Review Article

Celiac disease and gluten-free diet: past, present and future

Peter Makovicky, Pavol Makovicky, Fabian Caja, Kvetoslava Rimarova, Gabriel Samasca, Luca Vannucci

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 1-7

A gluten-free diet is a special type of diet intended for people with gluten intolerance. The introduction of targeted screening into the practice has improved celiac diagnosis, with an increase of newly diagnosed patients who have remained life-long dependents on a gluten-free diet. On the other hand, the gluten-free diet has also been voluntarily adopted by people with other diagnoses, or even healthy individuals. It is expected that in the future, the gluten-free diet’s consumption is set to increase, due to its increased popularity with these populations. In this situation, gluten-free diets have been misinterpreted as a "miracle drug" that is effective on a variety of problems. Here we report on the past and present production and supply of gluten-free products and ultimately about their future position. The medical community will also be confronted with the future problems of people who are dependent on a gluten-free diet and, on the contrary, with the complications arising with the consumers of a gluten-free diet without medical reasons. Compliance to the principles of a gluten-free diet should be maintained, and should not be recommended to healthy persons or persons without relevant reasons.

Original Article

SE Translocation gene but not Zinc Finger and X-Linked Factor is down-regulated in gastric cancer.

Shiva Soleimani, Negin Nasim, Farbod Esfandi, Morteza Karimipoor, Vahid Kholghi-Oskooei, Maryam Naby Gol, Mohammad Taheri, Soudeh Ghafouri-Fard

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 8-13

SE Translocation (SET) has been first identified as a component of a fusion protein produced by chromosomal rearrangement in a patient with acute undifferentiated leukemia. Subsequently, multiple functions have been attributed to this gene in different disorders such as cancer and Alzheimer’s disease. Expression of SET is regulated by Zinc Finger and X-Linked Factor (ZFX), a transcription factor which has a putative role in gastric cancer. We evaluated expression of SET and ZFX in gastric cancer tissues and their corresponding adjacent non-cancerous tissues (ANCTs). SET1 gene was down-regulated in tumoral tissues compared with ANCTs (expression ratio=0.25, P=0.01). However, expression of ZFX was similar between tumoral tissues and ANCTs (expression ratio=0.97, P=0.94).  We detected significant association between site of primary tumor and SET1 relative expression in tumoral tissues versus ANCTs in a way that this gene was down-regulated in all tumors originated from cardia. Based on the area under the receiver operating characteristic curve, the diagnostic power of transcript levels of SET1 in gastric cancer was 0.68. Finally, we reported remarkable correlations between expression levels of SET1 and ZFX both in tumoral tissues (R2=0.38, P<0.05) and in ANCTs (R2=0.23, P<0.05). Consequently, our results imply the role of SET1 in gastric cancer and the putative functional associations between this gene and ZFX in gastric tissues.

Royal jelly Accelerate healing of acetate induced gastric ulcer in male rats

Mohammad Sofiabadi, Fatemeh Samieerad

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 14-22


Background: Scientific reports suggest that bee products are useful for healing of wounds.

Objective: The healing potential of royal jelly on the acetic acid induced wounds healing in male rat’s gastric mucosa were studied.

Materials: 96 male Wistar rats divided into in 4 groups includes: Control (without treatment), Omeprazole (20 mg/kgw), and Royal jelly (50, 200 mg /kgw). Gastric ulcer was induced in all rats with100% acetic acid. Treatment groups received omeprazole or royal jelly from 1nd to 14th day after acetic ulceration.  The histopathological parameters were evaluated on 4, 7, 10,15th days after ulceration.

Results:  The administration of royal jelly significantly reduced depth of gastric lesion (p<0.05) and attuned histopathological changes compere to control group. The largest healing effect of royal jelly was on the 10 day of treatment, and at its higher used concentration (200 mg/kg).  

Conclusion: These findings supported that royal jelly has valuable effects on Gastric ulcer healing, and can used for peptic ulcer therapy.

The association of SMAD7 polymorphisms with colorectal cancer susceptibility and clinicopathological features in the Iranian population

Zahra Akbari, Nahid Safari-Alighiarloo, Hamid Asadzadeh Aghdaei, Mohsen Vahedi, Mahdi Montazer Haghighi, Maryam Matani Borkheili, Ehsan Nazemalhosseini-Mojarad, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 23-30

Background: Genome-wide association studies (GWAS) have identified 18q21 as a risk locus for colorectal cancer (CRC), which maps to the SMAD7 gene. Our aim was to investigate the association between two single nucleotide polymorphisms (SNPs) of SMAD7 and the risk of CRC in the Iranian individuals.

Methods: This case–control study was conducted on 109 CRC cases and 109 controls in the Iranian population to evaluate the influence of two SNPs of SMAD7, rs2337106 and rs6507874, on the risk of CRC as well as on clinicopathological features. Genotype determination was performed by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) for DNA of peripheral blood. Descriptive analysis and logistic regression model were used for statistical analyses.

Results: Genotyping of the SNPs in the SMAD7 gene showed that the frequency of G allele of rs2337106 was 53.7% in controls and 56.4% in cases (p-value=0.564) and the frequency of C allele of rs6507874 was 55.5% in controls and 56.3% in cases (p-value=0.772). Besides, there were no significant differences in genotype frequencies of these SNPs between CRC patients and controls. The SMAD7 genotypes were also not associated with the risk of CRC as well as with any clinicopathological characteristics such as tumor site, tumor grade and stage TNM in CRC patients (p-value>0.05), even after adjustment for sex, age and smoking status.

Conclusion: Our results provided the first evidence that SMAD7 genotypes, rs2337106 and rs6507874, could not be predisposing markers in genetic susceptibility to CRC in an Iranian population, at least in the studied population.

Mortality risk factors in patients with gastric cancer using Bayesian and ordinary Lasso logistic models: a study in the Southeast of Iran

Abolfazl Hosseinnataj, Mohammad Reza Baneshi, Abbas Bahrampour

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 31-36

Aim: The aim of this study was to apply 2 types of statistical models to determine the factors that influence the mortality rate in patients with gastric cancer.

Background: In Iran, gastric cancer ranks the first and second among men and women, respectively. This cancer is the first cause of death in Iran in both sexes.

Materials and Methods: In the present study, data were obtained from 339 (216 male) patients diagnosed with gastric cancer in city of Kerman (South-East of Iran) during 2001-2015. In this study, ordinary and Bayesian Lasso logistic regression models, with goodness-of-fit indexes, were compared and the models' risk factors were also determined.

Results: The mean age of the participants was 62.84 ±14.53 years, and 12.4% of them were younger than 45 years. Also, mortality rate was 57.7%. Sex, morphology of the tumor, and time of diagnosis were found to be significant factors in the survival of the patients in both models. This study found that the Bayesian Lasso model had better fitness.

Conclusion: The high mortality rate of gastric cancer and its high prevalence at age below 45 years are alarming. Thus, great attention should be paid to prevention, early diagnosis, especially in females, and adenocarcinoma to improve the survival of patients with gastric cancer.

Diagnosing celiac disease in the elderly: A United Kingdom cohort study

Mohamed G Shiha, Lauren J Marks, David S Sanders

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 37-43


Aim –To assess whether there are benefits to diagnosing CD in an elderly population compared to younger adults.

Background – Coeliac disease in the elderly has been underdiagnosed due to the heterogeneity of presentation as well as lack of physician awareness of CD in this population. However, the benefits of diagnosing CD in the elderly may be contentious.

Methods – Newly diagnosed CD patients were prospectively recruited from the Coeliac Specialist Clinic at the Royal Hallamshire Hospital, Sheffield, between 2008 and 2017. All patients had villous atrophy (VA) on biopsy with positive coeliac serology. Additionally, patients were retrospectively recruited from 1990 to 2008 to determine the trend in elderly CD diagnostic frequency over time.

Results – 1605 patients with CD were recruited (n=644 prospectively, n=961 retrospectively). Of these, 208 patients (13.0%) were diagnosed over the age of 65 years between 1990 and 2017. The proportion of elderly CD diagnoses increased from 0% in 1990-1991 to 18.7% in 2016-2017 (p<0.001). Younger patients more commonly presented with fatigue (p<0.001) and gastrointestinal symptoms including diarrhoea (p=0.005), abdominal pain (p=0.019), and IBS-type symptoms (p=0.008), Older people more frequently presented with B12 deficiency (p=0.037) and had partial VA (24%) compared to younger patients (16.5%) (p=0.005).

Conclusion –The prevalence of CD in the elderly has significantly increased over the last two decades but elderly patients tend to present with fewer symptoms and a milder degree of VA. Further research is needed to determine whether a strict gluten-free diet in these patients is a necessity or a burden.

Comparison of thyroid disease prevalence in patients with celiac disease and controls

Parastoo Baharvand, Maryam Hormozi, Asghar Aaliehpour

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 44-49

Aim/Background: Celiac disease (CD) is a form of intestinal malabsorption syndrome that is closely related to endocrine disorders, especially autoimmune thyroid disease and diabetes. The prevalence of thyroid disease (TD) is likely increased among patients with CD which necessitates the need for screening for TD among them. This study aimed to screen for TD in untreated CD patients and to evaluate the effect of gender and age on its prevalence.

Methods: This comparative cross-sectional study conducted on 288 consecutive untreated patients with CD (mean age 27.9±14) and 250 controls (mean age 29.01±13.15) referred for endoscopy in a hospital located in Iran. Thyroid function was assayed by measuring T3, T4, and TSH levels using ELISA technique, and testing anti-thyroperoxidase (anti-TPO) antibodies measured using Electrochemiluminescence method. Data analysis was conducted in SPSS v.22 software using descriptive statistics and chi-squared test and ANOVA.

Results: Thyroid disease was 4-fold higher in patients than in controls (13.6% vs. 3.2%, p<0.05). Hypothyroidism was diagnosed in 30 patients and 7 controls, while hyperthyroidism was in 9 patients and in one control. Chi-squared test results reported a significant difference in TD prevalence between patients and controls based on gender and age (p<0.05). In both groups, women were signi?cantly more affected than men, and the TD prevalence was higher in younger patients compared to adults.

Conclusion: There is a strong association between thyroid dysfunction and CD in Iranian patients. In this regard, it is necessary to screen them for TD.

Impact of Reperfusion with Blood Venting on Outcomes of Liver Transplantation; a Prospective Case-Control Study

Nasir Fakhar, Abdolhamid Chavoshi Khamneh, Atabac Najafi, Ali Sharifi, Zeeshan Hyder, Javad Salimi

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 50-56

Introduction: Post reperfusion syndrome (PRS) during liver transplantation (LT) remains a serious issue for the surgeon and anesthetist. This study aimed to evaluate the impact of two different reperfusion techniques on outcomes of LT patients.

Methods: In this prospective case-control study, liver transplant recipients were divided into two groups of vented (reperfusion with 300cc blood venting) and non-vented (reperfusion without blood venting) then30-minuteintra-operative hemodynamic and biochemical changes as well as 2- month complications and 6-month mortality were compared between the groups.

Results: 57 LT cases (31 vented and 26 non-vented) were studied (50.9% female). The two groups had similar age (p = 0.107), sex (p = 0.885), MELD score (p = 0.61), donor warm ischemic time (p = 0.85), recipient warm ischemic time (p = 0.36), cold ischemic time (p = 0.99), comorbid disease (p = 0.502), and etiology of end-stage liver disease (p = 0.281). There was no significant difference between the groups regarding mean arterial pressure (p > 0.20), mean heart rate (p > 0.39), mean systemic vascular resistance (p > 0.26), and mean cardiac output (p > 0.20). PRS occurred in 3 (11.5%) patients in vented group and 4 (12.9%) in non-vented group (p = 0.69). The frequency of primary non-function (p = 1.00), hepatic artery thrombosis (p = 1.00), portal vein thrombosis (p = 0.44), biopsy proven rejection (p = 1.00), need for dialysis (p = 1.00), biliary complications (p = 1.00), wound infection (p = 0.08), and pneumonia (p = 1.00) was same in the two groups. 1 (3.8%) patient in non-vented group and 4 (12.9%) patients in vented group died (p = 0.229).

Conclusion:Reperfusion with and without blood venting has the sameoutcome regarding intra-operation hemodynamic and biochemical changes, PRSrate, and post-operation complication, as well as 6-month survival. So it seems thatblood venting could be omitted as a method for decreasing post reperfusion complications following LT.

The enhancing impact of amino termini of Hepatitis C virus core protein on activation of Hepatic Stellate Cells

Khashayar Shahin, Seyed Younes Hosseini, Hoshang Jamalic, Mohammad-Hossein Karimi, Negar Azarpirad, Mastaneh Zeraatiana

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 57-63

Background: The core protein is recognized as the most important fibrosis inducer of Hepatitis C virus (HCV). While the exogenous fibrotic effect of HCV core protein has been reported previously, the endogenous effect and role of two termini is yet to be investigated.

Aim: To study the potential effect of carboxyl and amino termini  of HCV core protein on HSCs activation.  

Methods: Plasmids expressing full length, carboxyl-truncated(T1) or amino-truncated(T3) versions of the core were transfected into LX?2 cells. MTT assay was performed to evaluate the cytotoxicity of the endogenous expression of different regions of core protein on these cells. Afterwards, the total RNA was reverse transcribed and introduced into quantitative polymerase chain reaction(qPCR) to measure the expression level of collagen type I (COL1A1), ?-smooth muscle actin (a-SMA), tissue metalloproteinase inhibitor?1 (TIMP-1) and transforming growth factor-?1 (TGF-?1). In addition, TGF-?1 as a fibrotic factor was also assayed in the supernatant of LX-2 cells using ELISA method.

Results: The full and T1 versions of the core exhibited a measurable proliferative effect on LX?2 cells (P<0.05). Analysis of the gene expression was also showed that in spite of amino-truncated version these constructs represented a significant activation impact when compared to the empty plasmid. Moreover, the result of TGF?? assay was also in agreement with the results of mRNA expression analysis.

Conclusion: The endogenous expression of the full and carboxyl-truncated versions of the core exhibited a significant activator effect on HSCs. Therefore,  it can be concluded that amino domain of HCV core protein performs a stellate cell activation role.

Protective effects of synbiotic soymilk fortified with whey protein concentrate and zinc sulfate against bile duct ligated induced hepatic encephalopathy

Yahya Jalilpiran, Nader Tanideh, Samane Rahmdel, Negar Azarpira, Maral Mokhtari, Zohreh Mazloom

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 64-76


Aim(s): Hepatic encephalopathy (HE) is seriously associated with neuromuscular and cognitive alterations. This study aimed to examine the hepato-protective effect of different soymilk products on bile duct ligated induced HE.

Methods: Eighty-two Sprague Dawley rats were randomly assigned into seven groups (Sham, bile duct ligation (BDL), BDL + lactulose, BDL + soymilk (SM), BDL + Synbiotic soymilk (SSM), BDL + SSM + whey protein concentrate (WPC), BDL + SSM + WPC + ZnSO4). Different SM products, lactulose, and normal saline were given via oral gavage. The serum and liver markers and liver histopathology were assessed at the end of the experiment.

Results: The SM products significantly reduced serum alanine aminotransferase, albumin, and ammonia (P < 0.05). The levels of Aspartate aminotransferase, endotoxin, and liver interleukin-6 were improved significantly in all treatments except for those receiving SM. SSM and SSM + WPC + ZnSO4 were the only effective products in reduction of serum Alkaline phosphatase (P < 0.05). Furthermore, liver total antioxidant capacity level was greater (P < 0.05) in the SSM + WPC and SSM + WPC + ZnSO4 groups. The histopathological examinations confirmed the efficiency of all SM products in the reduction of the liver fibrosis. Liver bile duct proliferation was reduced only in the SSM + WPC and SSM + WPC+ ZnSO4 groups (P < 0.05).

Conclusion: This study showed positive effects of different SM products, especially SSM + WPC and SSM + WPC + ZnSO4 in HE. Further studies are required to elucidate our findings

Frequency and molecular epidemiology of class A ESBLs producing Enteroinvasive Escherichia coli (EIEC) isolates among patients with diarrhea

Ahmad Farajzadeh-Sheikh, Mohammad Savari, Hossein Hosseini Nave, Khadijeh Ahmadi Ahmadi, maryam afzali

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 77-85


Aim: The aim of the present study was to evaluate the Multi-Locus VNTR Analysis (MLVA) method for genotyping of class A ?-lactamase genes harboring-EIEC strains isolated from patients with diarrhea.

Background: Enteroinvasive E. coli (EIEC) is one of the most important causes of acute diarrhea in adults and children. The production of extended-spectrum ?-lactamases (ESBLs) enzymes among diarrheagenic E. coli (DEC) is one of the main mechanisms for resistance to antibiotics.

Materials and methods: In this cross-sectional study, between September 2016 to August 2017, 569 stool samples were collected from patients with diarrhea referring to two hospitals, in Ahvaz, Iran. PCR was used for the presence of the ipaH gene to detected EIEC strains. The antibiotic resistance pattern of all EIEC isolates was determined by the disk diffusion method. EIEC isolates have been screened for class A ?-lactamase genes. Genotyping of harboring ?-lactamase genes were performed by MLVA.

Results: Among 13 EIEC isolates, 9 isolates (69.2%) were found ESBL positive by DDST and PCR. Furthermore, blaCTX-M-15and blaCTX-M-1genes were detected in 77.8% (n=7) and 44.5% (n=4) of the blaCTX-M-1group. On the other hand, the blaTEM-1gene was detected in 66.6% (n=6).  None of the isolates had blaSHV-1, blaKPC, and blaGES genes. MLVA analysis revealed high genetic diversity among ESBLs genes-harboring isolates.

Conclusion: Our study emphasized the increasing role of ESBLs genes. The presence of ESBLs genes in different MLVA types showed that one specific clone was not responsible for spreading the EIEC isolates, and the dissemination of ESBLs in our isolates was due to the horizontal dissemination of mobile genetic elements in the unrelated isolates.

Case Report

Glutamine Powder Induced Hepatotoxicity: It Is Time to Understand the Side Effects of Sports Nutritional Supplements

Behzad Hatami Hatami, Ali Saffaei, Faezeh Jamali, Mohammad Abbasinazari

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 86-89

Glutamine has been considered as a dietary supplement with a non-essential amino acid structure. Some studies found that liver failure may be associated with a high plasma glutamine level. Consumption of this product may be associated with potential adverse effect. This report describe the first case of glutamine induced hepatotoxicity. A 35-year-old female athlete with severe abdominal pain and scleral icterus was referred to the hospital. She has been taking glutamine powder for the past three weeks ago. Impaired liver function test and imaging evaluation suggested hepatotoxicity. Glutamine consumption was discontinued and the patient was closely monitored. Finally, after two weeks, the patient recovered successfully. This novel case was the first report regarding glutamine induced hepatotoxicity. Health care providers must know that consumption of dietary supplement such as glutamine may be associated with serious side effects. Liver damage is a possible side effect of glutamine. Hence it is necessary to consider hepatotoxicity as an adverse reaction in case of glutamine supplement consumption.

Intractable parastomal bleeding in a portal hypertensive patient managed by direct sclerotherapy: a case report

Niloofar Ayoobi Yazdi, Najmeh Aletaha, Mohammad-Mehdi Mehrabinejad, Ali Zare Dehnavi, Hadi Rokni Yazdi

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 90-94

Patients with a stoma have a 5% developing parastomal varices chance, which tend to repetitive massive and life-threatening hemorrhages. Treatment of choice in parastomal varices have not been established, and Transjugular Intrahepatic Portosystemic Shunt (TIPS) has been revealed as the most successful measure.

We report a hemodynamically unstable patient with the history of Ulcerative Colitis (UC) & Primary Sclerosing Cholangitis (PSC) with colostomy, because of colon cancer who presented with massive parastomal bleeding. Non-operative treatments and TIPS was failed to control the symptoms. Color Doppler ultrasound showed a hepato-fugal flow. The direct antegrade technique, using Sodium Tetradecyl Sulfate (STS 1%) and glue-Lipiodol, was applied under ultrasonography guidance, and complete stoppage of bleeding was achieved. No immediate or late complication or follow-up recurrence were noted after 2 month.

In case of hepatofugal flow, direct percutaneous mesenteric parastomal venous access, and sclerotherapy is a rapid and relatively safe procedure for parastomal variceal bleeding.

Abdominal Wall Schwannoma: a new case report

Mohamed Tarchouli, Mohamed Essarghini, Abdennasser El Kharras, Ouadie Qamouss, Ahmed Bounaim

Gastroenterology and Hepatology from Bed to Bench, Vol. 13 No. 1 (2020), 22 January 2020, Page 95-100

Schwannomas or neurilemmomas are benign and slow-growing tumors that arise exclusively from Schwann cells in peripheral nerve sheaths. These neoplasms theoretically can occur anywhere in the body, but most frequently affect extremities, head and neck region. However, their presentation in the abdominal wall is extremely rare and only few cases have been reported in the literature. Subcutaneous lesions may be asymptomatic and only incidentally discovered on physical examination or imaging. However, occasionally they induce mass effects on surrounding large nerves. We present the case of a 34-year-old man with abdominal wall pain localized in the right iliac fossa and palpable subcutaneous mass. Ultrasound and CT scan revealed a solid well-defined mass of the abdominal wall. After surgical excision under general anesthesia, histological examination was consistent with the diagnosis of benign schwannoma.