Gastroenterology and Hepatology from Bed to Bench

Aim: This review sought to evaluate the significance of a functional assessment for liver transplant candidates, i.e., frailty, in the pre-transplant setting and its association with mortality and morbidities.

Background: Liver transplantation (LT) remains the treatment of choice for patients with end-stage liver disease. Due to the shortage of organs for LT, a careful selection of suitable recipients is essential. Frailty, a measure of physiologic reserve and increased vulnerability to stressors, was initially used in geriatrics and then introduced to the field of transplantation for better patient selection.

Methods: PubMed, Scopus, and Web of Science databases were reviewed up until January 2023. The search terms included: “frail*”, “liver”, and “transplant*”. A Meta-analysis was conducted for the hazard ratios (HRs) obtained from the COX regression models. Fifty-four studies were included in this review; ten were included in the meta-analysis.

Results: The prevalence of frailty varied from 2.82% to 70.09% in the studies. Meta-analysis showed that overall frailty had a significant association with mortality ((pooled adjusted HR: 2.66 [1.96−3.63]). Subgroup analyses revealed that both the Liver Frailty Index and Fried Frailty Index were significantly associated with mortality. Furthermore, these studies have demonstrated that this population's frailty is associated with ascites, hepatic encephalopathy, and esophageal varices.

Conclusion: According to emerging evidence, frailty is associated with increased morbidity and mortality of the patients on the LT waiting list. Further randomized trials are required to determine the efficacy and safety of variable interventions in the frail population.

Subepithelial lesions formerly known as subepithelial tumors are incidentally discovered protrusions throughout the gastrointestinal tract with normal overlying mucosa. Studies related to the diagnosis and methods of therapy are limited due to the low incidence and low malignant potential of these lesions. They are commonly originating from the second, third and fourth layers (muscularis mucosa, submucosa and muscularis propria) of gastrointestinal wall. They are reported to be more prevalent in stomach and esophagus than small intestine and colon. Subepithelial lesions located in the stomach and duodenum are more prone to malignancy than the lesions in the esophagus. Despite the presence of different strategies in the management of subepithelial lesions based on their size and location, there is still not a unique consensus on the issue. In this review we have attempted to introduce the most practical approach to the management of gastrointestinal subepithelial lesions based on current guidelines.

Maintaining a healthy balance between commensal, and pathogenic bacteria within the gut microbiota is crucial for ensuring the overall health, and well-being of the host. In fact, by affecting innate, and adaptive immune responses, the gut microbiome plays a key role in maintaining intestinal homeostasis and barrier integrity. Dysbiosis is the loss of beneficial microorganisms and the growth of potentially hazardous microorganisms in a microbial community, which has been linked to numerous diseases. As the primary inducer of circadian rhythm, light can influence the human intestinal microbiome. Photobiomodulation therapy (PBMT), which is the use of red (630-700 nm), and near-infrared light (700 and 1200 nm), can stimulate healing, relieve pain, and reduce inflammation, and affect the circadian rhythm and gut microbiome beneficially. Our focus in this paper is on the effects of PBMT on gut microbiota, to provide an overview of how it can help control gut microbiota dysbiosis-related disorders.

Aim: Because gastric ulcer is a psychosomatic disease involving many psychological factors like assertiveness and cognitive beliefs, this study aimed to investigate the effectiveness of emotion regulation training on pain intensity and quality of life in patients with peptic ulcer disease.

Background: Gastric ulcer, a recurrent and common disease worldwide, is associated with gastrointestinal symptoms and lower health-related quality of life. Psychological factors and stress have been recognized as important contributors to the onset and duration of gastric ulcer, highlighting the need for effective psychological interventions to improve pain intensity and quality of life in patients.

Methods: The research method was semi-experimental and based on the pretest-posttest control group design, with follow-up after three months. The sample included 46 participants selected by a Purposive Sampling method and placed randomly in the experimental and control groups. At first, simultaneously, and under the same conditions, all the participants responded to the Chronic Pain Grade Questionnaire (CPG) and Quality of Life Questionnaire (SF-12). The emotion regulation training was performed on the experimental group. In the end, both groups were evaluated by posttests, and then they were tracked after three months. To analyze data, the ANCOVA test was applied through SPSS 22.

Results: Findings showed that emotion regulation training was meaningfully effective in decreasing pain intensity and increasing life quality (p<0.01), but after three months interval, no significant changes were found in the results.

Conclusion: Due to the results about emotion regulation training protocol that has successfully reduced pain intensity symptoms in PUD patients and increased life quality, it is suggested that this protocol can be added to other treatments for PUD patients.

Aim: Due to weak diagnosis and treatment of PDAC, detection of PDAC possible biomarkers in early stage is the main aim of this study.

Background: Pancreatic ductal adenocarcinoma (PDAC) is known as an exocrine cancer with a 5-year overall survival of 11%.

Methods: Gene expression profiles of early stage of PDAC tissue and normal tissue are downloaded from gene expression omnibus (GEO) and evaluated via GEO2R. The significant differentially expressed genes (DEGs) are investigated via protein-protein interaction (PPI) network analysis and gene ontology.

Results: Among 104 DEGs, ALB, COL1A1, COL1A2, MMP1, POSTN, PLAU, and COL3A1 were pointed out as hub nodes. “Gelatin degradation by MMP1, 2, 3, 7, 8, 9, 12, 13” group of 52 biological terms were identified as the main affected terms.

Conclusion: In conclusion, ALB, MMP1, and COL1A1 genes were highlighted as possible biomarkers of early stage of PDAC. Dysfunction of extracellular matrix was identified as a main event in patients.

Aim: In this study, we aim to propose consensus-based interpretations to enhance both automatic, and manual analysis and then present our recommendations about reflux-related variables to enhance Multichannel Intraluminal (MII) measurements.

Background: Multichannel Intraluminal Impedance-pH (MII-pH) monitoring is the most sensible option to evaluate Gastroesophageal Reflux Disease (GERD), specifically for the patients with normal endoscopy findings, and persistent symptoms without response to Proton Pomp Inhibitor therapy. There were only a few studies on the interpretation of reflux events in MII tracings.

Methods: Several 200 episodes of reflux events were reviewed during several meetings in five steps, to discuss and categorize unresolved issues within existing interpretations, and propose technical principles for accurate characterization of reflux events.

Results: In this study, we show that baseline impedance is determined using a moving average procedure to the impedance data of each channel with a time window of 60 seconds based on this finding; a liquid reflux event is defined as a retrograde 50% drop in baseline impedance, gas reflux event is defined as a rapid increase in impedance greater than 5 kΩ, Mixed liquid-gas reflux is defined as gas reflux occurring immediately before or during liquid reflux.

Conclusion: The reliability of final diagnosis is significantly dependent on the accurate detection of reflux events, which is currently confronting technical limitations. A pathological reflux event propagates to at least three of the impedance sites, according to the literature. We think that taking three impedance locations into account might be too strict.

Background: Antimicrobial peptides such as RT2 showed anticancer properties against wild range of tumors. Molecular mechanism of anticancer effect of RT2 is a challenging subject. Aim: The goal of this study is to investigate the anticancer molecular mechanism of RT2 through protein-protein interaction (PPI) network analysis. For this aim, this bioinformatics evaluation of proteome profile of colon cancer is carried out. Methods: By the application of Cytoscape V.3.9.1 and integrated apps, the profile of interaction network and related centrality is analyzed. Enrichment analysis of hub-bottlenecks was also performed and highlighted biological processes were visualized and determined. Results: A number of 207 differentially expressed proteins were retrieved by PPI network analysis that 10 hub-bottlenecks were introduced. Among these differentially expressed proteins (DEPs), only AKT1 is from the queried DEPs. Key biological processes contributing to RT2 targeting mechanism include “Regulation of fibroblast proliferation”, “Positive regulation of cyclin-dependent protein serine/threonine kinase activity”, “positive regulation of miRNA transcription”, and “fungiform papilla formation”. Conclusion: In conclusion, central proteins Tp53, MYC, EGFR, AKT1, HDAC1, and SRC can be introduced as a targeted biomarker panel of bioactive peptide treatments. However, extensive research are required to establish this claim prior to clinical application.

Aim: This study aims to correct undercounts in cancer data before initiating a population-based cancer registry program, employing an innovative Bayesian methodology.

Background: Underestimation is a widespread issue in cancer registries within developing countries.

Methods: This secondary study utilized cancer registry data. We employed the Bayesian approach to correct undercounting in cancer data from 2005 to 2010, using the ratio of pathology to population-based data in the Golestan province as the initial value.

Results: The results of this study showed that the lowest percentage of undercounting belonged to Khorasan Razavi province with an average of 21% and the highest percentage belonged to Sistan and Baluchestan province with an average of 38%.

The average age-standardized incidence rate (ASR) for all provinces of the country except Golestan province was equal to 105.72 (Confidence interval (CI) 95% 105.35-106.09) per 100,000 and after Bayesian correction was 137.17 (CI 95% 136.74-137.60) per 100,000. In 2010 the amount of ASR before Bayesian correction was 100.28 (CI 95% 124.39-127.09) per 100,000 for women and 136.49 (CI 95% 171.20-174.38) per 100,000 for men. Also, after implementing the Bayesian correction, ASR increased to 125.74 per 100,000 for women and 172.79 per 100,000 for men.

Conclusion: The study demonstrates the effectiveness of the Bayesian approach in correcting undercounting in cancer registries. By utilizing the Bayesian method, the average ASR after Bayesian correction with a 29.74 percent change was 137.17 per 100,000. These corrected estimates provide more accurate information on cancer burden and can contribute to improved public health programs and policy evaluation. Furthermore, this research emphasizes the suitability of the Bayesian method for addressing underestimation in cancer registries. It also underscores its pivotal role in shaping the trajectory of future investigations in this field.

Aim: To evaluate the effects of N-acetylcysteine (NAC) supplementation in cirrhotic patients.

Background: Chronic hepatic inflammation leads to fibrosis and cirrhosis through various mechanisms such as oxidative stress. NAC is one of the intracellular precursors of glutathione that can degrade most reactive oxygen species. Recently, the beneficial effects of NAC in animal and human studies on preventing liver injury progression and improving liver function have been examined. However, more studies on human subjects are still required.

Methods: Well-known cirrhotic patients with a specific etiology and aged 18 to 70 years who referred to the gastrointestinal clinic of Ayatollah Taleghani Hospital from December 2018 to December 2019 were enrolled in the present randomized double-blind controlled trial. Patients in the intervention group received NAC tablets at a dose of 600 mg daily, and the control group received a placebo. Demographic and medical characteristics including whole blood tests, liver and kidney function tests were measured and Child-Pugh and MELD scores calculated for all patients at baseline and after 6 months.

Results: Totally, 60 patients completed the present study (30 patients in the intervention group, and 30 patients in the control group). Hematological and biochemical parameters were normal in both groups with no significant differences at baseline and 6 months after intervention values. Moreover, the renal function indicators including serum creatinine (Cr) and urea (BUN) decreased significantly after intervention. Hepatic parameters also decreased significantly 6 months after intervention. Decreases in the renal and hepatic parameters 6 months after baseline in the control group were not statistically significant.

Conclusion: The results of this study showed that NAC improved hepatic and renal function by decreasing serum urea and creatinine levels but had no significant effect on hematological and biochemical parameters. Furthermore, NAC significantly improved hepatic profiles by decreasing ALT, AST, and ALP in the liver enzymes between the intervention and control groups. Moreover, NAC caused a significant decrease in Child-Pugh and MELD scores.

Hereditary hemochromatosis (HH) is an autosomal recessive metabolic disorder. Mutations in different encoding genes, mostly HFE, lead to iron overload in different organs of the body. We herein report a case of HH caused by a novel variant in the HFE2 (HJV) gene. A 27-year-old man was admitted to the internal medicine ward of Shahid Rahimi Hospital in Khorramabad, Iran, on 6/6/2018. He first sought medical care for impotence and was diagnosed with increased serum iron. He ceased follow-up and was referred to our center with advanced symptoms of hemochromatosis, including central hypogonadism, heart failure, and ascites. The genetic test revealed that he was homozygote for a variant defined as c.950G>A (p.Cys317Tyr) in exon 4 of the HJV gene. The patient’s symptoms improved following medical intervention. At a 4th year follow-up, he was alive and his clinical status was stable.

Atypical/complement-mediated hemolytic uremic syndrome (A-HUS/CM-HUS) is a hereditary or sporadic disease with thrombotic microangiopathy (TMA). Diarrhea is a trigger that can cause attacks of CM-HUS. Although there are opinions that complement system activation plays a role in intestinal inflammation in patients with inflammatory bowel disease, the association of TMA with inflammatory bowel disease (IBD) has rarely been reported. In our case, a CM-HUS case that developed without an additional triggering factor in the course of ulcerative colitis (UC) was successfully treated with eculizumab, and then UC remission was also achieved. In this context, we would like to point out that the irregularities in the alternative pathway of the complement system may cause clinical findings in extra-renal organs, and the complement system may also play a role in the pathogenesis of inflammatory bowel disease. In addition, we think that our case may guide further studies on the usability of anti-complement therapies in treating patients with IBD who are resistant to conventional treatments.

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