Lancet Gastroenterology & Hepatology最新文献

{"title":"Can targeting de novo lipogenesis improve liver health?","authors":"Manuel Castro Cabezas, Vivian D de Jong","doi":"10.1016/s2468-1253(25)00161-x","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00161-x","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"26 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756369","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":"Efficacy and safety of ervogastat alone and in combination with clesacostat in patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis and F2–F3 fibrosis (MIRNA): results from a phase 2, randomised, double-blind, double-dummy study","authors":"Vincent Wai-Sun Wong, Neeta B Amin, Hirokazu Takahashi, Amanda Darekar, Frank Tacke, Jan Kiszko, Hector Rodriguez, Atsushi Nakajima, Naim Alkhouri, Michael Charlton, Quentin M Anstee","doi":"10.1016/s2468-1253(25)00128-1","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00128-1","url":null,"abstract":"<h3>Background</h3>Ervogastat, a diacylglycerol acyltransferase 2 (DGAT2) inhibitor, and clesacostat, an acetyl-coenzyme A carboxylase (ACC) inhibitor, have shown promise in reducing hepatic steatosis. Increased circulating triglycerides, a mechanistic consequence of ACC inhibitors, has been shown to be downregulated by DGAT2 inhibitor co-administration. We assessed the efficacy and safety of ervogastat alone and ervogastat plus clesacostat in adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis stage 2 or 3.<h3>Methods</h3>This phase 2 double-blind, double-dummy, randomised study was conducted at 198 clinical sites across 11 countries. A computer-generated randomisation code (random permuted blocks method) was used to allocate patients to treatment groups in equal ratios, and stratified based on degree of fibrosis (F2 <em>vs</em> F3), using an interactive response technology system to ervogastat (25 mg, 75 mg, 150 mg, or 300 mg), ervogastat plus clesacostat (150 mg plus 5 mg or 300 mg plus 10 mg), or placebo, twice daily for 48 weeks. The primary endpoint was the proportion of patients achieving MASH resolution without fibrosis worsening, at least 1 stage fibrosis improvement without MASH worsening, or both, at week 48. Patients were analysed according to the treatment group they were assigned to. The primary endpoint was analysed based on the full analysis set (all randomly assigned patients who took at least one dose of study treatment who provided evaluable baseline biopsy data) in which patients missing a week 48 biopsy were considered non-responders. This completed trial was 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>NCT04321031</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>Recruitment began June 15, 2020; randomisation was completed Feb 22, 2023, with 255 patients randomly assigned and given treatment (73% of planned sample size; ervogastat 25 mg: N=35; ervogastat 75 mg: N=48; ervogastat 150 mg: N=42; ervogastat 300 mg: N=31; ervogastat 150 mg plus clesacostat 5 mg: N=35; ervogastat 300 mg plus clesacostat 10 mg: N=30; placebo: N=34). 13 (38%) patients in the placebo group achieved the composite primary endpoint, as did 16 (46%) in the ervogastat 25 mg group (difference from placebo in the proportion of patients achieving the primary endpoint 0·08 [90% CI –0·11 to 0·27]), 25 (52%) in the ervogastat 75 mg group (0·14 [–0·04 to 0·32]), 21 (50%) in the ervogastat 150 mg group (0·12 [–0·07 to 0·30]), and 14 (45%) in the ervogastat 300 mg group (0·07 [–0·12 to 0·27]). 23 (66%) patients in the er","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"26 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756574","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":"Breaking barriers to hepatitis C elimination in the WHO Eastern Mediterranean Region","authors":"Ahmed Sabry Alaama, Muhammad Shahid Jamil, Nevin Wilson, Benedetta Allegranzi","doi":"10.1016/s2468-1253(25)00240-7","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00240-7","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"19 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710919","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":"World Hepatitis Day 2025: elimination at a critical juncture","authors":"","doi":"10.1016/s2468-1253(25)00237-7","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00237-7","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"706 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694084","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":"Let's break it down: combating hepatitis stigma and discrimination","authors":"Rachel Halford, Jessica Hicks, Md Reazul Islam, Cary James, Gamal Shiha, Thomas Tu","doi":"10.1016/s2468-1253(25)00229-8","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00229-8","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"122 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694184","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":"Patient and public health perspectives to inform expansion of hepatitis B treatment guidelines","authors":"Chari Cohen, Thomas Tu, Philippa C Matthews, Su Wang, Jessica Hicks, Manal H El-Sayed, John E Tavis","doi":"10.1016/s2468-1253(25)00052-4","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00052-4","url":null,"abstract":"Chronic hepatitis B is associated with considerable morbidity and mortality worldwide. People living with hepatitis B face physical, emotional, social, and professional impacts, reducing their quality of life. Treatment with nucleoside or nucleotide analogues reduces the risk of liver cirrhosis and liver cancer and improves quality of life. However, few people globally are offered and can access affordable and long-term antiviral treatment. Moreover, little progress has been made towards meeting WHO hepatitis B elimination targets. The global landscape has been shifting towards expanding treatment criteria, but discussion surrounding patient and community perspectives has been inadequate. We should view treatment eligibility for hepatitis B virus infection from a public health and patient-centred approach. Here, we discuss the potential benefits and risks of expansion, implementation considerations, public health questions, and data needs surrounding the expansion of treatment eligibility. We conclude that there is a strong public health and community rationale for expanding treatment eligibility for people living with chronic hepatitis B.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"58 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694052","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":"Estimating the annual number of hepatitis C virus infections through vertical transmission at country, regional, and global levels: a data synthesis study","authors":"Adam Trickey, Adelina Artenie, Jordan J Feld, Peter Vickerman","doi":"10.1016/s2468-1253(25)00189-x","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00189-x","url":null,"abstract":"<h3>Background</h3>The burden of hepatitis C virus (HCV) among women of childbearing age remains high globally. Studies have estimated that 7–12% of children born to women with HCV infection will acquire HCV, although around two-thirds of children will then clear their HCV infection by 5 years of age. We aimed to estimate the annual number of vertically transmitted HCV infections and how many cases remain at 5 years of age at the country or territory, regional, and global levels.<h3>Methods</h3>In this data synthesis study, we produced estimates of vertical HCV transmission by combining data from several sources: data on the number of women, age-specific fertility rates, mortality rates among children aged 0–5 years, and HIV prevalence among women aged 15–49 years from the UN; modelled data on HCV prevalence among women aged 15–49 years; meta-analysis data on HCV–HIV co-infection prevalence; and recent estimates of the probabilities of vertical HCV transmission and subsequent clearance by age 5 years. The annual number of births with HCV was estimated by multiplying the number of women with HCV in 5-year age bands by age band-specific birth rates, separately by HIV status, and multiplying by HIV status-specific HCV vertical transmission probabilities. The number of births with HCV was multiplied by the probability of spontaneous clearance of HCV by 5 years of age, accounting for mortality. All estimates were sampled 1000 times from their uncertainty intervals (UIs) to produce 95% UIs.<h3>Findings</h3>The estimated annual global number of new HCV infections occurring through vertical transmission was 73 862 (95% UI 69 808–78 279). Southern Asia (21 245 [18 095–24 847]), western Africa (16 482 [14 873–18 283]), and eastern Africa (8182 [7479–9085]) were the regions with the most infections. Pakistan (16 350 [13 325–19 844]) and Nigeria (8483 [6944–10 184]) had the largest burden and together accounted for around a third of new infections. We estimated that 23 120 (20 596–25 813) of these children would be alive and still have HCV when aged 5 years.<h3>Interpretation</h3>Targeted screening policies that test and treat pregnant women with HCV could prevent substantial numbers of new HCV infections; however, data on the safety of HCV treatments in pregnant women are required.<h3>Funding</h3>None.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"31 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694090","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":"Scientific and medical evidence informing expansion of hepatitis B treatment guidelines","authors":"Patrick T Kennedy, Lena Allweiss, Antonio Bertoletti, Markus Cornberg, Adam J Gehring, Luca G Guidotti, Hélène A Kerth, Maud Lemoine, Massimo Levrero, Seng Gee Lim, John E Tavis, Barbara Testoni, Thomas Tu","doi":"10.1016/s2468-1253(25)00053-6","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00053-6","url":null,"abstract":"Chronic hepatitis B treatment relies on nucleoside or nucleotide analogue drugs that suppress hepatitis B virus (HBV) replication, normalise liver enzymes, and slow disease progression with excellent safety profiles. Treatment is not curative, and patients remain at risk of cirrhosis and hepatocellular carcinoma. Treatment guidelines have generally restricted antiviral therapy to individuals with high HBV DNA and elevated ALT or hepatic fibrosis, often requiring longitudinal testing that can be scarcely available in resource-limited settings. Consequently, fewer than 3% of people living with HBV infection are receiving antiviral therapy. Guidelines from China and WHO recently broadened access criteria to antiviral therapy, but there are people who fall outside these guidelines who could still benefit from treatment initiation. The pathological processes induced by HBV infection are still active in these patients. We present the benefits and risks of expanding treatment eligibility. We believe that the benefits of reduced hepatic damage and carcinogenic stimuli greatly outweigh the risks.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"123 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694095","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":"Launching the Center for Operational Research on Hepatitis B","authors":"Gibril Ndow, Neil Gupta, Lindsey Hiebert-Suwondo, John W Ward","doi":"10.1016/s2468-1253(25)00227-4","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00227-4","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"52 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694085","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":"Effect of gluten and wheat on symptoms and behaviours in adults with irritable bowel syndrome: a single-centre, randomised, double-blind, sham-controlled crossover trial","authors":"Caroline Larissa Seiler, Gaston Horacio Rueda, Pedro Miguel Miranda, Andrea Nardelli, Rajka Borojevic, Amber Hann, Sara Rahmani, Russell De Souza, Alberto Caminero, Valentina Curella, Manjusha Neerukonda, Stephen Vanner, Detlef Schuppan, Paul Moayyedi, Stephen Michael Collins, Elena Francisca Verdu, Maria Ines Pinto-Sanchez, Premysl Bercik","doi":"10.1016/s2468-1253(25)00090-1","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00090-1","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Many patients with irritable bowel syndrome (IBS) believe gluten or wheat triggers their symptoms. We compared symptomatic responses to wheat and gluten with gluten-free sham challenge in patients with IBS who previously perceived benefit from a gluten-free diet.&lt;h3&gt;Methods&lt;/h3&gt;We conducted this randomised, double-blind, sham-controlled crossover study at McMaster University Medical Centre, ON, Canada. Eligible participants were adults aged 18 years or older who met Rome IV criteria for IBS and had previously self-reported improvement on a gluten-free diet, which was implemented for at least 3 weeks before enrolment. Eligible participants were randomly assigned (1:1:1:1:1:1) to receive one of six sequences of wheat, gluten, and sham (containing gluten and wheat free flour) in three periods of 7 days, separated by 14-day washout periods. Randomisation was done using the randomizeBE package in R and the cereal bars were designed to have the same appearance, taste, and smell to maintain blinding. The primary outcome was worsening of IBS symptoms of at least 50 points on the IBS Symptom Severity Score (IBS-SSS) after dietary challenges. Outcome and safety analyses were done in all patients who completed all three challenges. This trial was registered with &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;NCT03664531&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;.&lt;h3&gt;Findings&lt;/h3&gt;Between Nov 15, 2018, and June 19, 2023, we assessed 101 people for eligibility. 72 people were excluded due to ineligibility (n=15), refusing screening (n=42), and refusing participation (n=15). 29 participants were enrolled and randomly assigned to wheat–gluten–sham (n=5), wheat–sham–gluten (n=5), gluten–wheat–sham (n=5), gluten–sham–wheat (n=5), sham–wheat–gluten (n=5), and sham–gluten–wheat (n=4). One participant in the wheat–sham–gluten group completed the first challenge but withdrew without providing a reason. In the 28 patients completing the study, there were no statistically significant differences in the proportion of participants with a worsening of IBS-SSS of at least 50 points after wheat (11 [39%] of 28 participants, risk difference &lt;em&gt;vs&lt;/em&gt; sham 0·11; 95% CI –0·16 to 0·35) or gluten (ten participants [36%], 0·07; –0·19 to 0·32) versus sham (eight participants [29%]). Adverse events were reported in 26 (93%) of 28 patients after wheat, 26 patients (93%) after gluten, and 26 patients (93%) after sham. Study emergent adverse events were similar between challenges (five [18%] of 28 participants after wheat, five [18%] after gluten, and seven [25%] after sham). No patients report","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"21 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678274","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}