Gastroenterology and Hepatology from Bed to Bench

Aim: The present study was conducted to evaluate the prevalence, clinical symptoms and pathological findings of celiac disease (CD) in irritable bowel syndrome (IBS) patients in Iran.

Background: Several studies show high prevalence of CD in IBS patients, but the results are contradictory.

Methods: The present study was conducted based on MOOSE protocol and results were reported according to PRISMA guideline. The search was done using international online databases (Scopus, PubMed, Science Direct, Cochrane Library, Embase, and Web of Science), national databases and Google Scholar search engine.

Results: The pooled prevalence of CD in 2,367 Iranian IBS patients was estimated to be 6.13% (95%CI: 4.11-9.05). The prevalence of CD in men and women with IBS was 4.28% (95% CI: 2.45-7.37) and 7.19% (95% CI: 4.51-11.28), respectively. The serological prevalence of anti tTG-IgA (11 studies with 2901 IBS patients) and AGA-IgG (4 studies with 936 IBS patients) was estimated to be 5.35% (95%CI: 3.60-7.89) and 6.35% (95%CI: 2.05-18.03), respectively. The clinical symptoms of CD among IBS patients included predominant diarrhea (47.87% [95%CI: 22.46-74.43]), predominant constipation (17.34% [95%CI: 9.17-30.35]), and alternative diarrhea and constipation (27.84% [95%CI: 11.57-53.23]). According to pathological findings based on marsh classification, the prevalence of CD at stages 1, 2 and 3 were 30.89% (95%CI: 13.25-56.68), 36.56% (95%CI: 21.74-54.45) and 52.87% (95%CI: 14.48-88.13), respectively.

Conclusion: In the present meta-analysis, we observed a high prevalence for CD among Iranian IBS patients, which is higher than global estimates. Examination of all IBS patients in terms of CD seems to be necessary, but cost-effectiveness should be considered.

Keywords: Celiac disease, Irritable bowel syndrome, Meta-Analysis, Iran.

(Please cite as: Azami M, Badfar GH, Abangah GH, Mahmoudi L. Celiac disease in Iranian irritable bowel syndrome patients: a systematic review and meta-analysis. Gastroenterol Hepatol Bed Bench 2019;12(2):85-97).

Human rotavirus is the predominant pathogen causing gastroenteritis in infants and children younger than 5 years of age globally. Before introduction and implementation of rotavirus vaccine, more than frothy percent of all caused acute gastroenteritis hospitalization and nearly half a million deaths per year was occurred due to Rotavirus infection mostly in the low-income countries. Rotaviruses are divided in G and P genotypes, based on two genomic segments’ nucleotide sequences VP7 and VP4, respectively. Currently, 27 G and 37 P types have been described; among them G1 to G4 and G9 and P[8], P[4], and P[6] genotypes are the most prevalent circulating rotavirus strains globally. Molecular epidemiological surveys revealed that G1P[8] is the predominant genotype in Iran, although other genotypes have also been reported. Rotavirus vaccine was recommended by the World Health Organization as a necessary part of national childhood immunization programs in 2009. Rotarix (monovalent) and RotaTeq (pantavalent) are two oral vaccines that have been available in more than one hundred countries around the world to control the viral infection and reduce the cases of diarrheal diseases. This article provides a review of frequency, molecular epidemiology and current situation of Rotavirus genetic diversity Iran. In addition, recent advances in rotavirus vaccine research are discussed.

(Please cite as: Tavakoli Nick SH, Mohebbi SR, Ghaemi A, Hosseini SM. Human rotavirus in Iran; molecular epidemiology, genetic diversity and recent updates on vaccine advances. Gastroenterol Hepatol Bed Bench 2019;12(2):98-109).

Aim: We aimed at determining the prognostic value of the albumin–bilirubin grade (ALBI) in patients undergoing transarterial Chemoembolization for unresectable Hepatocellular carcinoma.

Background: Various noninvasive liver reserve markers are used to predict the severity of liver injury. The role and probability of these markers in predicting the prognosis of patients with hepatocellular carcinoma (HCC) is still unknown.

Methods: Patients who underwent TACE from 2013 to 2017 were included. Patient’s age, gender, cause of cirrhosis, ALBI Grade along with the site, size and number of tumors were recorded. Radiological response to TACE was assessed by CT scan at 1 and 3 months after the procedure, respectively. Survival assessment was performed and all patients were assessed for survival until the last follow-up.

Results: A total of 71 patients were included. Majority of them were male (80.3 %). The mean tumor size of 6 ± 3.9 cm. Majority of patients (54.9 %) had a single lesion and it was mostly localized to the right lobe (60.5 %). The most common cause of chronic liver disease was HCV (65.3%). Median Child class score (CTP) and MELD score were 7 and 10, respectively. Ascites was treated prior to TACE in 12 patients (16.9 %).

Mean ALBI score in the study population was -1.59 ± 0.69, with the majority (49. 2 %) falling in grade 2. The mean duration of survival at the last follow up was of 12.1 ± 12.14 months (1- 49).

Univariate analysis showed serum albumin (p = 0.003), serum bilirubin (p = 0.018), CTP score (p = 0.019), ALBI grade (p = 0.001) and presence of varices (p = 0.04) to be the main predictors of 6 months survival after TACE. On Cox analysis, only ALBI score (p = 0.038) showed statistical significant association.

Conclusion: ALBI grade may serve as a surrogate marker in predicting the prognosis of HCC patients undergoing Transarterial Chemoembolization.

Keywords: Hepatocellular carcinoma, Unresectable disease, Transarterial chemoemobolization, ALBI grade, CTP score, MELD score.

(Please cite as: Khalid MA, Achakzai IK, Hanif FM, Ahmed SH, Majid Z, Luck NH. To determine the prognostic value of the albumin–bilirubin grade (albi) in patients underwent transarterial chemoembolization for unresectable hepatocellular carcinoma. Gastroenterol Hepatol Bed Bench 2019;12(2):110-115).

Aim: To determine whether combined laboratory and ultrasonography results can be used to select patients for biliary tract imaging (BTI) or intervention.

Background: Despite ongoing research, selection of patients with suspected CBD stone (CBDS) for BTI or direct intervention without imaging is still a subject of debate.

Methods: Patients aged?18 with symptomatic gallstone disease (SGD) who underwent MRCP over 3 years (2014-2017) were divided into the following cohorts: Group A: Normal liver enzymes with normal CBD diameter; Group B: Normal liver enzymes with dilated CBD; Group C: Isolated rise of liver enzymes with normal CBD diameter; Group D: Isolated rise of liver enzymes with dilated CBD; Group E: Hyperbilirubinemia with normal CBD diameter; Group F: Hyperbilirubinemia with dilated CBD. Binary logistic regression models were constructed for analyses.

Results: Overall, 1022 patients were included. The frequency of CBDS was 7.2% in Group A; 3.8% in Group B; 6.3% in Group C; 22% in Group D; 24.2% in Group E; 47.4%  in Group F. Hyperbilirubinemia with normal CBD (OR:1.52,P=0.010) and hyperbilirubinemia with dilated CBD (OR:5.12,P<0.001) independently predicted CBDS. Normal or isolated rise of liver enzymes with or without dilated CBD did not predict CBDS. Combined laboratory and ultrasonography had positive predictive value and negative predictive value of up to 47.37% and 100%, respectively.

Conclusion: Patients with isolated rise of liver enzymes or hyperbilirubinemia with or without dilated CBD should undergo BTI prior to ERCP. Direct ERCP could be preserved for patients with high suspicion of CBDS where clinical features do not allow waiting for BTI.

Keywords: Liver function test, Biliary calculi, Common bile duct, Magnetic resonance cholangiopancreatography.

(Please cite as: Hajibandeh S, Hajibandeh S, Thompson J, Mohammed J, Smith C, Prince J, et al. Use of combined laboratory and ultrasonography results to select patients for biliary tract imaging or intervention: a retrospective cohort study. Gastroenterol Hepatol Bed Bench 2019;12(2):116-123).

Aim: We aimed to determine these parameters in patients with non-alcoholic fatty liver disease using pro-oxidant antioxidant balance assay.

Background: In human, pro-oxidants and antioxidants are normally produced and there is a balance between production and deletion of them. When the balance between oxidants and antioxidants are disrupted oxidative stress occurs. Oxidative stress is known one of the main mechanisms for the development of nonalcoholic fatty liver disease. Many investigations have evaluated some oxidants and/or antioxidant status in these patients. However, studies explaining the antioxidant status and the oxidant burden in these patients are lacking.

Methods: Sera from 35 healthy subjects and 38 patients with non-alcoholic fatty liver disease were recruited. Then, the pro-oxidant burden and the antioxidants capacity were measured by pro-oxidant antioxidant balance assay.

Results: There was no significant difference in the mean pro-oxidant antioxidant balance values between the two study groups. The results demonstrated that serum pro-oxidant antioxidant balance values were positively correlated with BMI and age in the patient group. Furthermore, the pro-oxidant antioxidant balance significantly increased in women when compared with men in all participants.

Conclusion: It demonstrated that increased antioxidant status could be as a response reflecting of the organism to elevated oxidants in NAFLD patients which may lead to unchanged PAB values.

Keywords: Oxidative stress, NAFLD, Pro-oxidants/ antioxidants balance.

(Please cite as: Nobakht Motlagh Ghoochani FB, Ghafourpour M, Abdollahi F, Tavallai SH. Pro-oxidant antioxidant balance in patients with non-alcoholic fatty liver disease. Gastroenterol Hepatol Bed Bench 2019;12(2):124-130).

Aim: Identification of prominent genes which are involved in onset and progress of steatosis stage of Nonalcoholic fatty liver disease (NAFLD) is the aim of this study.

Background: NAFLD is characterized by accumulation of lipids in hepatocytes. The patients with steatosis (the first stage of NAFLD) will come across nonalcoholic steatohepatitis (NASH) and finally hepatic cirrhosis. There is correlation between cirrhosis and hepatic cancer. However, ultrasonography is used to diagnose NAFLD, biopsy is the precise diagnostic method.

Methods: Gene expression profiles of 14 steatosis patients and 14 controls are retrieved from gene expression omnibus (GEO) and after statistical validation top 250 differentially expressed genes (DEGs) were determined. The characterized DEGs were included in network analysis and the central DEGs were identified. Gene ontology (GO) performed by ClueGO analysis of DEGs to determine critical biological terms. Role of prominent DEGs in steatosis is discussed in details.

Results: Numbers of 31 significant DEGs including 20 up-regulated and 11 down-regulated ones were determined. Nine biological groups including 27 terms were recognized. Negative regulation of low-density lipoprotein particle receptor catabolic process, TRAM-dependent toll-like receptor signaling pathway, and regulation of hindgut contraction which were related to ANXA2, PRKCE, and OXT respectively were determined as critical biological term groups and DEGS.

Conclusion: Deregulation of ANXA2, PRKCE, and OXT is a critical event in steatosis. It seems these three genes are suitable biomarker to diagnosis of steatosis.

Keywords: Nonalcoholic fatty liver disease, Biomarker, Gene.

(Please cite as: Rezaei Tavirani M, Rezaei Tavirani M, Zamanian Azodi M. ANXA2, PRKCE, and OXT are critical differentially genes in Nonalcoholic fatty liver disease. Gastroenterol Hepatol Bed Bench 2019;12(2):131-137).

Aim: This study was performed to evaluate the potential efficacy of silymarin in the management of anti-tuberculosis medication’s induced liver injury.

Background: Hepatic toxicity is the most serious complication in treatment of tuberculosis.

Methods: In a randomized double blind clinical trial (ACTRN12610000643077), 55 cases with hepatotoxicity caused by anti-tuberculosis drugs were divided into two groups. Informed consents were obtained. The intervention group received silymarin and the control group received placebo. Severity of liver injury, the duration necessary for normalization of liver function and hospital stay were compared between the two groups.

Results: There was not any statistically significant difference in the rate of adverse effects between silymarin and placebo groups.

Conclusion: Although silymarin is considered a safe herbal medication, it was not effective to treat hepatic toxicity of anti-tuberculosis drugs.

Keywords: Tuberculosis, Adverse effects, Silymarin, Drug induced hepatitis.

(Please cite as: Marjani M, Fahimi F, Sadr  M, Kazempour Dizaji M, Moniri A, Shadi Khabiri6, et al. Evaluation of Silymarin for management of anti-tuberculosis drug induced liver injury: a randomized clinical trial. Gastroenterol Hepatol Bed Bench 2019;12(2):138-142).

Aim: To evaluate the association between dietary protein sources with disease severity, malnutrition and anthropometric measurements in cirrhotic patients.

Background: Although the beneficial effects of protein and some amino-acids have been shown previously, no study has evaluated the effects of different dietary sources of proteins in patients with hepatic cirrhosis.

Methods: In this cross-sectional study, dietary intakes of patients with hepatic cirrhosis were assessed using a valid and reliable food frequency questionnaire. The association between different dietary sources of proteins and nutritional status, anthropometric measurements, and disease severity were evaluated.

Results: Muscle strength (MS) increased significantly in highest tertile of dairy and vegetable protein sources compared with the lowest one (p=0.045). Dietary dairy and vegetable protein intakes had a positive significant correlation with body weight, MS, visceral fat percentage (VFP), and triceps skin-fold thickness (TST), and negative significant correlation with malnutrition stage.

Conclusion: Our results indicate that consumption of proteins from dairy and vegetable sources is associated with improvement in nutritional and anthropometric status of patients with hepatic cirrhosis. Further prospective studies are needed to confirm these results.

Keywords: Cirrhosis; Malnutrition; Dietary Protein.

(Please cite as: Pashayee-khamene F, Kord-varkaneh H, Saber-firoozi M, Hatami B, Rashidkhani B, Hekmatdoost A. Dietary protein sources and disease severity, malnutrition and anthropometric measurements in cirrhotic patients. Gastroenterol Hepatol Bed Bench 2019;12(2):143-148).

Aim: Identifying crucial genes related to colorectal cancers via protein-protein interaction (PPI) network analysis is the aim of this study.

Background: colorectal cancer as major reason of mortality is evaluated by genetic and proteomic approaches to find suitable biomarkers. Chromosomal instability plays crucial role in CRC. Expression change of large numbers of genes is reported.

Methods: Differentially expressed genes related to CRCs which obtained from different proteomic methods were extracted from a review article of Paula Álvarez-Chaver et al. The genes interacted by Cytoscape software via STRING database. The central nodes determined and were enriched for biological terms by ClueGO. Action map for central genes was illustrated by CluePedia. The critical genes in CRC were introduced.

Results: Among 123 query genes, 114 one recognized by software and were included in the network. SRC, EGFR, PCNA, IL8, CTNNB1, TIMP1, CDH1, and HSPD1 were determined as central genes. After gene ontology analysis SRC, EGFR, and CDH1 were identified as critical genes related to CRC.

Conclusion: It seems that SRC, EGFR, and CDH1 and the related pathways are possible biomarkers for CRC.

Keywords: Colorectal cancer, Biomarker, Gene.

(Please cite as: Mansouri V, Rezaei Tavirani M, Rezaei Tavirani S. Gene screening of colorectal cancers via network analysis. Gastroenterol Hepatol Bed Bench 2019;12(2):149-154).

Aim: The aim of present study is to investigate the effect of fatty acids on the outer membrane vesicles (OMVs) produced by Bacteroides spp.

Background: Bacteroides spp. is the important member of Gut microbiota that employ OMVs production for interact with host. Besides, dietary fatty acids could influence on determination of gut microbiota composition and immune response. In this regard, we evaluated the effect of fatty acids on the growth and OMVs production of Bacteroides fragilis and Bacteroides thetaiotaomicron.

Methods: B. fragilis and B. thetaiotaomicron were grown on BHI broth with and without palmitic and palmitoleic acids as saturated and unsaturated fatty acids, respectively. OMVs were extracted using multiple centrifugation and tris-ethylene diamine tetra acetic acid (EDTA)-Sodium deoxy cholate buffers.  Physicochemical properties of OMVs were detected by electron microscopy (SEM), Bradford Coomassie brilliant blue assay and SDS-PAGE. Data were analyzed with One-way ANOVA using SPSS.

Results: The growths of both Bacteroides were significantly increased by palmitic acid. Nevertheless, palmitoleic acid had no significant effect on them. Palmitic acid significantly decreased and increased the production of B. fragilis OMVs at low and high concentration, respectively. However, the production of B. thetaiotaomicron OMVs was not significantly affected by palmitic acid. Although palmitoleic acid had a significant decreasing effect on the production of B. fragilis OMVs, it significantly increased the production of B. thetaiotaomicron OMVs at low concentration.

Conclusion: In conclusion we reported that palmitic acid had a stimulatory effect on the growth of B. fragilis and B. thetaiotaomicron and had a dose dependent effect on the production of B. fragilis OMVs. Also producing of B. thetaiotaomicron OMVs was affected by palmitoleic acid in a dose dependent manner.

Keywords: Bacteroides fragilis, Bacteroides thetaiotaomicron, Outer membrane vesicle, Palmitic acid, Palmitoleic acid.

(Please cite as: Mirjafari Tafti ZS, Moshiri A, Ettehad Marvasti F, Tarashi S, Sadati Khalili SF, Motahhary A, et al. The effect of saturated and unsaturated fatty acids on the production of outer membrane vesicles from Bacteroides fragilis and Bacteroides thetaiotaomicron. Gastroenterol Hepatol Bed Bench 2019;12(2):155-162).

Aim: We assessed effect of Akkermansia muciniphila and its extracellular vesicles on toll-like receptors and tight junction expression in human epithelial colorectal adenocarcinoma cells (Caco-2).

Background: The intestinal microbiota plays an important role in the intestinal homeostasis through its metabolites and derivatives. Interacting with immune cells and intestinal epithelial pattern recognition receptors (PRRs), intestinal microbiota regulates the function of the digestive barrier and inflammation caused by the metabolic diseases.

Methods: A. muciniphila was cultured on a mucin-containing medium and its EVs was extracted by ultracentrifugation. This bacterium was treated in the MOI=10 and its EVs at the concentrations of 0.1, 0.5 and 5 µg on Caco-2 cells. After 24 hours, the expression of tight junction and toll-like receptor genes were investigated by quantitative real time PCR method.

Results: A. muciniphila increased the expression of tlr2 and tlr4. However, EVs at all of the concentrations showed a decrease in tlr4 expression. EVs at the concentrations of 0.1 and 0.5 µg/ml decreased the expression of tlr2. A. muciniphila significantly increased the expression of ocldn and cldn4. Both this bacterium and EVs increased the expression of zo2 in the cell line. Furthermore, this data show that A. muciniphila derived EVs have a dose-independent effect on Caco-2 cells.

Conclusion: This preliminary research shows A. muciniphila and its EVs both may increase the integrity of the intestinal barrier. A. muciniphila derived EVs also reduces the inflammation so that EVs of this bacterium can be used as an appropriate target for the treatment of metabolic syndrome and inflammatory bowel diseases.

Keywords: Gut microbiota, Akkermansia muciniphila, Toll-like receptor, Tight junction protein, Extracellular vesicle.

(Please cite as: Ashrafian F, Behrouzi A, shahriary A, Ahmadi Badi S, Davari M, khatami SH, et al . Comparative study of effect of Akkermansia muciniphila and its extracellular vesicles on toll-like receptors and tight junction. Gastroenterol Hepatol Bed Bench 2019;12(2):163-168).

A notable proportion of surgically created stomas develop high output. Ongoing monitoring and treatment of hight stoma output is imperative to avoid risk of complications. Prevailing management guidelines focus mainly on supportive measures and medications that alter bowel motility. However, some patients fail to respond to these measures, leaving few substitutes. This report documents the use of semi-elemental diet in the management of a high-output ileostomy case. A 58-year-old patient underwent multiple bowel resections that resulted in a small intestine measuring 90 cm, with an end ileostomy being performed. He was on home parenteral nutrition (HPN) for over 9 years and was admitted to the hospital with an episode of sepsis from an infected line. One day prior to the hospital admission, the stoma was producing 7.2 litres/day. The Patient was advised to start Vital 1.5 10-15/day (2.5-3 litres/day) exclusively, in addition to his 1.5 litres of IV fluid, based on the nutritional requirement as calculated by a dietitian. Following the introduction of the semi-elemental diet, the ileostomy output dropped swiftly to 2 litres/day, 9 days post admission, and the BMI remained stable. This report suggests a possible role for semi-elemental diet in the management of ileostomies with short bowel syndrome. Based on our previous experience and this case, elemental or semi-elemental diet may both be used as a mono-therapy, in patients with high ileostomy output, even in cases with small bowel length as short as 90cm.

Keywords Elemental diet, Short bowel, Ulcerative colitis, Ileostomy, High-output stoma.

(Please cite as: Ahmad SJS, Khan A, Madhotra  R, Aristomenis K. Exadaktylos, Maria Elena Milioto, Macfaul G, et al. Title: Semi-elemental diet is effective in managing high output ileostomy; a case report. Gastroenterol Hepatol Bed Bench 2019;12(2):169-173).

Non-cirrhotic portal hypertension (NCPH), defined as elevated portal pressures in the absence of cirrhosis, is a relatively rare cause of elevated portal pressures in western countries. In NCPH decompensated liver disease is common, but complications are often mitigated by appropriate medical therapy. Liver synthetic function loss is uncommon. We present a unique case of a patient with biopsy proven NCPH, who eventually developed progressive loss of hepatic synthetic function in the setting of long standing portal hypertension. This loss of synthetic function corresponded with the interval development of incomplete septal cirrhosis (ISC), and progression of previously noted nodular regenerative hyperplasia in biopsies performed 7 years apart. Our patient’s clinical course was complicated by multiple hospitalizations for gastrointestinal hemorrhage. Patients with ISC have higher rates of bleeding varices when compared to patients with macronodular cirrhosis. While patients with NCPH typically have better overall survival and fewer bleeding complications than cirrhotic patients, this is typically attributed to the former having preserved synthetic function. It appears that the presence of ISC may be a poor prognosticator in patients with NCPH.

Keywords: pathology, portal hypertension, gastrointestinal hemorrhage.

(Please cite as: Kline K, Al Hanayneh M, Bilal M, Stevenson-Lerner H. Portal vein thrombosis leading to pre-sinusoidal non-cirrhotic portal hypertension resulting in decreased synthetic function of the liver. Gastroenterol Hepatol Bed Bench 2019;12(2):174-177).