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Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver disease which is associated with Inflammatory Bowel Disease (IBD) in 70% of cases. It seems PSC/IBD is a distinct phenotype that is different from PSC, and IBD alone. Hence, we review the epidemiology, pathogenesis, natural course and management of PSC/IBD before and after LT for PSC. Extensive colitis, rectal sparing, backwash ileitis, and mild symptoms are the characteristics of IBD coexisting with PSC. Moreover, PSC patients with concurrent IBD have higher risk of cholangiocarcinoma, and colorectal neoplasia predominantly in right colon and at younger age. Therefore, it is essential to monitor these individuals continuously. It is interesting to note that the course of IBD (ulcerative colitis) after liver transplantation (LT) for PSC varies greatly, and some patients may develop worsening colitis after LT despite immunosuppressive regimens. As well, management of these patients was discussed in this review., Competing Interests: There is no conflict of interest for authors of this article., (© 2023, Gastroenterology and Hepatology From Bed to Bench (GHFBB).)

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 data, medical characteristics, and Child-Pugh and MELD scores evaluated 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., Competing Interests: The authors declare that they have no conflict of interest., (© 2023, Gastroenterology and Hepatology From Bed to Bench (GHFBB).)

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, as each one of them has a unique pathophysiology, thereby making their management approaches completely different. There are clinical clues that help physicians distinguish these two. Direct vision via upper endoscopy is often mandatory to establish the diagnosis, and sometimes biopsy is required. In this review, we sought to discuss different aspects of both conditions and highlight clinical evidence that may help in identifying and managing the disease appropriately., Competing Interests: The authors have no conflicts of interest to declare., (©2022 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

Aim: This study aimed to perform a head-to-head comparison of changes during NASH progression throughout 6-11 weeks of an experiment to supply a faster nutritional model in mimicking NASH to decrease the duration and cost of in vivo studies., Background: New therapies are urgently needed because of the growing prevalence of non-alcoholic steatohepatitis (NASH) and the lack of an effective treatment approach. Currently, dietary interventions are the most efficient options., Methods: This study compared features of NASH in a murine model using protocol that combined special nutritional regimes based on the combination of 21.1% fat, 41% sucrose, and 1.25% cholesterol with weekly intraperitoneal injections of carbon tetrachloride (CCl4). Male C57BL/6J mice received either special compositions + CCl4 (NASH group) or standard chow diet (healthy control group) for 11 weeks. Liver histopathology based on hematoxylin and eosin (H&E) and Masson's Trichrome (TC) staining and biochemical analyses were used to assess disease progression., Results: In C57BL/6J mice administered a high fat, high cholesterol, high sucrose diet and CCl4 for 8 weeks, steatohepatitis with pronounced hepatocyte ballooning, inflammation, steatosis, and fibrosis was observed. According to the NAFLD activity scoring system, the maximum NAS score was manifested after 8-9 weeks (NAS score: 6.75). Following this protocol also led to a significant increase in AST and ALT, total cholesterol, and total triglyceride serum levels in the NASH group., Conclusion: Following the special nutritional regime based on high fat, cholesterol, and sucrose in combination with CCL4 injections resulted in a NASH model using C57BL/6J mice in a shorter time compared to similar studies. The obtained histopathological NASH features can be advantageous for preclinical drug testing., Competing Interests: The authors declare that they have no conflict of interest.

Aim: This study aimed to evaluate hepatic steatosis index (HSI) as a non-invasive tool in diagnosing and predicting nonalcoholic fatty liver disease (NAFLD) and to compare it with abdominal ultrasound as the gold standard tool., Background: NAFLD is a general term attributed to the deposition of adipose tissue in the liver leading to hepatitis, fibrosis, cirrhosis, and also hepatocellular carcinoma (HCC). Rapid and valid screening can remarkably prevent the progression of this disease., Methods: A total of 464 people were included in the present study based on inclusion criteria. Patients were evaluated for body mass index (BMI), AST, ALT, and ALP indices. The liver echogenicity of patients was evaluated by abdominal ultrasound technique., Results: The results showed that out of 464 people included in the study, 32.33% represented fatty liver. It was found that 79.1% of patients were female. There was no significant difference between the two groups in terms of age. Furthermore, it was found that ALT, AST, and ALP levels were significantly increased in the two groups of patients compared to the control group. It was determined that out of 150 patients, 75.3% were grade I and 24.7% were grade II NAFLD cases; no grade III cases were observed. The mean HSI for the NAFLD- group was 35.51±5.72 and for the NAFLD+ group was 42.84±5.70, a significant difference. The receiver operating characteristic (ROC) curve also showed that the area under the curve (AUC) of HSI was 0.833 (95% CI, 0.796-0.870) for detecting NAFLD patients. At the cutoff point of > 36.0, the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 88.7% (95% CI, 82.5-92.5), 63.4% (95% CI, 57.9-68.5), 92.1%, and 53.6%, respectively. Pearson correlation showed a direct and significant correlation between ultrasound data and HSI values., Conclusion: Overall, the present study results showed that HSI as a non-invasive and non-imaging tool can diagnose NAFLD., Competing Interests: The authors declare that they have no conflict of interest.

Aim: This study aimed to identify the risk factors of metabolic (dysfunction)-associated fatty liver disease (MAFLD) among adults in northeastern Iran., Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and hepatic manifestation of metabolic syndrome that threatens global public health. Recently, MAFLD has been proposed as a new terminology updated from NAFLD and diagnosed based on modified criteria., Methods: A nested case-control study was performed on the participants of the first phase of the Persian Sabzevar Cohort Study (PSCS), a survey that was conducted in northeastern Iran and enrolled 4,242 participants aged 35-70 years. In total, 968 MAFLD cases and 964 controls adjusted for age and sex were recruited. Data including demographic, lifestyle, anthropometric, biochemical, sleep pattern, and dietary intake information was collected., Results: The mean (SD [standard deviation]) age of participants was 49.2 (8.8) years, and 39.9% of the participants were males. The prevalence of MAFLD was 22.8% (95% CI [confidence interval] 19.2 - 26.3%). Increased body mass index (BMI) (OR [odds ratios] 5.51, 95% CI 2.73 - 11.10), waist circumference (WC) (OR 1.85, 95% CI 1.44 - 2.38), blood concentrations of triglycerides (TG) (OR 1.10, 95% CI 1.06 - 1.15), total cholesterol (TC) (OR 1.02, 95% CI 1.003 - 1.04), and alanine aminotransferase (AST) (OR 1.10, 95% CI 1.05 - 1.16) were significantly associated with an increased risk of the MAFLD ( p- value <0.05). Furthermore, the odds of MAFLD risk was 43% higher in subjects who slept ≤ 5 hrs/day than those with ≥ 7 hrs per day of sleep (OR 1.43; 95% CI 1.07 - 1.92, p- value = 0.01)., Conclusion: In this study, it was found that MAFLD was best predicted by BMI, WC, and serum levels of TG, total cholesterol, and AST. Sleeping ≤ 5hrs/day compared to ≥ 7hrs/day was associated with an increased risk of MAFLD., Competing Interests: The authors declare that they have no conflict of interest., (©2021 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

Aim: Evaluation of deregulated genes after long-term consuming of omeprazole via network analysis., Background: Proton pump inhibitors (PPIs) are used to inhibit gastric high rate of acid secretion in patients. Omeprazole as a PPI is a common drug in this regard. Evaluation of long-term consumption of omeprazole is studied in the present study via its effects on the gene expression of "human coronary artery endothelial cells"., Methods: Net effect of the presence of omeprazole on gene expression profiles of "human coronary artery endothelial cells" was evaluated through data from gene expression omnibus (GEO). Results of protein-protein interaction (PPI) network analysis were assessed via biological process examination to find the critical deregulated genes after long-term consumption of omeprazole., Results: "Negative regulation of muscle cell apoptotic process", "negative regulation of DNA binding", "telencephalon cell migration", "forebrain cell migration" "response to cadmium ion", "cell-cell recognition", "positive regulation of protein targeting to mitochondrion", and "central nervous system neuron development" were the clusters of biological processes that were associated to the long -term presence of omeprazole. The final critical deregulated genes were JAK2, PTK2, and NRG1., Conclusion: It can be concluded that cell cycle, proliferation, and apoptosis and several essential biological processes are affected and nervous system is a possible target related to the long-term consumption of omeprazole., (©2020 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

Aim: To evaluate the association between dietary protein sources with disease severity, malnutrition and anthropometric measurements in cirrhotic patients., Background: Although the beneficial effects of protein and some amino-acids have been shown previously, no study has evaluated the effects of different dietary sources of proteins in patients with hepatic cirrhosis., Methods: In this cross-sectional study, dietary intakes of patients with hepatic cirrhosis were assessed using a valid and reliable food frequency questionnaire. The association between different dietary sources of proteins and nutritional status, anthropometric measurements, and disease severity were evaluated., Results: Muscle strength (MS) increased significantly in highest tertile of dairy and vegetable protein sources compared with the lowest one (p=0.045). Dietary dairy and vegetable protein intakes had a positive significant correlation with body weight, MS, visceral fat percentage (VFP), and triceps skin-fold thickness (TST), and negative significant correlation with malnutrition stage., Conclusion: Our results indicate that consumption of proteins from dairy and vegetable sources is associated with improvement in nutritional and anthropometric status of patients with hepatic cirrhosis. Further prospective studies are needed to confirm these results., Competing Interests: The authors declare that they have no conflict of interest.

Aim: The aim of this study was to compare the different phases of chronic Hepatitis B virus (HBV) infection with different values for normal ALT., Background: For many years, the upper limit of 40 IU was considered normal for ALT for both sexes, but in recent years this value is challenged and some guidelines have lowered their limit., Methods: In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital, Tehran, Iran, from 2011 through 2018 were classified in four groups according to American Association of the study of the liver disease (AASLD), European Association of the study of the liver (EASL) /Asian-Pacific Association of the study of the liver (APASL) and American Collage of Gastroenterology (ACG) guidelines. The frequency of each group based on 3 different guidelines was compared., Results: In HBeAg positive patients (n=100), the percentage of immune tolerance phase was 43% according to AASLD cutoff for normal ALT (35 IU for men, 25 IU for women), while it was 68% and 28% with regard to EASL/APASL and ACG (30 IU for men, 19 IU for women) cutoffs respectively. In HBeAg negative patients (n=1900), 66.68% were inactive carriers according to AASLD, but the percentage changed to 82.89% and 52.42% considering EASL/APASL and ACG values, respectively., Conclusion: Using ACG and to a lesser extent AASLD cutoff for ALT, many patients shift from immune tolerance and inactive carrier state into the immune active phase. Thus, more patients are candidates for treatment or intensive workup to determine the extent of liver damage., Competing Interests: The authors declare that they have no conflict of interest., (©2019 RIGLD.)

Aim: To investigate routes of transmission, demographic characteristics, and frequency of different phases of chronic hepatitis B (CHB) in 2000 Iranian patients., Background: Knowledge about the most frequent risk factors of CHB and its different phases is very important for optimal prevention and management policy making., Methods: In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital from 2011 through 2018 were enrolled. ELISA method was employed to detect serological markers of CHB. Taking into account the HBV DNA and ALT levels and HBeAg status, the patients were classified in four groups, according to AASLD 2017 guideline., Results: Male and female patients had nearly equal frequencies in our study and 82.5 % of them aged more than 20 years. A great number of our patients (95%) were HBeAg negative and the most frequent risk factors of HBV infection were positive periodontal and family history (40.3% and 24.9%, respectively). The majority of our patients were inactive carriers (63.35%), while s mall number of them were in the immune tolerant group (2.15 %)., Conclusion: Immune tolerance phase group had the minimum number of members in our study and most of them were above 20 years old. This can be due to the mass vaccination of neonates since 1993. Most of CHB patients were in inactive carrier group. Although it is recommended not to treat these patients, performing periodic liver function tests and disease severity assessment is warranted, especially in patients above 40 years old ., Competing Interests: The authors declare that they have no conflict of interest., (©2019 RIGLD.)

Aim: Our goal was to identify the putative association of rs4072111 variant in IL-16 gene and HCV susceptibility in an Iranian population., Background: Interleukin 16 (IL-16), a multifunctional cytokine, plays a vital role in modulation of immune system., Methods: In present case control and cross sectional study, IL-16 gene variant in 300 patients with hepatitis C (HCV) infection and 300 healthy individuals were analyzed. To evaluate this possible association, genomic DNA from venous blood was extracted and genotypes of IL-16 rs4072111 variant were determined by polymerase chain reaction- Fragments Length Polymorphism Technique (PCR-RFLP). Then, rs4072111 C/T genotypes frequency and allelic distribution were evaluated in each group., Results: The results of genotyping showed 82% CC, 17.3% CT, 0.7% TT in the control group and 78% CC, 20% CT and 2% TT in the case group. The distribution of rs4072111 C allele was 90.7% in controls and 88% in case group respectively.However, no correlation between IL-16 rs4072111 C/T variants and susceptibility to chronic HCV infection was found in the present study., Conclusion: We concluded the rs4072111 C/T cannot be considered as a proper biomarker to identify susceptibility to chronic hepatitis C virus infection.

Aim: To assess the possible correlation between single nucleotide polymorphisms (SNPs) of two members of TNF ligand superfamily genes, tumor necrosis factor-α (TNF-α) and lymphotoxin-α (LTA), and HCV chronic disease., Background: The causes of disease progression from hepatitis C virus (HCV) infection to chronic liver disease still remains unclear. Abnormal production of the cytokines alleged to be contributed to progression of the disease or viral persistence. Regulatory mechanisms that control the production of cytokines including genetic polymorphisms, especially at coding/regulatory regions of genes, may affect expression and secretion of the cytokines., Methods: In this case-control investigation, 258 individuals with serologically proven chronic HCV infection and 277 healthy controls were studied. Genotyping of rs1799964 variant of TNF-α and rs909253 intronic variant in LTA gene were performed. To confirm the results of genotyping, 10% of the specimens analyzed again by sequencing approach., Results: In this investigation, a significant association was observed between the TNF-α TC genotype and chronic HCV infection (P = 0.035). Moreover, the frequency of C allele was significantly different between control subjects in comparison with chronic HCV patients (P=0.02). On the other hand, no association was found between LTA gene polymorphism and susceptibility to chronic HCV infection., Conclusion: These findings indicate that genetic variants like single nucleotide polymorphism in TNF-α rs1799964, could be a host factor associated with susceptibility to HCV chronic infection. However, further large scale investigations are needed to confirm this finding., Competing Interests: The authors declare that they have no conflict of interest.

Aim: The objective of this study was to determine the epidemiologic characteristics of patients with liver cirrhosis., Background: Liver cirrhosis is an end-stage condition of chronic liver disease. Liver disease is an important cause of morbidity and mortality worldwide., Methods: In this cross-sectional study, demographic and epidemiologic characteristics of 203 patients with liver cirrhosis who were admitted in Taleghani Hospital over a period of two years were determined., Results: A total of 203 patients with liver cirrhosis consisted of 136 (67%) males and 67 (33%) females and the mean age was 53.7±15.2 years. No etiology were found in (59.6%) cirrhotic patients; therefore, they were labeled as cryptogenic cirrhosis, but according to clinical evidence and ultrasonography findings, (29.7%) of these patients were probable NAFLD. The other causes of liver cirrhosis in this study were HBV (20.2%), HCV (11.8%) and autoimmune hepatitis (AIH) (8.4%), respectively. Esophageal varices were present in (41.9%), ascites in (36.5%), variceal bleeding in (8.9%), encephalopathy in (7.4%) and spontaneous bacterial peritonitis (SBP) in (5.4%) of patients. When cirrhotic patients were grouped according to Child-Pugh classification, 26.1%, 54.7% and 19.2% were in classes A, B and C respectively. The mean MELD score was 16.16±7.7., Conclusion: In this study we found that the leading etiology of cirrhosis is cryptogenic cirrhosis 59.6% (in all age groups) and followed by HBV. Noteworthy, according to the clinical and ultrasonography findings, 29.7% of patients who were labeled as cryptogenic cirrhosis were consistent with NAFLD., Competing Interests: The authors declare that they have no conflict of interest.

Aim: This study investigates the effect of fat diet on gene expression profile in rat liver via protein-protein interaction mapping analysis., Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition of liver in the world. This progressive metabolic disease is representative with fat accumulation in the patients' liver that can led to advance stages, namely, cirrhosis and eventually cancer., Methods: Differentially expressed genes of NAFLD rat liver after 2, 4 and 6 weeks fat diet feeding were analyzed via GEO2R and protein-protein interaction network by Cytoscape v3.6.0. and the related plug-ins. The important genes were assigned based on degree and betweenness centrality analysis and enriched using ClueGO+CluePedia Plug-in., Results: GAPDH, PRDM10, TP53, AKT1, INS, ALB, SRC, MAPK1, ACLY, ACACA, DECR1, ACACB, MBOAT4, TNF, EHHADH and JUN genes were introduced as key genes related to the fat diet fed NAFLD rats. Fatty acid biosynthesis and four other terms were introduced as the main related ones to the essential genes., Conclusion: The introduced critical genes and the related terms may describe NAFLD molecular condition and its progression to the other severe metabolic diseases. Moreover, these potential biomarkers may be monitored for diagnosis and treatment approaches after validation investigations., Competing Interests: The authors declare that they have no conflict of interest.

Aim: This study is presenting an effective method of inducing liver fibrosis by CCL4 as a toxin in two different breeds of rat models., Background: Liver fibrosis is a result of inflammation and liver injury caused by wound healing responses which ultimately lead to liver failure. Consequently, after liver fibrosis, the progression will be continued to liver cirrhosis and at the end stage hepatocellular carcinoma (HCC). Many studies have demonstrated that one of the most important causes of liver fibrosis is Non-alcoholic steatohepatitis (NASH). Fibrotic Liver is affected by an excessive accumulation of extracellular matrix (ECM) proteins like collagen and α-SMA., Methods: In two different experiments, male Vistar, and Sprague Dawley Rat models ranging from 200±60, corresponding to an age of approximately 10 weeks were utilized in order to induce CCL4 treated liver fibrosis., Results: After 6 weeks of CCL4 injection, different tests have been carried out to verify the liver fibrosis including serum markers such as Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), molecular tests containing, laminin and α-SMA and also pathological observation by Hematoxylin and eosin staining in both fibrosis and control group., Conclusion: The results of Pathology and Real-time PCR showed that fibrosis was induced much more effectively in Sprague Dawley rat model compared with Wistar rats., Competing Interests: The authors declare that they have no conflict of interest.