Editorial


Review Article


Non-alcoholic fatty liver disease is one of the main liver diseases worldwide. The most common cause of death in patients with non-alcoholic fatty liver disease is cardiovascular diseases. Currently, the relationship between them is well established. Indeed, identical reasons may contribute to the development of cardiovascular diseases and non-alcoholic fatty liver disease, with lifestyle factors such as smoking, sedentary lifestyle with poor nutrition habits, and physical inactivity being major aspects. This review focuses on potential pathophysiological mechanisms of cardiovascular disorders in non-alcoholic fatty liver. PubMed, EMBASE, Orphanet, MIDLINE, Google Scholar, and Cochrane Library were searched for articles published between 2006 and 2022. Relevant articles were selected by using the following terms: “Non-alcoholic fatty liver disease”, “Сardiovascular diseases”, “Pathophysiological mechanisms”. Then the reference lists of identified articles were searched for other relevant publications as well. The pathophysiological mechanisms of cardiovascular disorders in non-alcoholic fatty liver remain largely speculative and may include systemic low-grade inflammation, atherogenic dyslipidemia, abnormal glucose metabolism and hepatic insulin resistance, endothelial dysfunction, gut dysbiosis, as well as the associated cardiac remodeling, which are influenced by interindividual genetic and epigenetic variations. It is clear that the identification of pathophysiological mechanisms underlying cardiovascular disorders in non-alcoholic fatty liver disease will make the choice of therapeutic measures more optimal and effective.

An update: the comparison of Portal Hypertensive Gastropathy and Gastric Antral Vascular Ectasia

Mohsen Rajabnia, Behzad Hatami, Pardis Ketabi Moghadam, Mahsa Mohammadi, Mitra Rafizadeh, Forogh Mangeli, Mobin Fathi, Ali Jahanian

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2561

Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are two distinct entities that are frequently mistaken with each other, because they present with similar manifestations. This issue may cause catastrophic outcomes, since each one of them has a unique pathophysiology and thereby their management is totally different. There are clinical clues that helps the physicians to distinguish these two. Upper endoscopy and biopsy are often required to establish the diagnosis. In this review, we ought to discuss about different aspects of the both conditions and highlight the clinical evidences that may help us identify the disease and manage it appropriately.

An Updated Review on Drug-Induced Esophagitis and A Helpful Management for Healthcare Providers

Saeed Abdi, Farnoosh Masboogh, Maryam Nazari, Mohammad Abbasinazari

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2591

In recent decades, the number of cases developing drug-induced esophagitis (DIE) has been identified to an increasing extent, which shows the significance of detecting medicines capable of causing this adverse reaction. This study aims to provide an updated review on recent case reports of DIE, evaluate the possible mechanism of this side effect, and provide helpful management. Data was gathered through searching three databases, including PubMed, Medline, and Cochrane. Seven drug categories were evaluated, including antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), cardiovascular medicines, bisphosphonates, chemotherapeutic agents, miscellaneous agents, and supplements. According to our findings, retrosternal pain, heartburn, odynophagia, and dysphagia are the typical symptoms. In most cases, DIE is a self-limiting side effect that can resolve by removing the causative agent and supportive therapy.

Original Article


Sequence variations of Epstein–Barr virus LMP1 gene in gastric cancer and chronic gastritis isolates from Iranian patients

Behrang Sarshari, Seyed Reza Mohebbi, Mehrdad Ravanshad, Shabnam Shahrokh, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2578

Aim: The aim of this study was to investigate sequence variations in the C-terminus of latent membrane protein 1 (LMP1) in Epstein-Barr virus (EBV) isolates from Iranian patients with chronic gastritis or gastric cancer (GC).


Background: EBV is an important member of gammaherpesviruses that causes persisting latent human infection. LMP1 is the essential viral oncoprotein that is a key element for B cells immortalization. LMP1 contains of a small twenty-four amino acid cytoplasmic N-terminal region, six transmembrane segments and a two hundred amino acid cytoplasmic C-terminal domain. Most LMP1-mediated signal transduction events are moderated by some functional parts of cytoplasmic C-terminal domain. Sequence variations of LMP1 gene have been described in numerous EBV-isolates.


Methods: This study included 32 EBV positive biopsy tissues from patients with gastric cancer and patients with chronic gastritis. The C-terminal nucleotide sequences of LMP1 were amplified using nested-PCR and analyzed by DNA sequencing.


Results: In the carboxyl-terminal site of patients was observed 4 to 8 copies of the 11 repeat elements (codon 254–302) and there was no relationship between the number of repeat sequences and disease status. The 30-bp deletion corresponding to codon 345–354 of the B95-8 strain was observed in 34% isolates and remaining samples were non-deleted. In group of gastric cancer, a high number of 33-bp repeats (>5 repeats) was observed in 30-bp-deletion (100%) than non-deleted (42%) isolates and the difference was also statistically significant. In addition, the analysis revealed that a gastritis isolate may be result of recombination between Alaskan and China1 strains.


Conclusion: Overall, our results showed no association between the C-terminal sequence variations of LMP1 and malignant or non-malignant isolate origin.

The most common form of esophageal cancer is esophageal squamous cell carcinoma (ESCC). miRNAs are well recognized as having a critical regulatory role in human cancer, but their responsibilities and mechanisms of miRNA-mRNA in ESCC are yet unknown. As a result, the miRNA microarray dataset (GSE66274) and gene expression microarray dataset (GSE38129) with similar samples were analyzed to better understand the miRNA-mRNA interactions. The differentially expressed miRNAs (DEmiRNAs) and differentially expressed mRNAs (DEmRNAs) were identified using the LIMMA package in R. In total, 478 DEmRNA (224 up-regulated & 254 down-regulated) and 39 DEmiRNA (15 up-regulated & 24 down-regulated) were screened out. miRNA-mRNA interactions were analyzed by RNAInter database, then the miRNA-mRNA network was visualized by Cytoscape software. On the other hand; ClusterProfiler packages were used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for DEmRNA as targets of DEmiRNAs. KEGG pathway analysis indicated that the p53 signaling pathway, ECM−receptor interaction, and AGE−RAGE signaling pathway were significant. Besides, cellular response to amino acid stimulus, negative regulation of apoptotic signaling pathway, and endoderm formation was most prevalent in the biological process category. Additionally, the collagen−containing extracellular matrix, actomyosin complex collagen trimers and basement membrane, and extracellular matrix structural constituent were more enriched. Taken together, the present survey provided evidence that could support the prognosis of esophageal tumors in the future.

Aim: The objective of this double-blinded placebo-controlled randomized clinical trial was to evaluate prophylactic use of acetylcysteine for prevention of liver injury in patients with severe COVID-19 pneumonia under treatment with remdesivir.


Background: Liver injury is reportedly common in patients with severe COVID-19 pneumonia, and can occur not only as a result of disease progression but as an iatrogenic reaction to remdesivir.


Methods: A total of 83 adult patients with severe COVID-19 pneumonia were randomly assigned in parallel groups to receive either acetylcysteine or placebo. All the patients received standard care according to institutional protocols including remdesivir for a total of five days. One gram acetylcysteine was administered intravenously every 12 hours for 42 patients, and 41 patients received the same volume of 0.9% sodium chloride as placebo.


Results: After 5 days, median aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in the acetylcysteine than in the placebo group. Of those who received placebo, 30 (73.2%), 4 (9.7%) and 3 (7.3%) patients had serum AST levels elevated between 1-2.5, 2.5-5 and over 5 times the upper limit of normal (ULN), respectively; while in the acetylcysteine group, 33 (78.6%) and 0 patients had AST levels between 1-2.5 and over 2.5 times ULN, respectively (p-value=0.037). In the acetylcysteine group, 23 (54.8%), 1 (2.4%) and 1 (2.4%) patients had serum ALT levels elevated between 1-2.5, 2.5-5 and over 5 times ULN, respectively; while in the placebo group, 24 (58.5%), 7 (17.1%) and 1 (2.4%) patients had serum ALT levels between 1-2.5, 2.5-5 and over 5 times ULN, respectively (p-value=0.073).


Conclusion: Intravenous administration of acetylcysteine significantly prevents liver transaminases elevation and liver injury in seriously ill COVID-19 patients treated with remdesivir. (Trial Registration: www.irct.ir identifier, IRCT20210726051995N1)

Down-regulation of TP53 Is a Highlighted Molecular Event in Gastric Ulcer

Reza Vafaee, Somayeh Jahani Sherafat, Mostafa Rezaei –Tavirani, Nayebali Ahmadi

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2544

Background:  Gastric ulcer as an acid related gastrointestinal disease is known as a one of the most public gastrointestinal disorders.


Aim: Explore the crucial dysregulate proteins and biochemical pathways in gastric ulcer is the main aim of this projects.


Methods: Number of 100 proteins from STRING database were analyzed by cytoscape and its applications to find the central proteins and also the related biochemical pathways. Action map analysis was applied to explore regulatory relationship between the critical proteins.


Results: Common results of network analysis and gene ontology revealed that IL6, ALB, TNF, INS, IL1B, IL10, TP53, CXCL8, and PTGS2 are the highlighted related proteins in gastric ulcer. Six clusters of biochemical pathways including “Response to external stimulus”, “multicellular organismal process”, “regulation of biological quality”, “cellular response to stimulus”, “cellular response to chemical stimulus”, and “transport” were identified as the dysregulated pathway in patients.


Conclusion: It seems that down-regulation of TP53 by IL2, PTGS2, and TNF is a main process that occurs in patients.  

Prevalence of Enteric Adenovirus Gastroenteritis and Co-infection with Rotavirus in under-Five-Year-Old Children, Qom-Iran

Saeed Shams, Javad Tafaroji, Mohammad Aghaali, Nayebali Ahmadi, Hosein Heydari, Seyed Dawood Mousavi Nasab, Vineet Kumar Maurya

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2483

Aim: The study was performed to determine the prevalence and co-infections with Rotavirus in children under five years of age.


Background: Gastroenteritis-associated viral infections are a cause of death among young children in Worldwide, especially in developing countries. The species F Adenovirus (40 and 41) is responsible for rang of the cases of acute diarrhea among infants children.


Methods: During 9 months, 130 children with intestinal symptoms referred to the pediatric ward of the hospital were enrolled in this study. After collecting fecal samples, viral genomes were extracted; and then amplified and typed using polymerase chain reaction by Adenovirus-specific primers. Rotavirus was detected in our previous study on the same samples and the results were used to evaluate for co-infection.


Results: Mean age of the patients was 32.09±32.68 months. 60% and 40% of the patients were males and females, respectively. Adenovirus infection was identified among 23 cases of the children (17.7%), 21 cases (91%) type 41 and 2 cases (9%) type 40. Fever was the most clinical manifestation and there were no significant relations between the clinical symptoms and the Adenovirus infection. Co-infection was found in only 5 cases (21.7%) of patients.


Conclusion: These data show that Adenovirus infection plays an important role in acute diarrheal infection in Qom. In addition, our findings indicated that there was a co-infection between Adenovirus and Rotavirus, stating a serious problem in children less than five years of age.

Detoxification of aflatoxin M1 from the reconstituted milk by probiotics Saccharomyces boulardii, Lactobacillus casei, and Lactobacillus acidophilus, using the HPLC method

Sama Rezasoltani, Niloufar Amir Ebrahimi, Reza Khadivi Boroujeni, Hamid Asadzadeh Aghdaei, Mohsen Norouzinia

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2402

Abstract


Aflatoxins are poisonous substances produced by certain kinds of fungi that are found naturally all over the world. They can contaminate food crops and pose a serious health threat to humans and livestock. The current study aimed at removing aflatoxin from the reconstituted milk by adding three probiotics Saccharomyces boulardii, Lactobacillus casei and Lactobacillus acidophilus.


Materials and Methods


The probiotics of S. boulardii , L.casei and L. acidophilus with 109 and 107 CFU concentration were exposed to aflatoxin M1 (0.5 and 0.75 ng/ml). The ELISA test was performed using 144 falcon tubes containing AFM1. Sterile water was added to each probiotic pellet and finally added to pre-prepare contaminated milk. After the specified times, the milk layer was analyzed to measure AFM1 levels. Each sample was analyzed using HPLC system. Subsequently, the percentage of AFM1, which was bound to the bacterial suspension, was calculated.


Results


boulardii had the greatest ability in AFM1 removal from milk medium (96.88 ± 3.79) over time in the early hours with increasing concentration of AFM1 (0.75 ng/ml) and a concentration of 109 CFU/ml at 37 °C. The highest activity of L.casei in the removal of AFM1 toxin was observed at a concentration of 107 CFU/ml in 0.75 ng/ml AFM1 level and 37 °C. And the highest marginal estimation percentage of AFM1 removal from the milk medium at 4 °C in initial minutes belonged to L. acidophilus.


Conclusion


The results revealed the possibility of using S. boulardii in combination with selected strains of LAB (L.casei, L. acidophilus) in detoxification of AFM1-contaminated milk.

Medical Education


Education case: A case-based approach to overlap autoimmune liver disease in patient with ulcerative colitis

Amir Sadeghi, Hamid Asadzadeh Aghdaei, Pardis Ketabi Moghadam, Forough Mangeli, Niloufar Salehi, Mohsen Rajabnia

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2332

Abstract


Simultaneous occurrence of immune-based gastrointestinal diseases and autoimmune hepatitis although is not common but is of clinical importance. Some clinical and laboratory findings such as severe pruritus and an elevation in alkaline phosphatase raise suspicion of a biliary disease which overlaps autoimmune hepatitis. A strong clinical suspicion of overlap syndrome in a patient with autoimmune hepatitis prompts more diagnostic evaluations like MRCP, liver biopsy and secondary laboratory tests.  Patients who fall into the category of overlap syndrome would be proceeded with timely  monitoring of known complications including colorectal carcinomas, cholangiocarcinomas and gallbladder cancers. So, it is highly recommended to search for all simultaneous immune-based involvements prior to labelling a patient as having pure autoimmune hepatitis.


In this study, attempts have been made to express all challenges about a case with overlap syndrome referred to gastroenterology ward of Taleghani hospital and  review the latest articles and related guidelines about the diagnosis, treatment, complications, and surveillance of the mentioned patient with autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and inflammatory bowel disease (IBD).


Keywords: Autoimmune Hepatitis, Primary Sclerosing Cholangitis, Inflammatory Bowel Disease, Ulcerative Colitis, overlap syndrome.

Case Presentation


Not Every Pancreatic Mass is Cancer: A Case of a Large Intra-Pancreatic Splenule

Nicholas McDonald, Daniyal Abbas, Mohammad Bilal

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2539

We report a case of a 72-year-old man who was referred to our tertiary medical center for endoscopic ultrasound (EUS) evaluation for an incidental 2 cm mass in the tail of the pancreas seen on computed tomography (CT).  On EUS, a 22 mm by 13 mm, well-defined hypoechoic mass was identified within the pancreatic tail and a fine needle biopsy was performed. Histopathology revealed benign pancreatic parenchyma and the presence of lymphocytes. A technetium-99m sulfur colloid scan was performed which demonstrated uptake in the pancreatic tail lesion, consistent with an intra-pancreatic splenule. This case demonstrates that a splenule or accessory splenic tissue should remain in the differential diagnosis of a pancreatic mass. An accurate diagnosis of pancreatic splenule can preclude surgical resection. 

Case Report


Plexiform Neurofibromatosis of the Liver: An Extremely Rare Case

Farideh Gharekhanloo, Saba Lorestani, Salman Khazaei

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2047

Herein, we report an extremely rare case of histopathologically proven neurofibromatosis of the liver. A 15-year-old male, a known case of type I neurofibromatosis (NF1), referred to our hospital with a complaint of right upper quadrant pain. He had a café-au-lait spot and positive family history of NF1 in her mother. Laboratory data were within normal limits, and computed tomography (CT) revealed a large predominantly less attenuated infiltrative liver mass along the porta hepatis with extension to both lobes of the liver. Moreover, magnetic resonance imaging showed a large hypo signal mass in T1-weighted images and hypersignal lesion in T2-sequences with faint enhancement, periportal distribution, and encasing of major branches of the portal vein without evidence of narrowing and invasion. Furthermore, the CT guided biopsy was taken from both liver lobe lesion, and pathological diagnosis of the biopsy specimens confirmed plexiform neurofibromas of the liver. According to the extensive intrahepatic extension and periportal infiltration, the mass was unrespectable. Therefore, the radiologists need to be familiar with the typical imaging features of the uncommon hepatic neoplasms. If imaging findings are not typical or diagnostic, a further biopsy should be performed once again.

Photo Quiz


Primary squamous cell carcinoma of the stomach: A rarity

Zain Majid, Danish Ratani, Abbas Ali Tasneem, Syed Mudassir Laeeq, Nasir Luck, Muhammad Mubarak

Gastroenterology and Hepatology from Bed to Bench, ,
https://doi.org/10.22037/ghfbb.v15i3.2609

Introduction: Squamous cell carcinoma of the stomach is of rare occurrence with only a few cases reported in the medical literature.
Case: We hereby present the case of a 73 year old male who presented to us with complains of abdominal pain, generalized weakness along with weight loss. His upper and lower GI endoscopies revealed no visible abnormality, following which a CT CAP was done and showed a soft tissue mass involving the stomach. EUS guided biopsies were done and revealed moderate to poorly differentiated squamous cell carcinoma. Later on radial EUS was done for staging purpose and showed T2/3, N1 disease. He was referred to the oncology team where he was administered chemotherapy on the lines of squamous cell carcinoma and is currently on regular follow-up.
Conclusion: Our case shows that in spite of having a poor come, early identification may have better consequences in the long run for these patients.