Middle East Journal of Digestive Diseases
Volume:14 Issue: 2, Apr 2022

Coronavirus disease 2019 (COVID-19) caused a global pandemic. Since its start, widespread safety measures have been adopted by nations worldwide. Crohn's disease (CD) and ulcerative colitis are two forms of inflammatory bowel disease (IBD). IBD is a common inflammatory illness with a high worldwide incidence. Its clinical symptoms include stomach discomfort, diarrhea, anorexia, and weight loss. Genetics, microbes, cigarette smoking, appendectomy, lack of personal hygiene, using anti-inflammatory agents, vitamin D deficiency, and stress are the main risk factors for IBD. COVID-19 pandemic raised concerns about the exacerbation of COVID clinical manifestations in patients with IBD and increasing the risk of mortality. During COVID-19 pandemic, intestinal inflammation, and promoting adherence need to be controlled using medications and vaccinations as a primary goal. In this review, we reviewed unique concerns about IBD risk in the population as well as management of the disease, and the effectiveness of vaccination during COVID-19 pandemic.

Non-alcoholic fatty liver disease (NAFLD) and its progressive subtype nonalcoholic steatohepatitis (NASH) are the most prevalent liver diseases, often leading to hepatocellular carcinoma (HCC). This review aims to describe the present knowledge of the risk factors responsible for the development of NAFLD and NASH. I performed a literature review identifying studies focusing on the complex pathogenic pathway and risk factors of NAFLD and steatohepatitis. The relationship between NAFLD and metabolic syndrome is well established and widely recognized. Obesity, dyslipidemia, type 2 diabetes, hypertension, and insulin resistance are the most common risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly suggests obesity and type 2 diabetes as risk factors of NASH and HCC. However, other elements, namely gender divergences, ethnicity, genetic factors, participation of innate immune system, oxidative stress, apoptotic pathways, and adipocytokines, take a leading role in the onset and promotion of NAFLD. Pathophysiological mechanisms that are responsible for NAFLD development and subsequent progression to NASH are insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell (HSC) activation, cytokine/adipokine signaling pathways, and genetic and environmental factors. Major pathophysiological findings of NAFLD are dysfunction of adipose tissue through the enhanced flow of free fatty acids (FFAs) and release of adipokines, and altered gut microbiome that generate proinflammatory signals and cause NASH progression. Understanding the pathophysiology and risk factors of NAFLD and NASH; this review could provide insight into the development of therapeutic strategies and useful diagnostic tools.

Immunosuppressive agents used in the treatment of inflammatory bowel diseases (IBDs) could potentially increase the risk of coronavirus disease 2019 (COVID-19). We aimed to compare COVID-19 frequency in patients with IBD with their households and identify the related risk factors.

Firstly, a multi-centered, observational study on 2110 patients with IBD and 2110 age-matched household members was conducted to compare COVID-19 frequency. Secondly, the data of patients with IBD and COVID-19 who had called the COVID-19 hotline were added. Multivariable logistic regression was used to evaluate the effect of age, type and severity of IBD, the number of comorbidities, and medications on the frequency of COVID-19 among the patients with IBD.

The prevalence of COVID-19 in patients with IBD and household groups was similar (34 [1.61%] versus 35 [1.65%]; P = 0.995). The prevalence of COVID-19 increased from 2.1% to 7.1% in those with three or more comorbidities (P = 0.015) and it was significantly higher in those with severe IBD (P = 0.026). The multivariable analysis only showed a significant association with anti-TNF monotherapy (OR: 2.5, CI: 0.97-6.71, P = 0.05), and other medications were not associated with COVID-19.

The prevalence of COVID-19 in patients with IBD was similar to the household members. Only patients with IBD receiving anti-TNF monotherapy had a higher risk of COVID-19 susceptibility. This finding could be attributed to the higher exposure to the virus during administration in health care facilities.

Inflammatory cytokines play roles in the pathogenesis of celiac disease. To introduce new diagnostic markers in patients with celiac disease for easy, fast, low cost, and non-invasive diagnosis, we evaluated the peripheral blood expression levels of interleukin-15 (IL-15), interleukin-17A (IL-17A), interleukin23A (IL-23A), granzyme B (GzmB), T-box transcription factor 21 (TBX21), and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) of patients compared with the healthy controls, which were extracted from public databases organized in a protein-protein interaction network, in this group.

Peripheral blood mononuclear cells were collected from 30 patients with celiac disease and 30 healthy subjects. Total RNA was extracted, and mRNA expression levels of targeted genes were investigated by the quantitative realtime polymerase chain reaction (PCR) method. SPSS software was used for statistical analysis. Receiver operating characteristic (ROC) curve analysis was performed to characterize the diagnostic ability of the studied genes.

The expression of IL-15, IL-17A, IL-23A, GzmB, TBX21, and TNFAIP3 genes in peripheral blood mononuclear cells of patients with celiac disease showed a significant increase compared with the control group. Among them, TNFAIP3, IL23A, and GzmB have better resolution and diagnostic value in differentiating patients with celiac disease from healthy controls.

Our results suggest that TNFAIP3, IL23A, and GzmB could be useful and sensible markers in differentiating patients with celiac disease from healthy controls. However, the diagnostic relevance of other genes recognized by pathway analysis needs to be further investigated.

Liver abnormalities in Celiac disease (CD) are common. The aim of this study was to investigate the children with CD who were followed up in our clinic presenting with elevated aminotransferase levels.

In this study, the data of 419 pediatric patients with CD were retrospectively analyzed, and those with elevated aminotransferase levels during the diagnosis of CD were assessed.

Elevation of aminotransferase levels was found in 66 (15.7%) patients among the 419 patients during the diagnosis of CD. The mean age of these patients was 7.33±3.96 years. Liver enzymes were mildly elevated in 63 (95.4%) patients. However, half of the patients with elevated liver enzymes had a 1.25-fold increase in aminotransferase levels. Patients with hypertransaminasemia had higher weight loss and lower folic acid values compared with patients with normal liver enzymes. Patients’ liver tests were reverted to normal, except for two patients with chronic liver disease, after 9.27±3.16 months of administering a gluten-free diet.

Patients with liver involvement should be investigated for CD. Especially, mildly elevation of aminotransferase levels should be taken into account by pediatricians for Celiac hepatitis.

In this study, efficacy and consistency of disc diffusion (DD) and agar dilution (AD) methods in determining Helicobacter pylori susceptibility to antibiotics were evaluated using Brucella blood agar (BBA) in both methods and tetrazolium egg yolk agar (TEYA) in AD.

Twenty H. pylori isolates were tested for susceptibility to nine antibiotics; metronidazole (MTZ), clarithromycin (CLR), amoxicillin (AMX), tetracycline (TET), ofloxacin (OFX), levofloxacin (LVX), ciprofloxacin (CIP), furazolidone (FRZ), and rifampin (RIF). Antibiotics solutions were impregnated into blank paper disks on BBA in the DD method or added to BBA (ADB) or TEYA (ADT) media in the AD method. Suspensions of H. pylori isolates were surface or spot inoculated on solid media. Plates were incubated in CO2 incubator at 37°C for 5-7 days.

The highest rate of susceptibility to MTZ (65%) was determined by DD method compared with AD method (ADB: 40%, ADT: 30%). Both methods showed similar CLR (85%) and AMX (100%) susceptibility rates. Susceptibility to remaining antibiotics, determined by DD and ADB/ADT media were in respective order as 95%, 75% / 75% for TET, 100%, 95% / 85% for FRZ, 85%, 85% / 75% for OFX, 90%, 95% / 85% for LVX, 90%, 85% / 85% for CIP, and 100%, 85% / 75% for RIF.

DD and AD methods showed consistency in determining 161 (89.4%) susceptibility and resistance and inconsistency in determining 19 (10.6%) susceptibility and resistance (P < 0.05). DD is recommended as a cheap and easy method with the efficacy and precision comparable to the AD method in determining H. pylori susceptibility to antibiotics.

Patients with chronic hepatitis C virus (HCV) usually have different abdominal complaints without any organic lesions. The functional cause of these complaints is claimed in most patients. This study aimed to evaluate functional gastrointestinal disorders (FGIDs) in patients with chronic hepatitis C using Rome IV diagnostic criteria.

This study included 1506 participants (1006 patients with chronic HCV, and 500 controls). All individuals were subjected to taking thorough medical history, basic investigations (complete blood counts, liver and renal functions tests), international normalized ratio (INR), alpha-fetoprotein, HCV RNA PCR (polymerase chain reaction), abdominal ultrasonography, and upper gastrointestinal tract (GIT) endoscopy for patients only), and Rome IV diagnostic questionnaire.

Patients with HCV had symptoms of FGIDs including functional dyspepsia (FD) (P=0.009), early satiety (P=0.002), postprandial distress (P=0.02), epigastric pain (P=0.03), Inflammatory bowel syndrome (IBS) (P<0.001), IBS predominant constipation (P<0.001), IBS predominant diarrhea (P<0.001), and IBS mixed (P<0.001). There were multiple factors for the prediction of FD in patients with HCV, including high body mass index (BMI), education level, positive polymerase chain reaction (PCR), and fibrosis stage. Also, there were multiple factors for the prediction of IBS in patients with HCV, including male gender, high BMI, urban residence, education level, positive PCR, and fibrosis stage.

FD is a prevalent finding in obese patients with HCV and with higher fibrosis scores. IBS is also prevalent in male patients with HCV.

Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal (GI) disorder. In this study, we aimed to evaluate the different aspects of IBS among Middle Eastern residents.

During the study period, patients attending gastroenterology clinics of nine tertiary referral centers in four Middle Eastern couturiers (Iran, Egypt, Kuwait, and Turkey) were evaluated by Rome IV diagnostic criteria, and those who fulfilled the diagnostic criteria of IBS were asked to fill in a questionnaire covering different demographics and clinical aspects.

Overall, during a 6-month period, 509 patients with IBS were included. 41.3% of the participants were male (210 patients), and 37.4% of them had academic education. 50% of the participants were Caucasian, and 34% were Arab, and originally, they were citizens of 18 countries. 77.4% of the participants were residents of subtropical areas, while 22.2% were living in temperate regions. The average age of the participants during the first presentation in subtropical and temperate areas were 38.4 ± 12.19 and 38.06 ± 12.18 years, respectively (P = 0.726). The most common subtypes of IBS in subtropical areas were unclassified (IBS-U, 44.4%), constipation dominant (IBS-C, 27.6%), mixed pattern (IBS-M, 21%), and diarrhea dominant (IBS-D, 6.8%) in descending order while in temperate areas the most common subtypes were IBS-U (43.3%), and IBS-D (22.1%), respectively (P < 0.001). Besides abdominal pain, the most common symptom of patients in each region was bloating (62.2% and 68.1%, respectively, P = 0.246). The rate of depression and anxiety were significantly higher among the residents of temperate areas in comparison with subtropical regions (41.6% vs. 16.5% and 80.5% vs. 58.4%, respectively, P < 0.001).

Although the average age of IBS presentation is the same in subtropical and temperate areas, it seems that in temperate areas, the rate of IBS-D is more prevalent than in subtropical regions. The rate of anxiety and depression are significantly higher among those who searched social media and the internet to get information about their problems.

Exhaustive eccentric exercise (EEE), along with a positive role in weight loss and physiological adaptation, increases liver enzymes and disturbs glucose homeostasis. Many studies have been considered to neutralize the adverse effects of EEE, including vitamin D (Vit D) supplementation. The present study aimed to investigate the effect of short-term Vit D supplementation on the alteration of glycemic variables in response to EEE in patients with nonalcoholic fatty liver disease (NAFLD).

In this clinical trial, 22 overweight women with NAFLD were randomly assigned to control (C; n=11) and experimental (Exp; n=11) groups. C group received a lactose placebo daily with the same color, shape, and warmth percentage; Exp group received 2000 IU of Vit D daily for 6 weeks (42 days). Blood samples were taken to measure the liver enzymes, lipid profile, and Vit D levels alteration at four stages: Pre1(before the first EEE session), post 1 (after the first EEE session), pre 2 (before the second EEE session), and post 2 (after the second EEE session). Repeated measures ANOVA and independent t test were used to analyze the data using SPSS software (version 26) at a significance level of P < 0.05.

The results show a significant increase in glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) levels in both C and Exp groups following the EEE (comparing pre 1 and post 1). Also, after 6 weeks of Vit D supplementation, glucose, insulin, and HOMA-IR increased significantly in both C (P = 0.001, P = 0.001, and P = 0.001, respectively) and Exp (P = 0.001, P = 0.001, and P = 0.001, respectively) groups following EEE (comparison of pre 2 and post 2). However, these increases were significantly lower in Exp group compared with the C group (comparing post 2).

Short-term Vit D supplementation downregulates the increased glucose, insulin, and insulin resistance induced by EEE in patients with NAFLD.

In recent decades, it has been shown that the association between intestinal bacterial imbalance (dysbiosis) and various diseases such as type 2 diabetes can play a role in the development of Alzheimer's and Parkinson's diseases. In this study, the beneficial effects of intestinal microbiota glucagon-like peptide 1 (GLP-1) in cognitive disorders were investigated.

PubMed-Medline, Web of Science, and Scopus were searched to identify experimental studies based on the bacterial strains along with GLP-1 1 expression in preventing or reducing cognitive impairment. Of the 233 studies, six were eligible for inclusion, and the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool was used to evaluate the risk of bias in individual studies.

The results showed that intestinal expression of GLP-1 1 could reduce the intestinal pathogenic genus such as Enterobacteriaceae and was obviously associated with a greater number of beneficial genera such as Lactobacillus and Akkermansia. Also, the neuroprotective effects of Clostridium butyricum with GLP-1 1 in a mice were approved. Therefore, the modulation of the intestinal microbiota, mediated by an increase in the intestinal GLP-1 1 level, consequently improved cognitive function.

In this review, we have indicated that the gut microbiota, by stimulating the expression of the intestinal hormones like GLP-1 1, and also with a beneficial effect in inhibiting some involved genes in inflammation, can declined the development of cognitive disorders.

Immune checkpoint inhibitors (ICIs) have promising clinical activity and are essential medications for patients with several malignancies. However, by deranging the immune system, these novel agents could lead to immune-related adverse events (IRAEs). Hepatotoxicity with checkpoint inhibitors usually results in acute hepatitis or drug-induced liver injury.

This review article discusses the recent clinical evidence available regarding checkpoint inhibitor-induced hepatitis and reviews an approach to their diagnosis and management.

The rate of liver injury with ICIs varies between different checkpoint inhibitors. It has been reported that the incidence of various grades of autoimmune hepatotoxicity with CTLA-4 inhibitors is between 3%-9%.The clinical characteristics of ICIs-induced hepatotoxicity are quite heterogeneous but they are usually in line with an autoimmune induced liver injury. Management of severe ICIs-related hepatitis should consist of termination of the ICI and treatment with corticosteroids.

ICIs have improved patients’ outcomes with different forms of malignancy; however, ICIs-related liver damage is a clinically significant entity in these patients. All patients should be monitored carefully for IRAEs while undergoing treatment with ICIs

Colorectal carcinoma (CRC) rarely metastasizes to the urinary system in isolated form. It usually spreads through direct invasion with intra-ureteric growth or local ureter mucosal metastasis without involving the muscular layer. We present a case of a 63-year-old man who came with uraemic symptoms and a ballotable right kidney. Laboratory and imaging showed acute renal failure with right renal mass suspicious of malignancy and left ureteric stricture causing hydronephrosis. He underwent right radical nephrectomy and left open ureteric stenting plus biopsy sampling. Adenocarcinoma was detected through the evaluation of the specimen. In view that adenocarcinoma rarely occurs in the urinary system, an investigation was carried out to search for the primary source. Colonoscopy was performed, which later showed adenocarcinoma of the rectum. Adenocarcinoma in the renal system should always raise the suspicion of another primary source of malignancy, especially colorectal origin. The advanced stage of this cancer should be managed with the best palliative treatment rather than aggressive surgical intervention.

Endoscopic electrocautery incisional therapy (EIT) is one of the methods for the treatment of refractory esophageal stricture among adult cases. There are few reports among children. Herein we report the successful use of EIT for a 13-year-old boy with an anastomotic stricture who was visited in our hospital due to poor feeding and inability to feed. The boy had undergone gastric resection due to gastric necrosis. This is the first report of electrocautery surgery using a needle knife for the treatment of benign esophageal stricture in our country.

In decompensated cirrhosis, massive ascites and pleural effusion (hepatic hydrothorax) can be complicated by infection, which manifests either as spontaneous bacterial peritonitis (SBP) or spontaneous bacterial empyema (SBE). SBE is a distinct and often underdiagnosed complication having different pathogenesis and treatment strategy when compared with parapneumonic empyema. Hepatic hydrothorax in the absence of ascites is rare in patients with cirrhosis. The occurrence of SBE without SBP or ascites is even more of a rarity in cirrhosis and carries great morbidity and mortality. Here we report a case of an elderly female patient with cirrhosis (Child-Pugh Class B) who had unusual features of isolated right-sided hepatic hydrothorax without clinically evident ascites and was later diagnosed as having SBE based on imaging of the thorax, pleural fluid analysis, and cultures. The patient was initially treated conservatively with antibiotics, and diuretics, and later pigtail insertion and drainage was done.

Coronavirus disease 2019 (COVID-19) had caused pandemia with a high rate of mortality and morbidity. Lung involvement is the main cause of mortality, but central nervous system and cardiac disease, and thromboemboli may participate in increasing mortality. A wide spectrum of organs involvement and complication has been reported as data gathering during the pandemia has progressed. We report a 69-year-old man who was admitted to Imam Khomeini hospital in Tehran and complained of severe abdominal pain and fever. He had been admitted 10 days earlier because of dyspnea and fever. At the first admission, based on the findings in the lung computed tomography (CT) and a positive nasopharyngeal polymerase chain reaction (PCR) test for COVID-19, he was treated with intravenous remdesivir for 5 days and prophylactic anti-coagulant heparin during hospital admission. Two days before the new admission, he was discharged with relative recovery. During the new admission, because of the absence of hypoxemia and leukocytosis diagnostic approach to abdominal pain was planned. In abdominal imaging, evidence of bowel perforation appeared. In laparotomy, suppurative peritonitis and proximal jejunal perforation without definite etiology were seen, and bowel resection and primary anastomosis were done. After 5 days, the patient was discharged in good condition. This case is reported to inform that bowel perforation due to ischemia or vasculitis may complicate the course of COVID-19 and, in cases of gastrointestinal symptoms, should be considered.