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.

Introduction

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

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 of one or more diagnostic indicators included in the criteria of the DILI Expert Working Group.

Results

Thirty-five studies comprising a total of 22193 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). In the subgroup analysis, no significant differences were found in the frequency of INH-ILI in patients older or younger than 50 years, children, patients with HIV, candidates to liver, kidney or lung transplant, or according to the type of study design.

 Conclusions

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

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

Methods: This trial is an open-labeled randomized controlled trial conducted among 70 patients with UC. Patients were randomly divided into two groups: flaxseed and control. Patients in the intervention were 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.

Finding: Totally, 64 patients (36 men and 28 women) with a mean age of 31.12 ± 9.67 were included in the final analysis. There wasn’t any significant difference between the two groups regarding baseline weight and height (p>0.05). After the 12 weeks' 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). Moreover, 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: It has been reported in this study that flaxseed supplementation could exert beneficial effects on adipokine levels in patients with UC.

Background: Functional dyspepsia usually accompanies other psychosocial disorders. According to previous studies, among these disorders, anxiety, and depression have the most correlation. In the current clinical trial study, we compared the potency of mirtazapine and nortriptyline in FD-patients who presented anxiety or depression.

Study design: This randomized clinical trial has been organized in Taleghani hospital (Tehran, Iran). In two parallel groups, 42 patients (22 patients in Mirtazapine 7.5 mg/daily arm and 20 in the Nortriptyline 25 mg/day group) were treated for 12 weeks. The patients with Positive history of antidepressant therapy, organic diseases, alcohol abuse, pregnancy, major psychiatric disorders were excluded. They were examined by three types of questionnaires (Nepean questionnaire, Hamilton questionnaires) three times: 1) before the onset of treatment, 2) during the treatment, and 3) at the end.

Results: Based on Gastrointestinal (GI) manifestation, Mirtazapine in comparison to Nortriptyline could significantly suppress the signs and symptoms, including epigastric pain (P=0.02), belching (P=0.004), and bloating (P=0.01). Although The results revealed that the Mirtazapine with the lower mean depression score of the Hamilton questionnaire at the end of the treatment led to a better result compared to Nortriptyline (P=0.002), but, there are no significant differences 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. Whereas, Mirtazapine revealed better outcomes in FD-patients with depression, but according to the level of anxiety, Mirtazapine showed no better outcome in comparison with Nortriptyline.

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

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

Results: One-hundred and three (53.4%) patients were men, with a mean 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%) had positive IgG anti-HSV antibodies. According to our findings, none of the patients were infected with HIV, but 9 (4.7%) 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: Due to changes in organ transplantation methods and changes in the response of infectious organisms to their treatment methods, the epidemiology of infections in recipients should always be examined over time. These new transplantation methods may lead to widespread changes in the epidemiology of transplant recipient infections and even the introduction of new pathogens.

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.

Abstract:

Aim: This study is aimed to confirm previous fundamental in vitro results investigating the role of PIWIL2 overexpression in cell cycle, proliferation, apoptosis and stem cells expression markers in colorectal cancer cells (CRC cells) at in vivo level.

Background: PIWIL2 has critical roles in maintaining the cellular stemness and proliferation. PIWIL2 is an oncogene whose expression in CRC is associated with 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 day 28^th after inoculation, the tumors were harvested for their total RNA extraction, and the expression profiling of the candidate genes were 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, as well as pluripotency marker SOX2 in the PIWIL2 over-expressing xenografts, compared to the control cell line. Moreover, PIWIL2 dramatically promoted the anti-apoptotic pathway through 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: Our research supports our prior in vitro findings, highlighting the critical role PIWIL2 plays in the development of CRC and its significant potential to be a leading candidate for CRC targeted therapy. 

Key words: PIWIL2, colorectal cancer, stemness, proliferation, apoptosis

Aim: This study aims to evaluate whether biochemical alterations caused by methylglyoxal (MG), improves by 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. GA and Cr can reduce inflammation.

Methods: In this study, 50 NMRI mice were divided into 5 groups (n=10): Control, MG (600 mg/Kg/d, p.o.), MG+GA (30 mg/kg/day, p.o.), MG+Cr (60 mg/kg/day, p.o.), MG+MT (150 mg/kg/day, p.o.). Our study was conducted at five weeks. After diabetes induction (forth weeks), GA, Cr, and MT were administered. Biochemical and histologic evaluations were assessed after plasma collection and tissue samples preparation.

Results: Ga and Cr receiving groups significantly reduced FBG, total cholesterol, triglyceride levels, and elevate insulin sensitivity. Administration of MG exerted marked increase in the levels of hepatic enzymes. Treatment with GA, Cr, and MT significantly decreased them. Inflammatory factors increased in MG group. GA, Cr, and MT significantly improved these variables. High levels of steatosis and RBCs accumulation in MG group, markedly recovered in other treated mice.

Conclusion: Harmful effects of accumulated MG in the liver of diabetic mice can be effectively attenuated by the use of GA and Cr.

Introduction: Exercise is probably regarded as an appropriate way to prevent and treat Non-Alcoholic Fatty Liver Disease (NAFLD) - the most common chronic liver disease. This study aimed to evaluate the effect of the same volume of moderate and high intensity aerobic exercise on patients' liver status.

Methods: This study was performed as a parallel RCT on 60 patients with NAFLD in 3 groups of 20 people. 40 patients remained in the study after 6 months of follow up. Fibrosis and steatosis of liver including Control Attenuated Parameter (CAP) determined by fibroscan device. 

The control group, as a routine management, was advised to adjust their lifestyle and received nutritional recommendations. The intervention groups additionally, participated on supervised exercise programs with two different intestines but the same volume of 1000 KCal per week. The intensities of 50 and 70 percent of V02 reserve were considered for moderate and vigorous programs respectively.

Results: On 6 months’ follow-ups, the mean of CAP scores changes were -20 (P=0.04), -10 (P=0.001), and -15 (P=0.002) within control, moderate, and high intensity groups, respectively. In the intervention groups, in addition to steatosis, this difference was also observed in the rate of fibrosis. The means of fibrosis changes were 0 (P=0.85), -0.5 (P=0.05), and -0.7 (<0.0001) within control, moderate, and high intensity groups, respectively. No significant differences between groups could be detected in steatosis, fibrosis, anthropometric, and laboratory findings were found.

Conclusion:

The data yielded by the present study appear to suggest that independent of intensity, aerobic exercise can improve the course of fibrosis and steatosis in NAFLD patients.

Aim: Development of a semi nested PCR method for HBV Surface gene amplification

Background: Pre-S/S variants in patients with chronic HBV infection may contribute to the progression of liver damages and HCC.

Methods: This study was performed on 10 patients with chronic HBV infection. DNA was extracted from patients' blood, primer design was performed, and a semi nested PCR method was used to amplify preS/S region. 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 the variants such as deletion 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 and the technique we used in this field has been useful and can lead to accurate analysis of the pre-S/S region in terms of variants.

Background: Severe alcoholic hepatitis is a disease with high mortality and poor medical options. Few studies from India have reported survival benefit with granulocyte colony-stimulating factor (GCSF), though real-world data and data outside of Asia is lacking.

Materials and 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. Patients receiving GCSF (5μg/kg subcutaneously every 12 hours for 5 consecutive days) (n=12) were compared to patients receiving standard of care (n=42).

Results: Thirty-day, 90-day and 1-year mortality rates was similar between 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 between groups.

Conclusions: In this real-world, United States-based study, GCSF does not improved survival in 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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