Pub Date : 2025-03-12DOI: 10.1016/s2468-1253(25)00016-0
Weizhong Jiang, Jianmin Xu, Ming Cui, Xiangqian Su, Pan Chi
No Abstract
{"title":"How reliable and generalisable are the results of the LASRE trial? – Authors' reply","authors":"Weizhong Jiang, Jianmin Xu, Ming Cui, Xiangqian Su, Pan Chi","doi":"10.1016/s2468-1253(25)00016-0","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00016-0","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"15 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608379","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}
Pub Date : 2025-03-11DOI: 10.1016/s2468-1253(24)00390-x
Markus F Neurath, David Artis, Christoph Becker
The intestinal barrier serves as a boundary between the mucosal immune system in the lamina propria and the external environment of the intestinal lumen, which contains a diverse array of microorganisms and ingested environmental factors, including pathogens, food antigens, toxins, and other foreign substances. This barrier has a central role in regulating the controlled interaction between luminal factors and the intestinal immune system. Disruptions of intestinal epithelial cells, which serve as a physical barrier, or the antimicrobial peptides and mucins they produce, which act as a chemical barrier, can lead to a leaky gut. In this state, the intestinal wall is unable to efficiently separate the intestinal flora and luminal contents from the intestinal immune system. The subsequent activation of the immune system has an important role in the pathogenesis of inflammatory bowel disease, as well as in metabolic dysfunction-associated steatohepatitis, primary sclerosing cholangitis, and colorectal cancer. Dysregulated intestinal barrier integrity has also been described in patients with chronic inflammatory diseases outside the gastrointestinal tract, including rheumatoid arthritis and neurodegenerative disorders. Mechanistic studies of barrier dysfunction have revealed that the subsequent local activation and systemic circulation of activated immune cells and the cytokines they secrete, as well as extracellular vesicles, promote proinflammatory processes within and outside the gastrointestinal tract. In this Review, we summarise these findings and highlight several new therapeutic concepts currently being developed that attempt to control inflammatory processes via direct or indirect modulation of intestinal barrier function.
{"title":"The intestinal barrier: a pivotal role in health, inflammation, and cancer","authors":"Markus F Neurath, David Artis, Christoph Becker","doi":"10.1016/s2468-1253(24)00390-x","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00390-x","url":null,"abstract":"The intestinal barrier serves as a boundary between the mucosal immune system in the lamina propria and the external environment of the intestinal lumen, which contains a diverse array of microorganisms and ingested environmental factors, including pathogens, food antigens, toxins, and other foreign substances. This barrier has a central role in regulating the controlled interaction between luminal factors and the intestinal immune system. Disruptions of intestinal epithelial cells, which serve as a physical barrier, or the antimicrobial peptides and mucins they produce, which act as a chemical barrier, can lead to a leaky gut. In this state, the intestinal wall is unable to efficiently separate the intestinal flora and luminal contents from the intestinal immune system. The subsequent activation of the immune system has an important role in the pathogenesis of inflammatory bowel disease, as well as in metabolic dysfunction-associated steatohepatitis, primary sclerosing cholangitis, and colorectal cancer. Dysregulated intestinal barrier integrity has also been described in patients with chronic inflammatory diseases outside the gastrointestinal tract, including rheumatoid arthritis and neurodegenerative disorders. Mechanistic studies of barrier dysfunction have revealed that the subsequent local activation and systemic circulation of activated immune cells and the cytokines they secrete, as well as extracellular vesicles, promote proinflammatory processes within and outside the gastrointestinal tract. In this Review, we summarise these findings and highlight several new therapeutic concepts currently being developed that attempt to control inflammatory processes via direct or indirect modulation of intestinal barrier function.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"92 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599111","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}
Pub Date : 2025-03-06DOI: 10.1016/s2468-1253(25)00006-8
Kavish R Patidar, Ann T Ma, Adrià Juanola, Anna Barone, Simone Incicco, Anand V Kulkarni, José Luis Pérez Hernández, Brian Wentworth, Sumeet K Asrani, Carlo Alessandria, Nadia Abdelaaty Abdelkader, Yu Jun Wong, Qing Xie, Nikolaos T Pyrsopoulos, Sung-Eun Kim, Yasser Fouad, Aldo Torre, Eira Cerda, Javier Diaz Ferrer, Rakhi Maiwall, Salvatore Piano
<h3>Background</h3>Acute kidney injury (AKI) is a serious complication of cirrhosis. A systematic, global characterisation of AKI occurring in patients with cirrhosis is lacking. We therefore aimed to assess global differences in the characteristics, management, and outcomes of AKI in hospitalised patients with cirrhosis.<h3>Methods</h3>In this prospective, multicentre, cohort study, we enrolled adults (≥18 years) with decompensated cirrhosis who were hospitalised for a cirrhosis-related complication, with or without AKI, at 65 centres across five continents. We captured AKI prevalence, stage, phenotype, and details on AKI management and clinical course. Universal health coverage index and gross national income per capita were also collected. The primary outcome was 28-day mortality. Multivariable models including demographic and clinical variables, cirrhosis cause, cirrhosis severity, AKI severity, AKI management variables, universal health coverage, and gross national income were used to analyse independent associations with 28-day mortality. Secondary outcomes were AKI classification, progression, and resolution. This study is complete and registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> (<span><span>NCT05387811</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>).<h3>Findings</h3>Between July 1, 2022, and May 31, 2023, we enrolled 3821 patients who were hospitalised for decompensated cirrhosis. Mean age was 57·7 years (SD 13·1), 2467 (64·6%) were men, and 1354 (35·4%) were women. Most patients were White (2128 [55·7%]). 1456 (38·1%, 95% CI 36·6–39·6) of 3821 patients had AKI (943 [64·8%] men and 513 [35·2%] women). Globally, patients presented with similar AKI stages, but patients from North America and Asia had the highest MELD-Na scores at presentation and the highest rates of peak AKI stage 3. Overall, hypovolaemic AKI was the most common phenotype (858 [58·9%] of 1456), followed by HRS–AKI (253 [17·4%]) and acute tubular necrosis (216 [14·8%]). The prevalences of hypovolaemic AKI and HRS–AKI were similar across regions, but acute tubular necrosis was more frequent in Asia (p<0·0001 across regions). Additionally, regional differences in the management of AKI (use of albumin, vasopressors, and diuretics) were found. 335 (28·6%) of 1171 patients with initial AKI stages 1 or 2 had progression to higher stages during hospitalisation. AKI resolved in 862 (59·2%) cases during hospitalisation. 333 (22·9%) patients with AKI had died by 28 days. Multivariable analyses showed that increased age, female sex, presence of ascites, presence of hepatic encephalopathy, increased white bloo
{"title":"Global epidemiology of acute kidney injury in hospitalised patients with decompensated cirrhosis: the International Club of Ascites GLOBAL AKI prospective, multicentre, cohort study","authors":"Kavish R Patidar, Ann T Ma, Adrià Juanola, Anna Barone, Simone Incicco, Anand V Kulkarni, José Luis Pérez Hernández, Brian Wentworth, Sumeet K Asrani, Carlo Alessandria, Nadia Abdelaaty Abdelkader, Yu Jun Wong, Qing Xie, Nikolaos T Pyrsopoulos, Sung-Eun Kim, Yasser Fouad, Aldo Torre, Eira Cerda, Javier Diaz Ferrer, Rakhi Maiwall, Salvatore Piano","doi":"10.1016/s2468-1253(25)00006-8","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00006-8","url":null,"abstract":"<h3>Background</h3>Acute kidney injury (AKI) is a serious complication of cirrhosis. A systematic, global characterisation of AKI occurring in patients with cirrhosis is lacking. We therefore aimed to assess global differences in the characteristics, management, and outcomes of AKI in hospitalised patients with cirrhosis.<h3>Methods</h3>In this prospective, multicentre, cohort study, we enrolled adults (≥18 years) with decompensated cirrhosis who were hospitalised for a cirrhosis-related complication, with or without AKI, at 65 centres across five continents. We captured AKI prevalence, stage, phenotype, and details on AKI management and clinical course. Universal health coverage index and gross national income per capita were also collected. The primary outcome was 28-day mortality. Multivariable models including demographic and clinical variables, cirrhosis cause, cirrhosis severity, AKI severity, AKI management variables, universal health coverage, and gross national income were used to analyse independent associations with 28-day mortality. Secondary outcomes were AKI classification, progression, and resolution. This study is complete and registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT05387811</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>).<h3>Findings</h3>Between July 1, 2022, and May 31, 2023, we enrolled 3821 patients who were hospitalised for decompensated cirrhosis. Mean age was 57·7 years (SD 13·1), 2467 (64·6%) were men, and 1354 (35·4%) were women. Most patients were White (2128 [55·7%]). 1456 (38·1%, 95% CI 36·6–39·6) of 3821 patients had AKI (943 [64·8%] men and 513 [35·2%] women). Globally, patients presented with similar AKI stages, but patients from North America and Asia had the highest MELD-Na scores at presentation and the highest rates of peak AKI stage 3. Overall, hypovolaemic AKI was the most common phenotype (858 [58·9%] of 1456), followed by HRS–AKI (253 [17·4%]) and acute tubular necrosis (216 [14·8%]). The prevalences of hypovolaemic AKI and HRS–AKI were similar across regions, but acute tubular necrosis was more frequent in Asia (p<0·0001 across regions). Additionally, regional differences in the management of AKI (use of albumin, vasopressors, and diuretics) were found. 335 (28·6%) of 1171 patients with initial AKI stages 1 or 2 had progression to higher stages during hospitalisation. AKI resolved in 862 (59·2%) cases during hospitalisation. 333 (22·9%) patients with AKI had died by 28 days. Multivariable analyses showed that increased age, female sex, presence of ascites, presence of hepatic encephalopathy, increased white bloo","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"38 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569470","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}
Pub Date : 2025-03-04DOI: 10.1016/s2468-1253(25)00050-0
Guillaume Fontaine, Natalie Taylor, Julie Bruneau, Nadine Kronfli, Christina Greenaway, Mia J Biondi, Marina B Klein, Sahar Saeed, Jason Grebely, Justin Presseau
No Abstract
{"title":"The urgent need for implementation science to achieve hepatitis C elimination","authors":"Guillaume Fontaine, Natalie Taylor, Julie Bruneau, Nadine Kronfli, Christina Greenaway, Mia J Biondi, Marina B Klein, Sahar Saeed, Jason Grebely, Justin Presseau","doi":"10.1016/s2468-1253(25)00050-0","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00050-0","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"11 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545941","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}
Pub Date : 2025-02-21DOI: 10.1016/s2468-1253(24)00442-4
Adelina Artenie, Adam Trickey, Katharine J Looker, Jack Stone, Aaron G Lim, Hannah Fraser, Louisa Degenhardt, Gregory J Dore, Jason Grebely, Evan B Cunningham, Behzad Hazarizadeh, Daniel Low-Beer, Niklas Luhmann, Paige Webb, Matthew Hickman, Peter Vickerman
<h3>Background</h3>Measuring progress towards the WHO 2030 target for hepatitis C virus (HCV) elimination among people who inject drugs (PWID)—an incidence of two or fewer infections per 100 person-years—has been challenging due to insufficient data. We aimed to estimate HCV incidence among PWID before and since 2015, progress towards the 2030 target, and the number of new annual HCV infections attributable to injecting drug use since 2015.<h3>Methods</h3>Four sequential steps were taken to estimate country-specific HCV incidence. First, we estimated HCV incidence from HCV antibody prevalence by duration of injecting using force-of-infection (FOI) modelling. Second, using Bayesian random-effects meta-analysis, we pooled FOI-derived estimates with any direct HCV incidence estimates from a published global meta-analysis, by country. Third, for countries with no FOI-derived or direct HCV incidence data, we applied incidence estimates from a published multi-country dynamic mathematical model. Fourth, for countries for which incidence could not be estimated using any of the aforementioned methods but that had data on overall HCV antibody prevalence (ie, not stratified by duration of injecting), we used a regression model to predict incidence based on prevalence and average duration of injecting. WHO regional and global HCV incidence, incidence rate ratios (IRRs) for 2015–21 versus pre-2015, and relative decline needed to achieve the 2030 WHO target were derived and weighted by the country-specific number of PWID at risk (ie, those who were HCV RNA-negative), provided that data from at least five countries were available within a WHO region. New annual HCV infections attributable to injecting drug use were estimated by multiplying country-specific HCV incidence for the 2015–21 period by the number of HCV RNA-negative PWID; for countries with no HCV incidence data but with evidence of an existing PWID population, incidence was imputed using the corresponding WHO regional incidence.<h3>Findings</h3>For the pre-2015 period, 146 HCV incidence estimates from 81 countries were included: 52 (36%) direct, 61 (42%) FOI-derived, and 33 (23%) regression-based estimates. For 2015–21, 114 estimates from 97 countries were included: 20 (18%) direct, 18 (16%) FOI-derived, 68 (60%) dynamic model-derived, and eight (7%) regression-based. Globally, pooled HCV incidence was 13·9 per 100 person-years (95% uncertainty interval [UI] 11·9–16·4) for pre-2015 and 8·6 per 100 person-years (7·1–10·7) for 2015–21. Based on a subset of countries with data for both periods, incidence was lower in the Western Pacific (IRR 0·32 [95% UI 0·23–0·50]), Eastern Mediterranean (0·67 [0·50–0·89]), and European (0·79 [0·63–1·02]) regions in 2015–21 versus pre-2015, but no difference was observed in the Americas. Insufficient data prevented comparisons over time for the African and South-East Asia regions and globally. Based on 2015–21 HCV incidence, the global decline needed to meet the 2030 W
{"title":"Global, regional, and national estimates of hepatitis C virus (HCV) infection incidence among people who inject drugs and number of new annual HCV infections attributable to injecting drug use: a multi-stage analysis","authors":"Adelina Artenie, Adam Trickey, Katharine J Looker, Jack Stone, Aaron G Lim, Hannah Fraser, Louisa Degenhardt, Gregory J Dore, Jason Grebely, Evan B Cunningham, Behzad Hazarizadeh, Daniel Low-Beer, Niklas Luhmann, Paige Webb, Matthew Hickman, Peter Vickerman","doi":"10.1016/s2468-1253(24)00442-4","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00442-4","url":null,"abstract":"<h3>Background</h3>Measuring progress towards the WHO 2030 target for hepatitis C virus (HCV) elimination among people who inject drugs (PWID)—an incidence of two or fewer infections per 100 person-years—has been challenging due to insufficient data. We aimed to estimate HCV incidence among PWID before and since 2015, progress towards the 2030 target, and the number of new annual HCV infections attributable to injecting drug use since 2015.<h3>Methods</h3>Four sequential steps were taken to estimate country-specific HCV incidence. First, we estimated HCV incidence from HCV antibody prevalence by duration of injecting using force-of-infection (FOI) modelling. Second, using Bayesian random-effects meta-analysis, we pooled FOI-derived estimates with any direct HCV incidence estimates from a published global meta-analysis, by country. Third, for countries with no FOI-derived or direct HCV incidence data, we applied incidence estimates from a published multi-country dynamic mathematical model. Fourth, for countries for which incidence could not be estimated using any of the aforementioned methods but that had data on overall HCV antibody prevalence (ie, not stratified by duration of injecting), we used a regression model to predict incidence based on prevalence and average duration of injecting. WHO regional and global HCV incidence, incidence rate ratios (IRRs) for 2015–21 versus pre-2015, and relative decline needed to achieve the 2030 WHO target were derived and weighted by the country-specific number of PWID at risk (ie, those who were HCV RNA-negative), provided that data from at least five countries were available within a WHO region. New annual HCV infections attributable to injecting drug use were estimated by multiplying country-specific HCV incidence for the 2015–21 period by the number of HCV RNA-negative PWID; for countries with no HCV incidence data but with evidence of an existing PWID population, incidence was imputed using the corresponding WHO regional incidence.<h3>Findings</h3>For the pre-2015 period, 146 HCV incidence estimates from 81 countries were included: 52 (36%) direct, 61 (42%) FOI-derived, and 33 (23%) regression-based estimates. For 2015–21, 114 estimates from 97 countries were included: 20 (18%) direct, 18 (16%) FOI-derived, 68 (60%) dynamic model-derived, and eight (7%) regression-based. Globally, pooled HCV incidence was 13·9 per 100 person-years (95% uncertainty interval [UI] 11·9–16·4) for pre-2015 and 8·6 per 100 person-years (7·1–10·7) for 2015–21. Based on a subset of countries with data for both periods, incidence was lower in the Western Pacific (IRR 0·32 [95% UI 0·23–0·50]), Eastern Mediterranean (0·67 [0·50–0·89]), and European (0·79 [0·63–1·02]) regions in 2015–21 versus pre-2015, but no difference was observed in the Americas. Insufficient data prevented comparisons over time for the African and South-East Asia regions and globally. Based on 2015–21 HCV incidence, the global decline needed to meet the 2030 W","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"47 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471000","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}
Locoregional therapies play a fundamental role in the treatment of patients with early and intermediate and locally advanced hepatocellular carcinomas. With encouraging recent advances in immunotherapy-based systemic therapies, locoregional therapies are being both promoted and challenged by new systemic therapy options. Combined locoregional and systemic therapies might enhance treatment outcomes compared with either option alone. This Series paper summarises the existing data on locoregional and systemic therapies for hepatocellular carcinoma, and discusses evidence from studies investigating their combination with a focus on their synergistic efficacy and safety.
{"title":"Combination locoregional and systemic therapies in hepatocellular carcinoma","authors":"Bin-Yan Zhong, Wenzhe Fan, Justin J Guan, Zhenwei Peng, Zhongzhi Jia, Haojie Jin, Zhi-Cheng Jin, Jian-Jian Chen, Hai-Dong Zhu, Gao-Jun Teng","doi":"10.1016/s2468-1253(24)00247-4","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00247-4","url":null,"abstract":"Locoregional therapies play a fundamental role in the treatment of patients with early and intermediate and locally advanced hepatocellular carcinomas. With encouraging recent advances in immunotherapy-based systemic therapies, locoregional therapies are being both promoted and challenged by new systemic therapy options. Combined locoregional and systemic therapies might enhance treatment outcomes compared with either option alone. This Series paper summarises the existing data on locoregional and systemic therapies for hepatocellular carcinoma, and discusses evidence from studies investigating their combination with a focus on their synergistic efficacy and safety.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"26 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470996","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：