Arab Journal of Gastroenterology最新文献

Background and study aims: Crohn's disease (CD) activity is a risk factor for non-alcoholic fatty liver disease (NAFLD); however, few studies have focused on NAFLD with different CD activities. This study aimed to analyze the prevalence, risk factors, and prognosis of NAFLD in patients with active and inactive CD.

Patients and methods: Consecutive patients diagnosed with CD between January 2014 and December 2017 were retrospectively enrolled in a tertiary center of China. The clinical characteristics and prognosis of NAFLD in patients with active and inactive CD were analyzed.

Results: A total of 844 patients with CD were enrolled. The prevalence of NAFLD was 20.38 % (172/844), and it was mainly lean NAFLD (80.23 %). The prevalence of NAFLD and lean NAFLD was higher in active CD than in inactive CD (23.1 % vs. 15.9 %, P = 0.012, 19.5 % vs. 11.3 %, P = 0.039, respectively). In patients with CD, higher body mass index (BMI), higher C-reactive protein, and lower albumin were risk factors. Risk factors for NAFLD was low ALB in active CD. In inactive CD, the risk factors for NAFLD were higher BMI and ongoing use of azathioprine/6-Mercaptopurine. In a follow-up period of 45.46 ± 18.67 months, NAFLD was alleviated in 74.73 % (68/91) and 64.10 % (25/39) patients with active and inactive CD, respectively, after CD-related treatment.

Conclusions: Approximately one-fifth of patients with CD developed NAFLD, mainly lean NAFLD. NAFLD in active and inactive CD exhibits different characteristics and risk factors, suggesting that the underlying mechanisms of NAFLD in different CD activities may differ. Most of CD patients with NAFLD were alleviated after CD-related treatment.

Background and study aims: Neutrophil extracellular trapping networks (NETs) are meshwork structures released by activated neutrophils and are composed of various components such as DNA, histones and granulins. The aim of this study was to evaluate the diagnostic value of NETs-related indicators (citH3, cfDNA, and MPO-DNA) as noninvasive fibrosis markers in patients with untreated chronic hepatitis B.

Patients and methods: A total of 186 patients with chronic hepatitis B and 56 healthy controls were included in this study. The Ishak scoring system was used to determine the fibrosis stage. NETs-related markers were measured by enzyme-linked immunosorbent assay (ELISA), and the relationship between NETs marker levels and inflammation and fibrosis was analyzed. The diagnostic value of NETs indicators was evaluated by the area under the receiver operating characteristic curve, sensitivity, and specificity.

Results: The levels of NETs markers were associated with the activity of liver inflammation. The levels of citH3, cfDNA, and MPO-DNA in the patient group were significantly higher than those in the control group. Additionally, there were differences in the levels of these markers among different fibrosis stages of chronic HBV infection (P < 0.001), with an increase in NETs markers corresponding to higher fibrosis stages. Receiver operating characteristic (ROC) curve analysis showed that the levels of citH3, cfDNA, and MPO-DNA distinguished the patient group from the control group, and the difference was statistically significant (P < 0.001).

Conclusion: Our results suggest that NETs markers can be used as indicators for the assessment of liver fibrosis in patients with chronic HBV infection.

A 64-year-old woman presented with abdominal pain, upper gastrointestinal bleeding, and purpura on her face and extremities. She had previously been treated with mesalazine for ulcerative colitis. Tests revealed anaemia, elevated inflammatory markers (erythrocyte sedimentation rate, 82 mm/h; C-reactive protein concentration, 13.05 mg/dL), and a high proteinase 3-specific antineutrophil cytoplasmic antibody level (94.8 U/mL). Computed tomography showed oedematous thickening of the intestinal wall from the ascending colon to the sigmoid colon. Colonoscopy revealed inflammation of the leukocytoclastic vasculitis, consistent with granulomatosis with polyangiitis mucosa, and the sigmoid colon had various ulcers with mucosal inflammation. Skin biopsy revealed leukocytoclastic vasculitis, indicative of granulomatosis with polyangiitis. Prednisolone (40 mg/day) and tacrolimus (4 mg) resolved the symptoms. To our knowledge, this is the first report of successful tacrolimus therapy for ulcerative colitis complicated by granulomatosis with polyangiitis.

Background and study aims: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition worldwide. Although forkhead box O4 (FOXO4) is implicated in liver diseases, its role in NAFLD remains unclear.

Material and methods: FOXO4 knockout mice were generated using CRISPR/Cas9 and fed a normal or high-fat diet (NFD/HFD). Human hepatic stellate cell line (LX-2) cells were transfected in vitro with a FOXO4 siRNA plasmid.

Results: Twelve weeks of HFD feeding downregulated FOXO4 expression and reduced its colocalization with hepatocyte nuclear factor 4α (HNF4α). HFD-fed mice exhibited increased liver-to-body weight ratios; marked lipid/glycogen accumulation; and elevated serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, and nonesterified fatty acid levels. These pathological manifestations were further exacerbated upon genetic ablation of FOXO4. Specifically, FOXO4 knockout aggravated HFD-induced upregulation of α-smooth muscle actin protein; increased the expression of profibrotic genes (including collagen type I alpha 1 chain, transforming growth factor-β1, and tissue inhibitor of metalloproteinases 1) and inflammatory mediators (such as interleukin-1β, IL-6, and tumour necrosis factor-α); and increased hepatocyte apoptosis. Mechanistically, FOXO4 suppressed secreted phosphoprotein 1 (SPP1) expression in LX-2 cells via direct binding to the SPP1 promoter and transcriptional suppression of its activity.

Conclusion: FOXO4 downregulation exacerbates HFD-induced NAFLD progression via SPP1-dependent steatosis, inflammation, and fibrosis, thereby suggesting its potential as a therapeutic target.

Background and study aims: Periampullary diverticula (PAD), often detected incidentally during imaging or endoscopy, has been linked to pancreaticobiliary diseases. Previous studies focusing on ERCP patients may overestimate PAD prevalence and its association with these diseases. This study aimed to explore the relationship between PAD characteristics, including size and type, and the occurrence of pancreaticobiliary diseases.

Patients and methods: Patients who underwent gastroscopy at the Second Affiliated Hospital of Soochow University from January 2018 to December 2022 and were found to have PAD (PAD group) were selected. A control group of patients without PAD was matched by gender and age in a 1:3 ratio. The characteristics of PAD and its correlation with pancreaticobiliary diseases were analyzed.

Results: The detection rate of PAD was 0.73 %. A total of 389 patients in the PAD group and 1,167 in the control group were included. The incidence of pancreaticobiliary diseases was significantly higher in the PAD group compared to the control group (51.2 % vs. 32.6 %, P < 0.001). Elderly PAD patients (>60 years) had larger diverticula and a higher incidence of pancreaticobiliary diseases than non-elderly PAD patients (≤60 years). Among different types of PAD, Type I PAD patients had the highest incidence of gallbladder stones and acute pancreatitis. No statistically significant correlation was found between PAD size and pancreaticobiliary diseases, and the incidence of bile duct stones was lower in the giant diverticulum group.

Conclusion: The presence of PAD is significantly associated with pancreaticobiliary diseases, particularly in elderly PAD patients and those with Type I PAD, where there is a strong correlation with biliary diseases and acute pancreatitis.

Background and study aims: There is no approved medication to rescue fat build-up in patients with nonalcoholic fatty liver disease (NAFLD). Some medications have been used to reduce the symptoms of these patients. In the present study, we aimed to investigate the effects of a gluten-free diet (GFD) on hepatic steatosis (HS), the lipid profile, blood pressure (BP), fasting blood sugar (FBS) and anthropometric indices in patients with NAFLD within 3 months of intervention.

Patients and methods: This study is an open-label, randomized clinical trial of 60 patients with NAFLD who were referred to the gastrointestinal (GI) clinic of Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran. Patients were randomly divided into two groups and classified into two groups: group I or the control group (follows lifestyle change training) and group II (follows both lifestyle change training and the GFD. The parameter variations, including body mass index (BMI), FBS, lipid profile, liver function test (LFT), waist circumference (WC), BP and grade of HS, were recorded and compared between the start of the study and 3 months after the intervention. SPSS statistics 25 software was used for data analysis, and the significance level was considered at the level of P < 0.05.

Results: After the 3-month intervention, both groups showed significant within-group improvements in most anthropometric and metabolic measures, likely reflecting the impact of lifestyle modification. However, when comparing outcomes between groups, only the FBS and triglyceride (TG) levels were significantly lower in the GFD group than in the control group, whereas the changes in all other parameters were not significantly different between the two groups.

Conclusion: In this trial, incorporating a GFD alongside lifestyle change training led to significant improvements in FBS and TG levels, whereas other parameters improved similarly in both groups.

Background and study aims: This study investigates the therapeutic potential of Ruta graveolens, a dicot herb known for its antioxidant properties, in protecting against oxidative stress and liver fibrosis caused by bile duct ligation (BDL). The research focused on assessing the biochemical and histological effects of Ruta graveolens extract on male Wistar rats subjected to BDL.

Material and methods: Forty male Wistar rats were divided into eight groups (n = 5): a control group, control experimental groups receiving three doses of Ruta graveolens extract (100, 200, or 400 mg/kg) without BDL, a BDL group, and BDL groups treated with the extract at the similar doses for 45 days. Liver function indicators, antioxidant enzymes, and fibrosis were analyzed using biochemical assays, histopathological staining, and quantitative real-time PCR to evaluate TGF-β and α-SMA gene expression. HPLC analysis was also conducted to identify the bioactive compounds in the extract.

Results: The HPLC results uncovered substantial compounds, including rutin, syringic acid, verbascoside, methoxsalen, cinnamoyl, coumaroyl, and chalepensin. Treatment with Ruta graveolens extract notably reversed the detrimental effects of BDL, significantly improving lipid profiles by lowering cholesterol, LDL, and triglyceride levels while increasing HDL. Further, liver enzymes, superoxide dismutase (SOD), and catalase (CAT) levels were reduced. Histological evaluation exhibited decreased liver impairment and inflammation at higher extract doses, besides downregulation of TGF-β and α-SMA expression.

Conclusion: The current findings suggest that Ruta graveolens extract improves liver function in cholestatic conditions in a dose-dependent manner, indicating its potential as a protective treatment for liver diseases.

Background: Incidence of ulcerative colitis (UC) is on the rise globally, highlighting the need for new diagnostic methods to alleviate UC burden.

Objectives: To explore the value of hypoxia-related genes (HRGs) as UC diagnostic markers.

Methods: UC-related datasets (GSE87466 and GSE92415) were obtained from GEO database. Differential analysis was undertaken on GSE87466 dataset, followed by intersection analysis of HRGs, thus yielding UC-related differentially expressed HRGs (DEHRGs). Enrichment analyses were undertaken on DEHRGs. Hub genes were identified through a PPI network. Small molecules associated with hub genes were predicted using CMap, and diagnostic value was validated via ROC curves in GSE92415 dataset. Clinical samples of UC were collected and subjected to qRT-PCR for detecting the diagnostic value of hub genes. Potential miRNAs and transcription factors (TFs) that may modulate hub genes, and biological functions and signaling pathways of hub genes, were analyzed.

Results: Our research obtained 28 DEHRGs and used PPI networks to identify 9 hub genes in UC. The prediction of small molecular drugs suggested that chloroquine and pantoprazole were potential drugs to treat UC. ROC results demonstrated that all 9 hub genes had great diagnostic ability (AUC > 0.7), of which PPARGC1A had the best diagnostic value. Detection of clinical samples from UC patients also revealed that the expression of 9 hub genes differed significantly between the UC and the control groups, and this result was consistent with the prediction results from bioinformatics. These 9 hub genes were potentially modulated by 32 miRNAs and 55 TFs. Twenty genes functionally similar to hub genes were identified, which were mainly enriched in biological functions such as response to corticosteroid, negative regulation of MAP kinase activity, and activating transcription factor binding.

Conclusion: HRGs play a pivotal part in UC occurrence and progression. Nine hub genes may be promising diagnostic biomarkers for UC.

Background: Patients with stage IV colorectal cancer (CRC) with liver metastasis represent a specific group that can be treated with surgery. However, the influence of genomic alterations on the therapeutic response and prognosis was not clear in CRC patients underwent simultaneous surgery of primary and metastatic lesions.

Methods: Fifty-two patients underwent simultaneous surgery on primary and metastatic lesions were retrospectively recruited. The mutational landscape of primary lesion was established by whole-exome sequencing(WES). Non-parametric test, Fisher's exact test, multivariate analyses, Kaplan-Meier analyses were performed to identify risk factors for response and prognosis, and a Nomogram model was established. Analyses were performed and figures were plotted using the Graphpad PRISM 5.0 and the R software.

Results: Several top mutated genes were identified from the mutational landscape of primary lesions, including APC, TP53, KRAS and TTN, and many co-mutations, mutually exclusive mutations and aberrant functions or pathways were revealed. KRAS(P = 0.047) and TTN(P < 0.001) exhibited significant differences in tumor mutational burden(TMB) between mutant and wild-type groups. TP53(P = 0.045), MUC12(P = 0.012) and CEL(P = 0.032) mutational status significantly stratified the patient therapeutic response, in which MUT12 was an independent risk factor(P = 0.02). CRC location(P = 0.014), patient therapeutic response(P < 0.001), and the mutational status of ANKRD20A4(P = 0.006), EVC(P = 0.05), FHOD3(P = 0.05), MYO15A(P = 0.008) and POTEE(P < 0.001) showed significant stratification on patient prognosis, in which cancer location, response to therapy and ANKRD20A4 and EVC mutational status were independent risk factors. These factors were used to establish a Nomogram model to predict the individual patient prognosis. Internal and external validation verified the effectiveness of the model.

Conclusions: Independent risk factors including cancer location, response to therapy and ANKRD20A4 and EVC mutational status were identified and were used in the establishment of a Nomogram model for patient prognosis prediction.

Background and study aims: Prolonged or inappropriate use of total parenteral nutrition (TPN) may lead to the development of intestinal failure-associated liver disease (IFALD), which causes significant morbidity in TPN recipients. However, the underlying mechanism remains unclear.

Patients and methods: Transcriptomic data of liver samples from Sprague‒Dawley rats treated with TPN or standard chow with 0.9% saline were downloaded from the Sequence Read Archive (SRA). The alternative splicing (AS) events and regulated alternative splicing (RAS) events between IFALD and normal samples were defined and quantified using the SUVA pipeline. The frequency and read proportion of the SUVA AS events (pSAR) of each AS event were calculated to identify the dominant transcripts.

Results: A total of 268 dominant IFALD-RAS events with pSAR ≥ 50 % were identified. The genes associated with these RAS events were enriched mainly in the biological process of cell matrix adhesion. Then, we identified 25 RAS events associated with cell adhesion, including Afdn in AS events clustered at 3p3777. Moreover, we found that the infiltration of M2 macrophages was significantly greater in IFALD livers than in normal livers. Clualt5p19266:Supt20h was significantly positively correlated with the infiltration of M2 macrophages. Finally, we identified 33 differentially expressed RNA-binding proteins (DE-RBPs) and constructed a regulatory network between RBPs and co-disturbed RAS events.

Conclusion: Changes in AS may play vital roles in the pathogenesis of IFALD under TPN. The Mbnl3-Zmynd11 axis may be a potential therapeutic target for IFALD.