out of 149 patients records, there was complete data for 134 patients. Results: 134 patients complied with the diet optimally. Ages ranged from 8 to 85 years, with mean age of 46.41± 17.388 years. Patients were predominantly female 109 (81.34%) in comparison to male 25 (18.66%). The majority had an improvement rate >70% and continued with the diet. 53% became completely or almost asymptomatic, while 27.6% had a poor response to the diet (scoring < 30%) to G/LFD. The improvement was excellent in patients with normal BMI and good in overweight, obese and where BMI <18. Over 50% didn’t require any follow-up within 12 months. Conclusions: Although, it is unclear whether symptoms are triggered by gluten, fructans or lactose, the elimination of gluten and lactose proved to be an effective treatment in these patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the algorithm developed as a result of this audit might prove to be both a cost effective and efficacious treatment option in IBS, that is also easier for patients to implement than a full FODMAP exclusion and so is an area recommended for further research.

Keywords: Non-coeliac gluten sensitivity (NCGS), gluten, fructans, amylase trypsin inhibitors, FODMAP, lactose intolerance, irritable bowel syndrome


Novel Somatic Variants in CTNNA1 Gene in Iranian Patients with Diffuse Gastric Cancer

Mohadeseh Naghi Vishteh, Tayyeb Ali Salmani, Amirreza Javadi Mamaghani, seyyed javad seyyed tabaei, Majid Kheirollahi

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021


Aim: Here we aimed to evaluate somatic mutations of CTNNA1 in DGC patients.

Background: Diffuse gastric cancer (DGC) is one of the main types of gastric cancer which most of the cases are sporadic diffuse gastric cancer (SDGC). It has been shown that mutations in CTNNA1 are responsible for some cases of hereditary diffuse gastric cancer (HDGC).

Methods: In the present work, 48 formalin-fixed paraffin-embedded tissues, including samples of 38 SDGC and 10 HDGC patients were examined by performing Sanger sequencing approach on PCR products amplified from 18 exons and boundaries of intron/exon of CTNNA1 gene.

Results: We revealed 9 novel mutations in the CTNNA1 gene in patients with HDGC and SDGC, from which one variant was intronic. Eight patients had at least one disease-causing mutation (16.6%). Most of the patients were in the III stage of cancer (50%). Except for one patient, histological type of the rest of mutation-harboring patients was signet ring cell carcinoma, and only one HDGC patient had CTNNA1 mutation.

Conclusion: Our study showed several novel variants in the CTNNA1 gene in Iranian DGC patients, and implies the potential role of ?-catenin in the pathogenesis of SDGC, as well as HDGC.

Increased Regulatory T cells in Peripheral Blood of Children with Eosinophilic Esophagitis

Mahnaz Abdolahy, Shima Rasouli, Delara Babaie, Naghi Dara, Farid Imanzadeh, Aliakbar Sayyari, Pejman Rouhani, Katayoun Khatami, Maryam Kazemiaghdam, Yalda Nilipour, Maliheh Khoddami, Farah Ghadimi, Fatemeh Mousavinasab, Mehrnaz Mesdaghi

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021

Background: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of gastrointestinal tract. Regulatory T cells (Tregs) have a confirmed regulatory role in allergic disorders. Considering the allergic basis of EoE, this study was done to evaluate peripheral blood Tregs in children with EoE.

Materials & Methods: Children with EoE, gastroesophageal reflux disease (GERD) and healthy controls (HC) (10 subjects in each group) were recruited after diagnosis by a pediatric gastroenterologist and allergist. After obtaining informed written consent, peripheral blood was obtained. Peripheral blood mononuclear cells were isolated by Ficoll gradient centrifugation. Flowcytometry was used to enumerate peripheral blood Tregs and CD4+CD25+FOXP3+ cells were considered as Tregs.

Results: The percentage of CD4+ lymphocytes was significantly higher in EoE and GERD groups compared to HC group (p= 0.018). The percentage of CD4+CD25+FOXP3+ Tregs was significantly higher in EoE comparing HC group (P=0.016). The higher percentage of Tregs in EoE comparing GERD group was not statistically significant.

Conlusion: Peripheral blood Tregs are increased in patients with EoE comparing healthy controls, which may be indicative of a feedback mechanism to regulate inflammatory responses.

Is gastric mapping needed in the endoscopy of dyspeptic Patients?

Seyed Mohammad Valizadeh Toosi, Seyede Fateme Sanayifar, Reza Ali Mohammadpour, somayeh sheidaei

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021


Intestinal metaplasia, which is defined as the replacement of normal gastric mucosa by metaplastic intestinal epithelial cells, have been described as premalignant gastric lesion. The aim of our study was detecting, intestinal metaplasia in dyspeptic patient who candidate for upper GI endoscopy.

Materials and Methods:

Six hundred two consecutive patients with dyspeptic symptoms and indication for upper GI endoscopy were included in the study. Gastric mapping was done for all patients to determine the presence or absence of intestinal metaplasia. All histologic samples were reported according to updated Sydney classification.


 61.3% of patients were female. The mean age of patients was 46±15 years. The overall prevalence of intestinal metaplasia was 21.7%. Distribution of intestinal metaplasia in stomach was 15.1% in antrum, 4.3% in body and 2.3% in antrum and body. The prevalence of intestinal metaplasia in age group of 10 to 30 years was less than 5% and in patients over 30 years was 25%.


 In our study, more than one-fifth of patients with dyspepsia have intestinal metaplasia. This indicates that, gastric mapping in patients with dyspepsia may lead to discovery of pre-cancerous lesion.

The frequency of HLA-DQ2/DQ8 haplotypes and celiac disease among the first-degree relatives of patients with celiac disease

Masoume Mansouri, Masoud Dadfar, Mohammad Rostami-Nejad, Golnaz Ekhlasi, Amirhossein Shahbazkhani, Bijan Shahbazkhani

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021

Aim: To evaluate the frequency of human leukocyte antigen (HLA) DQ2/DQ8 haplotypes as well as celiac disease (CD) among the first-degree relatives (FDRs) of CD patients, compared with healthy controls, and to compare the HLA typing with serologic tests in this population.

Background: Until now, no study has examined the frequency of HLA-DQ2/DQ8 haplotypes among the FDRs of Iranian patients with CD.

Methods: In the current case-control study, 100 FDRs of CD patients and 151 healthy controls were included. Demographic characteristics were assessed using a research-made questionnaire. A blood sample was collected from each participant for HLA-DQ typing and measuring serum levels of anti-gliadin and anti-transglutaminase (anti-tTG) antibodies.

Results: Mean age of the FDRs of CD patients and controls was 30 and 35 years, respectively. Also, 51% (n=51) of the FDRs and 51.7% (n=78) of controls were female. CD was diagnosed among 3% (n=3) of the FDRs of CD patients. No significant difference was found in terms of the frequency of HLA-DQ alleles between the FDRs of CD patients and controls. Out of 100 FDRs of CD patients, 40% had HLA-DQ2 allele, 16% carried HLA-DQ8 allele, and 4% had both alleles. Surprisingly, the CD was diagnosed in three subjects among 60 FDRs of CD patients with HLA-DQ2 allele (3% of the whole population). This diagnosis was based on the results of serological tests as well as endoscopy and intestinal biopsy.

Conclusion: CD was confirmed among 3% (n=3) of the FDRs of CD patients. We found that HLA typing is not effective in predicting CD among FDRs of CD patients. Other methods such as serological tests have a higher priority compared with HLA-DQ typing.

KEYWORDS: Celiac disease, HLA-DQ2, HLA-DQ8, HLA typing, Iran

Efficacy of Vitamin D Supplementation on Adult Patients with Non-Alcoholic Fatty Liver Disease: A Single Centre Experience

Ahmed Gad, Mohamed Elmedames, Ayman Ramadan, Ayman Mohamed Marei, Hesham Atia Abdel-Ghani

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021

Background and Aim

The association between vitamin D level and NAFLD has not been determined yet. The aim of this study was to determine the efficacy of 6-months intramuscular vitamin D supplementation in improving the liver parameters in adult patients with NAFLD.

A single-blinded non-randomized controlled trial was conducted in 80 NAFLD patients assigned to receive a monthly single intramuscular dose of 200,000 IU cholecalciferol/vitamin D3 (n=40), or placebo (n = 40) for six months. Transient elastography for measurement of controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), as well as fibrosis 4 score (FIB4) and NAFLD fibrosis score (NFS) were performed.


The mean serum 25(OH)D was significantly increased after six months of vitamin D treatment (16.31±10.23 Vs 39.37 ±11.99 ng/ml). In the vitamin D group, most of vitamin D deficiency patients (70% deficiency, 10% insufficiency, and 20% sufficiency) had changed to be sufficient (7.5% deficiency, 5% insufficiency, and 87.5% sufficiency). On the other hand, the values of CAP (311.9±42.2dB/m) and LSM (6.8±2 kPa) had significantly reduced after six months of supplementation (287.0 ±44.3dB/m and 6.1 ±1.1 kPa, respectively) with significantly higher mean CAP and LSM change from baseline in vitamin D group compared to the placebo group. Furthermore, the ALT and AST levels were significantly improved in Vitamin D group compared to the placebo group (P<0.05). Multivariate regression analysis showed that lower serum 25(OH)D level was the only significant predictor for NAFLD [OR=0.89, p=0.001) in this study.


A monthly single intramuscular dose of 200,000 IU cholecalciferol is effective in improving the laboratory and fibroscan parameters of the liver disease in NAFLD patients, which confirm the significant relationship between vitamin D deficiency and the risk of NAFLD.

Keywords: NAFLD, vitamin D, CAP, and LSM

Background: the efficacy of the standard triple therapy (STT) for H. pylori eradication has decreased with the rise of antibiotic resistance. Other factors could influence the eradication failure, although the available results are conflicting.

Aim: to evaluate the influence of socioeconomic and demographic factors on the eradication rate of H. pylori, using standard triple therapy.

Methods: retrospective study, including adults with H. pylori infection treated de novo with STT (proton pump inhibitor, amoxicillin and clarithromycin). Eradication success was checked by 13C-urea breath test. Demographic and socioeconomics variables were evaluated and correlated with eradication treatment outcome. The confounder variables were controlled by logistic regression analysis.

Results: Out of 902 patients with H. pylori diagnosis 693 achieve inclusion criteria (average age 53 years; females 55.2%). Non-significant differences were observed in relation to economics income between rural and urban areas (p=0.316). The eradication rate of H. pylori was 71.1%; male 78.9% vs female 65.9%; urban area 73.4% vs rural area 64.1%. In reference to age, income and nationality the eradication rates were similar in all groups. According to logistic regression analysis, females had almost twice more likelihood of eradication failure in relation to males (OR 1.92; 95%CI: 1.38–2.72); and rural residents had OR 1.55 (95%CI: 1.03–2.33) for having eradication failure in contrast with urban population.

Conclusions: Female sex and rural residence are factors associated to H. Pylori eradication failure with standard triple therapy.

Introduction: abdominal bloating imposes significant clinical and social and economic burden on the healthcare systems; however, treatment of bloating is limited and not effective in all individuals with this symptom. Prokinetic agents are one of those treatments recommended to be used in the treatment of bloating in individuals without underlying disorders traditionally. The present study aims to compare the effect of a short duration postprandial walking and prokinetic medications on bloating reported by healthy individuals.

Methods: the study participants were randomized into two groups of control and intervention. In control group, individuals were given daily domperidone plus activated dimethicone as a prokinetic medication. While, the subjects in the intervention group were asked to perform a 10-15 minutes of walking after each meal. The study duration was 4 weeks and afterwards the subjects were visited again and their symptoms before and after study was compared.

Results: This study consists of 94 individuals including 24 men and 70 women with mean age of 44.47 ± 12.25 years with 49 participants in control group and 45 participants in the intervention group. Both prokinetic medication use and minimal exercise after meals were associated with significant improvements in the GI tract symptoms such as belching, flatus, postprandial epigastric fullness/ bloating, gas incontinency and abdominal discomfort/pain (p-value <0.001). The changes in the score of the gastrointestinal symptoms from beginning to end of study between the two arms of study were not statistically significant except for postprandial epigastric fullness/ bloating symptoms that the intervention was superior to the control product(p-value=0.002).

Conclusion: this study shows that physical activity could be considered for relieve of abdominal bloating symptoms. In contrast to other means of treatment proposed for abdominal bloating and its related symptoms, this one needs no materials or equipment and can be performed easily by any individual.


Aim: In this study, was investigated the variation of miR-21 and miR-29 expressions in a cell line of gastric cancer exposed to low-frequency electromagnetic fields with 0.25 and 2.5 ml Tesla strength, in two type of continuous and discontinuous radiations.

Case Report

Syphilitic hepatitis – a rare manifestation of a common disease

Flávio Pereira, Mariana da Silva Leal, Daniela Meireles, Susana Cavadas

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021

ABSTRACT: Syphilis is a sexual transmitted disease caused by Treponema pallidum and an underdiagnosed and underreported cause of acute hepatitis.  In later years, reported cases of primary and secondary syphilis are increasing, mostly in men who have sex with men. Clinical manifestations of syphilis are very diverse, earning the name of “the great imitator”. It can virtually affect any organ. Nonetheless hepatic involvement is rare, but hepatic involvement can occur at any stage of the disease.

We present the case of a 41-year-old immunocompetent male, that presents to us with a cholestatic hepatitis and a diffuse erythematous rash with palmo-plantar affection. Patient had no history of primary syphilis. After throughout aetiologic study it was diagnosed with syphilitic hepatitis and treated with intramuscular Benzathine benzylpenicillin, with disappearance of the rash and normalization of liver enzymes after 3 months.

We would like to highlight that this aetiology should be considered in patients with unexplained elevation of liver enzymes (mainly cholestatic enzymes) and an epidemiologic context of unsafe sexual exposure.

Keywords: acute hepatitis, secondary syphilis, syphilitic hepatitis, immunocompetent patient, sexually transmitted infection


An Elemental Diet is Effective in the Management of Diversion Colitis

Andrew Lane, Nicholas Dalkie, Lisa Henderson, James Irwin, Kamran Rostami

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021

The use of an elemental diet in the management of inflammatory gastroenterological diseases has long been accepted as standard management and has shown to both induce and maintain remission in Crohn’s disease, but the evidence for its use in diversion colitis is lacking. An elemental diet is one which provides all the required nutrition in a more easily absorbed and hypoallergenic form.  In this case report, we present a patient who had a flare of diversion colitis treated with diet alone. She had a significant improvement in her symptoms with a decrease in bowel motions, rectal discharge and pain. This case suggests that there may be some role for the use of an elemental in the management of diversion colitis. We also look at some of the potential mechanisms which may lead to the benefit observed.


Neuroendocrine tumors of the gastrointestinal tract and pancreas include a range of rare and diverse neoplasms with unique tumor biology, natural history, and clinical management. Neuroendocrine tumors of the ampulla of Vater, are extremely uncommon cancers that account for only about 0.3%-1% of all gastrointestinal neuroendocrine tumors. Approximately 139 cases have been reported to date.

Materials and methods

In this paper, we describe two patients with low to intermediate grades of ampullary neuroendocrine tumors that underwent multiple courses of chemotherapy with Capecitabine (Xeloda®) and Temozolomide (Temodal®).


Our two patients had a very dramatic response to this regimen. 


According to our study, it seems that ampullary neuroendocrine tumors have behavior like pancreatic neuroendocrine tumors and confirmation of this finding needs further investigations in more patients.

Acute severe Autoimmune Hepatitis with anti-Rods and Rings autoantibodies: Literature first evidence.

Roberto Assandri, Alessandro Montanelli

Gastroenterology and Hepatology from Bed to Bench, , 26 January 2021

Autoimmune hepatitis (AIH) was defined as a progressive, chronic inflammatory autoimmune liver disease (ALD). The diagnosis of AIH requires the presence of characteristic clinical and laboratory features, and the exclusion of other clinical conditions that cause chronic hepatitis and cirrhosis.

AIH can have an acute onset that mimics an acute viral or toxic hepatitis or an acute severe (fulminant, ASF) presentation that satisfies criteria for acute liver. Guidelines from the european Association for the Study of Liver Diseases define ALF with absence of pre-existing liver disease, acute onset of ? 26 weeks, coagulopathy (international normalised ratio (INR) ? 1.5) and presence of hepatic encephalopathy (HE). In recent years, autoantibodies (Aab) targeting subcellular structures described as the rods and rings (R&R) pattern in HEp-2 ANA have been presented as a unique and particular case of Aab generation. These R&R structures are composed of inosine monophosphate dehydrogenase type 2 (IMPDH2), and their formation can be induced in vitro by several small-molecule inhibitors. Aab targeting these relatively unknown structures have been observed in hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferona/ ibavirin (IFN/RBV) therapy. Now We present and characterized a case patient with  R&R and SMA Aab in AIH (ASF, fatal, without liver trasnplantation). For our knowledge this is the first evidence described in the Literature.Our early experience showed the R&R circulating Aab in one patient with Primary biliary cholangitis (PBC). This work now demonstrate that R&R Aab can be also present in AIH case.