Clinical Gastroenterology and Hepatology最新文献

{"title":"Liver Decompensation in Patients With Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab: A Real-life Study.","authors":"Leonardo Stella, Maria Pallozzi, Lucia Cerrito, Francesco Santopaolo, Francesco Tovoli, Clemence Hollande, Sabrina Sidali, Bernardo Stefanini, Claudia Campani, Elisa Pellegrini, Giuseppe Cabibbo, Fabio Marra, Fabio Piscaglia, Antonio Gasbarrini, Maurizio Pompili, Mohamed Bouattour, Francesca Romana Ponziani","doi":"10.1016/j.cgh.2024.12.028","DOIUrl":"10.1016/j.cgh.2024.12.028","url":null,"abstract":"<p><strong>Background & aims: </strong>Atezolizumab plus bevacizumab (atezobeva) has changed the treatment landscape of advanced hepatocellular carcinoma, but its efficacy and safety in patients with impaired liver function are still debated. This study aimed to evaluate the prognostic impact of baseline liver function and liver decompensation during treatment on clinical outcomes.</p><p><strong>Methods: </strong>In this multicenter study, we included 247 patients with advanced or unresectable hepatocellular carcinoma treated with atezobeva. We analyzed data on survival, tumor progression, and liver decompensation and introduced time to decompensation as a new safety endpoint.</p><p><strong>Results: </strong>The reported overall survival (OS) was 18.30 months, time to progression 13.07 months, and progression-free survival (PFS) 9.83 months. Although OS was better in Child Pugh A compared with Child Pugh B patients (20.20 vs 9.83 months; P = .0008), no differences were observed in time to progression and treatment safety. Liver decompensation occurred in 63 patients (25.51%), specifically 27.89% Child Pugh A and 51.16% Child Pugh B patients; in 41.26% of patients, atezobeva was resumed after decompensation, achieving an OS comparable to those who never decompensated (20.87 vs 20.2 months; P = .77), and better than those who permanently stopped treatment (8.07 months; P = .02). Time to decompensation was similar for patients with albumin-bilirubin score 2 regardless of Child Pugh class, and the probability of recovery from decompensation was similar for Child Pugh A and B patients.</p><p><strong>Conclusion: </strong>Atezobeva is effective in both Child Pugh A and B patients. The possibility to resume treatment after an episode of decompensation underscores the importance of integrated hepato-oncological management.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gallbladder Cancer and Dysplasia in Cholecystectomy Specimens: A Large Study in High-Incidence Regions of South America.","authors":"Felix Boekstegers, Carol Barahona Ponce, Erik Morales, Cesar Muñoz-Castro, Cristian Lindner, Ivan Schneider Lira, Belarmino Manques, Alicia Colombo Flores, Catalina Valenzuela, Jaime Castillo, Gonzalo de Toro, Mauricio Almau, Cristina Inklemona, Carolina Ituarte, Gerardo F Arroyo, Loreto Spencer, Hector Losada, Juan Carlos Araya, Bruno Nervi, Claudio Mengoa Quintanilla, Paola Montenegro, Ana Lineth Garcia, Sidney Rojas Orellana, Alejandro Ortega, Francisco Rothhammer, Justo Lorenzo Bermejo","doi":"10.1016/j.cgh.2024.12.027","DOIUrl":"10.1016/j.cgh.2024.12.027","url":null,"abstract":"<p><strong>Background and aims: </strong>Gallstone disease has been causally linked to gallbladder cancer (GBC) via the carcinogenesis model of gallstones and inflammation leading to gallbladder dysplasia then GBC. Efficient GBC prevention through cholecystectomy requires accurate prediction of individual GBC risk, especially in low- and middle-income regions, where studies tend to be small and of low quality, and where financial and surgical capacity are limited.</p><p><strong>Methods: </strong>In a collaborative study from high GBC incidence regions of Argentina, Bolivia, Chile, and Peru, we collected and validated clinical information from 10,561 patients with gallstone disease who underwent cholecystectomy. After checking data reliability, we used multiple logistic regression to identify the main factors associated with GBC and dysplasia risk.</p><p><strong>Results: </strong>The highest GBC and dysplasia risk was found in patients with clinical suspicion of GBC, followed by planned open cholecystectomy, female sex, gallstones over 3 cm, hypercholesterolemia, smoking, and age at cholecystectomy. Clinical suspicion of GBC and age at cholecystectomy showed heterogeneous odds ratios depending on the recruitment site. The identified risk factors, and the magnitude of their effects, were different for GBC and dysplasia. The mean age at cholecystectomy was 47 years, compared with 50 years for low-grade dysplasia, 62 years for high-grade dysplasia, and 64 years for GBC.</p><p><strong>Conclusions: </strong>These recruitment site-specific risk factors may help refine current prevention strategies by prioritizing prophylactic cholecystectomy in high-risk patients. The approach used in this study may guide future investigations on GBC prevention in high-incidence, low-income regions.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Screening Strategies for Lynch Syndrome in Latin America.","authors":"Anthony Vladimir Campos-Segura, Karin Alvarez, Alexis German Murillo Carrasco, Benedito Mauro Rossi, Mabel Bohorquez, Florencia Spirandelli, Claudio Benavides, Aina Balto, Adriana Della Valle, Luisina Inés Bruno, Francisco Lopez-Kostner, Marcia Cruz-Correa, Julio Sanchez Del Monte, Jorge Rugeles, Jesica Magalí Ramirez, Ivana Nascimento, Nora Manoukian Forones, Alicia Maria Cock-Rada, Carlos Reyes-Silva, Silvia Avila, Leandro Apolinario, Norma Teresa Rossi, Claudia Martin, Yasser Sulcahuaman, Carlos Alberto Vaccaro, Maria Del Carmen Castro-Mujica, Carlos Mario Muñeton Peña, Roseane Bicalho Assis, Elizabeth Silveira-Lucas, Chahuan Badir, Daniel Velez-Bohorquez, Gaston Boggio, Enrique Spirandelli, Florencia Neffa, Patricia Esperon, Florencia Carusso, Carolina Vergara, Mora Amat, María Teresa Pombo, Laura Noro, Marjorie De la Fuente, Tamara Canales, Alessandra Cassana, Gonzalo Carrasco-Avino, Julyann Pérez-Mayoral, Maria Gonzalez Pons, Angélica Hernández Guerrero, Silvia Vidal Millán, Sandra Beatriz Furfuro, Taisa Manuela Bonfim Machado Lopes, Thais Ferreira Bomfim Palma, Juliana Cortes Freitas, Maria Betânia Pereira Toralles, Thamara Claudia Ferreira Melo, Celia Aparecida Marques Pimenta, Luis José Palacios Fuenmayor, Gabriela Galvez-Salazar, Gabriela Jaramillo-Koupermann, Mariella Torres, Walter Hernán Pavicic, Ignacio Alberto Herrando, Juan Pablo Santino, Fabiana Alejandra Ferro, Carlos Afanador Ayala, Luri Drumond Louro, Silvio Conedera, Vessela Kristensen, Giovana Tardin Torrezan, Constantino Dominguez-Barrera, María de la Luz Ayala Madrigal, Melva Gutierrez, Patrik Wernhoff, Eivind Hovig, John-Paul Plazzer, Pål Møller, Yesilda Balavarca, Mev Dominguez-Valentin","doi":"10.1016/j.cgh.2024.12.026","DOIUrl":"10.1016/j.cgh.2024.12.026","url":null,"abstract":"<p><strong>Background & aims: </strong>In Latin America, genetic testing for Lynch syndrome (LS) has been partially implemented. Traditionally, LS diagnosis relied on the Amsterdam criteria and Bethesda guidelines, collectively known as traditional screening (TS). However, TS may miss up to 68% of LS cases. To improve detection rates, universal tumor screening (UTS) has been introduced. UTS involves screening all newly diagnosed patients with colorectal cancer for molecular markers to more effectively identify LS cases.</p><p><strong>Methods: </strong>Clinical and molecular data on 1684 patients with colorectal cancer, collected between 1999 and 2020, were provided by 24 Latin American genetic cancer registries and centers. Germline genetic testing was not consistently performed across all cases.</p><p><strong>Results: </strong>LS screening strategies were available for 72% (1209/1684) of cases, with germline testing conducted in one-quarter (304/1209) of these. Most cases (78%; n = 943) underwent UTS, primarily in Argentina, Chile, and Uruguay, whereas 22% (266/1209) were screened through TS. UTS identified deficient mismatch repair tumors in 29% (272/943) of cases. The rate of LS confirmed by sequencing was higher with UTS (53.3%; 65/122) compared with TS (47.8%; 87/182), although the difference was not statistically significant (P = .175).</p><p><strong>Conclusions: </strong>UTS is widely implemented in Latin America; however, the low detection rate of LS demonstrated in this study raises concerns about the routine use of germline genetic testing in our region. Our study provides real-world outcomes that highlight disparities in screening uptake and counseling referrals, illustrating the challenges that Latin American countries face in hereditary cancer syndrome screening. These results contribute to the rationale for designing effective screening strategies for LS, which may also be applicable to other hereditary cancer syndromes, ultimately.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness of Lynch Syndrome Identification Strategies in Individuals with Colorectal Cancer and the Impact on At-Risk Relatives.","authors":"Sheila D Rustgi, Josephine Soddano, Myles Ingram, Heather Hampel, Chin Hur, Fay Kastrinos","doi":"10.1016/j.cgh.2025.01.007","DOIUrl":"10.1016/j.cgh.2025.01.007","url":null,"abstract":"<p><strong>Background and aims: </strong>Universal screening for Lynch Syndrome (LS) is recommended for all patients diagnosed with colorectal cancer (CRC). A benefit of LS screening in CRC is cascade testing (CT), whereby at-risk relatives are tested for the familial pathogenic LS variant and undergo intensive surveillance for CRC prevention/early detection if identified with LS. There is not yet universal uptake of CT; we quantify the impact on CRC-related outcomes in first-degree relatives (FDRs).</p><p><strong>Methods: </strong>We developed a microsimulation model to quantify the impact of CT on CRC incidence and mortality in FDRs (parents, siblings, children) of individuals with CRC screened for LS. For FDRs, the primary outcome was the number of CRC cases and CRC related deaths, by age of relative; secondary outcomes included life years gained (LYG), quality-adjusted life years (QALYs), number of colonoscopies, and costs associated with CT, surveillance, and cancer care.</p><p><strong>Results: </strong>With CT for all eligible FDRs, we estimate 61.0% decrease in CRC cases and 78.5% decrease in CRC-mortality. While CT led to an average 11 more lifetime colonoscopies, there was modest increase in LYG and QALYs and decreased costs due to savings from cancer treatment.</p><p><strong>Discussion: </strong>This model quantifies the benefits of CT for at-risk FDRs of newly identified individuals with CRC and LS. The decrease in CRC incidence across generations can be used to facilitate discussions with relatives to improve uptake of CT. Further studies to optimize the uptake of CT are paramount to decrease risk of CRC in LS.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study.","authors":"Evan S Dellon, David A Katzka, Vincent A Mukkada, Margaret H Collins, Gary W Falk, Camilla A Richmond, Brian Terreri, Manoj Thakur, Mena Boules, Bridgett Goodwin, Ikuo Hirano","doi":"10.1016/j.cgh.2024.12.024","DOIUrl":"10.1016/j.cgh.2024.12.024","url":null,"abstract":"<p><strong>Background & aims: </strong>We investigated the long-term safety and efficacy of budesonide oral suspension (BOS) in eosinophilic esophagitis (EoE).</p><p><strong>Methods: </strong>This study (SHP621-303) was a 4-year, phase 3, open-label study in patients with EoE who completed up to 52 weeks of BOS therapy in 2 preceding phase 3 studies. On the basis of treatment assignments in previous studies, patients were assigned to BOS-BOS or placebo-BOS groups. All patients received BOS 2.0 mg twice daily; dose reductions to once daily and interruptions were permitted. The safety and tolerability of BOS were primarily investigated, with exploratory efficacy endpoints also examined.</p><p><strong>Results: </strong>Overall, 131 patients were included. BOS was well-tolerated, with no unexpected safety signals observed. Treatment-emergent adverse events (TEAEs) occurred in 76.3% of patients; most were mild/moderate in severity and unrelated to study drug. The most frequently reported BOS-related TEAEs included abnormal adrenocorticotropic hormone stimulation test results (8.4%, 11/131; number of events [m] = 12) and adrenal insufficiency (2.3%, 3/131; m = 3). Esophageal candidiasis occurred in 3.1% of patients (4/131). The aforementioned TEAEs resolved in most patients. At month 48 of treatment, 50.0% and 58.3% of patients achieved/maintained a histologic response (≤6 and <15 eosinophils per high-power field, respectively). The initial reduction (-3.6) in total EoE Endoscopic Reference Score from baseline to the first visit was maintained until month 48.</p><p><strong>Conclusions: </strong>Long-term treatment with BOS was well-tolerated. Despite dosing changes/interruptions, approximately half of patients achieved/maintained a histologic response; initial improvements in endoscopic outcomes were maintained over 48 months.</p><p><strong>Clinicaltrials: </strong>gov number: NCT03245840.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics-guided Biomarker Discovery, Validation, and Pathway Perturbation in Infection-related Acute Decompensation of Cirrhosis.","authors":"Pratibha Garg, Nipun Verma, Arun Valsan, Vivek Sarohi, Trayambak Basak, Tarana Gupta, Parminder Kaur, Samonee Ralmilay, Shreya Singh, Arka De, Madhumita Premkumar, Sunil Taneja, Ajay Duseja, Virendra Singh, Jasmohan S Bajaj","doi":"10.1016/j.cgh.2025.01.005","DOIUrl":"10.1016/j.cgh.2025.01.005","url":null,"abstract":"<p><strong>Background & aims: </strong>Inappropriate treatment of infections fuels drug resistance, organ failures, and costs in cirrhosis. We explored proteomics to improve infection diagnosis and management in acutely decompensated (AD) cirrhosis.</p><p><strong>Methods: </strong>We enrolled 391 patients with AD cirrhosis (92% males, median-age: 41 years), 84 in the discovery cohort (54 infected, 30 non-infected), 147 in the validation cohort I (106 infected, 41 non-infected), and 160 in the validation cohort II (108 infected, 52 non-infected). High-throughput proteomics identified biomarkers in the discovery cohort, validated through enzyme-linked immunoassay in subsequent cohorts. A model for infection was evaluated through discrimination, calibration, and decision curves and was externally validated.</p><p><strong>Results: </strong>Infected patients exhibited higher leucocyte counts, procalcitonin, organ failures, Model for End-stage Liver Disease scores, and 30-day mortality (P < .001 each). Proteomics identified 516 proteins, 27 upregulated and 38 downregulated, in infections. LGALS3BP, PLTP, CFP, and GPX3 were independently linked to infections (adjusting for severity and systemic inflammatory response syndrome), with composite area under the receiver operating characteristic curve (AUC) of 0.854 (95% confidence interval [CI], 0.787-0.922) in validation cohort I. A PACIFY model (LGALS3BP + procalcitonin + CLIF-COF + lactate) predicted infections with AUC of 0.965 (95% CI, 0.933-0.997) and 0.906 (95% CI, 0.860-0.952) in validation cohorts I and II, outperforming procalcitonin, systemic inflammatory response syndrome, white blood cell, neutrophil-to-lymphocyte ratio, neutrophil %, and composite models (P < .001). The model demonstrated fair calibration, with decision curves indicating a net benefit of the model in treating infections and reducing unnecessary antimicrobial use. Consistent findings were observed on external validation (AUC, 0.949; 95% CI, 0.916-0.982), re-enforcing the accuracy and clinical utility of the model. A deployable app was developed for infection risk estimation, enhancing practical applicability. Impaired phagocytosis, complement functions, hypocoagulation, hypofibrinolysis, dysregulated carbohydrate metabolism, autophagy, heightened cell death, and proteolysis were key perturbed pathways in infections.</p><p><strong>Conclusion: </strong>The study identifies novel protein signatures and pathways linked with infections in AD cirrhosis. A biomarker-guided treatment of infections can limit unnecessary antimicrobial use and the burden of drug resistance in cirrhosis.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extended Risankizumab Treatment in Patients With Crohn's Disease Who Did Not Achieve Clinical Response to Induction Treatment.","authors":"Remo Panaccione, Marc Ferrante, Iris Dotan, Julian Panés, Tadakazu Hisamatsu, Peter Bossuyt, Silvio Danese, Alexandra Song, Jasmina Kalabic, Namita Joshi, Javier Zambrano, Yafei Zhang, W Rachel Duan, Kristina Kligys, Marla C Dubinsky, James O Lindsay, Severine Vermeire, Britta Siegmund, Peter M Irving, Geert D'Haens","doi":"10.1016/j.cgh.2024.12.023","DOIUrl":"10.1016/j.cgh.2024.12.023","url":null,"abstract":"<p><strong>Background & aims: </strong>The efficacy and safety of extended treatment with risankizumab (RZB), an anti-interleukin-23 p19 monoclonal antibody, were evaluated in patients with moderate to severe Crohn's disease (CD) who did not achieve clinical response to 12 weeks (W) RZB induction treatment ('initial nonresponders').</p><p><strong>Methods: </strong>Initial nonresponders to intravenous (IV) RZB induction (600 mg or 1200 mg at W0, W4, and W8) were rerandomized 1:1:1 to receive extended blinded RZB treatment (1200 mg IV at W12, W16, and W20, or subcutaneous [SC] 180 mg or 360 mg at W12 and W20). Patients with clinical response to SC RZB at W24 ('delayed responders') continued their dose in FORTIFY. Clinical, endoscopic, and safety outcomes were evaluated.</p><p><strong>Results: </strong>Most initial nonresponders achieved stool frequency (SF)/ abdominal pain score (APS) clinical response by W24 (76.2% [180 mg SC], 63.7% [360 mg SC], 62.3% [1200 mg IV]), whereas a subset also achieved W24 SF/APS clinical remission (43.0%, 45.1%, and 22.1%), endoscopic response (32.4%, 32.5%, and 40.5%), and endoscopic remission (25.1%, 18.0%, and 23.5%). Most delayed responders to SC RZB continued to demonstrate clinical response at FORTIFY W52 (56.7% [180 mg SC], 69.7% [360 mg SC]), along with SF/APS clinical remission (43.3% and 54.5%), endoscopic response (36.7% and 45.5%), and endoscopic remission (40.0% and 42.4%). Numerically greater efficacy was generally observed with 360 mg SC vs 180 mg SC. The safety profile of extended treatment was consistent with previously reported trials.</p><p><strong>Conclusion: </strong>Most initial nonresponders to IV RZB induction who received 12W of extended RZB treatment demonstrated improved clinical and endoscopic outcomes at W24. Improvements in patients who received SC RZB extended treatment were maintained during FORTIFY. Extended treatment was well tolerated with no new safety risks identified.</p><p><strong>Clinicaltrials: </strong>gov: MOTIVATE (Number: NCT03104413), ADVANCE (Number: NCT03105128), and FORTIFY (Number: NCT03105102).</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Alcohol and Incremental Cardiometabolic Risk Factors With Liver Disease: A National Cross-sectional Study.","authors":"Brian P Lee, Justene Molina, Steve Kim, Jennifer L Dodge, Norah A Terrault","doi":"10.1016/j.cgh.2025.01.003","DOIUrl":"10.1016/j.cgh.2025.01.003","url":null,"abstract":"<p><strong>Background & aims: </strong>New nomenclature allows a single cardiometabolic risk factor (CMRF) with alcohol to classify metabolic dysfunction-associated steatotic liver disease (MASLD) and with \"increased alcohol intake\" (MetALD), which is controversial because alcohol causes CMRFs. Studies regarding incremental CMRFs and liver-related outcomes among alcohol users would be informative.</p><p><strong>Methods: </strong>Using the National Health and Nutrition Examination Survey (NHANES) (1/2001-3/2020), we included participants aged ≥20 years with complete alcohol and CMRF status. CMRFs were defined by the National Cholesterol Education Program's Adult Treatment Panel III. Increased alcohol use corresponded to ≥140 g/week (women)/≥210 g/week (men). The primary outcome was Fibrosis-4 (FIB-4) >2.67.</p><p><strong>Results: </strong>Among 40,898 participants, 2282 had increased vs 38,616 without increased alcohol use. Prevalence of high FIB-4 among increased vs without increased alcohol use was higher at each quantity of CMRFs, and with each incremental CMRF: 0 (2.3%; 95% confidence interval [CI], 1.0%-5.0% vs 0.7%; 95% CI, 0.5%-0.9%), 1 (3.0%; 95% CI, 1.6%-5.6% vs 1.7%; 95% CI, 1.4%-2.1%), 2 (3.3%; 95% CI, 2.1%-5.1% vs 2.1%; 95% CI, 1.8%-2.4%), 3 (5.9%; 95% CI, 3.5%-9.6% vs 2.5%; 95% CI, 2.1%-2.9%), and 4 or 5 (6.1%; 95% CI, 3.3%-9.7% vs 4.0%; 95% CI, 3.5%-4.5%) CMRFs. Among increased alcohol users, in multivariable logistic regression, 3 (adjusted odds ratio [aOR], 2.57; 95% CI, 0.93-7.08), 4 or 5 (aOR, 2.64; 95% CI, 1.05-6.67) CMRFs were associated with 2-fold higher odds of high FIB-4 (vs 0 CMRFs), but not 1 (aOR, 1.24; 95% CI, 0.41-3.69) or 2 (aOR, 1.39; 95% CI, 0.56-3.50) CMRFs. Among individuals with increased alcohol use, sensitivity/specificity-based Euclidean distance suggested an optimal cutoff of ≥3 CMRFs to differentiate higher probability of high FIB-4.</p><p><strong>Conclusions: </strong>Stratifying MetALD as ≥3 CMRFs, rather than 1 CMRF, may provide more optimal fibrosis stratification. Diabetes, high waist circumference, and hypertension are associated with significant liver fibrosis among individuals with increased alcohol use, but not dyslipidemia.</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heartburn Relief Is the Major Unmet Need for Drug Development in Gastroesophageal Reflux Disease: Threshold Value Analysis","authors":"Eric D. Shah ,&nbsp;Michael A. Curley ,&nbsp;Amit Patel ,&nbsp;Wai-Kit Lo ,&nbsp;Walter W. Chan","doi":"10.1016/j.cgh.2024.01.049","DOIUrl":"10.1016/j.cgh.2024.01.049","url":null,"abstract":"<div><h3>Background and Aims</h3><div><span>Heartburn<span> symptoms contribute to healthcare-seeking among patients with gastroesophageal reflux disease (GERD). Despite clinical guidance, management is often dictated by insurance restrictions. Several potassium-competitive acid blockers (PCABs) are under development as a new class of therapy. We performed economic analyses to align GERD </span></span>drug development with the needs of gastroenterologists, insurers and patients in a value-based environment.</div></div><div><h3>Methods</h3><div>A decision-analytic model was constructed to compare vonoprazan 20 mg daily (an example of a PCAB), common over-the-counter or prescription proton pump inhibitor regimens, and no treatment over a 1-year time horizon. Clinical responses were evaluated based on the proportions of heartburn-free days in a recent phase 3 multicenter trial. Healthcare utilization for persistent reflux symptoms was derived from national observational studies compared with healthy control subjects. Costs and quality-adjusted life years were reported.</div></div><div><h3>Results</h3><div>Without insurance coverage for appropriate therapy, patients spend $4443 and insurers spend $3784 on average per year for inadequately treated GERD symptoms. Our model estimates that PCABs could save at least $3000 in annual costs to patients and insurers, could generate quality-adjusted life year gains (+0.06 per year), and could be cost-saving to insurers as a covered option at a price up to $8.57 per pill, if these drugs are able to demonstrate similar effectiveness to proton pump inhibitors in future trials evaluating heartburn relief and erosive esophagitis healing to regulators. Threshold prices reflect pricing after all pharmacy benefits manager rebates and discounts.</div></div><div><h3>Discussion</h3><div>We demonstrate that aiming GERD-related drug development toward heartburn relief appears critical to align cost-effective incentives for industry and insurers with those of patients and gastroenterologists.</div></div>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":"23 2","pages":"Pages 263-271"},"PeriodicalIF":11.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139897902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucosal Healing With Vedolizumab in Patients With Chronic Pouchitis: EARNEST, a Randomized, Double-Blind, Placebo-Controlled Trial","authors":"Vipul Jairath ,&nbsp;Brian G. Feagan ,&nbsp;Mark S. Silverberg ,&nbsp;Silvio Danese ,&nbsp;Paolo Gionchetti ,&nbsp;Mark Löwenberg ,&nbsp;Brian Bressler ,&nbsp;Marc Ferrante ,&nbsp;Ailsa Hart ,&nbsp;Dirk Lindner ,&nbsp;Armella Escher ,&nbsp;Stephen Jones ,&nbsp;Bo Shen ,&nbsp;Simon Travis","doi":"10.1016/j.cgh.2024.06.037","DOIUrl":"10.1016/j.cgh.2024.06.037","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Vedolizumab is indicated for the treatment of chronic pouchitis in the European Union. We assessed whether vedolizumab induced mucosal healing (MH) and if MH was associated with clinical improvements.</div></div><div><h3>Methods</h3><div>EARNEST, a randomized, double-blind, placebo-controlled study, evaluated vedolizumab efficacy and safety in adults with chronic pouchitis. Centrally read endoscopic and histologic evaluation was performed at baseline, Week (W)14, and W34. Ulcer count, adapted Simple Endoscopic Score for Crohn’s Disease in the pouch, and Pouchitis Disease Activity Index histologic component were evaluated. Pouchitis Disease Activity Index and Inflammatory Bowel Disease Questionnaire remission at W14 and W34 were compared by MH status at W14.</div></div><div><h3>Results</h3><div>Following treatment, mean (standard deviation) number of ulcers in vedolizumab-treated patients reduced from 15.1 (16.4) to 5.0 (4.9) at W14 and 2.7 (3.2) at W34 versus placebo-treated patients with corresponding values of 11.8 (11.3), 13.4 (18.4), and 9.7 (13.8) (vedolizumab vs placebo difference [95% confidence interval]: W14: −8.4 [−14.3, −2.6]; W34: −7.0 [−12.0, −2.0]). More patients receiving vedolizumab versus placebo achieved reduction in ulcerated pouch surface area (W14: 52.4% vs 20.0%; difference, 32.4 percentage points [p.p] [9.7, 51.4]; W34: 52.1% vs 12.9%; difference, 40.2p.p [15.6, 60.3]), absence of ulceration (W14: 23.8% vs 7.5%; difference, 16.3p.p [1.1, 31.6]; W34: 34.4% vs 15.6%; difference, 18.8p.p [−2.0, 39.5]), Simple Endoscopic Score for Crohn’s Disease remission (W14: 23.8% vs 7.5%; difference, 16.3p.p [1.1, 31.6]; W34: 34.4% vs 15.6%; difference, 18.8p.p [−2.0, 39.5]), and MH (W14: 16.7% vs 2.5%; difference, 14.2p.p [1.9, 26.4]). Patients with MH at W14 had higher rates of Pouchitis Disease Activity Index and Inflammatory Bowel Disease Questionnaire remission at W14 and W34 than those without.</div></div><div><h3>Conclusions</h3><div>Vedolizumab induced endoscopic improvements in patients with chronic pouchitis, which was associated with improved outcomes at W34, particularly in patients achieving MH at W14. (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> number, NCT02790138.)</div></div>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":"23 2","pages":"Pages 321-330.e3"},"PeriodicalIF":11.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}