Background and Aims Barrett's esophagus surveillance relies on subjective biopsy grading that misses fast progressors. Although the Tissue Systems Pathology test (TSP-9) and p53 immunohistochemistry (IHC) have each been evaluated separately, no prior study has directly compared the two within a single analytic framework. We compared both biomarkers for predicting progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Methods PubMed, Embase, Cochrane, and Web of Science were searched through December 2025. Studies were included if they evaluated TSP-9 or p53 IHC in patients with non-dysplastic Barrett's esophagus (NDBE), indefinite for dysplasia (IFD), or low-grade dysplasia (LGD) and reported prognostic outcomes. Pooled sensitivity, specificity, negative predictive value (NPV), odds ratios, and hazard ratios were estimated using random-effects models. Results Twenty-three studies (7 TSP-9, 16 p53 IHC; 6,655 patients) met inclusion criteria. TSP-9 yielded a higher pooled hazard ratio (HR 7.65; 95% CI: 5.86–9.99) compared with p53 IHC (HR 5.05; 95% CI: 4.27–5.97). Sensitivities were comparable (TSP-9: 57.1% vs. p53 IHC: 60.1%), while p53 IHC demonstrated higher specificity (91.5% vs. 83.5%). Both biomarkers exhibited robust NPVs exceeding 90% (p53 IHC: 94.7%; TSP-9: 91.1%). Conclusion Both TSP-9 and p53 IHC substantially outperform standard histology for risk stratification in Barrett's esophagus. The higher HR with TSP-9 may reflect its multiplexed approach. The strong NPV of both assays supports safely extending surveillance intervals in low-risk patients.
Background Depression is a critical yet under-recognized comorbidity in chronic liver disease, with important implications for treatment adherence, self-management, and clinical outcomes. However, nationally representative estimates of comorbid depression using contemporary elastography-defined advanced chronic liver disease (ACLD) and clinically significant portal hypertension (CSPH) are lacking. Methods We analyzed adults from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 and 2021–2023 cycles using valid vibration-controlled transient elastography (VCTE), PHQ-9 (Patient Health Questionnaire) data, and complete covariates. Survey-weighted logistic regression identified factors associated with depression in ACLD patients, adjusting for the identified covariates. Sensitivity analyses were used to evaluate alternative PHQ-9 scoring assumptions. Results Among 13,291 participants representing the U.S. adult population, the weighted prevalence of comorbid depression was 12.16% with 95% confidence interval (CI) 8.65,15.66%. In multivariate analysis, female sex (adjusted odds ratio [aOR] 3.51; 95% CI 1.98,6.23; P <.001) and greater sedentary time (aOR 1.012 per hour/day; 95% CI 1.006,1.018; P=.021) were independently associated with higher odds of comorbid depression. Older age (aOR 0.97 per year; 95% CI 0.94,1.00; P=.025) and Non-Hispanic Black race compared with Non-Hispanic White race (aOR 0.27; 95% CI 0.10,0.71; P=.010) were associated with lower odds of depression in ACLD. The odds of depression were 78% higher in the post-pandemic period than in the pre-pandemic (aOR 1.78; 95% CI 1.04,3.02; P=.035). The findings were robust across sensitivity analyses. Conclusions Approximately 14–15% of US adults with ACLD or CSPH experience comorbid depression, with an increase in the post-COVID-19 era. Depression burden was the highest among women, younger adults, individuals with high sedentary time, and Non-Hispanic Black adults with CSPH. Therefore, there is a need to integrate behavioral health pathways into hepatology care.
Importance The incidence of colorectal cancer (CRC) diagnosed before age 50 years has increased, prompting lowering of screening initiation to age 45. However, age-based screening strategies treat younger adults as a homogeneous population and do not account for heterogeneity in inherited susceptibility. Objective To evaluate whether an integrated inherited risk measure (GenProbCRC) stratifies risk of early-onset CRC (EOCRC; <50 years). Design, Setting, and Participants Prospective cohort study conducted in two independent biobanks: the UK Biobank (UKB) and the Genomic Health Initiative (GHI), a US health system–based biobank. Participants younger than 50 years at recruitment and free of CRC at baseline were followed for incident CRC until age 50. Exposure Four pre-specified inherited risk groups defined by GenProbCRC, an integrated genetic risk measure incorporating a polygenic risk score, family history, and pathogenic variants in Lynch syndrome genes. Main Outcomes and Measures Incident EOCRC. Associations between GenProbCRC and EOCRC were evaluated using Cox proportional hazards models with age as the underlying time scale. Cumulative incidence by age 50 was estimated using Kaplan–Meier methods. Results Among 102,797 UKB participants, 109 developed EOCRC. Compared with the low-risk group, hazard ratios (95% CIs) were 1.36 (0.68–2.71) for the intermediate-risk group, 5.95 (3.77–9.38) for the high-risk group, and 28.41 (13.88–58.17) for the very-high-risk group. Cumulative incidence by age 50 increased progressively across risk groups: 0.08% (low), 0.11% (intermediate), 0.46% (high), and 2.06% (very high), log-rank P<0.001. Although representing approximately 21% of the population, individuals in the high- and very-high-risk groups accounted for 61% of EOCRC cases. Associations were directionally consistent in GHI, although estimates were imprecise due to smaller sample size (7,206 participants; 14 EOCRC cases). Conclusions Risk of EOCRC varies substantially across inherited risk strata. These findings highlight marked heterogeneity among adults younger than 50 years and support evaluation of genomics-informed risk-based screening approaches beyond age-, family history–, and monogenic-based strategies.
Background and Aims Screening uptake among individuals at high-risk for esophageal and gastric cardia adenocarcinoma (EAC/GCA) remains poor. We conducted a pilot study to evaluate the real-world implementation of two approaches for endoscopic screening uptake in high-risk individuals identified by an automated risk assessment tool, with the aim of identifying facilitators, barriers, and implementation gaps. Methods Pilot 1 involved notifying primary care physicians (PCP) of patients at high risk and due for colorectal cancer (CRC) screening. Pilot 2 used nurse outreach to offer esophagogastroduodenoscopy (EGD) to high-risk patients scheduling a screening colonoscopy. The primary outcome was feasibility – EGD ordered among eligible patients. Secondary outcomes included EGD completion and acceptability, assessed through semi-structured interviews with patients, PCPs, gastroenterologists, and facility leadership. Results In Pilot 1, PCPs were notified of 97 high-risk patients; EGDs were ordered in 28 (29%) and completed in 15 (54% of ordered). If CRC screening was ordered, PCPs were more likely to discuss EAC/GCA risk (69% vs. 36%, p<0.01). EGD was more likely ordered if colonoscopy was ordered vs. fecal testing (88% vs. 39%, p<0.01). In Pilot 2, 9 of 86 eligible patients were contacted; EGDs ordered for 6 (7%) and completed in all 6 (100% of ordered). Providers valued decision support tools and automatic electronic health record alerts, but cited lack of supporting evidence, guideline recommendations, and clinic time as barriers. Conclusion Both provider notifications and nurse outreach demonstrated high acceptability and completion, but limited feasibility for increasing EGD orders due to provider and system-level barriers, highlighting implementation gaps and targets for guideline and workflow integration.
Background and Aims Bowel urgency is a particularly burdensome symptom for adults with ulcerative colitis (UC). This post hoc analysis of three phase 3 studies evaluated the effects of vedolizumab on bowel urgency using selected items from the Inflammatory Bowel Disease Questionnaire (IBDQ). Methods Data were pooled from three phase 3 randomized trials: GEMINI 1 (NCT00783718), VISIBLE 1 (NCT02611830), and VARSITY (NCT02497469). Adults with moderate to severe UC who received vedolizumab or placebo and completed the IBDQ were included. Items Q11, Q16, and Q26 from the IBDQ were combined to create a bowel urgency composite score. Bowel urgency resolution was defined as the absence of symptoms across all three items. Primary outcomes were the change in bowel urgency composite score and the proportion of patients with bowel urgency resolution at week 52. Exploratory outcomes included change in bowel urgency composite score and bowel urgency resolution stratified by anti-tumor necrosis factor (TNF)-α exposure status, disease activity, and treatment arm (intravenous vedolizumab once every 8 weeks versus placebo), and the relationship between bowel urgency and clinical and endoscopic outcomes. Results Overall, 1,225 patients were included. Patients receiving vedolizumab had greater changes in bowel urgency composite scores than placebo overall and when stratified into subgroups. A greater proportion of patients in the vedolizumab group (44%) attained bowel urgency resolution than the placebo group (22%). Bowel urgency resolution at week 6 was significantly associated with attaining all clinical and endoscopic outcomes at week 6, and with attaining clinical remission, endoscopic improvement, and symptomatic remission at week 52 (all P < .05). Conclusion Bowel urgency-related symptoms, assessed by the IBDQ, were improved in patients receiving vedolizumab versus placebo.
Background and Aims:Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to dyslipidemia, insulin resistance, and impaired glucose metabolism. Herbal products are widely used in MASLD, but their comparative metabolic effects and certainty of evidence remain unclear. We conducted a systematic review and network meta-analysis to evaluate herbal products on metabolic outcomes in MASLD. Methods:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and International Prospective Register of Systematic Reviews registration (CRD420251236813), we searched PubMed, Web of Science, EMBASE, and Cochrane through September 2025 for randomized trials of herbal products in adults with MASLD. Primary outcomes were triglycerides (TG), fasting blood glucose (FBG), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR); secondary outcomes included cholesterol fractions, hemoglobin A1c, and body mass index. Random-effects network meta-analysis estimated mean differences (MDs) (95% confidence interval); certainty was assessed using CINeMA (Confidence in Network Meta-Analysis). Results:A total of 123 trials were included (n = 8595). For TG, significant reductions vs placebo occurred with Korean red ginseng (MD: -99.00), naringenin (MD: -92.50), and artichoke leaf (MD: -52.60; all P < .01); surface under the cumulative ranking curve (SUCRA) favored naringenin and Korean red ginseng (both 0.96). For FBG, green tea (MD: -16.98; P = .03), hesperidin + flaxseed (MD: -14.44), and garlic (MD: -13.51) were top-ranked (SUCRA: 0.90, 0.89, 0.87). For HOMA-IR, sumac (MD: -2.32; P < .01), green tea (MD: -1.81), and berberine + tocotrienols + green coffee (MD: -1.80) showed greatest improvements (SUCRA: 0.94 for sumac). Artichoke leaf, curcumin, and green tea improved total cholesterol, low density lipoprotein-cholesterol, and body mass index; no intervention reduced hemoglobin A1c. CINeMA showed high confidence only for artichoke leaf on total cholesterol; moderate for select TG, high density lipoprotein-cholesterol, and HOMA-IR outcomes; remaining were low or very low. Conclusion:Selected herbal products, particularly artichoke leaf, curcumin, green tea, flaxseed, and garlic may offer modest, domain-specific metabolic improvements in MASLD, though confidence was low for most outcomes. These therapies may serve as adjuncts, not substitutes for approved treatments. Larger randomized controlled trials with standardized formulations, long-term safety data, and liver-specific outcomes are needed.
Background and Aims:While Gα13 transduces signals from G protein-coupled receptors to regulate inflammation, its role in pancreatitis remains poorly understood. This study aims to understand how Gα13 regulates pancreatitis-induced inflammation and acinar injury. Methods:Expression of Gα13 in mouse and human pancreas tissue was examined by immunostaining. Experimental pancreatitis was induced by administering cerulein to mice with wild-type and conditional knockout of Gα13 in the pancreas. The impact of Gα13 loss on pancreatitis was assessed by histology, immunostains, and cytokine proteome array. The Gα13-deficient mice were cotreated with the mammalian target of rapamycin (mTOR) inhibitor rapamycin during cerulein treatment to determine the effects of mTOR inhibition on pancreatitis. Results:We found reduced Gα13 expression in acute and chronic human pancreatitis samples. We show that induction of acute and chronic pancreatitis in mice with cerulein treatment reduces Gα13 expression. Moreover, we found worsening of acute and chronic pancreatitis-induced acinar injury in mice with pancreas-specific deletion of Gα13. While pancreatic deletion of Gα13 did not exacerbate acute pancreatitis-induced inflammation, we found that Gα13 loss mildly exacerbated chronic pancreatitis. Gα13 loss increased cerulein-induced mTOR signaling in the acute and chronic pancreatitis mouse models; however, the mTOR inhibitor rapamycin attenuated the effects of cerulein only in the acute pancreatitis model, whereas it exacerbated the effects of cerulein in the chronic pancreatitis model. Conclusion:This work demonstrates that Gα13 loss promotes tissue damage in acute and chronic pancreatitis, which can be attenuated by the mTOR inhibitor rapamycin in acute pancreatitis.
Background and Aims Intestinal tuft cells are rare chemosensory epithelial cells critical for mucosal immunity. However, the molecular features of human intestinal tuft cells remain incompletely defined due to limited access to human tissue and known species-specific differences from murine models. We sought to establish a human tuft cell–enriched intestinal organoid system derived from pluripotent stem cells. Methods Human pluripotent stem cell–derived intestinal organoids containing epithelial, stromal, and neural components were subjected to Notch pathway inhibition and T helper 2 cytokine stimulation to promote tuft cell differentiation. Induced tuft cells were analyzed by immunofluorescence, quantitative polymerase chain reaction (qPCR), and single-cell RNA sequencing, followed by integrated transcriptomic comparison with primary human small intestinal tuft cells. Results Tuft cell–enriched organoids were reproducibly generated from 3 independent human pluripotent stem cell lines. Integrated single-cell transcriptomic analyses demonstrated strong concordance between in vitro-derived and primary human tuft cells. The organoid-derived tuft cells exhibited distinct molecular features, including low and non-enriched interleukin-25 expression and predominant DCLK2 expression, distinguishing them from murine tuft cells. Under defined experimental conditions, murine-reported regulatory mechanisms, including bone morphogenetic protein-dependent negative feedback and goblet cell–mediated lateral inhibition, were not recapitulated. Conclusion We establish a human pluripotent stem cell–derived intestinal organoid model that enables enrichment and molecular characterization of human tuft cells. This platform provides a human-specific system for elucidating molecular programs governing tuft cell differentiation and epithelial–immune signaling.
Background and aims Metabolic dysfunction–associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide. In vitro MASLD studies predominantly rely on hepatocellular carcinoma–derived cell lines such as HepG2 that are poorly differentiated and exhibit cancer-associated metabolic reprogramming that suppresses key adult hepatic functions. Primary human hepatocytes offer greater physiological relevance and capture inter-individual biological variability that reflects human population diversity, but their use is limited by high costs, availability, and rapid dedifferentiation in culture. Here, we characterized the immortalized primary human hepatocyte cell line Fa2N-4 as an alternative in vitro model for MASLD. Methods We performed a comparative analysis of Fa2N-4 and HepG2 cells, assessing their genomic architecture, lipid-induced steatosis, and pharmacological responsiveness. Results The Fa2N-4 and HepG2 cell models exhibited pronounced differences, including distinct karyotypes, divergent MASLD-associated genetic risk variant profiles, and markedly different transcriptional responses to lipid loading and drug treatment. We further examined the hepatic response to resmetirom, a first-in-class FDA-approved therapy for treating metabolic dysfunction–associated steatohepatitis. Resmetirom, a thyroid hormone receptor-β agonist, reduced intracellular triglyceride accumulation in Fa2N-4 cells but not HepG2 cells, and this was accompanied by transcriptional changes in mitochondrial glycolysis and oxidative phosphorylation pathways. Conclusions These findings demonstrate that hepatocyte model selection critically influences experimental outcomes in MASLD research and highlight Fa2N-4 cells as a physiologically relevant platform for mechanistic and translational studies of MASLD therapeutics.
Background and Aims:Food insecurity (FI), limited or uncertain access to enough food, has been linked to poor clinical outcomes. Given that dietary management is central to many gastrointestinal (GI) and hepatologic diseases, these populations may be uniquely vulnerable to the effects of FI. Our primary aim was to determine the prevalence rates of FI among patients with chronic GI and liver conditions within the United States and evaluate reported associations with clinical outcomes. Methods:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search of PubMed, Web of Science, and Embase from inception to July 17, 2025. Eligible studies reported FI prevalence and were conducted in the United States. Clinical and nutritional outcomes were collected as well as risk of bias assessment for each study. Results:Of the 1279 references identified, 25 studies (54,034 participants) meet inclusion criteria. FI prevalence varied widely (5%-45.5%) across disease types, including liver disease (n = 12), inflammatory bowel disease (n = 5), cystic fibrosis (n = 5), and celiac disease (n = 3). Eight studies utilized the gold standard, 18-item US Household Food Security Survey. Of the 17 studies reporting clinical outcomes, 13 found possible associations with FI. Seventeen out of 25 studies met ≥80% of quality criteria. The most commonly unmet criteria across studies related to insufficient control of confounding variables. Conclusion:FI is prevalent and clinically significant across a range of chronic GI and hepatologic conditions. Though prevalence estimates vary substantially by disease type and measurement approach, FI may be associated with worse clinical outcomes, dietary nonadherence, and social disadvantage. Routine screening and intervention strategies to address FI may be a critical component to comprehensive GI care.
Background and Aims:Anal cancer incidence is rising, primarily due to increasing rates of human papillomavirus infection. High-resolution anoscopy (HRA) is the gold standard diagnostic modality for evaluating human papillomavirus-related anal lesions; however, its broader adoption is limited by subjectivity and interobserver variability. This study aims to develop and validate a deep learning-based trinary classification model that detects and classifies high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), and non-dysplastic lesions (eg, inflammation) on HRA frames. Methods:A multicentric study was conducted to develop a convolutional neural network for automatic detection and classification of HSIL, LSIL, and non-dysplastic lesions. A You Only Look Once (YOLO)-v11 model was trained and validated on 191,951 frames (from 107 HRA procedures) containing histologically confirmed lesions, collected from 5 different imaging devices across 5 independent centers. Performance metrics (recall, precision, accuracy, and F1-score) were calculated at the object classification level as weighted averages across 5 confidence thresholds (0.45, 0.47, 0.50, 0.52, and 0.55). Results:For HSIL and LSIL, recall was 97.9% and 98.9%, and precision was 93.9% and 98.5%, respectively. For non-dysplastic lesions, recall was 98.7%, and precision was 96.0%. The overall classification accuracy on the test set was 88.1% (95% CI: 78.2-98.1). Conclusion:This is the first interoperable artificial intelligence model capable of simultaneous detection and trinary classification of anal canal lesions (HSIL, LSIL, and non-dysplastic mimickers). By addressing key limitations of HRA, this model supports broader clinical applicability and represents a significant step toward real-world deployment and personalized artificial intelligence-assisted care.
Background and Aims:Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic cholestatic liver diseases with overlapping features but distinct biology. While bile acids (BAs) are central to cholestatic pathophysiology, the extent to which circulating BAs define disease-specific states remains unclear. Methods:Plasma BA profiling and clinical laboratory tests were performed in patients with PSC (n = 269), PBC (n = 262), and matched controls (n = 269/262), respectively. BA composition, conjugation patterns, and pool characteristics were compared within and across diseases. Associations with hepatic decompensation were evaluated using univariable and exploratory multivariable analyses, including comparison with established prognostic scores. Results:Both PSC and PBC exhibited elevated total BA levels compared with controls; however, BA composition and conjugation patterns differed between diseases. PSC was characterized by increased BA conjugation fraction and reduced glycine-to-taurine ratios, whereas PBC showed preserved overall conjugation with increased glycine predominance. In PSC, BA composition was further modulated by inflammatory bowel disease and colectomy, with depletion of secondary BA species. Across both diseases, advancing liver disease stage was associated with shifts toward primary and conjugated BA dominance. BA variables and clinical laboratory tests were associated with hepatic decompensation, particularly in PSC. Exploratory multivariable models showed comparable performance of BA-based and clinical laboratory-based models, and their combination did not materially improve prediction. Conclusion:Plasma BA profiles define distinct cholestatic states in PSC and PBC that reflect disease type, intestinal modifiers, and liver disease stage. While BA variables are associated with clinical outcomes, their principal value lies in complementing established clinical laboratory-based assessments rather than improving predictive accuracy.
Background and Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is progressive, with an estimated global prevalence exceeding 30%. Social determinants of health (SDOH) may impact MASLD risk and progression. However, this has not been fully characterized. We harnessed the power of the All of Us Research Program (AoU) dataset to conduct a comprehensive analysis examining the association between various SDOH and MASLD. Methods We conducted a retrospective cross-sectional analysis of the AoU database. We identified participants with MASLD using ICD-9 and -10 codes and excluded individuals with other chronic liver diseases (CLD) or self-reported heavy alcohol use. Healthy control participants were devoid of CLD, heavy alcohol use, and comorbidities associated with MASLD if obese. We examined SDOH by combining relevant questions from various AoU surveys and conducted univariate and multivariate logistic regression to examine the association between various SDOH and MASLD. Results After matching cases to controls by age and race/ethnicity, the sample of 57,895 participants had a 1:3 case to control ratio; 16,666 had complete SDOH survey data (MASLD to controls, 1:3.4). Compared to controls, individuals with MASLD were more likely to have less than high school education (10.7% vs 9.7%, P < .001) and annual income ≤$35,000 (42.4% vs 34.3%, P < .001). Compared to controls, participants with MASLD had significantly higher levels of social isolation, neighborhood disorder, perceived stress, food insecurity, and transportation insecurity (P < .001 for all). Conclusion The study identified significant associations between MASLD and multiple SDOH. Future studies should investigate how SDOH interact to drive MASLD risk and progression.
Helicobacter pylori(H. pylori) infection represents a global public health issue strongly associated with gastric cancer and peptic ulcer disease. Increasing antibiotic resistance has markedly reduced the efficacy of standard eradication regimens, resulting in a growing prevalence of refractory infection and a critical clinical challenge. Refractory H. pylori causes substantial patient discomfort and economic costs while worsening antimicrobial resistance. This review summarizes the mechanisms underlying eradication failure and advances in diagnostic approaches from conventional culture to molecular testing. We critically evaluate evidence for personalized salvage therapies based on drug susceptibility and novel acid-suppressive agents including potassium-competitive acid blockers. We propose an integrated clinical framework for diagnosis, treatment and management, and highlight future directions such as new antimicrobials, vaccines, digital health and global antibiotic stewardship. We stress that a shift from empirical therapy to test-guided precision medicine is essential. Optimized diagnostics, individualized regimens and comprehensive management will help achieve successful first-line eradication and control the further spread of antibiotic resistance.
Background We aimed to evaluate the impact of a comprehensive lifestyle program that integrates dietary, behavioral, and peer support strategies on gastrointestinal and extraintestinal symptoms in patients with irritable bowel syndrome (IBS). Methods We performed a cross-sectional study analyzing a consecutive series of patients with IBS according to Rome IV criteria who participated in a structured, three-week digital program between July 2022 and January 2025. The intervention combined a low-FODMAP, low-starch, low-sucrose diet with continuous guidance from a nutritionist-coach, daily educational materials (recipes, meal planning tips), peer support through shared group participation, and non-pharmacological tools such as mindfulness and physical activity. Symptom severity was assessed before and after the program using the IBS Severity Scoring System (IBS-SSS), the Patient Health Questionnaire-9 (PHQ-9) for depression, and Likert scales for extraintestinal symptoms. Results A total of 14,186 patients with IBS were analyzed; the mean age was 44.5 (16-86) years and 13,323 (93.9%) were female. IBS-M (mixed bowel habits) was the more frequent IBS subtype (n=6,496, 45.8%); 8,729 (61.5%) had ≥ 2 extra-intestinal symptoms, and 6,923 (48.8%) reported moderate or severe depressive symptoms. IBS-SSS scores significantly decreased from 287.3 ± 69.5 to 188.3 ± 87.6 (p < 0.001), and PHQ-9 scores improved from 10.2 ± 5.4 to 3.6 ± 3.4 (p < 0.001). All extraintestinal symptom scores showed significant reductions (p < 0.001), and 5,540/8,729 (63.5%) and 8,403/11,746 (71.5%) reported >50% reduction of intensity in at least two extra-intestinal digestive and non-digestive symptoms, respectively. Conclusions A structured multidisciplinary intervention with dietary guidance and non-pharmacological strategies significantly improved both gastrointestinal and extraintestinal symptoms of IBS. A holistic approach addressing patients’ diet, exercise habits, well-being and mental health is recommended for the management of this complex disease.
Background Autoimmune hepatitis–primary sclerosing cholangitis (AIH-PSC) variant syndrome is characterized by concurrent hepatitic and cholestatic liver injury, yet data on long-term outcomes relative to both component diseases remain limited. Methods Using the TriNetX Research Network, we performed two separate 1:1 propensity score-matched (PSM) analyses comparing AIH-PSC to AIH alone and to PSC alone, matching on demographics, comorbidities, and baseline laboratory values. A 180-day landmark was applied. Primary outcomes included cirrhosis, hepatocellular carcinoma (HCC), liver transplantation, all-cause hospitalization, and long-term steroid use. Cholangiocarcinoma (CCA) was analyzed separately using multivariable Cox regression. Hazard ratios (HRs) served as the primary effect measure. Results After matching, 985 patients per cohort were included in the AIH comparison and 961 per cohort in the PSC comparison. Compared with AIH alone, AIH-PSC had significantly higher hazards of cirrhosis (HR 3.138), HCC (HR 2.360), liver transplantation (HR 4.351), and long-term steroid use (HR 1.690; all p ≤ 0.012). Compared with PSC alone, AIH-PSC carried higher hazards of cirrhosis (HR 2.361), liver transplantation (HR 1.400), and long-term steroid use (HR 2.283; all p ≤ 0.048). Hospitalization did not differ in either comparison. AIH-PSC was the strongest independent predictor of CCA versus AIH (adjusted HR 14.546), yet CCA rates were nearly identical between AIH-PSC and PSC (3.6% vs. 3.4%; p = 0.457), indicating CCA risk is attributable to the PSC component. Conclusions AIH-PSC variant syndrome confers additive liver-related morbidity exceeding either component disease, with significantly higher risks of cirrhosis, hepatobiliary malignancy, liver transplantation, and steroid dependence. CCA risk is driven by the PSC component. These findings support intensified surveillance and early transplant evaluation in this population.
Background and Aims Accurate detection and treatment of HDV-infected patients can reduce disease-related morbidity and mortality. This study developed and validated real-world evidence-based algorithms to detect RNA-positive HDV patients from administrative claims data. Methods This retrospective observational study identified HBV and HDV patients from laboratory testing data linked to administrative claims (HealthVerity; 2015–2022), with external validation performed using electronic health records (TriNetX; 2005–2023). Both diagnosis-based and machine-learning algorithms were evaluated. Performance metrics included area under the receiver operating characteristic curve (AUROC), area under precision-recall curve, sensitivity, specificity, positive predictive value (PPV), and accuracy. Internal validation results showed that diagnosis code-based algorithms identified HDV RNA-positivity with ≥88% accuracy. Results The best performing algorithm-based approach in terms of optimism-adjusted AUROC was a random forest model with the following covariates: age, gender, hepatitis complications, HDV and HBV diagnosis, inpatient/outpatient diagnosis, hepatitis medication, and physician specialty (AUROC 97%). Decision curve analysis showed that the random forest algorithm with covariates excluding physician specialty, both inpatient/outpatient diagnosis, and physician specialty performed best. External validation indicated the random forest algorithm using equivalent covariates but without physician specialty had the best performance (PPV 34%; accuracy 92%). Conclusions Algorithms based on HDV diagnosis were more effective for identifying HDV RNA-positive patients than algorithms using HDV-based variables from claims data. Further research into improving such algorithms is needed. Although fair discrimination may occur without claims data, key metrics were not able to replace traditional testing methods. The proposed models could help identify high-risk patients where certain strategies could be prioritized.
