Gastroenterology and Hepatology from Bed to Bench

Common and rare diseases continue to impose a significant burden on healthcare systems worldwide. Viruses and molecular markers are increasingly recognized as pivotal in pathogenesis, early diagnosis, and the development of targeted therapies. Recent studies from Iran and other parts of the world have underscored the critical role of these factors in disease identification and management.

Primary biliary cholangitis (PBC) is the most common autoimmune diseases of the liver. Patients with PBC in characterised by typical biliary pattern symptoms and the presence of anti-mitochondrial autoantibodies (AMAs) in more than 90% of patients and around 50% also show antinuclear antibodies (ANAs).

Based on different studies, anti-Sp100 and anti-PML autoantibodies can

be detected in 20–30% of patients with PBC, mostly in AMA-negative PCB. In recent years, autoantibodies (Aab) targeting subcellular structures described as the Rods and Rings (R&R) have been presented as a unique and particular case of Aab generation.

Now we characterized a patient with contemporary presence of Sp100, PML and R&R Aab (AC-23 pattern following ICAP nomenclature) in PBC, without any laboratory evidence of HCV and/or other hepatic virus infection. For our knowledge, this is the first case of AMA-negative PCB with R&R Aab described in the Literature.

Review of the Literature showed that the AC-23 pattern are present not only in HCV-patient in interferon-ribavirin treatment but, also in ALD.

R&R Aab in patients with PCB confirm and reinforce the association of these Aab to ALD.

Aim: This systematic review aimed to comprehensively evaluate the existing literature on the epigenetic influence of diet-induced gut microbiome changes in the context of precision nutrition.

Background: Diet influences gut microbiome composition, which regulates epigenetic modifications affecting inflammation, metabolism, and disease susceptibility. Precision nutrition seeks to personalize dietary strategies based on these interactions, yet the role of microbiome-driven epigenetic regulation remains under investigation.

Methods: A systematic review was conducted in 2025 following PRISMA guidelines. Studies exploring the relationship between dietary interventions, gut microbiome composition, and epigenetic changes were identified via PubMed and Google Scholar. Thirty-five studies, including randomized controlled trials, cohort studies, and observational research, met the inclusion criteria. Data on dietary interventions, microbial composition, epigenetic modifications, and health outcomes were synthesized.

Results: Diets rich in fiber and polyphenols enhanced microbial diversity, increased short-chain fatty acid production, and positively influenced epigenetic markers related to metabolic health. In contrast, Western-style and high-fat diets were associated with gut dysbiosis, inflammation, and negative epigenetic changes linked to metabolic disorders. Dietary interventions impacted DNA methylation, histone modifications, and microRNA expression, influencing long-term health.

Conclusion: This review highlights the key role of diet-induced changes in the gut microbiome in modulating epigenetic mechanisms like DNA methylation and histone modifications. These alterations influence metabolic health, disease risk, and precision nutrition strategies. While dietary interventions show promise, challenges such as individual variability and methodological inconsistencies require further research to refine clinical applications of microbiome-driven nutrition.

Gastrointestinal (GI) endoscopy is a fundamental tool for diagnosing and managing digestive diseases. Standardized classification systems have enhanced the consistency, accuracy, and clinical decision-making in endoscopic evaluation. This review explores key classification systems, their applications, and challenges in their implementation (1).

A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, Embase, Cochrane Library, Google Scholar, Medline, and ClinicalTrials.gov. Relevant classification systems for upper GI endoscopy were categorized based on anatomical regions and adverse event reporting. Artificial intelligence (AI)-assisted tools were used to refine descriptions of classification criteria, and a structured figure was developed to visually represent these classifications.

Major classification systems reviewed include the Los Angeles Classification (2) for reflux esophagitis, Prague Classification (3) for Barrett’s esophagus, and the Forrest Classification (4) for peptic ulcer disease. The AGREE Classification (5) was highlighted for its role in adverse event reporting. Advances in high-definition imaging and narrow-band imaging (NBI) (6) have refined these classifications, improving diagnostic precision. However, practical challenges remain, including the complexity of these systems and the need for continuous education among endoscopists (7).

Endoscopic classification systems play a crucial role in standardizing the assessment of GI diseases, improving diagnostic accuracy, treatment decisions, and communication among clinicians. As these classifications evolve, their continued refinement and integration into clinical practice will enhance their utility, ensuring consistency in endoscopic evaluations and better patient outcomes.

Celiac disease is an enteropathy caused by intolerance to gluten, with genetic and environmental factors playing a key part in its pathogenesis. This review addresses the use of the gluten-free diet as the primary treatment for patients with celiac disease and the use of probiotics as an adjunctive therapy. The gluten-free diet is the sole treatment for preventing symptoms and allowing the inflamed intestinal mucosa to recover. The gluten-free diet, however, also has some very significant challenges like its complexity, the need for ongoing monitoring by dieticians, and the risk of contamination with gluten even in gluten-free labelled foods.

At the same time, the growing interest in the use of probiotics as an adjunct therapy in celiac disease management is based on the hypothetical contribution of the gut microbiota to the pathophysiology of the disease. It has been hypothesized that gut dysbiosis could be involved in the development and maintenance of celiac disease symptoms. Probiotics, in particular the genera Lactobacillus and Bifidobacterium, are among the promising adjuvants for the improvement of gut health. These beneficial microorganisms may play an essential important, crucial role in the breakdown or modification of gluten polypeptides and in the reduction of intestinal epithelial cell damage caused by gliadin.

While probiotic use is not a replacement for a gluten-free diet, it can have additive benefits by assisting in the preservation of a healthy balance of gut microbiota and lessening some chronic gastrointestinal symptoms.

Aim: We evaluated their diagnostic potential compared to histopathology and standard biochemical tests of liver function.

Background: Liver fibrosis is considered a reversible condition, making early diagnosis essential. Serum levels of matrix metalloproteinase (MMP) -1 and MMP-2 are investigated as parameters for diagnosing fibrosis in chronic liver disease.

Methods: Commercially available ELISA assays were used to study serum levels of MMP-1 and MMP-2 in 50 patients with nonalcoholic fatty liver disease (NAFLD). Fibrosis stages were evaluated using the METAVIR scoring system. Spearman’s coefficient analysed correlations of serum levels of MMP-1, MMP-2, and liver biopsy score, and specificity and sensitivity were calculated through receiver operating characteristic (ROC) analysis.

Results: MMP-1 levels in fibrosis stage F1 (14.20±3.10 ng/mL) were not significantly different from stage F2 (9.26±2.21 ng/mL) but were higher (p<0.001) than F3 (7.15±1.56 ng/mL) and F4 (4.53±0.62 ng/mL). MMP-2 levels in F1 (68.57±8.22 ng/mL) were similar to F2 (76.31±9.25 ng/mL) but lower (p<0.001) than F3 (103.34±17.59 ng/mL) and F4 (214.24±46.72 ng/mL). Significant differences were seen between mild fibrosis (F1-2) and severe fibrosis/cirrhosis (F3-4) for MMP-1 (p<0.01) and MMP-2 (p<0.001). Correlation analysis revealed a weak inverse correlation for MMP-1 (r=-0.383, p<0.01) and a weak direct correlation for MMP-2 (r=0.392, p<0.01) with fibrosis stages. MMP-2 levels >86.78 ng/mL had a sensitivity of 73.7% and specificity of 61.3% for fibrosis detection, while MMP-1 levels <4.96 ng/mL had a sensitivity of 52.6% and specificity of 32.3%. Using ROC analysis, MMP-2 had significant diagnostic ability in detecting liver fibrosis stages (area under the curve 0.722, p<0.01).

Conclusion: Serum levels of MMP-2 are able to detect liver fibrosis. Despite the limited sample size, these findings support further investigation and potential integration of MMP-2 testing into routine clinical practice.

Aim: This study aimed to evaluate the preventive and therapeutic effects of Cepharanthine on APAP-induced liver and kidney injury in an experimental model.

Background: Acetaminophen (APAP) is widely used as an analgesic and antipyretic drug; however, its overdose can cause acute liver and kidney injury. Cepharanthine, a natural alkaloid with antioxidant properties, has been proposed as a potential protective agent.

Methods: In this experimental study 40 Male NMRI mice were divided into 5 groups: Control, Sham, APAP-treated, APAP + preventive Cepharanthine, and APAP + therapeutic Cepharanthine groups. Liver and kidney function markers, including ALT, AST, BUN, creatinine, total antioxidant capacity (TAC), and malondialdehyde (MDA), were measured. Histopathological analysis was performed to assess tissue damage. Statistical analysis was conducted using ANOVA with a significance threshold of p < 0.05.

Results: APAP administration significantly increased ALT, AST (p < 0.001), and MDA (p < 0.01) while reducing TAC levels (p < 0.01) in liver and kidney tissues. Cepharanthine, particularly in the therapeutic group, reduced ALT levels (p < 0.05) and improved liver histology but did not significantly alter AST or TAC in the prevention group. In contrast, Cepharanthine failed to improve kidney function markers and worsened histological damage, leading to increased tubular casts and hemorrhagic areas.

Conclusions: Cepharanthine exhibited partial hepatoprotective effects against APAP-induced liver injury but did not improve kidney damage. Its therapeutic potential appears to be dose- and time-dependent. Further studies with chronic models are required to determine its efficacy in long-term oxidative stress conditions.

Aim: The aim of this study was to develop a simple and reliable scoring system for colorectal cancer risk assessment considering the effectiveness of different screening options.

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. As a preventable disease, accurate risk assessment plays a critical role in early detection and prevention strategies.

Methods: This study analyzed data from 3,465 individuals, including patients, first-degree, second-degree, and third-degree relatives of patients, and volunteers participating in a national CRC screening program. The dataset reflects nine years of prevention efforts targeting at-risk populations. Machine learning algorithms—Logistic Regression, Naïve Bayes, Neural Networks, Random Forest, and Support Vector Machines (SVM)—were applied to the data. Model performance was evaluated using cross-validation, ROC curves, F1 score, classification accuracy (CA), and overall accuracy metrics.

Results: Of the 3,465 participants, 2,240 were diagnosed with colorectal cancer, 60 were relatives of affected patients, and 1,086 were non-patient relatives. Among CRC patients, 1,979 were over the age of 40. Logistic Regression and Naïve Bayes achieved the highest AUC values (0.910 and 0.907, respectively), with corresponding accuracies of 84.5% and 82.8%. Logistic Regression demonstrated the highest overall accuracy. The proposed scoring system incorporated variables such as age, sex, diabetes, inflammatory bowel disease (IBD), smoking, alcohol consumption, tobacco use, BMI, family history, and five key symptoms: rectal bleeding, abdominal pain, unintended weight loss, changes in bowel habits, and anemia. The highest score was assigned to individuals over 60 years of age, while a score of 2 was allocated for a family history involving more than two affected relatives.

Conclusion: A scoring system based on easily measurable variables offers a practical and efficient tool for widespread clinical use. Such systems can assist healthcare professionals in streamlining risk assessment and improving early identification of high-risk individuals.

Aim: In this study, we investigated the relationship between serum uric acid (SUA) and metabolic dysfunction-associated steatotic liver disease (MASLD) in patients detected through abdominal ultrasound. The second aim was to determine if there were any gender differences.

Background: High SUA levels may contribute to the mechanisms underlying various metabolic disorders, including MASLD.

Methods: We conducted a retrospective study among patients older than 18 who had been admitted to a tertiary hospital's gastroenterology outpatient clinic for over two years. A total of 200 patients diagnosed with either Grade 1, 2, or 3 hepatosteatosis by ultrasound screening and 200 patients without hepatosteatosis were included in the study. Patients' demographic features, laboratory parameters, and detailed medical history were extracted from the hospital's medical records.

Results: The mean age of the 400 patients enrolled in the study was 47.92±0.78 years, and 70.25% were men. SUA (5.34 mg/dL ± 1.52 vs. 4.64 mg/dL ± 1.28, p=0.001), alanine aminotransferase (ALT) (26.55 U/L ± 23.82 vs. 19.57 U/L ± 20.81, p=0.002), aspartate aminotransferase (AST) (22.68 U/L ± 20.35 vs. 18.07 U/L ± 9.89, p=0.005), and glycosylated hemoglobin (HbA1c) (6.45% ± 1.69 vs. 5.76% ± 1.23, p=0.001) levels were higher in the MASLD group. In the MASLD group, HbA1c, AST, and ALT were significantly higher in the Grade 2-3 group than in the Grade 1 (p=0.038, p=0.038, p=0.001, respectively).

Conclusion: Elevated SUA levels are strongly linked to MASLD, particularly in males. Ease of measurement and low cost suggest that SUA could serve as a non-invasive biomarker for MASLD detection in at-risk groups.

Aim: The objective of this study was to develop a real-time PCR method to detect hepatitis C virus (HCV), human immunodeficiency virus-1 (HIV-1), and also recently discovered human hepegivirus-1 (HHpgV-1) through melting curve analysis using SYBR Green dye in a single reaction.

Background: It is estimated that chronic viral infections affect millions of people worldwide, and a significant number of these individuals are unaware of their infection. In addition, infection with newly discovered and emerging viruses may put public health at potential risks. Precise and early detection is a primary and important task for controlling infections and helping patients.

Methods: A set of specific primers were designed for detection of HCV, HIV-1, and HHpgV-1 in a single tube. The real-time polymerase chain reaction was performed and melt curves were analyzed. Specificity was assessed by cross-reaction tests with other common blood-borne pathogens. The established assay was evaluated for the detection of viruses in clinical samples.

Results: The three viruses were clearly distinguished by their respective melting temperature values. The detection limits of this assay were 10² copies/ml for each virus. The clinical evaluation of this assay was demonstrated by analyzing 134 patients’ serum samples. The specificity of the developed assay considered as 100%.

Conclusion: The developed multiplex real-time PCR based on SYBR Green dye is a well-suited detection assay of single or co-infections of HCV, HIV, and HHpgV-1 in clinical and research laboratories. It can be used as a cost-effective, rapid tool for routine diagnostic in-house tests.

Cystic fibrosis (CF)-like disorders, which present with overlapping clinical features of CF but with distinct genetic causes, are often challenging to diagnose. Recent studies have identified AGR2 mutations as a novel cause of an autosomal recessive disorder resembling CF which is known as RIFTD syndrome (recurrent respiratory infection, failure to thrive with or without diarrhea). We reviewed the clinical, genetic, and imaging findings of two sibling patients presenting with a CF-like phenotype. Sweat chloride testing, chest radiography, and genetic sequencing for AGR2 mutations were performed. We assessed treatment responses and clinical outcomes over a one-year period.

The purpose of this report is to describe two siblings of AGR2-related disease to broaden the clinical understanding of this condition and highlight the importance of genetic testing for proper diagnosis.

Granular cell tumor (GCT) is a rare, usually benign neoplasm of Schwann cell origin, infrequently seen in the gastrointestinal tract, especially the stomach. We report an atypical gastric GCT in a 42-year-old female presenting with dysphagia and weight loss, initially suspected to be a gastrointestinal stromal tumor (GIST). Endoscopic and radiological evaluations revealed a submucosal lesion at the gastric cardia. Surgical resection and histopathology confirmed atypical GCT, characterized by PAS-positive granular cytoplasm and immunopositivity for S100, NSE, and CD68. Differentiation from GIST is crucial due to differing management.