Gastroenterology and Hepatology from Bed to Bench

Aim: We performed a systematic review and meta-analysis to identify the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with gastroparesis.

Background: Several studies have suggested an association between SIBO and gastroparesis, which is characterized by delayed gastric emptying in the absence of mechanical obstruction.

Methods: A comprehensive search was performed using MEDLINE, EMBASE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) through January, 2022 for randomized controlled trials and observational studies reporting the prevalence of SIBO in gastroparesis. Pooled prevalence was estimated using a random effects model. Heterogeneity was assessed by using the inconsistency index (I2).

Results: Among the 976 articles identified, 43 studies were selected for full text review. Six studies, with 385 patients, were deemed eligible for inclusion, with a perfect agreement between investigators (kappa=1.0). Overall, 379 patients were diagnosed with gastroparesis by gastric emptying scintigraphy and six were diagnosed with a wireless motility capsule. The pooled prevalence of SIBO was 41% (95% confidence interval 0.23-0.58). SIBO was diagnosed using jejunal aspirate cultures (N=15, 8.4%), lactulose breath test (N=80, 44.7%), glucose breath test (N=30, 16.8%), D-xylose breath test (N=52, 29.1%), and hydrogen breath test (N=2, 1.1%). Heterogeneity was significant and noted to be high at 91%. Only one study reported SIBO diagnosis in controls, therefore no pooled odds ratio was calculated.

Conclusion: SIBO was present in almost half of the patients with gastroparesis. Future studies should examine and identify the association between SIBO and gastroparesis.

Aim: The aim of the present study was to conduct a meta-analysis of the frequency of isoniazid-induced liver injury (INH-ILI) in patients receiving isoniazid (INH) preventative therapy (IPT).

Background: The frequency of hepatotoxicity (drug-induced liver injury: DILI) of antituberculosis drugs has been studied, especially when INH, rifampin, and pyrazinamide are co-administered. However, little is known about the frequency of DILI in patients with latent tuberculosis infection (LTBI), where IPT is indicated.

Methods: We searched PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews for studies reporting the frequency of INH-ILI in patients with IPT using one or more diagnostic indicators included in the criteria of the DILI Expert Working Group.

Results:

Thirty-five studies comprising a total of 22,193 participants were included. The overall average frequency of INH-ILI was 2.6% (95% CI, 1.7-3.7%). The mortality associated with INH-DILI was 0.02% (4/22193). Subgroup analysis revealed no significant differences in the frequency of INH-ILI in patients older or younger than 50 years, children, patients with HIV, candidates for liver, kidney, or lung transplant, or according to the type of study design.

Conclusion: The frequency of INH-ILI in patients receiving IPT is low. Studies on INH-ILI are needed where the current DILI criteria are used.

Aim: This study aimed to evaluate the effect of supplementation with ground flaxseed (GF) on the concentrations of adiponectin, resistin, and visfatin in patients with ulcerative colitis (UC).

Background: Inflammatory bowel disease (IBD) is one of the most common gastrointestinal diseases affecting people of all ages. Adipokines secreted from adipose tissue have been shown to play an essential role in the pathogenesis of UC.

Methods: This trial is an open-labeled randomized controlled trial conducted on 70 patients with UC. The patients were randomly divided into two groups: flaxseed and control. The patients in the intervention received 30 g/day flaxseed powder for 12 weeks. Patients' anthropometric, nutritional, and biochemical factors were evaluated at the beginning and end of the intervention period.

Results: Totally, 64 patients (36 men and 28 women) with a mean age of 31.12±9.67 were included in the final analysis. There was no significant difference between the two groups regarding baseline weight and height (P>0.05). After the 12-week intervention, flaxseed supplementation led to a significant reduction in the resistin (-4.85±1.89 vs. -1.10±2.25, P<0.001) and visfatin concentration (-1.33±1.14 vs. -0.53±1.63, P=0.018). Further, we found a significant increase in the adiponectin levels after the GF supplementation (3.49±1.29 vs. -0.35±0.96, P<0.001).

Conclusion: Flaxseed supplementation could exert beneficial effects on adipokine levels in patients with UC.

Aim: In the current clinical trial study, the potency of mirtazapine and nortriptyline was compared in patients with Functional Dyspepsia (FD) who had anxiety or depression.

Background: FD usually accompanies other psychosocial disorders. According to previous studies, among these disorders, anxiety and depression have the most correlation.

Methods: This randomized clinical trial was organized in Taleghani hospital (Tehran, Iran). In two parallel groups, 42 patients were treated for 12 weeks, with 22 patients receiving 7.5 mg of mirtazapine and 20 patients receiving 25 mg of nortriptyline per day. To gain robust results, the patients with a positive history of antidepressant therapy, organic diseases, alcohol abuse, pregnancy, and major psychiatric disorders were excluded from the study. The subjects were examined by three questionnaires, including Nepean and Hamilton questionnaires. The patients were asked to answer the questions three times during the study: once before the onset of the treatment,  second during the treatment, and third at the end of the treatment.

Results: Based on Gastrointestinal (GI) manifestations, mirtazapine, in comparison to nortriptyline could significantly suppress the signs and symptoms of FD, including epigastric pains (P=0.02), belching (P=0.004), and bloating (P=0.01). Although the results from the use of mirtazapine compared to the use of nortriptyline (P=0.002) showed a lower mean depression score on the Hamilton questionnaire, no significant differences were found between the effects of these drugs on the anxiety scale of patients (P=0.091).

Conclusion: Mirtazapine is more effective for GI symptoms related to gastric emptying. Considering the level of anxiety, mirtazapine, compared to nortriptyline, revealed better outcomes in FD patients suffering from depression.

Aim: The present study aimed to study the prevalence of various latent infections in pre-transplanted patients.

Background: Due to chronic immunosuppressive therapy, patients receiving organ transplants are at risk for reactivation of various infections. Due to the complications in the course of diagnosing and treating the post-transplant infection, screening transplant recipients and donors is vital.

Methods: This retrospective cohort study was performed between March 2020 and 2021. A total of 193 patients receiving a liver transplant in Taleghani Hospital, Tehran, Iran were enrolled.

Results: One-hundred and three (53.4%) patients were men, with an average age of 48.4 ± 13.3 years. Among viruses, 177 (91.7%) patients had a positive IgG titer for CMV. Anti-EBV IgG was positive in 169 (87.6%) patients. One-hundred and seventy-five (90.7%) patients had a positive IgG titer for the VZV. One-hundred and sixty-six (86.0%) cases had positive IgG anti-HSV antibodies. According to our findings, none of the patients were infected with HIV, but 9 (4.7%) cases and 141 (73.1%) had positive anti-HCV and anti-HAV IgG antibodies, respectively. HBV surface (HBs) antigen was also reported positive in 17 (8.8%) patients, while the HBs antibody was positive in 29 (15.0%) patients.

Conclusion: In our study, most of the patients had positive serology for latent viral infections such as CMV, EBV, VZV, and HSV, but the prevalence of latent tuberculosis and viral hepatitis was low among transplant candidates.

Aim: We evaluated the Persian version of the pediatric constipation score-parent report (PCS) validity and reliability.

 Background: Functional constipation in children results in physical and psychological problems. Therefore, it is necessary to utilize a questionnaire to assess the health-related quality of life in children with chronic constipation.

 Method: First, our team translated the English version of the questionnaire into the Persian language. Second, we collected the psychometric properties of the Persian version in 149 children with constipation referred to a pediatrics hospital by an expert team. We assessed content validity through the content validity index (CVI) and content validity ratio (CVR). We evaluated the construct validity by exploratory factor analysis, and reproducibility was tested based on test-retest reliability using the intra-class correlation coefficient (ICC). We calculated internal consistency using Cronbach's α. we also evaluated the ceiling or floor.

Results: Results showed acceptable CVI in relevancy, clarity, and simplicity, acceptable CVR for all items, moderate internal consistency (Cronbach's alpha= 0.548), and almost perfect reproducibility (ICC= 0.93). We saw no ceiling or floor effect.

Conclusion: The Persian version of PCS showed good validity and reliability in children with functional constipation in Iran. Therefore, we can use it in clinical and research domains in Persian-speaking countries.

Aim: This study aims to confirm previous fundamental in vitro findings about the PIWIL2 gene by investigating the effects of its overexpression on cell cycle, proliferation, apoptosis, and stem cell expression markers in colorectal cancer cells (CRC cells) at in vivo level.

Background: PIWIL2 has a critical role in maintaining cellular stemness and proliferation. PIWIL2 is an oncogene whose expression in CRC is associated with the occurrence, metastasis, and poor prognosis.

Methods: SW480 cells harboring expression vectors with/without PIWIL2 were cultured and inoculated in BALB/c nude mice. Tumor formation and growth were monitored every 3 days. On the 28th day after inoculation, the tumors were harvested for their total RNA extraction, and the expression profiling of the candidate genes was performed by Real-time PCR.

Results: Our results for the expression profiling of the xenografted tumors showed a significant increase in the expression of cancer stem cell markers, including CD24, CD133, and pluripotency marker SOX2 in the PIWIL2 over-expressing xenografts, compared to the control cell line. Moreover, PIWIL2 dramatically promoted the anti-apoptotic pathway by inducing STAT3 and BCL2-L1 genes in the PIWIL2 over-expressing xenografts, along with the up-regulation of Cyclin D1 and Ki-67 genes.

Conclusion: This research supports our prior in vitro findings, highlighting the critical role that PIWIL2 plays in the development of CRC and its substantial promise as a leading candidate for CRC-targeted therapy. 

Aim: This study aims to evaluate whether biochemical alterations caused by methylglyoxal (MG), improves by the administration of gallic acid (GA), crocin (Cr), and metformin (MT) in the liver.

Background: MG is produced naturally through various physiological processes, but high levels of MG cause inflammation in hepatocytes. Normal liver function is essential for maintaining glucose homeostasis. Gallic acid and crocin can reduce inflammation.

Methods: This experiment was done in 5 weeks. 50 male NMRI mice were randomly divided into 5 groups (n=10): 1) Control, 2) MG (600 mg/Kg/d, p.o.), 3) MG+GA (30 mg/kg/day, p.o.), 4) MG+Cr (60 mg/kg/day, p.o.), 5) MG+MT (150 mg/kg/day, p.o.). After one week of habituation, MG was administered for four weeks. Gallic acid, crocin, and metformin were administered in the last two weeks. Biochemical and histologic evaluations were assessed after plasma collection and tissue sample preparation.

Results: Gallic acid and crocin-received groups significantly reduced fasting blood glucose, total cholesterol, triglyceride levels, and elevated insulin sensitivity. Administration of MG exerted a marked increase in the levels of hepatic enzymes. Treatment with gallic acid, crocin, and metformin significantly decreased them. The altered levels of inflammatory factors in the diabetic group were significantly improved in the diabetic-treated groups. High levels of steatosis and red blood cells (RBCs) accumulation in the MG group markedly recovered in other treated mice.

Conclusion: Harmful effects of accumulated MG in the liver of diabetic mice were effectively attenuated by using gallic acid and crocin.

Aim: This study aimed to compare the effect of the same volume of moderate- and high-intensity aerobic exercise on patients' liver steatosis and fibrosis.

Background: Exercise is known strategy to deal with Non-Alcoholic Fatty Liver Disease (NAFLD).

Methods: This Randomized Control Trial was performed on 60 patients randomly assigned to three arms of the study (1:1:1). Fibrosis and steatosis of liver including Control Attenuated Parameter (CAP) determined using Transient Elastography (TE). The control group was advised to adjust their lifestyle, as a routine management. The intervention groups additionally, participated on supervised exercise programs with two different intensities but the same volume of 1000 KCal per week. The intensities of 50% and 70% of V02 reserve were considered for moderate-intensity and vigorous programs, respectively.

Results: On six-month follow-up, none of outcomes were statistically significant among three arms of study. However, changes in some outcomes were reached to statistically significant difference in follow-up in comparison with baseline. The mean of CAP score changes was -19.43 (31.43) (P=0.03), 9.92 (26.81) (P=0.21), and 14.61 (18.03) (P=0.01) in control, moderate- and high-intensity groups, respectively. In the high-intensity group, in addition to steatosis, this difference was also observed in the rate of fibrosis. Besides, the level of serum aminotransferases in the group with moderate exercise after six months had a significant decrease compared to baseline. (P=0.01)

Conclusion: Improvement in steatosis and fibrosis was more evident in high- intensity group. As the rate of drop out was high, caution is needed in interpretation of the results.

Aim: Development of an amplification method for further investigation of HBV S gene variation patterns.

Background: Pre-S/S variants in patients with chronic HBV infection may contribute to the progression of liver damage and Hepatocellular carcinoma (HCC).

Methods: This study was performed on ten patients with chronic HBV infection. Viral DNA was extracted from patient's plasma, primer design was performed, and a semi-nested PCR method was set up to amplify the pre-S/S region of HBV genome. Subsequently, sequencing was performed to analyze the variants of this region.

Results: In the current study, the semi-nested PCR method was successfully set up, and types of variation in the studied samples were investigated.

Conclusion: Pre-S/S variants should be routinely determined in HBV carriers to help identify individuals who may be at a high risk of less favorable liver disease progression. This study showed that the technique could accurately amplify the pre-S/S region, and the product can be successfully used for variation detection by direct sequencing.

Aim: To assess the role of granulocyte colony-stimulating factor (GCSF) in the patients with severe alcoholic hepatitis (SAH) using real world experience in the United States.

Background: There are few effective treatments for severe alcoholic hepatitis, which has a significant fatality rate. GCSF has been associated with improved survival in a small number of Indian studies, while there is a dearth of information from other parts of the globe.

Methods: We performed a single-center retrospective study of consecutive patients admitted to a tertiary care, liver transplant center with severe alcoholic hepatitis from May 2015 to February 2019. The patients receiving GCSF (5μg/kg subcutaneously every 12 hours for 5 consecutive days) (n=12) were compared to the patients receiving standard of care (n=42).

Results: Thirty-day, 90-day and 1-year mortality rates was similar among groups (25% vs. 17%, P=0.58; 41% vs 29%, P=0.30; 41% vs 47%, P=0.44, respectively). There was no difference in liver transplant listing and orthotopic transplantation among groups.

Conclusion: In this real-world, United States-based study, GCSF does not improved survival in the patient with several alcoholic hepatitis compared to standard of care.

Extramedullary hematopoiesis is a common complication of ineffective erythropoiesis and bone marrow replacement disorders. Owing to its nonspecific presentation and or radiological appearances, diagnosing focal intrahepatic extramedullary hematopoiesis is challenging, and it is often misdiagnosed as a hepatic tumor. Herein, we describe the case of a 48-year-old male with thalassemia and AE Bart’s disease with secondary hemochromatosis and cirrhosis who developed focal intrahepatic extramedullary hematopoiesis mimicking hepatocellular carcinoma. After hepatic resection, extramedullary hematopoiesis was not observed at any site, including in the remaining liver, at 4-year follow-up.

Collagenous sprue is a rare and unrecognized cause of diarrhea and weight loss, mainly affecting the duodenum and small bowel. The clinical picture often resembles that of coeliac sprue, the main differential diagnosis, albeit being refractory to gluten-free diet. The histological features are fundamentally characterized by the deposition of collagen beneath the basement membrane of gut mucosa. Treatment should be initiated as soon as the diagnosis is established, as to prevent the progression of fibrosis. We will describe the case of a 76-year-old woman with collagenous sprue, the underwent diagnostic workup, histopathological examination, and response to treatment.

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