Gastroenterology and Hepatology From Bed to Bench Journal
Volume:14 Issue: 1, Winter 2021

Coeliac disease (CD) is a gluten-induced enteropathy affecting 1% of the population and has extra intestinal manifestations. One 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 the 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 play a role in the emergence of central pathology if not the key contender. Moreover, the association of neurological injury with noncoeliac gluten sensitivity (NCGS), a related but pathologically different condition implies an independent mechanism of neuronal injury by gluten in the absence of CD. This review will touch on the salient features of CD and the nervous system and will highlight current controversies in relation to gluten and GA

The aim of this clinical audit was to assess patient-reported outcomes on the effect of dietary intervention, to enhance our understanding of possible treatment options in irritable bowel syndrome (IBS).

A large number of food-related gastro-intestinal disorders have been attributed to IBS for decades.

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.

A total of 134 patients complied with the diet optimally. The majority had an improvement rate >70% and continued with the diet. Fifty-three percent 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 and obese and where BMI <18. Over 50% did not require any follow-up within 12 months.

Although it is unclear whether symptoms are triggered by gluten, fructans or lactose, elimination of gluten and lactose proved to be an effective treatment in patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.

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

Diffuse gastric cancer (DGC) is a major type of gastric cancer where most 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).

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

We revealed 9 novel somatic mutations in 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.

Our study showed several novel variants in the CTNNA1 gene in Iranian sporadic and hereditary DGC patients, and implies that the CTNNA1 gene mutations could be involved in the pathogenesis of DGC, either hereditary or in sporadic cases

Considering the allergic basis of Eosinophilic esophagitis (EoE), this study was conducted to evaluate peripheral blood Tregs in children with EoE.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of gastrointestinal tract. Regulatory T cells (Tregs) have a confirmed role in allergic disorders.

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 (CD4 +CD25+FOXP3+ gated lymphocytes were considered as Tregs).

CD4+ gated lymphocytes significantly increased in EoE and GERD groups compared to HC group (p= 0.018). Tregs also was significantly increased in EoE in comparison to HC group (p=0.016). There were no statistically significant differences in Tregs of EoE as compared to GERD subjects (p=0.085).

Peripheral blood Tregs increase in patients with EoE as compared to healthy controls, which may be indicative of a feedback mechanism to regulate inflammatory responses.

We evaluated 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 compared the HLA typing with serologic tests in this population.

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

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.

The 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.

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

We evaluated 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 compared the HLA typing with serologic tests in this population.

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

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.

The 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.

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.

The aim of this study was to determine the efficacy of a 6-month intramuscular vitamin D supplementation in improving the liver parameters in adult patients with non-alcoholic fatty liver disease (NAFLD).

The association between vitamin D level and NAFLD has not been determined.

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 the 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 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±42.2 dB/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 a significant relationship between vitamin D deficiency and the risk of NAFLD.

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

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 available results are conflicting.

Retrospective study, including adults with H. pylori infection treated de novo with STT (proton pump inhibitor, amoxicillin and clarithromycin). Eradication success was assessed 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.

Out of 902 patients with H. pylori diagnosis, 693 met inclusion criteria (average age 53 years; females 55.2%). Nonsignificant 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%. With 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.

Female gender and rural residence are factors associated with H. Pylori eradication failure with standard triple therapy

The present study aims to compare the effect of a short duration postprandial walking and prokinetic medications on bloating reported by healthy individuals

Abdominal bloating imposes significant clinical, 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 recommended in the treatment of bloating in individuals without underlying disorders traditionally.

The study participants were randomized into two groups of control and intervention. In the 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-minutewalk after each meal. The study duration was 4 weeks, the subjects were re-visited afterwards, and their symptoms was compared before and after the study.

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 the 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 where the intervention was superior to the use of prokinetics (p-value=0.002).

This study shows that physical activity could be effective in relieving abdominal bloating symptoms. In contrast to other means of treatment proposed for abdominal bloating and its related symptoms, it needs no materials or equipment and can be easily performed by any individual.

Extremely low frequency electromagnetic fields affect miRNAs expression in cancer cell. In this study, electromagnetic fields exposed to low frequency were used to compare miR-21 and miR-29 expressions in a gastric cancer cell line.

It has been recently suggested that the low frequency electromagnetic fields probably function as a treatment for cancers.

A cultured cell line of gastric cancer was exposed to an electromagnetic radiation system. The cell line was assigned to 4 groups under continuous and discontinuous radiations of 0.25 and 2.5 ml Tesla field strength. Then, the groups were compared with a non-radiation control group. Later, RNA extraction and cDNA synthesis were prepared for miR-21 and miR-29. Real Time PCR method was used to determine how expressions of these two microRNAs differ. Finally, the results were statistically analyzed.

The percentage of cell viability in the electromagnetic field radiation experienced a significant decrease compared to that of the control group. In addition, expression of miRNA-21 and miRNA-29 had a significant increase as the strength of the electromagnetic field radiations was on an upward trend. Similarly, the percentage of cell viability saw a significant decline in the upregulation of miRNA-21 and miRNA-29 regardless of radiation types.

Findings of this study showed the therapeutic effect of low frequency electromagnetic fields on the gastric cancer cell line. They also indicated that novel biomarkers (miRNA-21 and miRNA-29) could be proposed as potential treatments of gastric cancer, but the results are required to be well established by future studies.

Syphilis is a sexual transmitted disease caused by Treponema pallidum and an underdiagnosed and underreported cause of acute hepatitis. In recent years, reported cases of primary and secondary syphilis have been increasing, mostly in men who have sex with men. Clinical manifestations of syphilis are diverse, earning the name of “the great imitator” which can affect virtually any organ. Nonetheless, hepatic involvement is rare, but it 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. The patient had no history of primary syphilis. After throughout aetiologic study, he was diagnosed with syphilitic hepatitis and treated with intramuscular Benzathine benzylpenicillin, with the 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.

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 is lacking for its use in diversion colitis. 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 diet in the management of diversion colitis. We also examine some 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. 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 dramatic response to this regimen. According to our study, it seems that ampullary neuroendocrine tumors have behavior like pancreatic neuroendocrine tumors which requires further studies in more patients.

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 has been observed in Hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferona/ ribavirin (IFN/RBV) therapy. We presented and characterized a case patient with R&R and SMA Aab in AIH (ASF, fatal, without liver transplantation). To the best of 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. This work now demonstrates that R&R Aab can also be present in AIH case.