ISSN: 2008-2258

Review Article

Type 2 diabetes mellitus and non-alcoholic fatty liver disease: a systematic review and meta-analysis

Nasrin Amiri Dash Atan, Mehdi Koushki, Morteza Motedayen, Majid Dousti, Fatemeh Sayehmiri, Reza Vafaee, Mohsen Norouzinia, Reza Gholami

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S1-S7

Aim: The aim of this study was the evaluation of the prevalence of NAFLD in patients with type 2 diabetes mellitus.

Background: Non-alcoholic fatty liver disease (NAFLD) is an emerging disease with high prevalence in patients with type 2 diabetes mellitus (T2DM). Many studies have reported the prevalence of NAFLD in type 2 diabetes mellitus patients. However, these results are inconsistent.

Methods: A Literature search was conducted in PubMed, Scopus, web of science and Science Direct from 2005 to August 2017. The necessary information was extracted. Heterogeneity was evaluated using I2 statistic. Meta-regression analyses were performed to the estimation of the relationship between the year of study and sample size with the prevalence of NAFLD. Publication bias was assessed by both Begg rank correlation and Egger tests. Subgroup analysis was performed for identification of sources heterogeneity.

Results: Seventeen studies involving 10897 type 2 diabetes mellitus patients with NAFLD were included in this meta-analysis. The overall prevalence of NAFLD in type 2 diabetes mellitus patients by random effects models was 54% (95% CI, 45%- 64%).  There is a significant heterogeneity across studies with (I2= 99%, p> 0.01). The funnel plot as graphically and Begg and Egger as statistically showed no publication bias among studies. Subgroup analysis indicated that the prevalence of NAFLD in type 2 diabetes mellitus patients differed in predictive factors such as lipid profile, BMI, HbA1c, AST, and ALT. This finding in spite of heterogeneity of documents is corresponding to the positive correlation between NAFLD and type 2 diabetes mellitus.

Conclusion: The findings indicated that the overall prevalence of NAFLD among type 2 diabetes mellitus patients is significantly higher. It can be concluded that type 2 diabetes mellitus patients should be managed to prevent NAFLD.

Management of multi-drug resistant Helicobacter pylori infection by supplementary, complementary and alternative medicine; a review

Nasim Rezaeimanesh, Nastaran Farzi, Samira Pirmanesh, Saeed Emami, Abbas Yadegar

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S8-S14

Helicobacter pylori is recognized as the most common bacterial pathogens colonizing the gastric epithelium of nearly half of the world’s population. This bacterium is the main etiological cause of gastroduodenal ulcers, and more importantly as the substantial risk factor for development of gastric cancer. The emergence and rapid increase in the prevalence of multi-drug resistant phenotypes have posed major pitfalls in effectiveness of various treatment regimens and eradication strategies against H. pylori infections. Several natural products and supplementary food components have been reported to have established anti-H. pylori activity. Herein, we review the application and efficacy of some specific natural products and foodstuffs such as milk, bee products (honey and propolis), fish oil, vitamins C and E, and also a nickel free-diet used as anti-H. pylori alternative treatment regimens

Original Article

The effect of education on the knowledge of patients with Celiac disease

Farnoush Barzegar, Mohammad Rostami Nejad, Hamid Mohaghegh-Shalmani, Amir Sadeghi, Maryam Allahverdi Khani, David aldulaimi

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S15-S19

Aim: The aim of this study was to investigate the effects of education on patients’ knowledge of celiac disease, in an Iranian population.

Background: Education can increase patients’ knowledge regarding their disease, leading to improvements in their health.

Methods: This cross-sectional study was conducted on patients who had been diagnosed with celiac disease. The patients attended an educational meeting in September, 2016. During the educational meeting information regarding the epidemiology, diagnosis and treatment of celiac disease was provided to the study subjects. Each patient completed a questionnaire regarding celiac disease before and after the educational meeting. The questionnaires were scored. Study data was analyzed using SPSS version 20.

Results: 90 patients were recruited (69 [77%] were women). Analysis of questionnaire responses showed that except for awareness of cross contamination with gluten, the education meeting significantly increased the knowledge of patients with celiac disease regarding epidemiology, diagnosis and treatment (p=0.001).

Conclusion: The result of this study shows that an educational meeting can increase the knowledge of CD patients in treatment. Increasing patients’ knowledge may lead to improvements in patients’ health. 

Changing the cause of liver cirrhosis from hepatitis B virus to fatty liver in Iranian patients

Behzad Hatami, Sara Ashtari, Afsaneh Sharifian, Hamideh Rahmani Seraji, Elmira Khalili, Yasin Hatami, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S20-S26

Aim: The objective of this study was to determine the epidemiologic characteristics of patients with liver cirrhosis.

Background: Liver cirrhosis is an end-stage condition of chronic liver disease. Liver disease is an important cause of morbidity and mortality worldwide.

Methods: In this cross-sectional study, demographic and epidemiologic characteristics of 203 patients with liver cirrhosis who were admitted in Taleghani Hospital over a period of two years were determined.

Results: A total of 203 patients with liver cirrhosis consisted of 136 (67%) males and 67 (33%) females and the mean age was 53.7±15.2 years. No etiology were found in (59.6%) cirrhotic patients; therefore, they were labeled as cryptogenic cirrhosis, but according to clinical evidence and ultrasonography findings, (29.7%) of these patients were probable NAFLD. The other causes of liver cirrhosis in this study were HBV (20.2%), HCV (11.8%) and autoimmune hepatitis (AIH) (8.4%), respectively. Esophageal varices were present in (41.9%), ascites in (36.5%), variceal bleeding in (8.9%), encephalopathy in (7.4%) and spontaneous bacterial peritonitis (SBP) in (5.4%) of patients. When cirrhotic patients were grouped according to Child-Pugh classification, 26.1%, 54.7% and 19.2% were in classes A, B and C respectively. The mean MELD score was 16.16±7.7.

Conclusion: In this study we found that the leading etiology of cirrhosis is cryptogenic cirrhosis 59.6% (in all age groups) and followed by HBV.  Noteworthy, according to the clinical and ultrasonography findings, 29.7% of patients who were labeled as cryptogenic cirrhosis were consistent with NAFLD.

Detailed analysis of total colectomy on health-related quality of life in adult patients with ulcerative colitis

Hamid Asadzadeh Aghdaei, Faranak Ghasemi, Mina Nooraliee, Mohammad Sadegh Fazeli, Fakhrosadat Anaraki, Dario Sorrentino, Hedieh Balaii, Shabnam Shahrokh

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S27-S32

Aim: The aim of this study was to explore the quality of life (QoL) in a group of patients who had an intractable disease on medical therapy including biologics and underwent surgery.

Background: Quality of life of patients with ulcerative colitis (UC) has been measured with a series of multiple questionnaires

Methods: An observational cross sectional study was carried out on 68 patients with documented UC referring to an IBD clinic in a tertiary hospital. Patients with UC who had a colectomy because of intractable disease and were in remission for a year were eligible for enrollment Patients were instructed to fill the SF-36 Questionnaire (interviewer-administered) regarding quality of life. Side effects were evaluated with another questionnaire. Results were compared with the normal population of the community.

Results: In comparison with normal population, patients having colectomy have better general QoL. Impotency and incontinency were most common adverse events after colectomy while the adverse events that decreased the QoL significantly were anal secretions and number of bowel movements per day without using antidiarrheal- drugs.

Conclusion: In conclusion, our study showed a significant improvement of general QoL in a selected group of UC patients, who were in clinical remission following IPAA and only number of bowel movements per day and anal secretions significantly impaired their QoL. We suggest that a disease-speci?c questionnaire should be designed, making changes in health-related QOL more detectable over time, since it is more sensitive to these changes in IBD patients than a general questionnaire.


The evaluation of functional results before and after laparoscopic Heller myotomy for achalasia: a single center experience

Abdollah Pooshani, Mojgan Frootan, Saeed Abdi, Somayeh Jahani-Sherafat, Fereshteh Kamani

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S33-S37

Aim: The aim of this study was to evaluate and compare the functional results before and after laparoscopic Heller myotomy for Iranian patients with achalasia.

Background: Achalasia is a severe neuromuscular disorder of the esophagus, characterized by the loss of peristalsis and an inability of the lower esophageal sphincter (LES) to reach optimal relaxation.

Methods: In this cross sectional study, patients who underwent Heller myotomy for achalasia via laparoscopy in Taleghani Hospital Tehran, Iran were evaluated. Symptoms including pressure of residual, integrated relaxation sphincter (IRP), pressure of free drinking, pressure of LES, dysphasia score and peristalsis movement was measured and recorded by manometry before and after (2 months)  treating with Heller myotomy.

Results: In this study, 23 patients with achalasia (12 females and 11 males) with a mean age of 30±3.5 years (minimum 20, maximum 44 years) who met the inclusion criteria of the study were examined. Results of this study showed that, all the diagnostic criteria that were measured before the treatment was significantly different from after the treatment (P<0.05). The average decline in LES, IRP, Residual Pressure, Free drinking esophagus, and dysphasia score were 23.1 mmHg, 16.24 mmHg, 18,7 mmHg, 18.9 mmHg, and 5.0 unit, respectively. Also the average increase of the peristalsis movement was 8.26±13.7 in 8 patients.

Conclusion: Considering the results of Heller myotomy surgery can be as a treatment of choice for achalasia. Free Drinking pressure can be a suitable criteria after treatment for evaluation and prediction of the reducing the dysphasia score after the surgery.

Demographic changes of hepatitis B virus infection in Iran for the last two decades

Hamid Mohaghegh shelmani, Peter Karayiannis, Sara Ashtari, Mohammad Amin Mahmanzar, Binazir Khanabadi, Niusha Modami, Fatemeh Gholipour, Fatemeh Zare, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S38-S43

Aim: The objective of this study was to evaluate the impact of the hepatitis B virus (HBV) vaccination program, 24 years after its implementation, by analyzing patients with hepatitis B surface antigen (HBsAg) infection based on gender and age group.

Background: Since the launch of the first universal vaccination program against HBV in Iran in 1993, the epidemiological pattern of HBV prevalence may have changed in our country.

Methods: All data for this cross-sectional study were collected from medical records of HBsAg positive patients, who were referred to the Golhak and Armin private laboratories and also to the Gastrointestinal Department of Tehran’s Taleghani Hospital and Day Hospital in Iran over a period of 5 years (2011-2016). In total, 8,606 HBsAg positive subjects were assessed according to gender and age group.

Results: The rates of HBsAg carriage were 0.8%, 7.8%, 49.3%, 27.9% and 14.1% among subjects under 14 years old, 15-24 years, 25-44 years, 45-59 years and those older than 60 years, respectively. According to the age subgroup analyses; the highest (26.2%) and lowest (0.6%) rate of HBsAg positivity was seen in the 31-40 age group and younger than 10 year old children, respectively.

Conclusion: Global vaccination against hepatitis B has significantly reduced carrier rates among children and teenagers under 20 years old in this country. Nevertheless, HBsAg carriers still remain highly prevalent among 25-35-year age group. Therefore, the decline is limited to the younger population born after 1993, and it remains high in the middle-aged individuals

Diabetes mellitus and hypertension increase the risk of colorectal cancer mortality; a robust Bayesian adjustment analysis

Maryam Naserinejad, Ahmad Reza Baghestani, Sadjad Shojaee, Mohamad Amin Pourhoseingholi, Hadis Najafimehr, Mehrdad Haghazali

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S44-S47

Aim: The aim of this study was to investigate the impact of diabetes and hypertension on colorectal cancer (CRC) mortality.

Background: One of the methodology in epidemiological studies is to use self-report questionnaires to gather data, this is the easiest and cheapest method but involves with misclassification bias. We use robust Bayesian adjustment to correct this bias.

Methods: One of the methodology in epidemiological studies is to use self-report questionnaires to gather data, this is the easiest and cheapest method but involves with misclassification bias. We use robust Bayesian adjustment to correct this bias.

Results: The effect size with ignorance misclassification bias was 0.78 for diabetes and 0.94 for hypertension respectively which both of them were not significant. After adjusting the misclassification and performing the robust Bayesian analysis, we arrived at region (0.27, 3.4) for OR of diabetes and (0.21, 2.31) for hypertension.

Conclusion: our study demonstrated that diabetes and hypertension increase the risk of mortality in CRC patients, using robust Bayesian analysis and misclassification in diagnosis these two exposure could change or confound the results of this association

Single Nucleotide Polymorphism (A870G) of the CCND1 gene: association with colorectal cancer susceptibility

Mahdi Montazer Haghighi, Mohsen Vahedi, Ehsan Nazemalhosseini Mojarad

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S48-S53

Aim: The aim of this study is to demonstrate the role of CCND1 gene polymorphism, A870G, in susceptibility to sporadic colorectal cancer in Iranian population.

Background: It has been distinguished that CCND1 gene is one of the main genes in Wnt signaling pathway which involves in generating colorectal cancer. Nonetheless, there is no consistent result in terms of association between the genetic variations of this gene and colorectal cancer risk.

Methods: We designed a case-control study consisting of 100 subjects with colorectal cancer (CRC) and 100 healthy controls to investigate the effect of A870G polymorphism on CRC susceptibility in an Iranian population. Genotype determination was performed by PCR-RFLP method.

Results: The frequency of GG, AG and AA genotypes for cases were 24%, 51% and 25% respectively, while the genotype frequency for controls were 21%, 50% and 29% respectively. It was identified that there is no significant association between A870G polymorphism and risk of CRC, even after adjusting sex, age and smoking status variables (P = 0.777; OR=1.32 95% CI: 0.6-2.93)..

Conclusion: Despite the well-known role of CCND1 gene in cell cycle regulation, our results revealed that A870G polymorphism could not be a potential predisposing risk factor in genetic susceptibility to CRC, at least in the studied population

Bayesian correction model for over-estimation and under-estimation of liver cancer incidence in Iranian neighboring provinces

Nastaran Hajizadeh, Ahmad Reza Baghestani, Mohamad Amin Pourhoseingholi, Hadis Najafimehr, Zeinab Fazeli, Luca Bosani

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S54-S61

Aim: The aim of this study was to obtain more accurate estimates of the liver cancer incidence rate after correcting for misclassification error in cancer registry across Iranian provinces.

Background: Nowadays having a thorough knowledge of geographic distribution of disease incidence has become essential for identifying the influential factors on cancer incidence.

Methods: Data of liver cancer incidence was extracted from Iranian annual of national cancer registration report 2008. Expected coverage of cancer cases for each province was calculated. Patients of each province that had covered fewer cancer cases than 100% of its expectation, were supposed to be registered at an adjacent province which had observed more cancer cases than 100% of its expected coverage. For estimating the rate of misclassification in registering cancer incidence, a Bayesian method was implemented. Beta distribution was considered for misclassified parameter since its expectation converges to the misclassification rate. Parameters of beta distribution were selected based on the expected coverage of cancer cases in each province. After obtaining the misclassification rate, the incidence rates were re-estimated.

Results: There was misclassification error in registering new cancer cases across the provinces of Iran. Provinces with more medical facilities such as Tehran which is the capital of the country, Mazandaran in north of the Iran, East Azerbaijan in north-west, Razavi Khorasan in north-east, Isfahan in central part, and Fars and Khozestan in south of Iran had significantly higher rates of liver cancer than their neighboring provinces. On the other hand, their neighboring provinces with low medical facilities such as Ardebil, West Azerbaijan, Golestan, South and north Khorasans, Qazvin, Markazi, Arak, Sistan & balouchestan, Kigilouye & boyerahmad, Bushehr, Ilam and Hormozgan, had observed fewer cancer cases than their expectation.

Conclusion: Accounting and correcting the regional misclassification are necessary for identifying high risk areas of the country and effective policy making to cope with cancer.

Identification of differentially-expressed of Olfactomedin-related proteins 4 and COL11A1 in Iranian patients with intestinal gastric cancer

Asma Dabiri, Kaveh Baghaei, Mehrdad Hashemi, Shokoofeh Sadravi, Habib Malekpour, Manijeh Habibi, Farhad Lahmi

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S62-S69

Aim: Due to limited information on these genes and to a better understanding of common biomarkers associated with cancer of the digestive tract routes, we aim to evaluated expression level of Olfactomedin4 (OLFM4) and (pro)collagen11A1/COL11A1 genes in people with gastric cancer in Iran.

Background: Gastric cancer is one of the main cause of cancer death. The early prognosis of gastric cancer is still a matter of debate. Human olfactomedin4 (OLFM4) is a glycoprotein that generally known as the antiapoptotic protein. (pro) collagen11A1/COL11A1 codes for the alpha-1 subunit of type XI collagen which exists in extracellular minor fibrillar collagen. In most cases, OLFM4 and COL11A1 are found to be up-regulated in many types of human cancers including gastric cancer.  

Methods: 35 tissue samples were collected including 25 sample of patients with intestinal gastric cancer and 10 healthy controls. Expression level of OLFM4 and COL11A1 genes identified by using RGQ software. For analysis of real time-PCR products, Rotor-Gene Q series software was used.

Results: Our finding showed that expression level of OLFM4 was significantly upregulated and COL11A1 did not show any significant difference in expression level in Iranian population with gastric cancer samples compared with those in normal samples.

Conclusion: The results recommend that expression profiling of OLFM4 can be used for diagnosis of gastric cancer, and OLFM4 seems to be used as a biomarker for the diagnosis of gastric cancer. Regarding to our result, unlike some studies, COL11A1 did not show any significant difference between normal and tumor tissue which could explain ethological role in distribution of gastric cancer

Occurrence of Helicobacter pylori and its major virulence genotypes in dental plaque samples of patients with chronic periodontitis in Iran

Sahel Valadan Tahbaz, Abbas Yadegar, Nour Amirmozafari, Siamak Yaghoobee, Mohammad Javad Ehsani-Ardekani, Homayon Zojaji

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S70-S78

Aim: This study was aimed to investigate the presence of H. pylori and its virulence genotypes in dental plaques of Iranian patients with chronic periodontitis.

Background: Helicobacter pylori is a Gram-negative bacterium that is associated with atrophic gastritis, peptic ulcer, and gastric cancer. Several studies have detected this bacterium in the oral cavity, suggesting it as a potential reservoir.

Methods: A hundred individuals were divided in 2 groups: 50 patients with chronic periodontitis (case group), and 50 subjects in non-periodontitis (control group). Supragingival and subgingival plaque samples were collected from the individuals using wood wedges and sterile paper points respectively, and prepared for PCR analysis.

Results: Totally, H. pylori DNA was detected in 5 out of 100 (5%) dental plaques. Of 5 dental plaques positive for H. pylori, cagA gene was detected in 4 specimen, 3 in periodontitis group and one in non-periodontitis group. The H. pylori vacA s1m1 genotype was predominantly detected in 2/5 samples. The babA2 gene was detected in all (5/5) H. pylori-positive dental plaques. There was no significant correlation between the presence of H. pylori genotypes from dental plaques and chronic periodontitis (P > 0.05).

Conclusion: Our results revealed that the rate of H. pylori is very low in the dental plaques of Iranian patients with chronic periodontitis. Majority of H. pylori strains from oral cavity were highly virulent based on the main clinically virulence factors they carried.

Evaluation of IL-17B and IL-17F mRNA expression in peripheral blood mononuclear cells and association with clinical outcome of IBD patients

Mohammad Taghi Safari, Vahid Chaleshi, Peyman Tarban, Mahyar Nourian, Hedieh Balaii, Shabnam Shahrokh, Hamid Asadzadeh Aghdaei

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S79-S84

Aim: In this study, we determined the gene expression analysis of IL-17 gene family for early detection of subclinical inflammation among IBD patients.

Background: Cytokines have a vital role in the pathogenesis of inflammatory bowel disease (IBD). Interleukin-17 is the signature cytokine of the recently identified T helper 17 (Th17) cell subset. IL-17F is mainly involved in mucosal host defense mechanisms whereas the functions of IL-17B remain largely elusive.

Methods: In this cross-sectional study, IBD patients divided into two active and inactive groups. Peripheral blood mononuclear cells (PBMCs) from 38 IBD patients which 20 inactive samples and 18 active individuals were collected.  Changes of IL-17 F and IL-17B mRNA expression level evaluated by quantitative-real time-PCR.

Results: mRNA expression level of IL-17B and IL-17F in CD, UC, active and inactive groups have been assessed and there were no significant differences (P>0.05). Patients were classified into five different categories as follows: i) 5?ASA; ii) 5?ASA + Pred; iii) 5?ASA + AZA; iv) 5?ASA + Pred + AZA; v) 5?ASA + Pred + AZA + IFX according to medication usage, expression of IL-17F and IL-17B had no differences (p>0.05).

Conclusion: Evaluation of IL-17B and IL-17F mRNA expression level illustrate no difference among active and inactive patients. Therefore, IL-17B and IL-17F are not biomarkers in an Iranian IBD patients.

Pancreatic adenocarcinoma protein-protein interaction network analysis

Mostafa Rezaei –Tavirani, Sina Rezaei tavirani, Nayebali Ahmadi, Nosratollah Naderi, Saeed Abdi

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S85-S92

Aim: Gene assessment of pancreatic adenocarcinoma disease via protein-protein interaction (PPI) Network Analysis.

Background: Diagnosis, especially early detection of pancreatic adenocarcinoma as a lethal disease implies more investigation. PPI Network Analysis is a suitable tool to discover new aspects of molecular mechanism of diseases.

Methods: In the present study the related genes to pancreatic adenocarcinoma are studied in the interactome unit and the key genes are highlighted. The significant clusters were introduced by Cluster-ONE application of Cytoscape software 3.4.0. The genes are retrieved from STRING date base and analyzed by Cytoscape software. The crucial genes based on analysis of central parameters were determined and enriched by ClueGO v2.3.5 via gene ontology.

Results: The number of 24 key genes among 794 initial genes were highlighted as crucial nodes in relationship with pancreatic adenocarcinoma. All of the key genes were organized in a cluster including 216 nodes. The main related pathways and cancer diseases were determined.

Conclusion: It was concluded that the introduced 24 genes are possible biomarker panel of pancreatic adenocarcinoma

Common and differential genetically pathways between ulcerative colitis and colon adenocarcinoma

Somayeh Akbari, Mostafa Hosseini, Majid Rezaei Tavirani, Mostfa Rezaei Tavirani, Seyed Hamid Salehi, Mahdi Alamrajabi, Padina Vaseghi Maghvan, Somayeh Jahani-Sherafat

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S93-101

Aim: In the present study, genes of Ulcerative Colitis and Colon Adenocarcinoma (COAC) were extracted by string App in Cytoscape software version 3.5.1. Then protein- protein interaction (PPI) networks analyzed.

Background: One of the most common chronic digestive problems is ulcerative colitis (UC) especially in developing countries. Prevalence of the disease is reported about 7.6 to 245 cases per 100,000 per year. UC can lead to colon cancer that is the third malignancy related death in the world.  So awareness of the future of the patient with UC and the possibility of colon cancer is a very helpful approach.

Methods: The analysis was based on centralities values. The goal is determining common gene pathways and differential gene pathways of the two diseases.

Results: Results showed there are 11 and 29 central genes related to COAC and UC respectively. At least five common key genes between the two diseases were introduced. The number of 26 terms related to the common key genes were determined and clustered in seven clusters.

Conclusion: ALB, AKT1, TP53, SRC and MYC are the common genes that play crucial roles in the related biological processes of UC and COAC. Besides introducing the common genes the differentiate genes related to the two diseases were proposed.

Study of prevalence, distribution and clinical significance of Blastocystis isolated from two medical centers in Iran

Tahereh Rezaei Riabi, Ali Haghighi, Hamed Mirjalali, Sara Mohammad Ali Gol, Seyed Ahmad Karamati, Mehrdad Ghasemian, Ayad Bahadori Monfared, Elham Aghamohammadi, Homayoun Zojaji

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S102-S107

Aim: This study aimed to survey prevalence and clinical significance of Blastocystis among symptomatic and asymptomatic groups.

Background: Blastocystis is a prevalent microorganism that is found in intestine of human and majority of animals. However, most studies have failed to establish correlation between the presence of the parasite and clinical manifestations.

Methods: from Dec 2016 to Jun 2017, 554 stool samples were collected from symptomatic and asymptomatic subjects referred to Imam Hossein Hospital and Gastroenterology and Liver Diseases Research Institute, Tehran, Iran. All samples were concentrated using conventional formalin-ethyl acetate concentration and then were microscopically examined using Lugol’s iodine staining and light microscope. The fresh stool samples were also cultivated in DMEM medium and were examined for growth of Blastocystis every 48 hours with direct smear slides for 10 days.

Results: Blastocystis was observed among 93 (16.8%) of stool samples cultivated in DMEM.  The findings represented that 64/398 (16.08%) and 29/156 (18.58%) of asymptomatic and symptomatic patients were infected with Blastocystis, respectively. In addition, there was no significant correlation between presence of symptoms and carrying Blastocystis (P=0.528), although statistically significant association was observed between presence of urticaria and carrying Blastocystis (P<0.05). Furthermore, a statistically significant correlation between observing the parasite and different age groups was seen (P<0.05).

Conclusion: Blastocystis is a prevalent parasitic eukaryote among symptomatic and asymptomatic populations despite the higher prevalence among symptomatic group that suggests the chance of infection with Blastocystis raises with age.


ATP binding cassette and cholecystokinin A receptor genetic variations in gallstone susceptibility

Saman Milanizadeh, Seyed Reza Mohebbi, Mahsa Khanyaghma, Amir Houshang Mohammad Alizadeh

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S108-S116

Aim: It was aimed to assess the association of four polymorphisms and relative haplotypes in the ATP binding cassettes and cholecystokinin A receptor (rs6720173, rs11887534, rs4148217, rs1800857) with the risk of gallstone.

Background: Gallstone is a multifactorial disease. Besides high penetrance genes, low or moderate penetrance polymorphisms may increase susceptibility to gallstone.

Methods: 200 gallstone patients and 251 healthy controls were analyzed in a case-control association model. Genotyping was carried out by restriction fragment length polymorphism. Randomly 10% of samples underwent for direct sequencing to confirm results.

Results: Heterozygote variant of rs11887534 demonstrated protective effect on the risk of gallstone susceptibility in males (P=0.013; OR=0.125; CI95%=0.048-0.325). In contrast, C/C genotype associated with gallstone susceptibility in females (P=0.004; OR=5.555 CI95%=1.975-10.632). Moreover, rs1800857 showed association only in females (P=0.019; OR=0.283; CI95%=0.099-0.811). Haplotype analysis for rs1800857 showed GC, CC and CA association with gallstone.

Conclusion: The most imperative polymorphisms of contributing genes to gallstone were analyzed in this study and rs11887534 and rs1800857 appeared to be associated with gallstone, which is expected to be further veri?ed in a larger cohort in the future.

Evaluation of promoter methylation status of MLH1 gene in Iranian patients with colorectal tumors and adenoma polyps

Ashkan Zarandi, Shiva Irani, Sanaz Savabkar, Vahid Chaleshi, Maryam Ghavidel Darestani, Reza Mirfakhraie, Mahsa Khodadoostan, Ehsan Nazemalhosseini Mojarad, Hamid Asadzadeh Aghdaei

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S117-S128

Aim: The aim of this study was to evaluate the methylation status of the promoter region of MLH1 gene in colorectal cancer (CRC) and its precursor lesions as well as elucidate its association with various clinicopathological characteristics among Iranian population.

Background: Epigenetic silencing of mismatch repair genes, such as MLH1, by methylation of CpG islands of their promoter region has been proved to be an important mechanism in colorectal carcinogenesis.

Methods: Fifty colorectal cancer and polyp tissue samples including 13 Primary colorectal tumor and 37 Adenoma polyp samples were enrolled in this study. Methylation-specific polymerase chain reaction (MSP) was performed to find the frequency of MLH1 Promoter Methylation.

Results: Promoter methylation of MLH1 gene was detected in 5 out of 13 tumor tissues and 4 out of 37 adenoma polyp. The frequency of MLH1 methylation in tumor samples was significantly higher compared to that in polyp tissues (P= 0.026). No significant association was observed between MLH1 promoter methylation and clinicopathological characteristics of the patients.

Conclusion: The frequency of MLH1 promoter methylation in CRC and colon polyp was 18%. Our findings indicated that methylation of MLH1 promoter region alone cannot be considered as a biomarker for early detection of CRC

Development of experimental fibrotic liver diseases animal model by Carbon Tetracholoride

Atoosa Gitiara, Samaneh Tokhanbigli, Sogol Mazhari, Kaveh Baghaei, Behzad Hatami, Behzad Hatami, Seyed Mahmoud Hashemi, Behzad Hatami, Ali Asadi Rad, Afshin Moradi, Nakisa Zarrabi Ahrabi, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S122-S128

Aim: This study is presenting an effective method of inducing liver fibrosis by CCL4 as a toxin in two different breeds of rat models.

Background: Liver fibrosis is a result of inflammation and liver injury caused by wound healing responses which ultimately lead to liver failure. Consequently, after liver fibrosis, the progression will be continued to liver cirrhosis and at the end stage hepatocellular carcinoma (HCC). Many studies have demonstrated that one of the most important causes of liver fibrosis is Non-alcoholic steatohepatitis (NASH). Fibrotic Liver is affected by an excessive accumulation of extracellular matrix (ECM) proteins like collagen and ?-SMA.

Methods: In two different experiments, male Vistar, and Sprague Dawley Rat models ranging from 200±60, corresponding to an age of approximately 10 weeks were utilized in order to induce CCL4 treated liver fibrosis.

Results: After 6 weeks of CCL4 injection, different tests have been carried out to verify the liver fibrosis including serum markers such as Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), molecular tests containing, laminin and ?-SMA and also pathological observation by Hematoxylin and eosin staining in both fibrosis and control group.

Conclusion: The results of Pathology and Real-time PCR showed that fibrosis was induced much more effectively in Sprague Dawley rat model compared with Wistar rats.

Evaluation of involved proteins in colon adenocarcinoma: an interactome analysis

Reza Valizadeh, Ayad Bahadorimonfared, Mostafa Rezaei–Tavirani, Mohsen Norouzinia, Mohammad Javad Ehsani-Ardakani

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S129-138

Aim: Assessment of related genes to colon cancer to introduce crucial ones, was the aim of this research.

Background: Colon cancer is one of the invasive colorectal diseases. This disease is preventable and manageable if it be diagnosed in early stage. The aggressive tools for its detection imply more investigation for new molecular diagnostic methods.

Methods: Numbers of 300 genes from String database (SD) are analyzed via constructed Protein-protein interaction (PPI) network by Cytoscape software 3.4.0. Based on centrality parameters the main connected component of network was analyzed and the crucial genes were introduced. Cluster analysis of the network and gene ontology for the nodes of the main cluster revealed more details about the role of the key proteins related to colon cancer disease.

Results: The constructed network was consisted of 300 genes which among them 68 genes were isolated and the 232 other genes formed the main connected component. Ten crucial genes related to colon adenocarcinoma were introduced that presented in cluster 1. Gene ontology analysis showed that cluster 1 is involved in 226 biological processes which are classified in 25 groups.

Conclusion: In conclusion, results indicate that the identified key proteins play significant roles in colon adenocarcinoma. It may be possible to introduce a few diagnostic biomarker candidates for colon cancer disease.

Protein profiling of infected human gastric epithelial cells with an Iranian Helicobacter pylori clinical isolate

Zeinab Fazeli, Masoud Alebouyeh, Vahid Mansouri, Habib Malekpour

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S139-S145

Aim: The main objective of this study was to use high throughput approach to characterize the response of human gastric epithelial cells to Helicobacter pylori (H. pylori) infection at protein level.

Background: Alteration of host cell protein profiles occurs due to H. pylori infection. This alteration seems to be strain specific. High throughput approaches, such as proteomics, can describe changes that occurs at the protein levelin the infected cells in response to H. pylori infection. In accordance with this point of view, we used two dimensional electrophoresis (2-DE)/MS to determine changes in proteome profile of gastric epithelial cells infected with a clinical isolate of H. pylori from an Iranian patient.

Methods: Human gastric epithelial cells (AGS) were infected by an Iranian H. pylori isolate (complete cagPAI, vacA s2m2, babA2, iceA1, sabA). The altered protein patterns separated by 2-DE were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis.

Results: The results showed 40 spots with significantly different intensities between the 2-DE gels. Protein SETSIP and Endoplasmic reticulum resident protein 29 were identified by MALD-TOF and Mascot search. Proteomic analysis for functional roles of these proteins showed that mechanisms to deal with stress conditions and transcriptional activator related to cell reprogramming are involved in H. pylori infection.

Conclusion: Using high throughput approaches, such as proteomics, we can provide further molecular details about interaction of H. pylori strains with the infected cells at protein level.

Protein interaction mapping interpretation of none alcoholic fatty liver disease model of rats after fat diet feeding

Hamed Abdolahi, Mona Zamanian Azodi, Behzad Hatami

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S146-S153

Aim: This study investigates the effect of fat diet on gene expression profile in rat liver via protein-protein interaction mapping analysis.

Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition of liver in the world. This progressive metabolic disease is representative with fat accumulation in the patients’ liver that can led to advance stages, namely, cirrhosis and eventually cancer.

Methods: Differentially expressed genes of NAFLD rat liver after 2, 4 and 6 weeks fat diet feeding were analyzed via GEO2R and protein-protein interaction network by Cytoscape v3.6.0. and the related plug-ins. The important genes were assigned based on degree and betweenness centrality analysis and enriched using ClueGO+CluePedia Plug-in.

Results: GAPDH, PRDM10, TP53, AKT1, INS, ALB, SRC, MAPK1, ACLY, ACACA, DECR1, ACACB, MBOAT4, TNF, EHHADH and JUN genes were introduced as key genes related to the fat diet fed NAFLD rats. Fatty acid biosynthesis and four other terms were introduced as the main related ones to the essential genes.

Conclusion: The introduced critical genes and the related terms may describe NAFLD molecular condition and its progression to the other severe metabolic diseases. Moreover, these potential biomarkers may be monitored for diagnosis and treatment approaches after validation investigations

Interleukin-21 rs2055979 and Interleukin-21 receptor rs3093390 genetic variants and hepatitis C virus chronic infection

Shahrzad Shoraka, Seyed Reza Mohebbi, Seyed Masoud Hosseini, Armin Hosseini Razavi, Amir Ghaemi, Shabnam Kazemian, Mohammad Rostami-Nejad

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S154-S160

Aim: The aim of this case-control study was to investigate association of G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) gene polymorphisms with chronic hepatitis C virus in Iranian Patients.

Background: Interleukin 21 (IL-21) has a significant function in the regulation of cellular immune responses. Its exclusive receptor, IL-21R, expressed on the surface of T, B and NK cells and is important for the proliferation and differentiation of these immune cells. Hence, it was suggested to be involved in response to viral infections.

Methods: This study follows a case-control study design and blood samples were collected from 290 patients with chronic HCV and 290 controls for both genes. Genomic DNA was extracted and then for each position, SNP was genotyped by the dedicated PCR and restriction fragment length polymorphism (RFLP) method. The results were analyzed by SPSS software using logistic regression and Chi-square tests.

Results: Genotype frequencies of GG, GT and TT in IL21 gene (rs3093390) were found to be 27.6%, 48.3%, 24.1% and 25.2%, 55,5%, 19,3% respectively in HCV infected patients and control group. For IL21R gene (rs2055979) genotype frequencies of CC, CT and TT were 63.8%, 31.4%, 4.8% and 61.4%, 29.7%, 9.0% respectively in HCV infected patients and control group. P values for genotype and allele frequencies were p=0.188, p=0.769 for IL21 gene, and p=0.144, p=0.179 for IL21R gene respectively.

Conclusion: As a result, there is no evidence for an association between IL-21 (rs2055979) and IL-21R (rs3093390) gene polymorphisms with chronic hepatitis C virus in Iranian Patients.

Case Report

Eosinophilic gastroenteritis; a report of two cases with different presentations

Amir Sadeghi, Elham Abdi, Negin Jamshidfar, Farnoosh Barzegar, Farhad Lahami

Gastroenterology and Hepatology from Bed to Bench, , 26 December 2017 , Page S161-S164

Eosinophilic gastroenteritis is a rare inflammatory disease, defined by infiltration of eosinophils in gastrointestinal (GI) tract, but the etiology of this disorder is unknown. Depends on the involvement region of Eosinophilic gastroenteritis, GI symptoms are variable including abdominal pain, malabsorption, gastric and duodenal ulcer. Due to its non-specific symptoms, the diagnosis is based on upper GI endoscopy followed by histopathological examination of the biopsies, which shows eosinophilic infiltration in different layers of GI tract. In this article we report two cases with gastrointestinal disorders. The first case was a 52-year-old man with a history of peripheral edema over the past 3 months and low level of serum albumin. All the necessary evaluations were done and increase number of eosinophils were found in duodenal biopsies. The second case was a 42-year-old man presented with a history of chronic diarrhea over the past two years. Main causes of diarrhea were ruled out and small intestine biopsies confirmed submucosal eosinophilic infiltration. Therefore, corticosteroid therapy was administered for both patients then they were followed for a year. During this time all of the symptoms were disappeared and they did not recur in the first year of follow up.