Clinical and Translational Gastroenterology最新文献

Introduction: Machine perfusion (MP) technology may reduce the incidence of biliary complications (BCs) by reducing ischemia-reperfusion injury. This meta-analysis aimed to compare the effects of MP and static cold storage (SCS) on the incidence of BCs, nonanastomotic stricture (NAS), and anastomotic stricture (AS) after liver transplantation.

Methods: Randomized controlled trials (RCTs) comparing the effects of MP versus SCS on BCs, NAS, or AS after liver transplantation were included for the systematic review in October 2024. Random-effects models were used to perform pooled analyses to calculate risk ratios (RRs) with 95% confidence intervals (CIs).

Results: A total of 9 RCTs including 6 hypothermic oxygenate perfusion (HOPE) and 3 normothermic MP (NMP) were eligible for inclusion. Compared with SCS, MP technology seemed to reduce the incidence of BCs (HOPE: RR 0.77, 95% CI 0.62-0.97, P = 0.03; NMP: RR 0.67, 95% CI 0.44-1.00, P = 0.05). In addition, MP technology could explicitly reduce NAS incidence (HOPE: RR 0.40, 95% CI 0.19-0.84, P = 0.01; NMP: RR 0.39, 95% CI 0.19-0.83, P = 0.01). However, MP technology was likely unable to reduce the incidence of AS (HOPE: RR 0.89, 95% CI 0.63-1.26, P = 0.51; NMP: RR 0.99, 95% CI 0.53-1.85, P = 0.99).

Discussion: This meta-analysis confirmed that MP technology could reduce the incidence of NAS, which might further lead to a reduction in the incidence of BCs. However, it did not seem to improve AS incidence.

Introduction: Reliable biomarkers for the diagnosis of chronic pancreatitis (CP) and pancreatic fibrosis severity are lacking, hindering effective treatment and management. Histologic fibrosis is a hallmark of late-stage CP, but noninvasive methods to evaluate fibrosis progression are limited. We used urine proteomics to discover biomarkers that identify patients with CP and predict fibrosis severity.

Methods: We performed a cross-sectional study of 130 total subjects (CP n = 50) selected based on clinical criteria in a tertiary care setting. Urine proteomics samples were quantified using data-independent acquisition mass spectrometry. Differential biomarker candidates were identified with false discovery rate-corrected pairwise comparisons. These proteins were validated with an independent paired urine and plasma sample cohort (n = 36). Machine learning was used to develop a protein panel that predicted Ammann scores for patients with histologic fibrosis.

Results: We found 34 proteins consistently differentially expressed between CP and controls in pairwise false discovery rate-controlled tests. Of these, 25 urine proteins outperformed 19 previously suggested CP blood-based biomarkers in an independent validation cohort. Isocitrate dehydrogenase (IDH1), calcyphosin (CAPS), synuclein gamma (SNCG), and protein S100-P (S100P) all produced receiver operator curve area under the curve values >0.95, while the best plasma marker was interleukin 2 receptor subunit alpha (receiver operator curve area under the curve = 0.80). A 12-protein panel of identified markers predicted fibrosis severity with a linear correlation R2 value of 0.61.

Discussion: We identified a panel of proteins that may diagnose CP in children and developed a model to predict pancreatic fibrosis severity, offering promising tools for improving diagnostics and patient care.

Introduction: Limited data exist regarding the portal hypertension progression in cirrhotic patients with variceal bleeding as the initial decompensation event. This study evaluated the impact of sequential endoscopic therapy on long-term clinical outcomes.

Methods: 196 hospitalized cases were included and divided into esophageal varices (EV), type 1 gastroesophageal varices (GOV1), type 2 GOV (GOV2), and type 3 GOV (GOV3) groups. The Fine-Gray test was used to analyze the cumulative incidence of outcome events. Survival was calculated using the Kaplan-Meier method, and the Cox proportional risk regression model was used for multivariate analysis of factors affecting outcomes.

Results: During a median follow-up period of 104.9 months, distinct cumulative outcomes were observed across esophageal and gastric variceal subtypes. The 1-, 3-, and 5-year cumulative rebleeding rates progressively increased across subtypes: EV (16.2%, 29.7%, 41.9%), GOV1 (18.8%, 39.6%, 45.8%), GOV2 (19.1%, 34.0%, 46.8%), and GOV3 (44.4%, 63.0%, 66.7%) (Gray test, P = 0.009). Corresponding survival rates demonstrated an inverse pattern, declining with longer follow-up: EV (91.9%, 82.4%, 58.1%), GOV1 (91.7%, 79.2%, 60.4%), GOV2 (91.5%, 76.6%, 55.3%), and GOV3 (74.1%, 55.6%, 48.1%) (log-rank test, P = 0.016). Rebleeding was an independent risk factor associated with survival (hazard ratio: 3.518, P < 0.001). Multivariate analysis showed that variceal shape, variceal type, and the treatment courses to variceal eradication (whether > 3) were significant risk factors for rebleeding ( P < 0.05).

Discussion: In this study, rebleeding dominated the clinical course of different subtypes and was an independent predictor of death. More aggressive treatments, such as salvage transjugular intrahepatic portosystemic shunt, should be considered in patients who were at higher risk of rebleeding.

Introduction: Early detection of pancreatic ductal adenocarcinoma (PDAC) improves survival. However, screening recommendations are limited to individuals with hereditary risk, accounting for only 10% of PDAC. We explore the feasibility of developing and validating an electronic health record-based model to identify high-risk individuals for PDAC screening within the asymptomatic general population.

Methods: Using multivariable Cox regression, we developed a diagnostic model to predict time to PDAC within 3 years in the Veterans Health Administration. We evaluated the final model using internal and temporally separate data sets using Akaike Information Criterion, Harrell c statistic, calibration curves, and sensitivity/specificity corresponding to a 3-year risk screening threshold of 1%.

Results: Among 9,351,261 individuals, 26,119 (0.3%) developed PDAC (107.6 cases per 100,000 person-years) within 3 years. The final model included age, pancreatic cyst, pancreatitis, smoking status, history of a localized solid tumor, race/ethnicity, and body mass index. Glucose and albumin values were highly important, in addition to other metabolic, inflammatory, and liver-related laboratory values. The c statistic (95% CI) was 0.75 (0.75-0.76) in development, 0.75 (0.75-0.76) in internal validation, and 0.74 (0.73-0.75) in temporal validation. At a 3-year risk threshold of 1.0%, 11% of the population would undergo screening, capturing 30% of the PDAC cases.

Discussion: We demonstrate good model discrimination in independent data. Compared with current screening practices targeting only genetically predisposed individuals, its implementation could identify 3 times as many PDAC cases. However, predictors beyond the electronic health record (EHR) may be needed to further improve the feasibility of generalized screening.

Introduction: This study used the novel C-reactive protein-albumin-lymphocyte (CALLY) index to explore its relationship with the risk of developing gallstones.

Methods: This study conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey data from 2017 to 2020; multivariable logistic regression examined the CALLY-gallstone association. Restricted cubic splines tested nonlinearity. Subgroup and mediation analyses explored population variations and mediating effects (Conicity, lipid accumulation product, and a body shape index). Receiver operating characteristic curves compared CALLY, systemic immune inflammation index, systemic inflammatory response index, and aggregate index of systemic inflammation predictive performance.

Results: After comprehensive adjustments, the highest CALLY quartile had significantly lower gallstone risk vs the lowest (odds ratio 0.56, 95% confidence interval 0.34-0.94). Restricted cubic splines revealed a linear inverse correlation. Subgroup analyses generally supported this inverse relationship. Mediation analysis identified the Conicity index as the strongest mediator (21.47%, P < 0.001), followed by lipid accumulation product and a body shape index (10.72% each, P < 0.001). Receiver operating characteristic analysis showed CALLY (area under the curve = 0.604) outperformed systemic immune inflammation index (0.540), systemic inflammatory response index (0.550), and aggregate index of systemic inflammation (0.546).

Discussion: A significant inverse association exists between the CALLY index and gallstone prevalence. The CALLY index demonstrates superior predictive ability compared with other indices, suggesting its potential utility as an objective biomarker for early gallstone risk identification.

Introduction: Factors associated with decline of hepatic function and increase in portal-systemic shunting, which herald clinical outcome in persons with compensated cirrhosis, are poorly characterized. We used cholate challenge to evaluate the associations of liver disease etiology, concomitant diabetes, and maintenance drug therapy, with the degree of hepatic dysfunction and portal-systemic shunting.

Methods: In the SHUNT-V study, there were 255 subjects with compensated (Child-Pugh class A) cirrhosis who underwent cholate challenge, involving oral administration of [2,2,4,4- 2 H] cholate and measurement of its serum concentrations at 20 and 60 minutes. Test outputs included a disease severity index (DSI) to assess global liver function and SHUNT% to assess portal systemic shunting.

Results: Eighty-seven percent of subjects were overweight, 65% were obese, 48% had metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH), 51% had type 2 diabetes mellitus, 49% were taking anti-diabetic drugs, and 45% were taking lipid-lowering drugs. Laboratory values and clinical scores of MASLD/MASH subjects were similar to subjects with other etiologies for liver disease. In univariable regression, MASLD/MASH, diabetes mellitus, metformin, and statins were associated with lower DSI and SHUNT%. In multivariable regression, lower DSI was attributable to statins ( P = 0.0354) and metformin ( P = 0.0561). The combined use of lipid-lowering and anti-diabetic drugs, compared with no use, was associated with 19% reduction in DSI.

Conclusion: Concomitant use of statins alone or in combination with metformin was independently associated with preserved hepatic function (DSI) and reduced portal-systemic shunting (SHUNT%).

Introduction: Polypectomy-related costs could potentially be reduced through optical diagnosis strategies, such as "diagnose-and-leave" and "resect-and-discard." Artificial intelligence, using computer-aided diagnosis (CAD), may provide a reproducible optical diagnosis of colorectal lesions. This study aimed to assess the performance of the CAD-EYE system in the real-time characterization of colonic polyps.

Methods: We conducted a cross-sectional, multicenter study evaluating the CAD-EYE system in patients undergoing screening colonoscopies at 5 French centers. CAD-EYE predictions and assessments by endoscopists (hyperplastic vs neoplastic) were compared with histopathology results. The primary outcome was the sensitivity of CAD-EYE for predicting neoplastic polyps, compared with the predefined threshold of 85%. The secondary outcomes were the specificity, positive predictive value, negative predictive value, endoscopists' performance, and polyp detection rates.

Results: Of 398 polyps analyzed, 343 were included in the primary analysis. CAD-EYE characterization was feasible in 96% of cases. The sensitivity was 0.80 (95% confidence interval, 0.74-0.85), which failed to achieve the predefined threshold of 85% ( P = 0.064). The specificity, negative predictive value, and positive predictive value were 0.79, 0.64, and 0.90, respectively. Performance was higher for diminutive rectosigmoid polyps (DRSPs). Endoscopists showed higher sensitivity than CAD-EYE (0.90 vs 0.80, P = 0.001). CAD-EYE-assisted colonoscopies detected more polyps per procedure (3.3 vs 2.3, P < 0.001) than endoscopists alone.

Discussion: The performance of CAD-EYE was insufficient for the characterization of neoplastic colonic polyps. CAD-EYE performed better for DRSPs. AI seems to be beneficial for polyp detection.

Introduction: Uncertainty persists regarding viral replication activity in untreated low-level viremia (LLV) patients and the need for antiviral therapy. This study compared serum hepatitis B virus (HBV) RNA levels in untreated LLV patients, those developing LLV post-nucleos(t)ide analogs (NAs), and patients achieving maintained virological response (MVR).

Methods: A cross-sectional study enrolled untreated LLV, treated LLV, and MVR patients. Propensity score matching (PSM) minimized confounding variables.

Results: Among 364 patients (61 untreated LLV, 60 treated LLV, and 243 MVR), PSM analysis of 38 untreated-treated LLV pairs demonstrated significantly lower HBV RNA in untreated LLV ( P < 0.001). Similarly, 1:2 PSM of untreated LLV vs MVR (58 vs 93 cases) revealed reduced HBV RNA in untreated LLV ( P = 0.03).

Discussion: Untreated LLV patients exhibited lower HBV RNA levels than both treated LLV and MVR patients, reflecting reduced viral transcription and replication. This suggests that antiviral treatment may not be immediately necessary for this subpopulation.

Introduction: In a national United States (US)-based group, we sought to describe barriers identified by sexual and gender minority (SGM) patients and primary care providers (PCPs) that challenge the provision of SGM-affirming digestive healthcare via qualitative methodology.

Methods: Forty patient participants and 24 PCPs were recruited from a random sample of 18 states within the 9 principal US Census Divisions and 2 states near the home institution. Patient participants selected completed a virtual semi-structured qualitative interview regarding their experiences with digestive healthcare and their views on barriers to engaging in digestive health care. PCPs were interviewed on treating SGM patients with GI disorders and interactions with GI consultants. Interviews were conducted until thematic saturation was achieved. The study was conducted from November 2023 to August 2024.

Results: Thematic saturation was achieved at 36 patient participants and 21 PCPs. Major themes included SGM discrimination in digestive healthcare, SGM issues in engaging in digestive healthcare, GI symptoms and other aspects of health-specific conditions, and ways to improve digestive healthcare for the SGM community. Participants noted a link between psychological distress in the SGM population and GI symptoms and offered actionable suggestions to improve SGM-focused digestive healthcare.

Conclusion: Systematic deficiencies were identified in the provision of SGM-affirming digestive care, related to bias within healthcare systems and a lack of understanding of unique SGM-related needs throughout the US. Further research studying improved shared clinician and SGM GI patient engagement is needed to address these sources of health inequity.

Introduction: Disparities in hepatocellular carcinoma (HCC) outcomes are shaped by intersecting social determinants of health. We hypothesized that patients experience distinct combinations of socioeconomic barriers that cluster into social risk phenotypes associated with differences in diagnosis, treatment, and survival.

Methods: We analyzed data from 4,877 adults diagnosed with HCC in the Indiana State Cancer Registry (2009-2020). Latent class analysis was performed using sex, race, insurance, marital status, occupation, neighborhood Social Deprivation Index, and distances to screening and Indiana University Hospital. Outcomes included early-stage diagnosis, receipt of curative therapy, and 2-year mortality.

Results: Among 4,877 patients, 15.8% were non-White and 24.7% were female. Latent class analysis identified 6 distinct risk classes: (i) minimal barriers, (ii) publicly insured-married women, (iii) publicly insured-unpartnered men, (iv) rural and geographically distant, (v) structurally marginalized, and (vi) unseen and uninsured. Class 1 had the most favorable characteristics (83.7% private insurance, 16.8% professional occupation) and best outcomes: 55.4% early-stage diagnosis, 24.4% curative therapy, and 55.4% 2-year mortality. All other classes had significantly worse outcomes. Compared with class 1, patients in class 6 had the lowest early-stage diagnosis (39.7%) and curative therapy (10.5%) and highest 2-year mortality (83.6%; odds ratio 4.12, 95% confidence interval 3.06-5.54, P < 0.001). Classes 4 and 5, reflecting rural and racially marginalized groups, also had significantly lower odds of early diagnosis and treatment.

Discussion: Social risk phenotypes based on intersecting social determinants of health were strongly associated with HCC outcomes and may inform future risk-based intervention strategies.