Clinical and Translational Gastroenterology最新文献

Introduction: Cirrhosis affects all structures of the kidney, in particular the tubules, which are responsible for secretion of protein-bound metabolites and electrolyte/water homeostasis. Yet, prevailing assessments of kidney function focus solely on glomerular filtration rate (GFR), which may incompletely reflect these processes. We sought to characterize markers of tubular function, injury, and viability in patients with and without cirrhosis.

Methods: We recruited outpatients undergoing liver transplantation evaluation for a collection of plasma and 24-hour urine, matching by GFR to control participants without cirrhosis. We measured urinary kidney injury molecule-1, a marker of proximal tubular injury, as well as epidermal growth factor (EGF), a marker of viability necessary for tubular epithelial cell proliferation after injury. We also estimated secretory clearance by measuring several highly secreted endogenous metabolites in urine and plasma.

Results: We recruited 39 patients with cirrhosis (mean model for end-stage liver disease 17 ± 4, Child-Pugh 8 ± 2, estimated glomerular filtration rate 66 ± 20 mL/min/1.73 m 2 ) and 58 GFR-matched controls without cirrhosis (estimated glomerular filtration rate 66 ± 21 mL/min/1.73 m 2 ). Urinary kidney injury molecule-1 was 4.4-fold higher than controls (95% confidence interval: 2.9-6.5), and EGF averaged 7.41-fold higher than controls (95% confidence interval: 2.15-25.53). We found that of 8 solutes, 5 had significantly greater kidney clearance in cirrhosis (1.3-2.1-fold higher): indoxyl sulfate, p-cresol sulfate, pyridoxic acid, tiglylglycine, and xanthosine.

Discussion: Cirrhosis was characterized by molecular signs of tubular injury in stable outpatients without acute kidney injury, accompanied by largely preserved tubular secretory clearance and greater signs of tubular viability. Within the limitations of the study, this suggests a phenotype of chronic ischemic injury but with initial preservation of tubular function in cirrhosis.

Introduction: Opioids are commonly prescribed to patients with chronic liver disease, but little is known regarding medication prescribing patterns of hepatologists. Opioid use increased until national guidelines limited opioid prescriptions in early 2016. We aimed to describe rates of opioid and nonopioid analgesics to Medicare beneficiaries by hepatologists from 2013 to 2017 and identify demographic characteristics associated with higher prescribing.

Methods: Prescription data from 2013 to 2017 by 761 hepatologists identified in the Centers for Medicare and Medicaid Services Part D Public Use File were analyzed. Annual prescription volumes were compared for providers with >10 annual prescriptions of a given drug type. Provider characteristics associated with opioid prescriptions were identified through multivariate logistic regression analyses.

Results: The proportion of hepatologists prescribing >10 annual opioid prescriptions decreased from 29% to 20.6%. Median annual opioid prescriptions per hepatologist significantly decreased from 24 to 20. Tramadol remained the most prescribed analgesic. Nonopioid analgesic prescription volume did not increase significantly. Provider characteristics associated with increased opioid prescriptions included male sex, practice location in the South and Midwest (vs West), more years in practice, and a greater proportion of beneficiaries who are white or with low-income subsidy claims. Characteristics associated with fewer prescriptions included non-university-based practice, having a greater proportion of female beneficiaries, and later prescription year.

Discussion: Hepatologists are prescribing less opioids. However, the prevalence of tramadol use and the lack of increase in nonopioid analgesic use highlights the need for advancing the science and training of pain management in chronic liver disease and targeted implementation of nonopioid treatment programs.

Introduction: Liver fibrosis is a major cause of morbidity and mortality among in patients with chronic hepatitis. Radiomics, particularly of the spleen, may improve diagnostic accuracy and treatment strategies. External validations are necessary to ensure reliability and generalizability.

Methods: In this retrospective study, we developed 3 radiomics models using contrast-enhanced computed tomography scans from 167 patients with liver fibrosis (training group) between January 2020 and December 2021. Radiomic features were extracted from arterial venous, portal venous, and equilibrium phase images. Recursive feature selection random forest and the least absolute shrinkage and selection operator logistic regression were used for feature selection and dimensionality reduction. Performance was assessed by area under the curve, C-index, calibration plots, and decision curve analysis. External validation was performed on 114 patients from 2 institutions.

Results: Twenty-five radiomic features were significantly associated with fibrosis stage, with 80% of the top 10 features originating from portal venous phase spleen images. The radiomics models showed good performance in the validation cohort (C-indices 0.723-0.808) and excellent calibration. Decision curve analysis indicated clinical benefits, with machine learning-based radiomics models (Random Forest score and support vector machine based radiomics score) providing more significant advantages.

Discussion: Radiomic features offer significant benefits over existing serum indices for staging virus-driven liver fibrosis, underscoring the value of radiomics in enhancing diagnostic accuracy. Specifically, radiomics analysis of the spleen presents additional noninvasive options for assessing fibrosis, highlighting its potential in improving patient management and outcomes.

Introduction: Reflux bile acids are believed to promote esophageal adenocarcinoma (EAC), but the role of systemic bile acids is unknown. This study aimed to assess associations between systemic bile acids and stages of Barrett's esophagus (BE) progression.

Methods: Subjects with and without BE were enrolled in this multicenter cross-sectional study. Targeted serum bile acid profiling was performed, and a subset of subjects completed a validated food frequency questionnaire. RNA sequencing was performed on BE or gastric cardia tissue to assess bile acid associations with gene expression.

Results: A total of 141 subjects were enrolled with serum bile acids profiled (49 non-BE; 92 BE: 44 no dysplasia, 25 indefinite/low grade dysplasia, 23 high-grade dysplasia/EAC). Lower Healthy Eating Index score, older age, higher body mass index, and no proton pump inhibitor use were associated with increased levels of multiple bile acids. Global bile acid pools were distinct between non-BE and stages of BE neoplasia ( P = 0.004). Increasing cholic acid was associated with high-grade dysplasia/EAC compared with non-BE, even after adjusting for EAC risk factors (adjusted odds ratio 2.03, 95% confidence interval 1.11-3.71) as was the combination of unconjugated primary bile acids (adjusted odds ratio 1.81, 95% confidence interval 1.04-3.13). High cholic acid levels were associated with tissue gene expression changes including increased DNA replication and reduced lymphocyte differentiation genes.

Discussion: Alterations in serum bile acids are independently associated with advanced neoplasia in BE and may contribute to neoplastic progression. Future studies should explore associated gut microbiome changes, proneoplastic effects of bile acids, and whether these bile acids, particularly cholic acid, represent potential biomarkers or viable therapeutic targets for advanced neoplasia in BE.

Introduction: Hepatitis B virus (HBV) infection is a contagious condition posing a major public health risk in various nations, including Vietnam. In 2019, the Ministry of Health introduced tenofovir alafenamide (TAF) to treat patients with chronic HBV infection and reduce the long-term toxicity of tenofovir disoproxil fumarate (TDF). This study aimed to assess the effectiveness and safety of these 2 medications in individuals with hepatitis B e antigen (HBeAg)-positive chronic HBV.

Methods: This retrospective cohort study included data collected from the medical records of patients with chronic HBV who visited the Liver Clinic at University Medical Center Ho Chi Minh City between 2018 and 2020.

Results: After 2 years of treatment, the proportion of HBeAg loss in the TAF group was twice that of the TDF group (22.4% vs 11.2%), indicating a statistically significant difference in the probability of HBeAg loss (adjusted hazard ratio = 2.22; 95% confidence interval [CI] 1.43-3.42; P < 0.01). In addition, there was a statistically significant difference in the rate and ability of antiviral response between patients treated with TAF and TDF (65% vs 54.5%, respectively; adjusted hazard ratio = 1.34; 95% CI 1.08-1.69; P < 0.01). A total of 93.9% of patients achieved the goal of restoring alanine aminotransferase to normal, a higher percentage compared with the 81.2% in the TDF group, and the likelihood of achieving normal alanine aminotransferase levels with TAF was greater compared with those on TDF (adjusted hazard ratio = 1.67; 95% CI 1.38-2.01; P < 0.01). Moreover, there was a statistically significant difference in the variation in renal function between the TAF and TDF groups. Serum creatinine levels in the TAF group increased less than those in the TDF group by 0.03 mg/dL every 6 months (95% CI -0.04 to -0.01, P < 0.01), and the estimated glomerular filtration rate in the TAF group was higher than that in the TDF group every 6 months by 2.78 mL/min/1.73 m 2 (95% CI 0.98-4.57, P < 0.01). However, there was no statistically significant difference in the likelihood of HBeAg seroconversion between patients with chronic hepatitis B treated with TAF or TDF (adjusted hazard ratio = 1.79; 95% CI 0.91-3.53; P = 0.09), nor in the risk of adverse events between the 2 groups (adjusted odds ratio = 1.34; 95% CI 0.88-2.05; P = 0.17). In addition, although the HBsAg concentration in the TAF group was lower than in the TDF group by an average of 0.05 log 10 IU/mL every 6 months (95% CI -0.15 to 0.05), this difference also did not reach statistical significance ( P = 0.35).

Discussion: TAF has been demonstrated to achieve some therapeutic efficacy goals and reduce nephrotoxicity better than TDF. However, no differences were found in seroconversion or adverse events between the patient groups.

Introduction: Mailed fecal immunochemical test (FIT) outreach is an effective strategy to increase colorectal cancer (CRC) screening. The aim of this study was to determine the patient-level, clinic-level, and geographic-level factors associated with CRC screening completion in a mailed FIT outreach program.

Methods: This retrospective cohort study was conducted in the integrated healthcare system of University of Washington Medicine and included patients aged 50-75 years, who were due for CRC screening, and had a primary care encounter in the past 3 years. Eligible patients received mailed outreach that included a letter with information about CRC screening, FIT kit, and a prepaid return envelope. CRC screening and factors associated with completion were obtained from electronic health records and the CRC screening program database.

Results: Of the 9,719 patients who received mailed outreach, 29.6% completed FIT mailed outreach. The median FIT return time was 27 days (interquartile range 14-54). On multivariate analysis, patients with a higher area deprivation index, insured through Medicaid, living without a partner, and whose last primary care visit was >12 months ago were less likely to complete a FIT compared with their counterparts. Over a 12-month period, overall CRC screening across the health system increased by 2 percentage points (68%-70%).

Discussion: Mailed FIT outreach in an integrated academic-community practice was feasible, with 32% of invited patients completing CRC screening by FIT or colonoscopy, on par with published literature. Patient and geographic-level factors were associated with CRC screening completion. These data will inform additional interventions aimed to increase CRC screening participation in this population.

Introduction: This study builds on previous research and its limitations, which indicate the need for further investigation in prospective cohorts. Our aim was to explore the association between estimated 24-hour urinary sodium excretion (indicative of daily sodium consumption) and the occurrence of pancreatic cancer in the UK Biobank's large prospective cohort.

Methods: Using the INTERSALT equation, the study computed estimated 24-hour urinary sodium excretion by analyzing the baseline spot urine sodium measurements of 434,372 individuals enrolled in the UK Biobank. Pancreatic cancer cases were identified through UK cancer registries. Adjusted Cox proportional hazards models were used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between estimated 24-hour urinary sodium excretion and the risk of pancreatic cancer.

Results: Over a median follow-up period of 13.8 years, 1,765 cases of pancreatic cancer were detected. The multivariable adjusted Cox model showed that each 1-gram rise in estimated 24-hour urinary sodium excretion corresponded to a 1.12 HR for incident pancreatic cancer (95% CI: 1.03, 1.22). The estimated HR for 24-hour urinary sodium excretion in binary form was 1.23 (95% CI: 1.05, 1.44). Compared with the lowest group, the group with the highest estimated 24-hour urinary sodium excretion exhibited an HR of 1.38 (95% CI: 1.21, 1.58).

Discussion: These results propose an association between elevated sodium consumption and a heightened risk of pancreatic cancer. Further validation and exploration of potential mechanisms are warranted.

Introduction: Empirical information on the evolution of reporting race and ethnicity information in gastroenterology research is lacking. To facilitate understanding of where improvements are needed to increase diversity, equity, and inclusion in gastroenterology research, we aimed to evaluate reporting and representation by race and ethnicity in studies published in flagship US-based gastroenterology journals over 20 years.

Methods: We manually reviewed reporting and representation by race and ethnicity in all original research articles published in the American Journal of Gastroenterology and Gastroenterology in 2000, 2010, and 2020.

Results: Of 1,168 publications, 24% reported information on race/ethnicity, significantly more commonly reported in US-based study samples vs non-US-based samples. While reporting significantly increased over time, reporting rates were still low as of 2020 (37% overall; 54% with US-based samples).

Discussion: We recommend that gastroenterology journals create standard reporting requirements for sociodemographic information, including information on race, ethnicity, and/or cultural background.

Introduction: Neutrophilic calprotectin (CP) and myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and eosinophil-derived neurotoxin (EDN) are suggested proxy markers for gut inflammation. However, there are insufficient supporting data for MPO, NGAL, and EDN.

Methods: In a cross-sectional investigation including adult patients, we studied the ability of CP, MPO, NGAL, and EDN, measured in fecal and serum samples, to differentiate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and to predict disease activity.

Results: Fifty-nine patients had ulcerative colitis (UC), 38 had Crohn's disease, and 100 patients had IBS. The protein concentrations were higher in patients with IBD in the fecal samples ( P < 0.001) and the serum samples ( P < 0.01), and they correlated weakly (r s ≤0.38) between the sample sources. Fecal EDN was higher in patients with Crohn's disease compared with UC (1.79 vs 0.50 mg/kg, P = 0.016). The neutrophilic proteins were superior to EDN in the fecal samples for differentiating between patients with IBD and IBS. Fecal MPO (cutoff: 0.86 mg/kg) had the highest sensitivity (74.7%) and specificity (84.6%). Combining fecal CP and MPO increased the sensitivity to 82.3% (specificity: 73.6%). NGAL (cutoff: 196.9 μg/L) showed the best discriminating performance in serum (sensitivity: 62.9%; specificity: 68.0%). Serum NGAL (cutoff: 272.4 μg/L) predicted active disease in UC (Partial Mayo Score ≥2) with a sensitivity and specificity of 57.1% and 83.3%, respectively.

Discussion: Fecal MPO and serum NGAL are promising novel biomarkers, in addition to fecal CP, for differentiating between IBD and IBS. Serum NGAL may also predict disease activity in patients with UC.

Introduction: Altered gut microbiota may play a role in slow-transit constipation (STC). We conducted a study of gut microbiota composition and functionality in STC using metagenomic analyses.

Methods: We assembled a clinical cohort of 24 patients with STC physiology age- and sex-matched to 24 controls. We performed shotgun metagenomic sequencing followed by prediction of metabolite composition from functional profiles.

Results: In a middle-aged (mean 55.3 years), predominantly female cohort, there were no significant differences in α-diversity indices, but permutational multivariate analysis of variance analysis showed significant between-group differences (R 2 = 0.050, P < 0.001) between STC patients and controls. Gordonibacter pamelaeae , Bifidobacterium longum , Firmicutes bacterium co-abundance gene group 94, and Anaerotruncus colihominis were more abundant in STC, whereas Coprococcus comes and Roseburia intestinalis were more abundant in controls. Gut-derived metabolites varying in STC relative to controls were related to bile acid and cholesterol metabolism.

Discussion: We found a unique metagenomic and metabolomic signature of STC.