Gastroenterology and Hepatology from Bed to Bench

Aim: The current systematic review and meta-analysis aimed to assess the association between Gastrointestinal (GI) cancers and opium use.

Background: GI malignancies are a global public health issue and are associated with many risk factors including genetic and lifestyle factors.

Methods: PubMed, Web of Science, Embase and Scopus and the Google Scholar search engine in addition to Persian databases including Magiran and SID were searched using relevant keywords. The associations of opium use, long duration of opium use, high daily amount opium use and high cumulative opium use and GI cancer and various subtypes of GI cancers were estimated and pooled in format of odds ratios (OR) and their corresponding 95% confidence intervals (CI) with a random effects model.

Results: 22 articles that were published between 1983 and 2022 entered the analyses. There were significant relationships between opium use based on crude effect sizes (OR: 2.53, 1.95-3.29) and adjusted effect sizes (OR: 2.64, 1.99-3.51), high daily opium use (or: 3.41, 1.92-6.06), long duration of opium use (OR: 3.03, 1.90-4.84) and high cumulative opium use (OR: 3.88, 2.35-6.41), all compared to never opium use, and GI cancer. The results were not sensitive to sensitivity analyses and no influential publication biases were found in these analyses.

Conclusion: Our meta-analysis showed that opium use could be associated with increased risk of overall and some particular GI cancers including oropharyngeal, gastric, pancreatic and colorectal cancers. Opium use as a potentially modifiable factor, therefore, should be more emphasized.

Polyomaviruses are a group of small, double-stranded DNA viruses that are known to be associated with the development of certain human diseases, but there is evidence that these viruses might be associated with gastrointestinal (GI) cancers. Several polyomaviruses have been identified, such as JC polyomavirus (JCPyV), BK polyomavirus (BKPyV) and recently Merkel cell polyomavirus (MCPyV). Although the direct effects of polyomaviruses on transformation of human cells and cancer development are not clearly recognized, their association with certain human diseases including GI cancers has been proposed through several molecular and epidemiological studies. For example, JCPyV and BKPyV have been linked to colorectal cancer, as there is growing evidence of finding viral genomes in cancerous tissues. Nevertheless, the major role of JCPyV, BKPyV and MCPyV in colorectal cancer progression is still under extensive investigation, and further surveys is required to establish a conclusive cause-and-effect relationship. Understanding the role of these viruses in cancer development has significant implications for diagnosis, treatment, and prevention strategies. It seems that proving a causal link between polyomaviruses and GI cancers might provide a novel path for targeted therapies or design and development of specific therapeutic vaccines. In addition, performing research on the possible link can provide insights into the underlying molecular mechanisms of carcinogenesis, potentially leading to the identification of novel biomarkers. This review focuses on polyomaviruses, in particular a recently discovered polyomavirus, MCPyV, and their possible link with human gastrointestinal disorders.

Gluten is a complex mixture of hundreds of related proteins, with the two major groups being gliadin and glutenin. Gliadin primarily affects the viscosity of dough, while glutenin contributes to its strength. Nowadays, there is evidence suggesting an increase in gluten exposure due to advancements in cereal technology. The consumption of gluten can lead to gluten-related disorders (GRDs) development in susceptible individuals. Some GRDs have been strongly associated with an increased risk of developing certain types of cancer. Colorectal cancer and lymphoma are among the most commonly reported malignancies associated with GRDs. Dietary factors, including gluten intake, have been recognized as significant modifiable risk factors for the development of digestive system cancers. The present study aimed to collect current information on the effect of gluten on the incidence of cancer in the general population and among GRDs patients. Protein-Protein Interaction (PPI) Network analysis of common genes between celiac disease (CD) and cancer was also conducted.

Aim: Our objective was to assess the efficacy and safety of adding alpha-pinene (a herbal terpenoid) to quadruple therapy compared to a placebo in improving symptoms and Helicobacter pylori (H. pylori) eradication rates in Functional dyspepsia (FD) patients.

Background: FD is a prevalent upper gastrointestinal condition, and no definitive pharmacological treatment is available for its management.

Methods: We conducted a randomized, double-blinded, placebo-controlled trial on FD patients diagnosed with H. pylori infection. We collected baseline demographic data and assessed FD symptoms in the participants. Patients were randomly allocated to receive either standard quadruple therapy with α-pinene capsules (0.25 mg/day) or quadruple therapy with a placebo for two weeks. We employed a validated questionnaire, the Short Form Leeds Dyspepsia Questionnaire (SF-LDQ), to evaluate FD symptoms. The eradication rate of H. pylori was compared between the two groups one month after completing the treatment regimens. Any reported adverse drug reactions (ADRs) were documented throughout the trial.

Results: Over four months, a total of 66 patients completed the trial. Notably, there were no significant differences in baseline SF-LDQ scores between the two groups (p=0.83); however, a significant divergence emerged at the trial's conclusion (p=0.03). The H. pylori eradication rates did not show notable differences between the two treatment arms (p=0.43). Importantly, there were no dropouts from the trial due to ADRs. Among reported ADRs, participants experienced abdominal pain, headache, diarrhea, and a metallic taste, with no significant variance in incidence rates observed between the two groups (p=0.62).

Conclusion: These findings suggest that α-pinene could be an effective and safe agent for reducing FD symptoms. 

Aim: The study was aimed to find out the efficacy of a stool color card (SCC) in differentiating biliary atresia (BA) from non-BA in resource-limited countries.

Background: stool color screening system was introduced in 2004 which lead to marked improvement in sensitivity of detecting BA.

Methods: This cross-sectional observational study was conducted from January, 2019 through July, 2022 on purposively sampled infants who developed jaundice before three months of age, had direct bilirubin of > 20 % of total with pale stool and dark urine.

Results: 144 cases (male, 96) were included in the study and their mean age at admission was 87.3±37.2 days and mean age at onset of jaundice was 6.1±7.7 days. BA was confirmed in 106 (73.6%) cases and 38 (26.4%) children were in non-BA group. Frequency of persistent pale stool between BA and non- BA were 88 vs 8 (83.0 % Vs 21.0 %) which was highly significant (p=0.000). Mean difference of total and direct serum bilirubin, median alanine transferase and alkaline phosphatase were not statistically significant between two groups. Median of serum gamma glutamyl transpeptidase (GGT) in BA was 570 U/L and in non-BA it was 138.0 U/L which was statistically significant (p=0.000). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SCC were 83%, 78.9%, 91.7%, 62.5% and 81.9% respectively.

Conclusion: SCC has good sensitivity to diagnose BA but failed to prove better specificity to rely simply on it. SCC may be used as early screening tool for prompt referral to appropriate medical care centers for final evaluation of BA.

Aim: The present study examined the protective potential of human adipose tissue-derived mesenchymal stem cells (hASCs) modified to overexpress alpha-1 antitrypsin (AAT), in a mouse model of the liver fibrosis.

Background: For the treatment of end-stage liver diseases, cell therapy has emerged as a promising noninvasive alternative to liver transplantation. Mesenchymal stem cells (MSCs) are being evaluated due to their dual capabilities of promoting liver regeneration and modulating the pathogenic inflammation of the immune system.

Methods: Liver fibrosis was induced in mice via the intraperitoneal injection of carbon tetrachloride (CCl4). MSCs were extracted from the human adipose tissue. After stemness confirmation, the cells were transduced with the lentiviruses containing the AAT gene, and then injected into the mice’s tail vein. Fourteen days’ post-transplantation, mice were sacrificed, and blood and tissue samples were collected for analysis. Important liver enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and total bilirubin (TB), were measured. Histological studies were carried out using the hematoxylin and eosin (H&E), as well as Masson’s trichrome (MT) staining.

Results: Compared to hASCs, treatment with AAT-hASCs resulted in greater reductions in ALT, AST, ALP, and TB, as well as normalized albumin levels. AAT-hASCs promoted enhanced liver regeneration histologically, likely attributable to anti-inflammatory and anti-proteolytic properties of AAT.

Conclusion: These findings indicate AAT-engineered hASCs as a promising cell-gene therapy candidate for further study in liver cirrhosis models.

Aim: Until now, there has been disagreement regarding the prevalence, causes, predisposing factors, and outcome of ACLF (Acute-on-chronic liver failure). As a result, we have undertaken this research study.

Background: ACLF is a complex syndrome with a poor prognosis.

Methods: In this cross-sectional study, we evaluated the prevalence, causes, predisposing factors, and outcomes of adult cirrhotic patients with ACLF and acute decompensation (AD). ACLF was defined based on the criteria established by APASL (Asian Pacific Association for the Study of the Liver). The severity of organ failure was assessed using both EASL-CLIF (European Association for the Study of the Liver- Chronic Liver Failure) and NACSELD (North American Consortium for the Study of End-Stage Liver Disease) scores. To investigate the impact of different independent variables on mortality, survival analysis methods were used.

Results: A total of 156 patients' data were analyzed in this study. The mean age of patients with ACLF (56.62±16.19 years) was significantly lower compared to the AD group (62.30±14.28 years). Nonalcoholic steatohepatitis and infection were the most common causes and predisposing factors in both AD and ACLF groups, respectively, but the difference between the two groups was not statistically significant. The most common organ failures observed were hepatic encephalopathy and respiratory failure. The probability of death at any given time for was significantly higher in ACLF patients than in the AD group (log rank test; P<0.001). The results of Cox regression analysis revealed that low blood pressure (HR 0.97; 95% CI 0.96-0.99; P<0.001) and decreased blood pH (HR 0.53; 95% CI 0.28-0.99; P=0.04) were significant risk factors associated with increased mortality.

Conclusion: ACLF patients had a lower average age and higher mortality rates compared to AD. Nonalcoholic steatohepatitis was found to be the most common underlying disease in ACLF patients, while infections were identified as the predominant predisposing factor. All cases of mortality in the ACLF group were categorized as grade 3 and 4 based on the EASL-CLIF severity score. Hemodynamic instability and metabolic acidosis emerged as the most significant risk factors associated with increased mortality.

Aim: The purpose of this retrospective single-center study was to determine the frequency of sarcopenia and its association with mortality and other morbidities in children with chronic liver disease who had undergone liver transplantation.

Background: Sarcopenia, a muscle-wasting syndrome, is common in patients with advanced liver disease and is associated with increased morbidity and mortality. While sarcopenia in adults has been extensively studied, there is little information in this regard about children and adolescents with chronic liver diseases.

Methods: The study included 108 children and adolescents who had undergone liver transplantation. Sarcopenia was measured using skeletal muscle index at the third lumbar vertebral level and assessed using abdominal computed tomography imaging.

Results: The frequency of sarcopenia in the studied population was found to be 45.7%. Patients with sarcopenia were more likely to be male (P<0.0001), older (P<0.0001), and had lower height-for-age z-scores (P=0.012). Genetic/metabolic diseases were the most common underlying cause of sarcopenia in children. Except for a higher rate of transplant rejection in the sarcopenia group (P=0.035), there was no significant difference in mortality rates (P=0.688) or post-LT complications between the two groups. One year after LT, computed tomography-derived body composition parameters revealed no significant differences between children who survived and those who did not.

Conclusion: Our findings indicated a high frequency of sarcopenia in children with chronic liver disease, implying that more research is needed to better understand its impact on clinical outcomes in this population.

Aim: The purpose of this investigation was to examine the potential association between non-alcoholic fatty liver disease (NAFLD) and adverse maternal and perinatal outcomes during pregnancy.

Background: Gaining insights into the effect of NAFLD on pregnancy outcomes is essential to ensure the health and well-being of mothers and infants.

Methods: This prospective cohort study was conducted at Imam Khomeini and Razi hospitals of Ahvaz City in 2022. Totally, 180 pregnant women in the NAFLD group to 180 in the control group.  In this study, a researcher-made checklist was used to collect the background information, medical history, and lab data during their initial visit using. Follow-up continued until one week after delivery, with pregnancy outcomes assessed. Statistical analysis used student's t-test and the Chi-Square test for group comparisons.

Results: Significant differences were observed between the NAFLD, and control groups in terms of age (P=0.003), BMI (P=0.016), ALT and AST measures (P<0.001), and hypertensive complications (P=0.044). The NAFLD group had higher rates of gestational diabetes (P<0.001) and gestational hypertension (P=0.003). However, no significant differences were found in gestational age at delivery, early postpartum hemorrhage rates, birth weight, and neonatal Apgar scores (P>0.05).

Conclusion: The pregnant women with NAFLD may be at risk for various complications during pregnancy, including a higher prevalence of gestational diabetes, elevated liver enzymes, and higher blood pressure compared to healthy pregnant women. However, the research failed to identify any statistically significant disparities between infants born to mothers with NAFLD and those delivered to healthy mothers in relation to birth weight, Apgar scores, or neonatal mortality.

Aim: This study aimed to determine the distribution of enteric parasitic infections and related risk factors among rural communities of Guilan province, Northern Iran, and to compare the results with the situation in the past.

Background: Intestinal parasitic infections are still considered as a major public health concern, particularly in human communities with poor economy and sanitation.

Methods: This cross-sectional study was performed in rural areas of Masal and Shanderman district from February to December 2020. A total of 917 stool samples were collected and examined for presence of intestinal helminthes and protozoa using direct, formalin-ether and Kato-Katz techniques.

Results: A total of 156 (17%) out of 917 examined individuals were infected with intestinal parasites. The overall prevalence of protozoa, helminths and mixed infections were 11.8% (108/917), 4.5% (41/917) and 0.8% (7/917), respectively. Blastocystis was the most prevalent intestinal protozoa (9.6%) followed by Giardia lamblia (1.9%), Endolimax nana (1.1%), E. coli (0.8%) and Entamoeba hartmani (0.1%). The highest prevalence of intestinal helminths belonged to Trichostongylus spp. (3.5%) and Strongyloides stercoralis (1.3%). Statistical analysis showed significant association between giardiasis and sex (P<0.03). On the other hand, prevalence of enteric helminths was influenced by close contact with livestock, keeping herbivorous animals at home, job, education, and consumption of uncooked vegetables (P<0.05).

Conclusion: The findings indicate a decreasing trend in the prevalence of intestinal parasitic infections in Guilan province in comparison to the past few decades. Hookworm infections, which was very prevalent in the area, are now rare, while trichostrongylosis showed a high prevalence in rural residents of the study area. 

Aim: The aim of this study was to translate and cross-culturally adapt the Constipation Severity Instrument (CSI) and assess its reliability and validity in the Iranian Persian language with chronic functional constipation.

Background:  Chronic functional constipation is a common complaint characterized by a range of symptoms. The use of a validated tool adapted to the culture is an important part of the treatment process.

 Methods:  CSI was translated into Persian language according to Beaton’s guidelines. One hundred and twenty-five patients with chronic functional constipation, according to ROME IV criteria, completed the questionnaires. Face validity was assessed in two qualitative and quantitative forms (impact score), internal consistency and test-retest reliability were assessed by Cronbach’s alpha coefficient and intraclass correlation coefficient (ICC), respectively. Convergent validity was assessed by correlating the total scores of the CSI and the WCSS. The floor/ ceiling effects of the questionnaire were also assessed.

Results:

The impact score of all questions was greater than 1/5. The Cronbach's alpha coefficient for the total score was 0/90 and the ICC was 0/90. The total score of the CSI was significantly correlated with the total score of the WCSS (Spearman's p = 0/74).  No floor/ceiling effects were found.

Conclusion: The Persian version of the CSI is a reliable and valid tool that can be used for psychometric evaluation. Clinicians can also benefit from this questionnaire when assessing treatment outcomes in Iranian patients.

Background: Chronic granulomatous disease (CGD) is a rare disorder normally diagnosed in infancy.

Case presentation: A 27-year-old man admitted with non-specific symptoms of CGD first underwent endoscopy and colonoscopy procedures as primary evaluation of clinical presentation. Eighteen months after the first admission, he was referred to the emergency department for hematemesis and critical situations, such as a severe anemic with Hgb= 2.6 mg/dl. Due to this clinical presentation, emergently critical management was done, and endoscopic investigation showed some ulcers and deformities at the duodenal bulb and jejunum. Other imaging procedures, such as sonography and abdominal CT scans, revealed splenomegaly. He underwent splenectomy, and after that, endoscopic treatment with balloon TTS dilation was scheduled, but this procedure failed. So, we decided to do a gastro-jujenostomy that alleviated the clinical symptoms. After nine months, he was referred to GOO, and endoscopic evaluation showed giant ulceration with severe stricture in the duodenum and a polyp in the jejunostomy. Finally, Based on clinical presentation and pathologic evidence of biopsies, the patient approached CGD as the final diagnosis.

Conclusion: Step-by-step rule out of different highly suspicious diseases may result in a definite CGD diagnosis, and rapid management of these patients may increase the chance of survival.