Clinical and Translational Gastroenterology最新文献

Background: Sex steroids modulate metabolic-dysfunction associated steatotic liver disease (MASLD) pathobiology. We hypothesized that testosterone therapy (TT) modulates progression of MASLD, and performed a systematic review to evaluate the efficacy of TT on liver steatosis and fibrosis.

Methods: We searched PubMed and Embase from inception until November 2023. We screened 1489 studies and identified 9 eligible studies. We assessed risk of bias for randomized trials using RoB-2 "Cochrane risk of bias tool for randomized trials", non-randomized studies using ROBINS-I tool "Risk of Bias in Non-randomized Studies-of Interventions", and Murad's Tool for single-arm studies. We pooled estimates using RevMan 5.

Results: 3 randomized controlled trials (RCTs), 4 non-randomized studies, and 2 single-arm studies were identified. The population of interest comprised men with MASLD. TT was administered at varying doses, routes, and frequencies, with follow-up ranging 12-weeks to 8-years. Liver fibrosis and steatosis were assessed using liver biopsy in 3 studies, CT/MRI in 5, and serum scores in 2. All studies provided evidence of reduction in liver steatosis with TT compared to no TT. In addition, the LiFT (RCT) trial demonstrated a resolution of MASLD / MASH and a regression in liver fibrosis. TT led to decrease in liver enzymes. Studies were heterogenous in terms of population characteristics, treatment modalities, endpoints, and follow-up. Adverse events were comparable between the 2 groups.

Conclusion: TT is a promising treatment option for men with MASLD and low testosterone. It may improve liver steatosis and reduce liver fibrosis. Large, double-blinded randomized placebo-controlled trials are needed.

Background: The impact of pelvic bone structure on fecal incontinence (FI) is unclear. We assessed the association between weight-adjusted pelvic area and FI.

Methods: This was a population-based analysis of the National Health and Nutrition Examination Survey in 2005-2006. Participants who completed the bowel health survey and dual-energy x-ray absorptiometry (DXA) were included.

Results: On multivariable analysis of 2,772 participants, the lowest pelvic area quartile predicted increased FI compared to the third (OR:2.05, CI:1.18-3.56, p=0.014) and fourth (OR:1.94, CI:1.02-3.70, p=0.045) quartiles. Sex-stratified analyses found similar association among female patients only.

Conclusion: Small pelvic area on DXA is a potential risk factor for FI.

Introduction: A link between inflammatory bowel disease (IBD), stressful life events and psychological factors has previously been reported. Our objective was to examine the relationship between childhood emotional, physical, and sexual abuse and risk of IBD using a large cohort of female health professionals.

Methods: We included participants in the Nurses' Health Study II who completed the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire and the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale in 2001. Diagnosis of IBD was determined by self-report and confirmed independently by two physicians through review of medical records. We used Cox proportional hazard modeling to estimate the risk of Crohn's disease (CD) and ulcerative colitis (UC) while adjusting for covariates.

Results: Among 68,167 women followed from 1989 until 2017, there were 146 incident cases of CD and 215 incident cases of UC. Compared to women with no history of abuse, the adjusted hazard ratios of CD were 1.16 (95% CI 0.67 - 2.02) for mild, 1.58 (95% CI 0.92 - 2.69) for moderate, and 1.95 (95% CI 1.22 - 3.10) for severe abuse (Ptrend = 0.002). We did not observe an association between childhood abuse and risk of UC.

Conclusions: Women who reported early life severe abuse had an increased risk of CD. These data add to the growing body of evidence on the critical role of early life stressors in development of CD.

Background: While Helicobacter pylori (H. pylori) infection is common in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, there are still individuals who test negative for it. The proportion and characteristics of these patients remain unclear.

Methods: We conducted a systematic search of the PubMed, Embase, and Cochrane Library databases for relevant articles. Using a random effects model, we performed a meta-analysis to assess the pooled proportion of gastric MALT lymphoma patients with negative H. pylori tests. Additionally, we compared characteristics between gastric MALT lymphoma patients with and without H. pylori infection to examine clinical features in H. pylori-negative cases.

Results: A total of 50 studies involving 6033 patients were included. The overall proportion of gastric MALT lymphoma patients with negative H. pylori tests was 20.5% (95% confidence interval: 17.0%-24.6%). This rate exhibited an increasing trend over the years, particularly in non-Asian countries and in studies published after 2013, as well as in cases with sample sizes exceeding 100 participants, in male individuals, and among those with proximal or multiple lesions, non-superficial type morphology, submucosal invasion, and advanced clinical staging. Compared to H. pylori-positive patients, those who tested negative were more likely to be male, have proximal lesions, exhibit submucosal invasion, and present with an advanced clinical stage.

Conclusions: This study provides comprehensive information on the proportion and characteristics of H. pylori-negative gastric MALT lymphoma cases, highlighting the need for future clinical attention to treatment and surveillance in this patient population.

Introduction: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970,A1073V;1073val/val) related to Nav1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question.

Methods: Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension(RBD).

Results: We analyzed 416 IBD patients (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in hypoalgesic IBD patients when compared to other IBD patients and healthy controls. Hypoalgesic IBD patients were also more likely to be homozygous for this polymorphism when compared to other IBD patients and healthy controls. Hypoalgesic CD (30%vs.12%,p=0.004) and hypoalgesic UC (32%vs.15%,p=0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals(n=50), rs6795970 homozygotes(n=11) also demonstrated reduced abdominal discomfort to RBD.

Discussion: These findings indicate that Nav1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain.

Background: Liver stiffness measurement is principal for staging liver fibrosis but not included in routine examinations. We investigated whether comparable diagnostic performance can be achieved by mining ultrasound images and developing a novel serum index (NSI).

Methods: Texture features were extracted from ultrasound images. Spearman correlation and logistics regression selected independent variables for significant (F≥2) and advanced (F≥3) fibrosis. We compared the diagnostic performance of transient elastography (TE), ultrasound image biomarker (UIB), conventional serum indices (APRI, FIB-4, GPR), and NSI in 365 chronic hepatitis B patients.

Results: Among patients, 52.1% had significant fibrosis and 24.2% had advanced fibrosis. PLT, GGT, prealbumin, and globulin were incorporated into NSI. In the validation group, TE achieved the best performance (AUC: 0.765 [0.690-0.849] for significant fibrosis; 0.812 [0.745-0.878] for advanced fibrosis), followed by UIB (AUC: 0.712 [0.629-0.795]; 0.678 [0.595-0.763]) and NSI (AUC: 0.630 [0.534-0.725]; 0.659 [0.572-0.745]), outperforming conventional indices.

Conclusions: Texture analysis enhances ultrasound's diagnostic utility, but TE remains superior. When TE is unavailable, ultrasound image analysis and NSI, incorporating prealbumin, can serve as alternative tools for fibrosis staging.

Background: A straightforward, reliable, and noninvasive method for predicting the development of liver-related events (LRE) in primary biliary cholangitis (PBC) has not been attained thus far. The present study investigated whether serum autotaxin (ATX) could predict liver-related events (LRE) in PBC patients.

Methods: This retrospective multicenter investigation included 190 biopsy-proven untreated PBC patients. All subjects were followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, esophagogastric varices, ascites, and hepatic encephalopathy, was investigated in relation to ATX levels at the time of liver biopsy.

Results: During the median follow-up period of 9.7 years, LRE were observed in 22 patients (11.6%). The area under the receiver operating characteristic curve and cut-off value of serum ATX for predicting LRE were 0.80 and 1.086 mg/L, respectively. Patients with serum ATX ≥ 1.086 had a significantly higher cumulative incidence of LRE compared with patients with ATX < 1.086 (33.3% vs. 3.6%, p < 0.00001). Notably, the predictive capability of ATX for LRE in PBC patients surpassed that of FIB-4, ALBI, APRI, and M2BPGi. A multivariate Cox proportional hazards model revealed ATX as an independent associated factor for LRE (hazard ratio 6.24, 95% confidence interval 1.87-20.80, p = 0.003) along with Nakanuma stage (hazard ratio 2.75, 95% confidence interval 1.52-4.99, p < 0.001). These results were closely replicated in a serologically diagnosed PBC validation cohort (n = 32).

Conclusion: Serum ATX levels may serve as a predictive marker for LRE in patients with PBC.

Introduction: Several studies suggest that new-onset diabetes mellitus is an early manifestation of pancreatic ductal adenocarcinoma (PDAC). Therefore, the International Cancer of the Pancreas Screening Consortium recommends glucose and hemoglobin A1c (HbA1c) monitoring in high-risk individuals (HRIs) undergoing surveillance. However, evidence that such monitoring improves PDAC detection is lacking. Our aim was to investigate the association between serum glucose and HbA1c values and the development of PDAC in HRIs undergoing surveillance.

Methods: Participants were recruited from the familial pancreatic cancer surveillance cohort, which follows hereditary predisposed HRIs yearly by magnetic resonance imaging and/or endoscopic ultrasound and blood sampling. Those who underwent fasting glucose and/or HbA1c monitoring at least once were eligible candidates.

Results: Four hundred four HRIs met the inclusion criteria. During a median follow-up of 41 months (range 14-120), 9 individuals developed PDAC and 4 (without PDAC) were diagnosed with new-onset diabetes mellitus. Glucose levels ranged from 3.4 to 10.7 mmol/L (mean 5.6 ± 0.7) and HbA1c levels from 25 to 68 mmol/mol (mean 37.7 ± 4.1). The mean values did not differ significantly between PDAC cases and controls. The percentage of individuals with at least one elevated value were comparable between PDAC cases and controls for glucose (33% and 27%, P = 0.707) and HbA1c (22% and 14%, P = 0.623). No consistent glucose or HbA1c trends over time suggested a correlation with PDAC development.

Discussion: In this HRI surveillance cohort, measuring glucose and HbA1c values did not contribute to PDAC detection. Larger and longer-term studies are needed to determine the final role of glucose and HbA1c monitoring in PDAC surveillance.

Introduction: Potassium-competitive acid blockers have emerged as a promising treatment of acid-related disorders. However, the optimal dosage for maximizing their efficacy remains unclear. The aim of this network meta-analysis was to compare the efficacy and safety of various dosages of potassium-competitive acid blockers and proton-pump inhibitors for treating acid-related disorders.

Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to July 16, 2023. Data extraction was performed independently by 2 authors. The Cochrane Risk of Bias in Randomized Trials tool (RoB 2.0) was used for bias assessment. The efficacy and safety were compared using the odds ratio with 95% confidence intervals.

Results: Twelve articles were included in the present meta-analysis. For gastric/duodenal ulcers, keverprazan 30 mg (K30) exhibited the highest surface under the cumulative ranking (SUCRA) value (92.8%) for healing rate. In terms of total adverse events, lansoprazole 30 mg (L30) exhibited the lowest SUCRA value (25.3%) in the treatment of gastric/duodenal ulcers. For the healing rate in erosive esophagitis, the maximum SUCRA value of vonoprazan 40 mg (V40) was 90.7% in the first subgroup (erosive esophagitis using vonoprazan, keverprazan, and lansoprazole) and the maximum SUCRA value of T50 was 72.1% in the second subgroup (erosive esophagitis using tegoprazan, fexuprazan, and esomeprazole). For the total adverse events in erosive esophagitis, L15 exhibited the lowest SUCRA value (12.2%) in the first group and E40 exhibited the lowest SUCRA value (24.4%) in the second group.

Discussion: K30 may be the most effective dosage for increasing the healing rate of gastric/duodenal ulcers. For erosive esophagitis, V40 and T50 may be the preferred dosages.

Introduction: Trastuzumab deruxtecan (T-DXd) has been approved for human epidermal growth factor receptor 2-positive locally advanced or metastatic gastric and gastroesophageal junction (HER2+ mG/GEJ) cancer since July 2022 in France, through an accelerated approval. The aim of this study was to evaluate its real-world use.

Methods: We characterized T-DXd users treated for HER2+ mG/GEJ cancer using data from the French National Health Insurance database.

Results: The cohort included 196 patients, mostly men (78.1%), with a median age of 65 years. Median overall survival reached 7.7 months (95% CI: 6.2-9.0).

Discussion: Patients treated with T-DXd for HER2+ mG/GEJ cancer in the real world showed lower outcomes than those in pivotal clinical trials, consistent with previous reports on accelerated approvals.