INTRODUCTION:Gastroesophageal varices are a major complication of portal hypertension in cirrhosis, associated with high morbidity and mortality. Noninvasive predictors are needed to reduce reliance on endoscopy. Splenic elastography has emerged as a potential tool to assess portal hypertension severity. METHODS:We conducted prospective, descriptive cross-sectional study at Hospital Roosevelt, Guatemala, in 2024, including 78 patients with recent diagnosis of cirrhosis confirmed by ultrasonography. Patients with hepatocellular carcinoma, acute decompensation, or conditions interfering with splenic stiffness measurement were excluded. Splenic stiffness was measured using transient elastography with the M probe. Endoscopy was performed within two weeks. Diagnostic accuracy for gastroesophageal varices was assessed using ROC analysis. RESULTS:Mean age was 56.1 years (SD 12.6), and 70.5% were female. The most frequent etiology was viral hepatitis (30.77%), followed by alcohol-related liver disease (19.23%) and metabolic dysfunction-associated steatotic liver disease (MASLD, 11.53%). Most patients were Child-Pugh A (80.76%), with a mean MELD-Na of 11.99 (SD 5.46). Gastroesophageal varices were present in 57.69%, and large varices in 26.92%. Splenic elastography showed an AUC of 0.72 (95% CI: 0.59-0.83), with sensitivity of 82.22% and specificity of 66.67% at ≥27 kPa. Median stiffness increased progressively with variceal size, from 25 kPa in absence of varices to 50 kPa in large varices (P <0.001). No significant correlation was found with Child-Pugh class (P=0.538) or MELD-Na (P =0.121). DISCUSSION:Splenic elastography demonstrated moderate accuracy for predicting gastroesophageal varices in cirrhosis. Stiffness values correlated significantly with variceal size, supporting its role as a noninvasive marker of variceal severity. Larger external validation studies are warranted.
Thymic stromal lymphopoietin (TSLP) is a key upstream epithelial cytokine and its over-expression is associated with inflammation leading to immune dysfunction, epithelial barrier disruption, and tissue remodeling. TSLP is implicated in the pathogenesis of multiple atopic diseases including asthma, chronic rhinosinusitis with nasal polyps and eosinophilic esophagitis (EoE). EoE is a chronic, type 2 (T2) inflammatory disease linked to a delayed-type hypersensitivity response to food antigens and characterized by eosinophil-predominant mucosal inflammation and esophageal dysfunction. TSLP expression and TSLP-mediated T2 inflammatory activity is elevated in esophageal biopsies in patients with active EoE compared with patients with inactive EoE and healthy individuals. In phase 3 clinical trials, a monoclonal antibody against TSLP, tezepelumab, has shown significant improvements in clinical outcomes compared with placebo in other atopic conditions that have a shared T2 inflammatory disease pathology and epithelial remodeling pathway with EoE such as asthma and chronic rhinosinusitis with nasal polyps. In this review, we present evidence of TSLP involvement in mediating and exacerbating EoE pathology and discuss how targeting TSLP activity could be a viable therapeutic option for EoE treatment.
Introduction: Hepatitis C (HCV) is associated with an immunosuppressive liver microenvironment, but whether HCV affects immune checkpoint inhibitor (ICI) outcomes in unresectable hepatocellular carcinoma (HCC) remains unknown. Methods: We performed a single-center retrospective cohort study of patients with unresectable HCC treated with ICIs. In patients with a history of HCV, viremia was defined as a detectable viral load prior to immunotherapy. The primary outcome was overall survival (OS); secondary outcomes were real-world progression-free survival (PFS), time on treatment, and time to hepatic decompensation. Results: Among 350 unresectable HCC patients treated with ICIs, 135 (39%) had a history of HCV, of which 37 (27%) were viremic. Viremia was not associated with OS (HR 0.88, 95% CI 0.53-1.44, p=0.600), but was associated with longer real-world PFS (HR 0.59, 95% CI 0.36-0.96, p=0.033) and longer time on treatment (HR 0.63, 95% CI 0.40-0.99, p=0.044). Compared to patients with non-HCV related unresectable HCC (n=215), viremic patients had longer real-world PFS (HR 0.65, 95% CI 0.44-0.97, p=0.037) but non-viremic patients did not (HR 0.87, 95% CI 0.66-1.17, p=0.359). Viremia was not associated with time to hepatic decompensation (HR 1.11, 95% CI 0.61-2.04, p=0.728), but in patients who survived at least one year without decompensating, viremia was associated with shorter time to decompensation (29.8 months vs. median not reached, log-rank p=0.010). Conclusions: Viremia was not associated with OS among ICI-treated HCV patients with unresectable HCC, but was associated with longer real-world PFS and time on treatment. Further studies are needed to investigate these findings.
INTRODUCTION:Ascites severity is an important prognostic marker of liver disease. We hypothesize that ascites pressure correlates with outcomes of patients undergoing therapeutic paracentesis. METHODS:Adults with portal hypertensive ascites (n = 87) undergoing therapeutic paracentesis (n = 261) had pressure measured during drainage using a noninvasive manometer setup and were followed for 365 days. RESULTS:Pressure drop during paracentesis was associated with event-free survival after adjusting for Model for End Stage Liver Disease 3.0 and age (adjusted hazard ratio 0.43 per 5 cmH 2 O, 95% confidence interval [0.21, 0.90], P = 0.02), but volume drained was not. DISCUSSION:Ascites pressure provides Model for End Stage Liver Disease-independent prognostic information in patients undergoing paracentesis.
INTRODUCTION:Irritable bowel syndrome with constipation (IBS-C) is a common disorder of gut-brain interaction, characterized by constipation and abdominal symptoms that negatively affect health-related quality of life (HRQoL). Best practices for adjusting treatments based on patient response remain undefined, leading to inconsistent clinical management. This study aimed to establish expert consensus on assessing therapeutic response and guiding treatment decisions in IBS-C using a modified Delphi process. METHODS:A 2-round Delphi panel was conducted with US-based health care professionals experienced in IBS-C. Sixteen statements addressing symptom assessment, treatment response, HRQoL, treatment side effects, patient satisfaction, and treatment decisions were rated on a 5-point Likert scale. Consensus was defined as ≥80% agreement. Statements not reaching consensus after round 1 were revised/excluded; 9 statements were rerated in round 2. RESULTS:Fourteen statements reached consensus. Key points for treatment-response assessment included integrating evaluations of bowel and abdominal symptoms. Recommendations highlight the value of assessing the severity of the most bothersome symptoms before treatment, impact on HRQoL, and patient satisfaction with the treatment. Although standardized measures in clinical settings were desired for treatment-response assessment, none were consistently recommended by the panelists. Other key factors influencing treatment decisions included balancing benefits against side effects, patient preferences and expectations, clinician familiarity with therapies, and shared decision-making. CONCLUSIONS:The consensus recommendations highlight the importance of comprehensive, patient-centered evaluation of therapeutic response in IBS-C and underscore the need for practical, standardized tools to guide individualized treatment decisions to improve outcomes and reduce variability in IBS-C management.
INTRODUCTION:Clostridioides difficile (C. difficile) is associated with reduced intestinal microbial diversity, and evidence links dysbiosis to increased disease severity in alcohol-associated hepatitis (AH). We therefore evaluated CDC as a predictor of clinical outcomes in AH. METHODS:We conducted a retrospective cohort study of 471 patients hospitalized with AH who underwent C. difficile surveillance from July 2017 to September 2024. CDC was defined as positive toxigenic C. difficile rectal swab PCR without symptoms. Patients were followed for 90 days after admission. RESULTS:69 AH patients (14.7%) had CDC. 163 (34.6%) developed infections, and infection rates were higher in CDC patients [53.6% vs. 31.3%, p=0.001], including C. difficile infection (CDI, 8.7% vs. 0.8%, p<0.01). Patients with CDC had more ascites (78.3% vs. 22.5%, p<0.001), gastrointestinal (GI) bleeding (39.1% vs. 27.9%, p=0.042), and ICU admission (46.4% vs. 34.6%, p=0.042), but MELD 3.0 was similar between groups [28 (IQR 23 - 35) vs. 26 (IQR 21 - 31), p=0.065]. 90-day survival was lower with CDC [66.7 (95% CI 58.9 - 74.4) days vs. 77.2 (95% CI 74.6 - 79.9) days, p=0.007]. Age [aHR 1.039 (95% CI 1.021 - 1.057), p<0.001], MELD 3.0 [aHR 1.103 (95% CI 1.083 - 1.124), p<0.001] and CDC [aHR 1.604 (95% CI 1.014 - 2.537), p=0.043] were associated with 90-day mortality. CONCLUSION:In AH, CDC is associated with more infection, ascites, gastrointestinal bleeding, and ICU admission, and independently predicts reduced 90-day survival. CDC may serve as a novel marker of disease severity and infection risk in AH.
OBJECTIVES:Type 1 gastric neuroendocrine tumors (T1g-NETs) are well-differentiated lesions with excellent survival but frequent recurrence. Tumor size is the main prognostic factor, yet optimal management for tumors >1cm remains uncertain. This study aimed to evaluate treatment strategies and outcomes in patients with T1g-NETs>1 cm. METHODS:We conducted a retrospective multicenter study including 106 adults with T1g-NETs>1 cm. Clinicopathologic and management data were collected. The primary outcome event was a composite unfavorable outcome (UO), defined as recurrence or progression, used to analyze progression-free survival as the main time-to-event outcome. Analyses included multinomial logistic regression, Cox models, and Kaplan-Meier curves (p<0.05). RESULTS:Among 106 patients (58.5% female; median age 59), median tumor size was 15mm. Most tumors were Grade 1 (61.4%) or Grade 2 (37.7%), with median Ki-67 of 2%. Endoscopic resection was performed in 76 patients (71.7%), surgery in 33 (31.1%, including 13 initially treated endoscopically), and 10 (9.4%) were surveilled. Over a median 61-month follow-up, 24 patients (22.6%) recurred, 8 (7.5%) progressed; only 2 deaths (1.9%) were tumor-related. Larger tumors were associated with UO (p=0.005), with lesions ≥24mm predicting shorter progression-free survival (HR 3.93;p<0.001). Endoscopic submucosal dissection (ESD) and modified-endoscopic mucosal resection (m-EMR) were associated with a significantly longer progression-free survival (p=0.004). R0 resection showed a borderline protective effect. Five-year overall survival approached 95%. CONCLUSIONS:T1g-NETs>1cm frequently recur and may exhibit aggressive potential, particularly when lesions are larger. When endoscopic resection is feasible, ESD or m-EMR should be preferred to optimize outcomes.
BACKGROUND:The liver outcomes of SGLT-2 inhibitor (SGLT-2i) in T2DM patients with cirrhosis have not been well studied. METHODS:We conducted a retrospective cohort study (January 1, 2010-December 31, 2025) using two databases. Adults ≥ 18 years with type 2 diabetes mellitus (T2DM) and cirrhosis newly treated with SGLT-2i were identified. Patients were grouped into those receiving SGLT-2i and those not receiving SGLT-2i. Baseline characteristics were compared before and after propensity score matching. The primary outcome was the incidence of hepatic decompensation among SGLT-2i users versus non-users. RESULTS:The intervention group consisted of 14,231 SGLT-2i users and the control group consisted of 249,746 non-SGLT-2i users. After 1:1 PSM, use of SGLT-2i was associated with reduced composite outcome of hepatic decompensation compared to control group at 1 year (9.9% vs. 12.5%, p=0.001), at 3 years (16.4% vs. 18.1%, p<0.001) and 5 years (19.9% vs 21.9%, p<0.001). HCC rates were significantly lower in the SGLT-2i users at 1 year (2.3% vs. 3.5%, p=0.001), at 3 years (2.9% vs. 4.2%, p=0.001) and at 5 years (3.4% vs. 4.8%, p=0.001). There was a 31% reduction in mortality in the SGL-T2i arm (HR: 0.69; CI: 0.56- 0.83, p<0.001), as compared to the non-SGLT-2i arm.These findings were validated in the EVERSANA database. CONCLUSIONS:Use of SGLT-2i was associated with a reduced composite outcome of hepatic decompensation and mortality among patients with T2DM and cirrhosis compared with non-SGLT-2i users across two independent datasets. Prospective randomized controlled trials are needed to confirm these findings.
Somatostatin analogs were the primary treatment for autosomal dominant polycystic kidney disease (ADPKD) or polycystic liver disease (PLD), including octreotide, lanreotide, and pasireotide. We compared the effects and safety of octreotide, lanreotide, and pasireotide on total kidney volume (TKV), total liver volume (TLV), and kidney function (eGFR) in patients with ADPKD or PLD using network meta-analysis and FDA Adverse Event Reporting System (FAERS) data. Pooled estimates from limited available trials suggested that, at 6 months or 1 year, octreotide (MD: -3.7, 95%CI: -4.3 to -3.2) and pasireotide (-5.0, -8.2 to -1.8) were associated with preliminary evidence of TKV reduction compared with placebo. However, lanreotide (-7.8, -10.2 to -5.4) obviously manifested a decrease in the TKV after more than 2 years. TLV analyses showed early directional effects of octreotide (-7.7, -12.1 to -3.3) and pasireotide (-9.0, -13.7 to -4.3) at 1 year, and for lanreotide (-5.0, -6.3 to -3.9) after more than 2 years. Lanreotide demonstrated inferior efficacy in reducing the TLV growth rate compared to octreotide (10.0, 2.7 to 18.0) following a 2-3 year administration period. Cholelithiasis is the most common biliary adverse event in three somatostatin analogs. Cox regression identified age (HR: 0.966, 95% CI: 0.949 to 0.982, P < 0.001) and drug (HR: 2.168, 95% CI: 1.411 to 3.332, P < 0.001) as independent predictors of cholelithiasis. The onset time of TKV/TLV reduction differs among the three somatostatin analogs. Age and drug were independent predictors of cholelithiasis. Younger patients or those receiving pasireotide are at higher risk of cholelithiasis.
INTRODUCTION:Primary biliary cholangitis (PBC) has steadily increased in incidence, but its causes remain to be completely elucidated. Moreover, the potential for disease progression is not uncommon, especially when normalization of hepatobiliary enzyme levels is difficult, making the emergence of new treatments highly anticipated. We clarified the therapeutic effects of glucosyl hesperidin (G-Hes), which activates the antioxidant NRF2/KEAP1 pathway, on improving PBC pathophysiology. METHODS:This randomized controlled trial evaluated changes in serum levels of hepatobiliary enzymes, lipids, and heme oxygenase 1, which is an NRF2/KEAP1 pathway target gene protein, after G-Hes administration (500 or 1,000 mg/d) for 24 weeks in 71 patients on maintenance therapy for PBC. RESULTS:Gamma glutamyl transferase at week 24, the primary end point of this study, decreased significantly by 6.2% only in the high dose group. Among the secondary end points, alkaline phosphatase increased plausibly because of G-Hes-induced bone metabolism enhancement and bilirubin decreased, both reaching significance only in the standard dose group. There were no significant changes in transaminases in either group. On subgroup analyses of patients with abnormal baseline biochemical levels, significant decrease in gamma glutamyl transferase at week 24 (6.4%) still remained only in the high-dose group. On the other hand, there was no significant change in alkaline phosphatase at any time point in both groups. The blood protein concentration of heme oxygenase 1 increased by 4.8% at week 24, although not significant. There were no G-Hes-related adverse events. DISCUSSION:Inclusion of G-Hes to existing treatment safely provided additional therapeutic effects in patients with PBC.
INTRODUCTION:This study provides comprehensive estimates of the global, regional, and national burden of liver cancer among middle-aged and older adults from 1990 to 2021, incorporating cross-country inequality assessment, decomposition of drivers, and frontier analysis. METHODS:Age-standardized rates and estimated annual percentage changes were used to quantify prevalence, incidence, deaths, and disability-adjusted life years (DALYs) rates. Decomposition analysis, cross-country inequality assessment, and frontier analysis were applied to dissect the burden dynamics. RESULTS:In 2021, the absolute numbers of liver cancer prevalence, incidence, deaths, and DALYs all increased compared with 1990; however, age-standardized death and DALYs rates slightly decreased. The burden was consistently higher in men than in women. Population growth was the primary contributor to increased burden, whereas aging and epidemiological changes significantly contributed to burden reduction. A V-shaped relationship existed between DALYs rate and Sociodemographic Index. Significant absolute cross-country inequalities were observed. Fifteen countries demonstrated substantial potential for burden reduction. DISCUSSION:This study reveals complex dynamic changes in the global burden of liver cancer among middle-aged and older people. Strengthening international cooperation, promoting equitable allocation of medical resources, and formulating differentiated strategies are essential future priorities.
INTRODUCTION:Obesity is prevalent in patients with alcohol-associated hepatitis (AH), but its impact on clinical outcomes remains incompletely defined. We aimed to evaluate the association between body mass index (BMI)-defined obesity and 90-day and 180-day survival in AH, as well as its association with complications and circulating inflammatory mediators. METHODS:We analyzed 778 patients with AH enrolled in the National Institute on Alcohol Abuse and Alcoholism-supported Alcohol-associated Hepatitis Network observational cohort and randomized clinical trial. Patients were categorized as normal weight, overweight, or obese by BMI. Multivariable Cox models were used to evaluate survival. Baseline serum cytokines were measured in a randomly selected subset of 168 patients. RESULTS:Of the 778 patients, 255 (32.8%) were overweight and 310 (39.8%) were obese. Obese patients had higher baseline Model for End-Stage Liver Disease scores, higher rates of bacterial infection during hospitalization, and higher 90-day and 180-day mortality than overweight and normal-weight patients. In multivariable analysis, obesity was associated with reduced 180-day survival (hazard ratio 1.50; 95% confidence interval [CI] 1.03-2.23, P = 0.041). In adjusted logistic models among severe AH cases, obesity remained associated with infection (odds ratio 1.84; 95% CI 1.15-2.93; P = 0.011) and acute kidney injury (odds ratio 2.25; 95% CI 1.42-3.57; P = 0.0005) within 180 days. In the cytokine subset, obese patients showed higher levels of proinflammatory cytokines and chemokines and lower levels of growth factors. DISCUSSION:Obesity in AH was associated with more severe disease at presentation, increased risk of complications, and worse survival, supporting obesity as an important adverse factor in AH.
INTRODUCTION:High bowel frequency after ileal pouch-anal anastomosis (IPAA) causes significant symptom burden. We aimed to evaluate the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in this setting. METHODS:We conducted a retrospective cohort study of patients with previous IPAA for ulcerative colitis who were treated with a GLP-1 RA (n = 20). Daily bowel frequency at baseline and 12 weeks after GLP-1 RA initiation was assessed. We also assessed the proportion of patients achieving ≥30% reduction in bowel frequency and ≤8 bowel movements per day. RESULTS:The median daily bowel frequency decreased from 9.0 (interquartile range [IQR], 6.0-12.5) at baseline to 6.0 (IQR, 5.0-8.1) at the 12-week follow-up ( P < 0.01). Overall, 7 of 20 patients achieved a ≥30% reduction in bowel frequency, and 15 of 20 had ≤8 bowel movements per day. DISCUSSION:In this retrospective cohort, we provide further evidence for the potential role of GLP-1 RAs in the management of high bowel frequency after IPAA.
INTRODUCTION:To evaluate the correlation between serum intestinal fatty acid-binding protein (IFABP) levels and quantitative duodenal morphometry in adult patients with celiac disease (CeD) at diagnosis and after long-term gluten-free diet (GFD), and to assess the role of this investigation as a noninvasive marker of mucosal injury and healing. METHODS:In this prospective cross-sectional study, adult patients with CeD on a GFD for ≥18 months (follow-up [FU]) and newly diagnosed untreated patients with CeD (ND) were enrolled. Serum IFABP levels were measured by enzyme-linked immunosorbent assay (ELISA). Duodenal biopsies from FU and ND patients underwent quantitative morphometric analysis, including villous height to crypt depth (Vh:Cd) ratio, intraepithelial lymphocyte (IEL) count, and calculation of the Vh:Cd and IEL scale index. Correlation between IFABP and histological parameters was assessed. RESULTS:IFABP levels were significantly higher in ND patients compared with FU ( P < 0.001). Across the cohort, IFABP levels correlated negatively with Vh:Cd ratio (ρ = -0.53, P < 0.001) and positively with IEL count (ρ = 0.46, P < 0.001). IFABP also showed a strong inverse correlation with the Vh:Cd and IEL scale index (ρ = -0.60, P < 0.001). In FU patients, IFABP remained significantly associated with subtle morphometric abnormalities, including reduced Vh:Cd ratio and increased IEL counts, but not with celiac serology or self-reported dietary adherence. DISCUSSION:Serum IFABP levels represent a promising, noninvasive biomarker of enterocyte damage for capturing subtle changes and current mucosal status in patients with CeD on a long-term GFD, when conventional serology and dietary questionnaires may fail.
INTRODUCTION:Standard forceps biopsies often provide insufficient cellular yield for single-cell and spatial transcriptomic analyses. We assessed the feasibility of cold-snare resection in inflammatory bowel disease (IBD) and compared immune cell composition with standard forceps biopsies. METHODS:Patients with active IBD at endoscopy were included. One cold-snare resection and 2 standard biopsies were obtained from inflamed mucosa in the ileum, colon, or rectum. Sample quality and cell yield were evaluated using histology staining and flow cytometry. Adverse events (AEs) were recorded periprocedurally, at a 7-day follow-up, and up to 30 days. RESULTS:Thirty-four patients with IBD were included. Cold-snare resection was successful in all cases and yielded significantly higher number of T-cells (median 71 × 10 3 vs 17 × 10 3 , P = 0.016) and rare innate lymphoid cells (median 576 vs 127, P = 0.016) compared with standard forceps biopsies. Four mild AEs were reported. DISCUSSION:Cold-snare resection improves mucosal tissue integrity and cellular quality compared with standard biopsies, supporting its use for translational studies in IBD.
The increasing global burden of digestive diseases, coupled with the complexity of their pathogenesis, underscores the urgent need for in-depth research into precise organ-specific therapies. The cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway, a crucial innate immune signaling axis, has garnered considerable attention for its roles in immune defense, inflammation regulation, tumorigenesis, and tissue homeostasis. In this review, we outline common digestive diseases linked to the cGAS–STING pathway, elucidate its mechanistic contributions to these conditions, and provide a detailed analysis of how targeting this signaling axis may influence disease progression. We hope this review will offer a theoretical foundation for developing novel therapeutics and innovative treatment strategies for digestive diseases, thereby contributing to improved clinical outcomes.
