ADaptive ASsessment of TReatments for influenzA: A Phase 2 Multi-centre Adaptive Randomised Platform Trial to Assess Antiviral Pharmacodynamics in Early Symptomatic Influenza Infection (AD ASTRA)

This trial will use a previously validated platform, to quantitatively assess antiviral effects in low-risk patients with high viral burdens and uncomplicated influenza, to determine in-vivo antiviral activity. In this randomised, open-label, controlled, group sequential, adaptive, platform trial, we will compare the performance of available influenza antivirals, and those with potential activity, relative to the control (no treatment) and each other.
AD ASTRA study is supported by the Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator

开始日期2023-02-22

申办/合作机构

University of Oxford

JPRN-jRCT1080224937

/ CompletedN/A

The special drug use surveillance of INAVIR for inhalation suspension set (Safety evaluation in pediatric patients under five years old)

开始日期2019-11-01

申办/合作机构

Daiichi Sankyo Co., Ltd.

JPRN-UMIN000035028

/ CompletedN/AIIT

Effect and safety of Baloxavir Marboxil in children with influenza: multicenter randomized controlled study

开始日期2018-12-01

申办/合作机构-

100 项与辛酸拉尼米韦相关的临床结果

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100 项与辛酸拉尼米韦相关的转化医学

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100 项与辛酸拉尼米韦相关的专利（医药）

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项与辛酸拉尼米韦相关的文献（医药）

2026-08-01·YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN

Fragment Molecular Orbital Calculation Analysis of Influenza Neuraminidase and Inhibitor Interactions

Review

作者: Fukuzawa, Kaori ; Masuda, Ayaka ; Taguchi, Tomoka ; Onishi, Mizuka

The interactions between 4 compounds used as influenza neuraminidase inhibitors-oseltamivir, zanamivir, laninamivir, and peramivir- and influenza virus neuraminidase were analyzed using pair interaction energy decomposition analysis based on fragment molecular orbital (FMO) method, quantitatively elucidating binding characteristics of each inhibitor. Our calculations revealed that structures with common functional groups showed similar binding characteristics, whereas structures with functional groups differing in hydrophilicity/hydrophobicity showed different types of intermolecular interactions for the same amino acid residues. Such analysis is expected to be effective for precise molecular design in structure-based drug design.

2026-05-01·INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Association of severe abnormal behavior of influenza patients and administered anti-influenza virus drugs: 2006-2022

Article

作者: Sugawara, Tamie ; Miyazaki, Chiaki ; Kato, Yoko ; Ohkusa, Yasushi ; Taniguchi, Kiyosu ; Okabe, Nobuhiko

OBJECTIVES:

Since February 2007, abnormal behaviors of influenza patients, especially of 10-19-year-olds, have raised public health concern in Japan. Those behavior-related events were caused putatively by anti-influenza drugs. The Ministry of Health, Labour and Welfare (MHLW) issued an administrative note to deter antiviral drug administration to 10-19-year-old patients, later withdrawing it on August 21, 2018, after detailed epidemiological study. The objective of this study using all reported data of abnormal behaviors from the 2006/2007 season through the 2021/2022 season in Japan was to evaluate the association of abnormal behavior types with anti-influenza virus drugs.

METHODS:

MHLW had requested that all physicians report influenza cases with associated abnormal behaviors from the 2006/2007 season through the 2021/2022 season by abnormal behavior type: running, jumping from high places, sudden cessation of communication, being spooked or panicked, hallucination, and others. Differences in incidence rates among patients administered anti-influenza virus drugs were tested using Fisher's exact test.

RESULTS:

Findings common to both age classes were that peramivir presented higher incident than oseltamivir for running, and that zanamivir or laninamivir presented higher incident for running and for jumping from high places. Peramivir presented a higher incident than either oseltamivir or zanamivir for abnormal behaviors of other types among 0-9-year-olds, but not among 10-19 year olds. Because patients with peramivir were presumed to have a more severe condition of influenza clinically, this result might suggest some association among the clinical condition and abnormal behaviors.

CONCLUSION:

Findings indicate that oseltamivir alone does not raise risks of abnormal behavior among influenza patients.

2026-04-30·PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES

Antiviral treatment for influenza.

Review

作者: Hui, David S

Seasonal influenza is a widespread acute respiratory infection that causes significant illness and death worldwide. Two major antiviral classes are neuraminidase inhibitors (NAIs) and polymerase inhibitors. NAIs, including oseltamivir, zanamivir, peramivir and laninamivir, block viral release, while polymerase inhibitors such as baloxavir disrupt viral RNA replication. Early administration within 48 h of symptom onset reduces illness duration, severity and complications, particularly in high-risk groups. Oseltamivir is the most widely studied NAI, demonstrating reduced viral shedding, faster symptom resolution and lower complication rates, though gastrointestinal side effects are common. Higher doses generally do not improve outcomes compared to standard dosing. Zanamivir is more effective against influenza B and is inhibitory for most influenza A viruses resistant to oseltamivir, but the inhaled formulation is less suitable for patients with severe illness or airway disease. Intravenous (IV) zanamivir is approved for hospitalized influenza patients in some countries. Peramivir offers IV treatment options, while laninamivir is mainly used in Japan. Baloxavir shows superior viral load reduction and comparable symptom relief to oseltamivir in outpatients, though resistance variants can emerge. Favipiravir and newer polymerase inhibitors are under investigation. Combination therapies may enhance recovery, with limited evidence. Overall, timely antiviral use is critical to reducing influenza's burden. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.

项与辛酸拉尼米韦相关的新闻（医药）

2026-10-12

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肝脏病学 84卷1-4期

Hepatology[Jour] AND 84[volume] AND 1[issue] 肝脏病学 84卷1期 https://journals.lww.com/hep/pages/currenttoc.aspx Hepatology Highlights（肝病学亮点） 1 Bile acids as the silent harbinger: Early signals of portal hypertension after “successful”Kasai 胆汁酸——沉默的预兆：Kasai术"成功"后的门脉高压早期信号 Sidhu, Guneet Hepatology. 84(1):1-2, July 2026. 2 What’s in a name? Reframing pediatric fatty liver disease in the Era of MASLD 名称之争：代谢相关脂肪性肝病（MASLD）时代儿童脂肪肝疾病的重新定义 Khalid, Mian B.; Ilyas, Sumera I. Hepatology. 84(1):3-4, July 2026. 3 One size does not fit all: Global variability in noninvasive testing for MASLD 一刀切不可取：MASLD无创检测的全球差异性 Erickson, Hanna Hepatology. 84(1):5-6, July 2026. 4 Good vibrations: Using VCTE to predict hepatic decompensation in MASLD 良好的振动：利用振动控制瞬时弹性成像（VCTE）预测MASLD患者的肝脏失代偿 Patel, Krishan S.; Arab, Juan Pablo Hepatology. 84(1):7-8, July 2026. Editorials（社论） 5 FIB-4 turns 20: A lesson of serendipity FIB-4二十周年：一次 serendipity（意外发现）的启示 Sterling, Richard K. Hepatology. 84(1):9-11, July 2026. 6 Cirrhotic portal vein thrombosis as a vascular rather than a thrombotic disorder 肝硬化门静脉血栓——一种血管性而非血栓性疾病 Huang, Xiaoquan; Lisman, Ton Hepatology. 84(1):12-14, July 2026. 7 From sex to size: Rethinking fairness in liver transplantation 从性别到体型：重新思考肝移植中的公平性 Rosenthal, Benjamin E.; Serper, Marina Hepatology. 84(1):15-16, July 2026. 8 Addressing the utility of a novel score for “at-risk” MASH in those with significant obesity 新型评分在显著肥胖人群中"高风险"代谢相关脂肪性肝炎（MASH）中的实用性探讨 Dillon, John F.; Leith, Damien; Brennan, Paul Hepatology. 84(1):17-19, July 2026. Original Articles（论著） Liver Cancer（肝脏肿瘤） 9 Tumor site influences efficacy of MEKi and immunotherapy combinations in a preclinical model of cholangiocarcinoma 肿瘤部位影响MEKi联合免疫治疗在胆管癌临床前模型中的疗效 Hammons, Jacklyn N.; Warren, Emilie K.; Wittling, Megen C.; More Hepatology. 84(1):20-36, July 2026. 10 RIPPLY1 suppresses cancer cell stemness via targeting TBX19 in CTNNB1-mutated hepatocellular carcinoma RIPPLY1通过靶向TBX19抑制CTNNB1突变型肝细胞癌的肿瘤干细胞特性 Zhangyuan, Guangyan; Yu, Weiwei; Tian, Wenfang; More Hepatology. 84(1):37-56, July 2026. 11 Anti-angiogenic therapy combined with immune checkpoint blockade mediates CCR7+CD8+ T-cell entry into HCC through high endothelial venules 抗血管生成治疗联合免疫检查点阻断通过高内皮微静脉促进CCR7+CD8+ T细胞进入HCC Tang, Lu; Hou, Yingwen; Di, Tian; More Hepatology. 84(1):57-73, July 2026. Liver Pathobiology（肝脏病理生物学） 12 Hepatocyte-derived extracellular vesicles promote endothelial dedifferentiation in chronic liver disease through the miR-153-3p-pyroptosis axis 肝细胞来源的细胞外囊泡通过miR-153-3p-焦亡轴促进慢性肝病中的内皮去分化 Abad-Jordà, Laia; Andrés-Rozas, María; Martínez-Alcocer, Ana; More Hepatology. 84(1):74-90, July 2026. Liver Failure/Cirrhosis/Portal Hypertension（肝衰竭/肝硬化/门脉高压） 13 Endothelial-to-mesenchymal transition: A targetable mechanism that contributes to portal vein thrombosis in cirrhosis 内皮-间充质转化：肝硬化门静脉血栓中可靶向的关键机制 Anton, Aina; Shalaby, Sarah; Botero, María Luisa; More Hepatology. 84(1):91-105, July 2026. 14 Sex and body size disparities under MELD 3.0: Evaluation of persisting gaps in liver transplant access MELD 3.0下的性别与体型差异：肝移植可及性中持续存在的差距评估 Tanaka, Tomohiro; Shane, Dan M.; Lai, Jennifer C. Hepatology. 84(1):106-116, July 2026. Pediatrics（儿科学） 15 Serum bile acid levels predict the development of portal hypertension and high-risk esophageal varices following successful Kasai in biliary atresia 血清胆汁酸水平可预测胆道闭锁Kasai术后成功患者门脉高压及高风险食管静脉曲张的发生 Grimaud, Emilie; Gardin, Antoine; Ackermann, Oanez; More Hepatology. 84(1):117-128, July 2026. 16 Reclassifying pediatric NAFLD using the steatotic liver disease framework: A multicenter retrospective study from the NASH CRN 利用脂肪性肝病框架重新分类儿童非酒精性脂肪性肝病（NAFLD）：来自NASH CRN的多中心回顾性研究 Lam, Tin Bo Nicholas; Yates, Katherine P.; Noon, Sheila L.; More Hepatology. 84(1):129-142, July 2026. Steatohepatitis（脂肪性肝炎） 17 KLF9 drives intermittent hypoxia-induced MASLD by suppressing the NR4A1–p38 MAPK hepatic metabolic axis KLF9通过抑制NR4A1–p38 MAPK肝脏代谢轴驱动间歇性缺氧诱导的MASLD Hua, Hongting; Wang, Dong; He, Lanqiaofeng; More Hepatology. 84(1):143-160, July 2026. 18 Global performance of non-invasive tests in MASLD: Insights from the G-MASLD study MASLD无创检测的全球表现：来自G-MASLD研究的洞察 Younossi, Zobair M.; de Avila, Leyla; Petta, Salvatore; More Hepatology. 84(1):161-174, July 2026. 19 Head-to-head comparison between vibration-controlled transient elastography and histology in predicting liver-related events due to metabolic dysfunction-associated steatotic liver disease 振动控制瞬时弹性成像与组织学在预测代谢功能障碍相关脂肪性肝病肝脏相关事件中的头对头比较 Zhang, Yangyue; Lee, Hye Won; Lin, Huapeng; More Hepatology. 84(1):175-190, July 2026. 20 Development and validation of a noninvasive score for at-risk metabolic dysfunction–associated steatohepatitis in individuals with obesity undergoing bariatric surgery 针对肥胖减重手术人群中"高风险"代谢功能障碍相关脂肪性肝炎的无创评分的开发与验证 Huang, Xin; Zhu, Tao; Li, Shumin; More Hepatology. 84(1):191-203, July 2026. Original Articles（论著） Steatohepatitis（脂肪性肝病） 21 Predictors of fibrosis, clinical events, and mortality in MASLD: Data from the Global-MASLD study MASLD中纤维化、临床事件及死亡率的预测因素：来自Global-MASLD研究的数据 Younossi, Zobair M.; de Avila, Leyla; Petta, Salvatore; More Hepatology. 84(1):204-215, July 2026. Viral Hepatitis（病毒性肝炎） 22 HBV induces liver fibrosis through the generation of reactive oxygen species in a pyruvate-dependent manner 乙肝病毒（HBV）以丙酮酸依赖方式通过活性氧生成诱导肝纤维化 Duan, Xiaoqiong; Li, Shasha; Li, Qingyuan; More Hepatology. 84(1):216-232, July 2026. 23 IL1β signaling mediates the interaction between hepatitis B and C viruses IL1β信号介导乙型与丙型肝炎病毒之间的相互作用 Zhang, Fan; Zhao, Yuanyuan; Bian, Lu; More Hepatology. 84(1):233-250, July 2026. Reviews（综述） 24 Reprogramming macrophages to treat liver diseases 巨噬细胞重编码治疗肝脏疾病 Simón-Codina, Blanca; Cacho-Pujol, Júlia; Moles, Anna; More Hepatology. 84(1):251-272, July 2026. 25 Mechanisms coupling lipid droplets to MASLD pathophysiology 脂滴与MASLD病理生理偶联的机制 Reid, Mari V.; Fredickson, Gavin; Mashek, Douglas G. Hepatology. 84(1):273-291, July 2026. 26 Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic 新一代抗病毒药物与肥胖流行时代的肝癌预防 Suzuki, Hiroyuki; Fujiwara, Naoto; Singal, Amit G.; More Hepatology. 84(1):292-320, July 2026. Special Article（专题论著） 27 Non-invasive tests: Establishing efficacy for metabolic dysfunction–associated steatohepatitis beyond the biopsy—Current perspectives from the Division of Hepatology and Nutrition, US Food and Drug Administration 无创检测：在超越活检的层面确立代谢功能障碍相关脂肪性肝炎的有效性——来自美国食品药品监督管理局肝病与营养部的当前观点 Anania, Frank A.; Hager, Rebecca; Higgins, Karen; More Hepatology. 84(1):321-327, July 2026. Correspondence（读者来信） 28 Letter to the Editor: Re-evaluating the clinical relevance of the RIPPLY1-TBX19 axis in CTNNB1-mutant hepatocellular carcinoma 致编辑信：重新评估RIPPLY1-TBX19轴在CTNNB1突变型肝细胞癌中的临床相关性 Zhang, Xiang; Gong, Hui; Gu, Kaikai; More Hepatology. 84(1):E1-E2, July 2026. 29 Letter to the Editor: Nuances in POCUS-guided hemodynamic assessment in cirrhosis 致编辑信：POCUS引导下肝硬化血流动力学评估中的细微之处 Koratala, Abhilash; Argaiz, Eduardo R. Hepatology. 84(1):E3-E4, July 2026. 30 Reply: Nuances in POCUS-guided hemodynamic assessment in cirrhosis 回复：POCUS引导下肝硬化血流动力学评估中的细微之处 Premkumar, Madhumita; Kajal, Kamal Hepatology. 84(1):E5-E6, July 2026. 31 Letter to the Editor: The PNPLA3 paradox—Does genotype modify the clinical utility of the MASLD framework in children? 致编辑信：PNPLA3悖论——基因型是否改变MASLD框架在儿童中的临床实用性？ Liu, Boyan; Li, Heran Hepatology. 84(1):E7-E8, July 2026. 32 Reply: The PNPLA3 paradox—Does genotype modify the clinical utility of the MASLD framework in children? 回复：PNPLA3悖论——基因型是否改变MASLD框架在儿童中的临床实用性？ Lam, Tin Bo Nicholas; Goyal, Nidhi P.; Newton, Kimberly P.; More Hepatology. 84(1):E9-E10, July 2026. 33 Letter to the Editor: The profile of HBsAg levels after nucleos(t)ide analogues treatment is crucial for achieving a functional cure 致编辑信：核苷（酸）类似物治疗后HBsAg水平的变化特征对实现功能性治愈至关重要 Tang, Qiao; Hu, Peng Hepatology. 84(1):E11-E12, July 2026. 34 Letter to the Editor: Comments on the Study—Body size disparities limit women’s access to liver transplantation under the MELD 3.0 scoring system 致编辑信：对"体型差异限制女性在MELD 3.0评分体系下获得肝移植机会"研究的评论 He, Jiahang; Xie, Qing; Cao, Zhujun Hepatology. 84(1):E13, July 2026. 35 Letter to the Editor: Clarifying validation and statistical aspects of AI-based risk prediction in liver disease 致编辑信：澄清AI基于风险预测在肝病中的验证与统计学问题 Liu, Jing; Zhang, Guo-Ming Hepatology. 84(1):E14-E15, July 2026. 36 Reply: Clarifying validation and statistical aspects of AI-based risk prediction in liver disease 回复：澄清AI基于风险预测在肝病中的验证与统计学问题 Zhang, Peng; Su, Grace L. Hepatology. 84(1):E16-E17, July 2026. 37 Letter to the Editor: Clarifying endothelial specificity and hemodynamic coupling of the miR-153-3p–pyroptosis axis 致编辑信：澄清miR-153-3p–焦亡轴的内皮特异性与血流动力学偶联 Weng, Dandan Hepatology. 84(1):E18-E19, July 2026. 38 Letter to the Editor: Placebo drift, dose heterogeneity, and the winner’s curse—Re-evaluating the hierarchy of MASH therapeutics 致编辑信：安慰剂漂移、剂量异质性与赢者诅咒——重新评估MASH治疗药物的层级 Philips, Cyriac Abby; Oommen, Tharun Tom; Ahamed, Rizwan Hepatology. 84(1):E20-E21, July 2026. 39 Reply: Placebo drift, dose heterogeneity, and the winner’s curse—Re-evaluating the hierarchy of MASH therapeutics 回复：安慰剂漂移、剂量异质性与赢者诅咒——重新评估MASH治疗药物的层级 Souza, Matheus; Huang, Daniel Q.; Loomba, Rohit Hepatology. 84(1):E22-E23, July 2026. 40 Letter to the Editor: Interpreting the clinical decision value of glycomic-based models for early HCC detection in CHB 致编辑信：解读糖组学模型在CHB早期HCC检测中的临床决策价值 Jiang, Qing-Bao; Zhang, Guo-Ming Hepatology. 84(1):E24-E25, July 2026. 41 Letter to the Editor: From weight to waist—Refining fibrosis prediction in the Global MASLD cohort 致编辑信：从体重到腰围——优化Global MASLD队列中的纤维化预测 Zeng, Hong; Huang, Xi Hepatology. 84(1):E26-E27, July 2026. 42 Reply: From weight to waist—Refining fibrosis prediction in the Global MASLD cohort 回复：从体重到腰围——优化Global MASLD队列中的纤维化预测 Stepanova, Maria; Younossi, Zobair M. Hepatology. 84(1):E28-E29, July 2026. Hepatology[Jour] AND 84[volume] AND 2[issue] 肝脏病学 84卷2期 https://journals.lww.com/hep/pages/currenttoc.aspx Hepatology Highlights（肝病学亮点） 1 PSC’s itch is worth scratching: Pruritus can be more than a symptom 原发性硬化性胆管炎瘙痒值得重视：瘙痒并非单纯伴随症状 Yigit Yazarkan Hepatology. August 2026: 84(2):329-330 2 The weight of progress: Why dynamic weight trajectories matter in MASLD 体重变化的临床意义：代谢相关脂肪性肝病中动态体重轨迹的价值 Guneet Sidhu Hepatology. August 2026: 84(2):331-332 3 The liver joins the CKM conversation: Fibrosis risk across the cardiometabolic spectrum 肝脏纳入心脏代谢疾病评估：横跨心脏代谢疾病谱的肝纤维化风险 Omar Albhaisi, Juan Pablo Arab Hepatology. August 2026: 84(2):333-334 4 Pizza versus Pi*ZZ: The metabolic amplifiers in alpha-1 antitrypsin deficiency 饮食与基因交互：α1-抗胰蛋白酶缺乏症的代谢放大因素 John Grady, Juan Pablo Arab Hepatology. August 2026: 84(2):335-336 Editorials（社论） 5 Stains in primary biliary cholangitis: Untangling promise from bias 原发性胆汁性胆管炎相关染色标志物：区分临床价值与研究偏倚 Therese Bittermann, Charles E. Leonard Hepatology. August 2026: 84(2):337-339 6 Multiomics and machine learning in cholangiocarcinoma: A paradigm shift toward molecular subtyping and precision therapy 多组学与机器学习在胆管癌中的应用：迈向分子分型与精准治疗的范式革新 Meng Xu, Ju-Seog Lee Hepatology. August 2026: 84(2):340-342 7 A targeted liver cancer therapy independent of immune checkpoint block 不依赖免疫检查点抑制剂的肝癌靶向治疗方案 Bangyan L. Stiles Hepatology. August 2026: 84(2):343-345 8 Alcohol use dominates determining liver-related events in steatotic liver disease: Rethinking the role of metabolic dysfunction 饮酒是脂肪性肝病肝脏不良事件的核心诱因：重新审视代谢功能障碍的作用 Luis Antonio Díaz, Winston Dunn, Ashwani K. Singal Hepatology. August 2026: 84(2):346-348 9 Shedding new light on the chicken-and-egg dilemma of hepatitis delta virus (HDV) replication initiation 厘清丁型肝炎病毒复制起始的因果先后难题 Julie Lucifora, Francesco Negro Hepatology. August 2026: 84(2):349-352 Original Articles: Immune-Mediated Diseases, DILI, and Biliary Tract Disease（论著：免疫介导性肝病、药物性肝损伤与胆道疾病） 10 Pruritus is common in primary sclerosing cholangitis, persists over time, and its intensity is associated with disease severity: a multicentre, prospective observational study 原发性硬化性胆管炎瘙痒高发且持续存在，瘙痒程度与疾病严重度相关：一项多中心前瞻性观察研究 Nasir Hussain, Rodrigo V. Motta, Usha Gungabissoon, Linda Casillas, Sumanta Mukherjee, Andrea Ribeiro, Megan M. Mclaughlin, Kaitlin Hagan, Khushpreet Bhandal, Penelope Rogers, Martine Walmsley, James Ferguson, Andreas E. Kremer, Emma L. Culver, Palak J. Trivedi Hepatology. August 2026: 84(2):353-366 11 Association between statin use and hepatic decompensation in patients with primary biliary cholangitis: A target trial emulation study 他汀类药物使用与原发性胆汁性胆管炎患者肝失代偿的关联：模拟目标临床试验研究 Jonggi Choi, Junqing Xu, Vy H. Nguyen, Eric Przybyszewski, Daniel S. Pratt, Jiunn Song, Allison Carroll, Megan Michta, Erik Almazan, Tracey G. Simon, Raymond T. Chung Hepatology. August 2026: 84(2):367-377 Original Articles: Liver Cancer（论著：肝脏肿瘤） 12 NEK7-induced phosphorylation of EGFR on serine 1070 drives the acquired lenvatinib resistance in hepatocellular carcinoma NEK7介导EGFR第1070位丝氨酸磷酸化诱发肝细胞癌的仑伐替尼获得性耐药 Qibo Huang, Weijian Wang, Qianyun Ge, Dafeng Xu, Renshun Dong, Ruizhi Chang, Xing Wu, Jie Mo, Chen Su, Deng Ning, Qiumeng Liu, Huifang Liang, Guihua Wang, Jin Chen, Xifeng Fu, Xiaoping Chen, Junnan Liang, Bixiang Zhang Hepatology. August 2026: 84(2):378-395 13 Multiomics combined with machine learning defines unique molecular subtypes of cholangiocarcinoma and identifies TNK1 as a therapeutic target 多组学联合机器学习鉴定胆管癌独特分子亚型并筛选TNK1为治疗靶点 Dong-Gi Mun, Erik Jessen, Jennifer L. Tomlinson, Danielle Carlson, Rohit Budhraja, Roberto Alva-Ruiz, Amro Abdelrahman, Ryan Watkins, Lindsey Gregory, Chantal McCabe, Chen Wang, Rondell P. Graham, Kathryn Woods, Martin Golkowski, Marshall Baker, Gregory J. Gores, Sumera I. Ilyas, Caitlin Conboy, Ellen L. Larson, Jack W. Sample, Enis H. Ozmert, Richard K. Kandasamy, Mitesh J. Borad, Lewis Roberts, Joshua Andersen, Akhilesh Pandey, Rory L. Smoot Hepatology. August 2026: 84(2):396-410 14 Distinct gut microbiota but common metabolomic signatures between viral and MASLD HCC contribute to outcomes of combination immunotherapy 病毒性与代谢相关脂肪性肝病相关肝癌肠道菌群存在差异，但代谢组特征趋同，共同影响联合免疫治疗疗效 Pei-Chang Lee, Chi-Jung Wu, Ya-Wen Hung, Chieh-Ju Lee, Hsien-Chen Mon, Chen-Ta Chi, I-Cheng Lee, Yu-Lun Kuo, Shih-Hsuan Chou, Jiing-Chyuan Luo, Ming-Chih Hou, Yi-Hsiang Huang Hepatology. August 2026: 84(2):411-423 15 Efficacious suppression of primary and metastasized liver tumors by polyIC-loaded lipid nanoparticles 载聚肌胞苷酸脂质纳米颗粒可有效抑制肝脏原发及转移性肿瘤 Yingluo Liu, Xinyi Wang, Nishta Krishnan, Timothy Hsiao, Yichun Ji, Kota Kaneko, Marcos G. Teneche, Peter D. Adams, Elina Zuniga, Susan M. Kaech, Liangfang Zhang, Gen-Sheng Feng Hepatology. August 2026: 84(2):424-439 16 Genomic and transcriptomic profiling of hepatocellular carcinoma in patients with Fontan-associated liver disease 丰坦手术相关性肝病合并肝细胞癌的基因组与转录组图谱分析 Taiji Yamazoe, Eiji Kakazu, Michitaka Matsuda, Masaaki Mino, Taizo Mori, Sachiyo Yoshio, Yuriko Tsutsui, Takashi Motomura, Shinji Itoh, Koichiro Haruki, Kenei Furukawa, Shinichiro Yamada, Takeshi Takamoto, Takehiro Noda, Hidetoshi Eguchi, Kiyoshi Hasegawa, Yuji Morine, Toru Ikegami, Tomoharu Yoshizumi, Tatsuya Kanto Hepatology. August 2026: 84(2):440-452 17 Deep learning-assisted tumor radiomic dynamics on MRI predict pathological complete response in HCC undergoing immune-based therapy followed by hepatectomy 深度学习辅助MRI肿瘤影像组学动态特征预测免疫治疗联合肝切除肝细胞癌患者的病理完全缓解 Shi-Qi Zhou, Lu-Na Wang, Li-Fang Wu, Li-Yu Sun, Yu-Chen Yang, Zi-Yue Yang, Zi-Yi Wang, Tian He, Fei Li, Ling-Li Chen, Hui Li, Xiao-Dong Zhu, Ying-Hao Shen, Cheng Huang, Yuan Ji, Qiang Gao, Jian Zhou, Jia Fan, Yong-Jun Chen, Tian-Qiang Song, Bin Xu, Hui-Chuan Sun Hepatology. August 2026: 84(2):453-468 Original Articles: Liver Pathobiology（论著：肝脏病理生物学） 18 Epigenetic repression of hepatocyte FoxO1 disrupts local immune homeostasis and promotes liver inflammation 肝细胞FoxO1表观遗传抑制破坏肝脏局部免疫稳态并诱发肝炎症 Zhigang Lei, Yu Wu, Weijie Xue, Dongmei Zhu, Junyao Shen, Chenxu Mao, Ziling Wang, Chuanhong Huang, Yuxin Zhang, Jifeng Zhu, Lei Xu, Yalin Li, Xiujun Zhang, Shouguo Liu, Xiaojun Chen, Chunyan Ye, Sha Zhou, Chuan Su Hepatology. August 2026: 84(2):469-486 19 CXCR6 defines a distinct resident state in γδ T cells for protecting from liver cirrhosis CXCR6标记具有独特定居表型的γδT细胞，可抵御肝硬化进展 Jiahao Ji, Zhitao Chen, Wenjing He, Yanxu Chen, Dongmei Ye, Yingqian Zhong, Xiaomin Shi, Xiaojun Ouyang, Zhimin Zeng, Qianyu Ye, Xiaoshun He, Zhinan Yin, Jianlei Hao, Yifang Gao Hepatology. August 2026: 84(2):487-502 Original Articles: Steatohepatitis（论著：脂肪性肝炎） 20 Differential associations of cardiometabolic risk factors with liver-related events by alcohol consumption category: Results from a large population-based study 不同饮酒分层下心代谢危险因素与肝脏不良事件的差异性关联：一项大样本人群研究 Hongliang Xue, Liqing Wang, Yuankai Wu, Yingxin Liao, Shijia Wang, Ailan Chen, Sun On Chan, Wenhua Ling, Xu Chen, Chao Yu Hepatology. August 2026: 84(2):503-513 21 Association between longitudinal weight change and clinical outcome in individuals with MASLD 代谢相关脂肪性肝病患者纵向体重变化与临床预后的相关性 Yu Shi, Ruoqi Zhou, Seung Up Kim, Terry Cheuk-Fung Yip, Emmanuel Tsochatzis, Salvatore Petta, Atsushi Nakajima, Hannes Hagström, Elisabetta Bugianesi, Wah-Kheong Chan, Jérôme Boursier, Boon-Bee George Goh, Arun J. Sanyal, Manuel Romero-Gomez, José Luis Calleja, Victor de Lédinghen, Philip Noel Newsome, Jian-Gao Fan, Michelle Lai, Laurent Castéra, Céline Fournier-Poizat, Hye Won Lee, Grace Lai-Hung Wong, Grazia Pennisi, Masato Yoneda, Ying Shang, Angelo Armandi, Marc de Saint-Loup, Clemence M. Canivet, Kevin Kim-Jun Teh, Amon Asgharpour, Rocio Gallego-Durán, Elba Llop, Carmen Lara-Romero, Mandy Sau-Wai Chan, Mirko Zoncape, Huapeng Lin, Wen-Yue Liu, Giovanni Targher, Christopher D. Byrne, Vincent Wai-Sun Wong, Ming-Hua Zheng, Hepatology. August 2026: 84(2):514-528 22 Cardiovascular–kidney–metabolic syndrome and the risk of liver fibrosis progression and liver-related events in MASLD 心肾代谢综合征与代谢相关脂肪性肝病肝纤维化进展及肝脏不良事件风险的关联 Xiao-Dong Zhou, Qin-Fen Chen, Qiong-Yue Fan, Seung Up Kim, Terry Cheuk-Fung Yip, Salvatore Petta, Atsushi Nakajima, Emmanuel Tsochatzis, Jérôme Boursier, Elisabetta Bugianesi, Hannes Hagström, Wah-Kheong Chan, Manuel Romero-Gomez, José Luis Calleja, Victor de Lédinghen, Laurent Castéra, Arun J. Sanyal, George Boon-Bee Goh, Philip Noel Newsome, Jian-Gao Fan, Michelle Lai, Céline Fournier-Poizat, Hye Won Lee, Grace Lai-Hung Wong, Angelo Armandi, Ying Shang, Grazia Pennisi, Elba Llop, Masato Yoneda, Marc de Saint-Loup, Clemence M. Canivet, Paloma Carrillo-Fernandez, Carmen Lara-Romero, Rocio Gallego-Durán, Amon Asgharpour, Kevin Kim-Jun Teh, Mandy Sau-Wai Chan, Huapeng Lin, Wen-Yue Liu, Giovanni Targher, Christopher D. Byrne, Vincent Wai-Sun Wong, Ming-Hua Zheng, Hepatology. August 2026: 84(2):529-541 23 Amplification of genetic and metabolic factors in alpha-1 antitrypsin deficiency α1-抗胰蛋白酶缺乏症中遗传与代谢危险因素的协同放大效应 Christina Schrader, Malin Fromme, Paul Ellis, Audrey Payancé, Mattias Mandorfer, Jan Stolk, Bart van Hoek, Katrine H. Thorhauge, Monica Pons, Marc Miravitlles, Guido Stirnimann, Sona Frankova, Jan Sperl, Andreas E. Kremer, Katharina Remih, Emily K. Weber, Lorenz Balcar, Annelot D. Sark, Benedikt Schaefer, Joanna Chorostowska-Wynimko, Elmar Aigner, Sophie Gensluckner, Heike Bantel, Jef Verbeek, Zoe Mariño, Rohit Loomba, Heinz Zoller, Michael Trauner, Joan Genesca, Virginia Clark, Aleksander Krag, Noel G. McElvaney, William J. Griffiths, Alice M. Turner, Pavel Strnad Hepatology. August 2026: 84(2):542-558 Original Articles: Viral Hepatitis（论著：病毒性肝炎） 24 CDK8 and CDK19 Mediator kinases are required for hepatitis delta virus replication 中介激酶CDK8与CDK19是丁型肝炎病毒复制的必需分子 Angga Prawira, Mattis Hilleke, Mengqian Chen, Igor B. Roninson, Ralf Bartenschlager, Stephan Urban, Yi Ni Hepatology. August 2026: 84(2):559-572 Reviews（综述） 25 Unmet needs in diagnosis and management of portopulmonary hypertension: How far have we reached? 门脉性肺动脉高压诊疗尚未满足的临床需求：当前研究进展综述 Michael J. Krowka, Hilary M. DuBrock, Sarah Raevens, Michael B. Fallon Hepatology. August 2026: 84(2):573-581 26 Getting to HBV cure—Will new biomarkers help? 迈向乙型肝炎治愈：新型生物标志物能否提供助力？ Jordan J. Feld, Adam J. Gehring, Fabien Zoulim Hepatology. August 2026: 84(2):582-600 Special Articles（专题论著） 27 A multisociety consensus statement on a new common definition and diagnostic criteria for PSVD or NCPF 多学会关于门窦血管病变/非肝硬化性门脉高压新统一定义与诊断标准的共识声明 Virginia Hernandez-Gea, Valerie Paradis, Maha Guindi, Venancio A.F. Alves, Amal Aqul, Eira Cerda, Sarwa Darwish Murad, Prasenjit Das, Angelo Di Giorgio, Luiz A.R. de Freitas, Tassos Grammatikopoulos, Kenichi Harada, Nelia Hernandez, Samar H. Ibrahim, Sanjay Kakar, Saul Karpen, David E. Kleiner, Necati Ormeci, Xiaolong Qi, Puja Sakhuja, Maria Isabel Schinoni, Romil Saxena, Alexandre Sayadi, Akash Shukla, Dina G. Tiniakos, Elizabeth Verna, Kerry Wong, Laure Elkrief, Christine Sempoux, Theo Heller, Pierre-Emmanuel Rautou Hepatology. August 2026: 84(2):601-616 28 Consistent efficacy of efruxifermin across PNPLA3 genotypes in phase 2b trials in MASH Ⅱb期临床试验证实依鲁西佛明在不同PNPLA3基因型代谢相关脂肪性肝炎人群中疗效稳定 Naga Chalasani, Erik J. Tillman, Sonja K. Billes, Timothy Rolph, Mazen Noureddin Hepatology. August 2026: 84(2):617-620 Correspondence（通信） 29 Letter to the Editor: Is fecal acetate a viable pan-etiological predictor of outcomes in HCC immunotherapy? 致编者信：粪便乙酸盐是否可作为全病因肝癌免疫治疗疗效预测标志物？ Zhou Zhao, Jian Sun, Qiuhong You, Zhixian Lan, Yinghong Zhu Hepatology. August 2026: 84(2):E30-E31 30 Reply: Is fecal acetate a viable pan-etiological predictor of outcomes in HCC immunotherapy? 回复：粪便乙酸盐是否可作为全病因肝癌免疫治疗疗效预测标志物？ Pei-Chang Lee, Yi-Hsiang Huang Hepatology. August 2026: 84(2):E32-E33 31 Letter to the Editor: Survival analysis pitfalls in MASLD: Proportional hazards, immortal time, and follow-up discrepancies 致编者信：代谢相关脂肪性肝病生存分析常见误区：比例风险、永生时间与随访偏差 Jian Huang Hepatology. August 2026: 84(2):E34-E35 32 Reply: Survival analysis pitfalls in MASLD—Proportional hazards, immortal time, and follow-up discrepancies 回复：代谢相关脂肪性肝病生存分析常见误区——比例风险、永生时间与随访偏差 Yu Shi, Ruoqi Zhou, Yuanjie Pang, Vincent Wai-Sun Wong, Ming-Hua Zheng Hepatology. August 2026: 84(2):E36-E37 33 Letter to the Editor: Beyond Semantics—Acknowledging diagnostic differences between NAFLD and MASLD 致编者信：不止命名差异——正视NAFLD与MASLD的诊断区分要点 Giovani Schulte Farina, Jonathan Soldera Hepatology. August 2026: 84(2):E38-E39 34 Reply: Beyond semantics—Acknowledging diagnostic differences between NAFLD and MASLD 回复：不止命名差异——正视NAFLD与MASLD的诊断区分要点 Madalina-Gabriela Indre, Federico Ravaioli Hepatology. August 2026: 84(2):E40-E41 35 Letter to the editor: Deep learning and digital pathology for HCC prediction in steatotic liver disease 致编者信：深度学习与数字病理用于脂肪性肝病肝癌发生风险预测 Luisa Giudice, Stefano Granieri, Stefania Galassi, Sante De Santis, Emmanuel Pio Pastore Hepatology. August 2026: 84(2):E42-E43 36 Reply: Deep learning and digital pathology power prediction of HCC development in steatotic liver disease 回复：深度学习联合数字病理可精准预测脂肪性肝病患者肝癌发病风险 Takuma Nakatsuka, Ryosuke Tateishi, Masaya Sato, Kazuhiko Koike Hepatology. August 2026: 84(2):E44-E45 Errata（勘误） 37 Erratum: Reciprocal regulation between forkhead box M1/NF-κB and methionine adenosyltransferase 1A drives liver cancer 勘误：FOXM1/NF-κB与甲硫氨酸腺苷转移酶1A相互调控促进肝癌发生 Yuan Li, Liqing Lu, Jian Tu, Jing Zhang, Ting Xiong, Wei Fan, Jiaohong Wang, Meng Li, Yibu Chen, Justin Steggerda, Hui Peng, Yongheng Chen, Tony WH Li, Zhi-Gang Zhou, José M Mato, Ekihiro Seki, Ting Liu, Heping Yang, Shelly C. Lu Hepatology. August 2026: 84(2):E46-E47 38 Erratum: AlphaB-crystallin complexes with 14-3-3zeta to induce epithelial-mesenchymal transition and resistance to sorafenib in hepatocellular carcinoma 勘误：αB-晶状体蛋白结合14-3-3ζ诱导肝细胞癌上皮间质转化与索拉非尼耐药 Huang Xiao-Yong, Ke Ai-Wu, Shi Guo-Ming, Zhang Xin, Zhang Chi, Shi Ying-Hong, Wang Xiao-Ying, Ding Zhen-Bin, Xiao Yong-Sheng, Yan Jun, Qiu Shuang-Jian, Fan Jia, Zhou Jian Hepatology. August 2026: 84(2):E48-E49 39 Erratum: AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis 勘误：美国肝病研究协会慢加急性肝衰竭与重症肝硬化患者管理临床实践指南 Constantine J. Karvellas, Jasmohan S. Bajaj, Patrick S. Kamath, Lena Napolitano, Jacqueline G. O’Leary, Elsa Solà, Ram Subramanian, Florence Wong, Sumeet K. Asrani Hepatology. August 2026: 84(2):E50-E50 40 Erratum: Noninvasive assessment of liver disease severity in NAFLD and T2D 勘误：非侵入性评估非酒精性脂肪性肝病合并2型糖尿病患者肝病严重程度 Grazia Pennisi, Marco Enea, Vincenzo Falco, Guruprasad P. Aithal, Naaventhan Palaniyappan, Yusuf Yilmaz, Jerome Boursier, Christophe Cassinotto, Victor de Lédinghen, Wah Kheong Chan, Sanjiv Mahadeva, Peter Eddowes, Philip Newsome, Thomas Karlas, Johannes Wiegand, Vincent Wai-Sun Wong, Jörn M. Schattenberg, Christian Labenz, Won Kim, Myoung Seok Lee, Monica Lupsor-Platon, Jeremy F. Cobbold, Jian-Gao Fan, Feng Shen, Katharina Staufer, Michael Trauner, Rudolf Stauber, Atsushi Nakajima, Masato Yoneda, Elisabetta Bugianesi, Ramy Younes, Silvia Gaia, Ming-Hua Zheng, Calogero Cammà, Quentin M. Anstee, Ferenc E. Mózes, Michael Pavlides, Salvatore Petta Hepatology. August 2026: 84(2):E51-E51 Retraction（撤稿声明） 41 Retraction: HSP72 interacts with PRDX6 to deubiquitinate mitochondrial PINK1, activating mitophagy to treat MASLD 撤稿声明：热休克蛋白72结合过氧化物还原蛋白6去泛素化线粒体PINK1，激活线粒体自噬改善代谢相关脂肪性肝病 Yong Rao, Rui Su, Wen-jie Cao, Yue Chen, Shu-heng Huang, Jun-jie Wu, Darren C. Henstridge, Lin-sheng Huang, Jin Liu, Fei-fei Liu, Zhong-ping Jiang, Cong-jun Xu, Zhi-shu Huang, Ji-ming Ye, Ling Huang Hepatology. August 2026: 84(2):E52-E52 Hepatology[Jour] AND 84[volume] AND 3[issue] 肝脏病学 84卷3期 https://journals.lww.com/hep/pages/currenttoc.aspx Hepatology Highlights（《肝脏病学》重点导读） 1 The road less traveled: Mapping the complex trajectories of PSC‑IBD 少有人走的路：原发性硬化性胆管炎‑炎症性肠病复杂病程轨迹解析 Mian B. Khalid Hepatology. September 2026: 84(3):621‑622 2 One cancer, four personalities: Transcriptomic signatures reveal molecular subtypes of advanced biliary tract cancer 一种肿瘤，四种表型：转录组特征揭示晚期胆道癌分子亚型 Muhammed Dogukan Aksu Hepatology. September 2026: 84(3):623‑624 3 Hepatic footprint of emerging antihyperglycemic therapies 新型降糖治疗的肝脏效应 P. Vineeth Daniel Hepatology. September 2026: 84(3):625‑626 4 No prescription needed: Remote nutrition care linked to fewer liver events 无需处方：远程营养干预可减少肝脏相关不良事件 Leandro Sierra, Juan Pablo Arab Hepatology. September 2026: 84(3):627‑628 Fellows' Corner（青年学者园地） 5 Fellows’ Corner 青年学者园地 Somaya Albhaisi Hepatology. September 2026: 84(3):629‑630 Editorials（社论） 6 Population‑level screening for liver disease: Opportunities and challenges 人群水平肝脏疾病筛查：机遇与挑战 Pedro Ochoa‑Allemant, Marina Serper Hepatology. September 2026: 84(3):631‑633 7 Two decades of hepatitis E in solid organ transplantation: From endemic insight to unresolved therapeutic questions 实体器官移植中戊型肝炎二十年：从流行特征到尚未解决的治疗难题 Patrick Behrendt, Christoph Neumann‑Haefelin Hepatology. September 2026: 84(3):634‑637 8 Interpreting surgical associations in primary sclerosing cholangitis: Caution in clinical messaging 解读原发性硬化性胆管炎的手术相关性：临床解读需审慎 Bregje Mol, Palak J. Trivedi Hepatology. September 2026: 84(3):638‑640 Original Articles: Immune‑Mediated Diseases, DILI, and Biliary Tract Disease（论著：免疫介导性疾病、药物性肝损伤与胆道疾病） 9 Statins halt polycystic liver disease by reprogramming metabolism and normalizing mitochondrial bioenergetics in cystic cholangiocytes 他汀类药物通过重编程囊胆管上皮细胞代谢、恢复线粒体生物能量功能抑制多囊肝进展 Enara Markaide, Laura Izquierdo‑Sanchez, Irene Olaizola, Josu Urretabizkaia‑Garmendia, Mikel Ruiz de Gauna, Xabier Buqué, Irune Lasa‑Elosegi, Ainhoa Lapitz, Thomas Bais, Beatriz Val, Pedro M. Rodrigues, Rui E. Castro, Maria J. Perugorria, Luis Bujanda, Ron Gansevoort, Joost P.H. Drenth, Patricia Aspichueta, Jesus M. Banales Hepatology. September 2026: 84(3):641‑657 10 Understanding hepatopancreatobiliary cancer risks in a population‑based primary sclerosing cholangitis–inflammatory bowel disease cohort 基于人群的原发性硬化性胆管炎‑炎症性肠病队列肝胆胰肿瘤风险研究 Kristel K. Leung, Wenbin Li, Bettina Hansen, Aliya Gulamhusein, Lauren Lapointe‑Shaw, Amanda Ricciuto, Eric I. Benchimol, Jennifer A. Flemming, Gideon M. Hirschfield Hepatology. September 2026: 84(3):658‑671 Original Articles: Liver Cancer（论著：肝脏肿瘤） 11 GPC3‑based circular RNA vaccine suppresses hepatocellular carcinoma progression by activating adaptive immune responses 基于GPC3的环状RNA疫苗通过激活适应性免疫应答抑制肝细胞癌进展 Yifan Jiang, Yu Li, Tong Wu, Linping Cao, Guangming Xu, Jiwei Liu, Chenguang Hua, Chaofeng Ding, Beng Yang, Rongliang Tong, Diyu Chen, Jian Wu Hepatology. September 2026: 84(3):672‑689 12 Laser‑activated nanoparticles rewire tumor microenvironment enhancing PD‑1 blockade and T cell response in cholangiocarcinoma 激光激活纳米颗粒重编程肿瘤微环境增强胆管癌PD‑1阻断疗效与T细胞应答 Mirko Minini, Giulio Avveduto, Sonia Becharef, Marie Meunier‑Thaens, Bouchra Lekbaby, Maria Perez‑Lazon, Alice Machado, Thomas Guilbert, Julie Lesieur, Gilles Renault, Sara Ceccacci, Ida Chiara Guerrera, Christophe Klein, Jérémy Augustin, Rana Bazzi, Stephane Roux, Jonathan Pol, Emmanuel Donnadieu, Florence Gazeau, Laura Fouassier Hepatology. September 2026: 84(3):690‑707 13 FXR splicing by SF3B3 promotes MYC‑driven hepatocarcinogenesis SF3B3介导FXR可变剪接促进MYC驱动的肝细胞癌发生 Xue Wang, Jiahua Luo, Lifeng Han, Tong Xu, Haichuan Wang, Mingzhe Zhang, Gen Li, Xichuan Li, Weihua Zhang, Youcai Zhang Hepatology. September 2026: 84(3):708‑725 14 Biology‑driven stratification of advanced biliary tract cancer treated with nab‑paclitaxel plus gemcitabine–cisplatin: A prospective observational cohort study 白蛋白结合型紫杉醇联合吉西他滨‑顺铂治疗晚期胆道癌的生物学分层：一项前瞻性观察队列研究 Seonjeong Woo, Beodeul Kang, Sung Hwan Lee, Jung Sun Kim, Haeyoun Kang, Seok Jeong Yang, Chansik An, Gwangil Kim, Gae Hoon Jo, Chang‑Il Kwon, Min Je Sung, Suk Pyo Shin, Sanghoon Jung, Sohyun Hwang, Chan Kim, Hong Jae Chon Hepatology. September 2026: 84(3):726‑739 15 Satellite lesions versus intrahepatic metastasis in multifocal intrahepatic cholangiocarcinoma: Prognostic impact and genomic profiling 多灶性肝内胆管癌卫星灶与肝内转移：预后价值及基因组特征分析 Tao Wei, Zhi‑Jie Ma, Shouliang Guo, Matthew Weiss, Irinel Popescu, Hugo P. Marques, Luca Aldrighetti, Shishir K. Maithel, Carlo Pulitano, Todd W. Bauer, Feng Shen, George A. Poultsides, Oliver Soubrane, Guillaume Martel, Bas Groot Koerkamp, Itaru Endo, Tingbo Liang, Yi Lyu, Timothy M. Pawlik, Xu‑Feng Zhang, Hepatology. September 2026: 84(3):740‑755 16 Long‑term outcomes of atezolizumab–bevacizumab in unresectable hepatocellular carcinoma: A real‑world study 阿替利珠单抗联合贝伐珠单抗治疗不可切除肝细胞癌的远期预后：一项真实世界研究 Francesco Tovoli, Massimo Iavarone, Giuseppe Cabibbo, Fabio Marra, Caterina Vivaldi, Andrea Dalbeni, Francesca Romana Ponziani, Andrea Palloni, Francesca Bergamo, Lorenza Rimassa, Lorenzo Lani, Piera Federico, Gianluca Svegliati‑Baroni, Luca Ielasi, Chiara Mazzarelli, Stefania De Lorenzo, Rodolfo Sacco, Mariangela Bruccoleri, Ciro Celsa, Alessio Mastro, Gianluca Masi, Alessandra Auriemma, Leonardo Stella, Pierluigi Toniutto, Rosanna Villani, Sara Lonardi, Tiziana Pressiani, Fabio Piscaglia, Hepatology. September 2026: 84(3):756‑768 Original Articles: Liver Pathobiology（论著：肝脏病理生物学） 17 Hepatic STEAP4 promotes liver regeneration by regulating lysosomal iron homeostasis and membrane integrity in acetaminophen‑induced liver injury 肝脏STEAP4通过调控溶酶体铁稳态及膜完整性促进对乙酰氨基酚肝损伤后的肝再生 Peng Cao, Mengwei Niu, Hualong Zhu, Chen Zhang, Hao Zhu, Hangfei Xu, Wanqing Liu, Hong‑Min Ni, Wen‑Xing Ding Hepatology. September 2026: 84(3):769‑784 18 ECM1 produced by hepatic stellate cells serves as a gatekeeper of liver homeostasis in hepatic fibrosis 肝星状细胞分泌ECM1是肝纤维化中肝脏稳态的关键调控因子 Aiting Yang, Xuzhen Yan, Yiwen Wang, Qi Han, Xiaofei Tong, Shuyan Chen, Xinyu Zhao, Wei Chen, Jidong Jia, Detlef Schuppan, Hong You Hepatology. September 2026: 84(3):785‑804 Original Articles: Liver Failure/Cirrhosis/Portal Hypertension（论著：肝衰竭/肝硬化/门静脉高压） 19 LiverRisk score (LRS) predicts long‑term liver‑related outcomes in a cohort of Veterans without evidence of liver disease LiverRisk评分（LRS）可预测无肝病证据退伍军人队列的长期肝脏相关预后 Ruben Hernaez, Yan Liu, Miquel Serra‑Burriel, Kavish R. Patidar, Adrià Juanola, Isabel Graupera, Elisa Pose, Núria Fabrellas, Avegail G. Flores, Jennifer R. Kramer, Fasiha Kanwal, Pere Gines Hepatology. September 2026: 84(3):805‑816 Original Articles: Steatohepatitis（论著：脂肪性肝炎） 20 Real‑world impact of AUD pharmacotherapy on healthcare utilization, cost, and cost‑effectiveness in the United States 美国酒精使用障碍药物治疗对医疗资源利用、费用及成本效益的现实影响 Chi M. Nguyen, Hanna L. Blaney, Jing Su, Shihui Jiang, Yang Li, Yining Li, Samer Gawrieh, Wanzhu Tu, Suthat Liangpunsakul Hepatology. September 2026: 84(3):817‑832 21 Repurposing Resmetirom suppresses MASH‑associated hepatocellular carcinoma, with mechanistic implications of MDK/LRP1‑mediated metabolic reprogramming and immunosuppression Resmetirom老药新用抑制MASH相关肝细胞癌：MDK/LRP1介导代谢重编程与免疫抑制的机制研究 Vanilla Xin Zhang, Tina Suoangbaji, Yu‑Man Tsui, Karen Man‑Fong Sze, Eva Lee, Lu Tian, Jingyi Lu, Huan Deng, Abdullah Husain, Charry Shuk‑Ching Hui, Joyce Man‑Fong Lee, Daniel Wai‑Hung Ho, Irene Oi‑Lin Ng Hepatology. September 2026: 84(3):833‑850 22 Impact of newer antihyperglycemic agents on hepatic complications: A systematic review and meta‑analysis of data from 5.3 million patients with type 2 diabetes mellitus 新型降糖药物对肝脏并发症的影响：基于530万2型糖尿病患者数据的系统综述与Meta分析 Jiwon Yang, Yeongseok Hwang, Jin‑Sung Ju, Seungbong Han, Jihyun An, Ju Hyun Shim Hepatology. September 2026: 84(3):851‑869 23 Reduced risk of liver‑related events among patients receiving individualized nutrition‑focused remote care in the United States 美国接受个体化营养导向远程照护患者的肝脏相关事件风险降低 Shaminie J. Athinarayanan, Adam J. Wolfberg, Priya V. Shanmugam, Bilal A. Hameed, Maurizio Bonacini Hepatology. September 2026: 84(3):870‑885 Original Articles: Viral Hepatitis（论著：病毒性肝炎） 24 T‑ and B‑cell–targeting DNA/MVA HCV vaccines induce strong and broad cellular and humoral immunity in mice and rhesus macaques 靶向T、B细胞的DNA/MVA丙型肝炎疫苗在小鼠与恒河猴体内诱导强效广谱细胞及体液免疫 Sheikh Abdul Rahman, Sailaja Gangadhara, John Gridley, Uchurappa Mala, Elizabeth J. Elrod, Nathalie Bédard, Julie Bruneau, Naglaa H. Shoukry, Arash Grakoui, Rama Rao Amara Hepatology. September 2026: 84(3):886‑899 25 Two decades of hepatitis E in solid organ transplantation: A retrospective monocentric analysis 实体器官移植中戊型肝炎二十年：单中心回顾性分析 Nassim Kamar, Florence Abravanel, Olivier Marion, Chloé Couat, Laure Esposito, Anne Laure Hebral, Laurence Lavayssière, David Ribes, Pierre Guy, Sébastien Lhomme, Olivier Cointault, Stanislas Faguer, Julie Bellière, Amandine Darres, Joelle Guitard, Chloé Médrano, Arnaud Del Bello, Jacques Izopet Hepatology. September 2026: 84(3):900‑909 Reviews（综述） 26 Portal sinusoidal vascular diseases: Assessment and therapy 门窦血管性疾病：评估与治疗 Maria Mironova, Harish Gopalakrishna, Christopher Koh, David E. Kleiner, Theo Heller Hepatology. September 2026: 84(3):910‑931 27 Assessment of liver injury potential of investigational medicines in drug development 药物研发过程中候选药物肝损伤风险评估 Naga Chalasani, Paul H. Hayashi, Debra Luffer‑Atlas, Arie Regev, Paul B. Watkins Hepatology. September 2026: 84(3):932‑951 28 Advances in imaging—Elastography 影像学进展——弹性成像 Elton Dajti, Adrian T. Huber, Giovanna Ferraioli, Annalisa Berzigotti Hepatology. September 2026: 84(3):952‑975 29 Hepatic stellate cell heterogeneity: Functional aspects and therapeutic implications 肝星状细胞异质性：功能特征与治疗价值 Yana Geng, Robert F. Schwabe Hepatology. September 2026: 84(3):976‑989 Special Article（专题论著） 30 Integrative Hepatology: Enhancing overall health to manage liver disease 整合肝病学：通过改善整体健康管理肝脏疾病 Jennifer C. Lai, Elliot B. Tapper, Puneeta Tandon Hepatology. September 2026: 84(3):990‑998 Position Paper（立场文件） 31 AASLD‑EASL Delphi consensus statement on surrogate endpoints and real‑world evidence in primary biliary cholangitis AASLD‑EASL关于原发性胆汁性胆管炎替代终点与现实证据德尔菲共识声明 American Association for the Study of Liver Diseases,European Association for the Study of the Liver Hepatology. September 2026: 84(3):999‑1024 Correspondence（读者来信） 32 Letter to the Editor: Clarifying the relative contributions of collagen architecture and stiffness to antitumor immunity in GIONF‑Enhanced PD‑1 blockade for cholangiocarcinoma 致编辑的信：阐明胶原结构与硬度在GIONF增强PD‑1阻断治疗胆管癌中对抗肿瘤免疫的相对作用 Dandan Weng, Guancheng Huang, Yingying Liu Hepatology. September 2026: 84(3):E53‑E54 33 Letter to the Editor: Hepatocyte‑derived extracellular vesicles promote endothelial pyroptosis in chronic liver disease: Undefined role of miR‑153‑3p 致编辑的信：肝细胞来源胞外囊泡促进慢性肝病内皮细胞焦亡：miR‑153‑3p作用尚不明确 Xinyi Hu, Qi Zhang, Lulu Wan, Mengyang Liu Hepatology. September 2026: 84(3):E55‑E56 Errata（勘误） 34 Erratum: NK‑cell–elicited gasdermin‑D–dependent hepatocyte pyroptosis induces neutrophil extracellular traps that facilitate HBV‑related acute‑on‑chronic liver failure 勘误：NK细胞诱导GSDMD依赖的肝细胞焦亡促进中性粒细胞胞外网状陷阱形成参与乙肝相关慢加急性肝衰竭 Qiang Zhao, Dong‑Ping Chen, Hua‑Di Chen, Ying‑Zhe Wang, Wei Shi, Yi‑Tong Lu, Yi‑Zheng Ren, Yuankai Wu, Yi‑Hua Pang, Hong Deng, Xiaoshun He, Dong‑Ming Kuang, Zhiyong Guo Hepatology. September 2026: 84(3):E57‑E59 35 Erratum: RNF128 aggravates metabolic dysfunction–associated steatotic liver disease progression via stabilization of SCD1 勘误：RNF128通过稳定SCD1加重代谢功能障碍相关脂肪性肝病进展 Lei Cao, Wei Yang, Chaofan Wang, Changhao Liu, Wenqian Qi, Ruiqing Ren, Jie Zhang, Shuting Yu, Qian Li, Liangyu Cai, Xinyu Zhang, Xiaohong Wang, Wenhai Sui, Meng Zhang, Cheng Zhang Hepatology. September 2026: 84(3):E60‑E60 Hepatology[Jour] AND 84[volume] AND 4[issue] 肝脏病学 84卷4期 https://journals.lww.com/hep/pages/currenttoc.aspx Reviews（综述） 1 Response evaluation to systemic therapy in HCC: Current challenges and future perspectives 肝细胞癌全身治疗的疗效评估：当前挑战与未来展望 Mario Matute-González, Maxime Ronot, Victoria Chernyak, Bruno Sangro, Jordi Rimola Hepatology. October 2026: 84(4):1025-1048 2 Pioneering precision: The evolution of immunotherapy for hepatocellular carcinoma 开创精准时代：肝细胞癌免疫治疗的发展历程 Friedrich Foerster, Lucas Wiesmann, Paula Bark, Peter Robert Galle Hepatology. October 2026: 84(4):1049-1077 3 Beyond second-line therapy: Strategic sequencing of systemic treatments in advanced hepatocellular carcinoma 二线治疗之外：晚期肝细胞癌全身治疗的序贯策略 Marta Fortuny, Landon L. Chan, Leonardo G. da Fonseca, Ghassan K. Abou-Alfa, Stephen L. Chan, María Reig Hepatology. October 2026: 84(4):1078-1095 4 Clinical utilization of testing for cell-free DNA in hepatocellular cancer 游离DNA检测在肝细胞癌中的临床应用 Jasmine J. Wang, Yi-Te Lee, Amy K. Kim, Augusto Villanueva, Amit G. Singal, Ju Dong Yang Hepatology. October 2026: 84(4):1096-1120 5 Incorporating artificial intelligence into imaging for surveillance and diagnosis of liver cancer: Innovations, challenges, and clinical translation 人工智能融入肝癌筛查与诊断影像：创新、挑战与临床转化 Maxime Ronot, Julien Calderaro Hepatology. October 2026: 84(4):1121-1132 6 Anatomic subsets of cholangiocarcinoma: More different than alike 胆管癌解剖亚型：共性有限，差异显著 Yawen Dong, Hannah E. Stumpf, Rory L. Smoot, Patrick P. Starlinger, Mark M. Yarchoan, Gregory J. Gores, Sumera I. Ilyas Hepatology. October 2026: 84(4):1133-1156 7 Evolving precision: Updates in targeted therapy for cholangiocarcinoma 精准治疗持续进展：胆管癌靶向治疗新进展 Giulia Tesini, Halima Ibrahim, Lorenza Rimassa, Chiara Braconi Hepatology. October 2026: 84(4):1157-1180 8 The rise of transplant oncology in primary liver cancer and metastatic disease 移植肿瘤学在原发性肝癌及转移性疾病中的兴起 Charles-Henri Wassmer, Maximiliano Gelli, Tiffany Cho Wong, Zhihao Li, Anudari Zorigtbaatar, Rebecca Marino, Laia Aceituno Sierra, René Adam, Albert Chi Chan, Julie Heimbach, Pål Dag Line, Vincenzo Mazzaferro, Gonzalo Sapisochin, Parissa Tabrizian, Arndt Vogel, Christian Toso Hepatology. October 2026: 84(4):1181-1208 9 Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma 纤维板层癌诊疗临床指南 Allison F. O’Neill, Emily L. Zeme, Ghassan K. Abou-Alfa, Marina Baretti, Alexander J. Bondoc, Alanna Church, Cristina R. Ferrone, Megan Fitzgerald, James I. Geller, Anne E. Gill, William P. Harris, Heung Bae Kim, Sunyoung S. Lee, Kevin X. Liu, Michael V. Ortiz, Arun Rangaswami, Kimberly J. Riehle, Abby R. Rosenberg, Michael S. Torbenson, Mark Yarchoan, John D. Gordan Hepatology. October 2026: 84(4):1209-1228 10 Unraveling the tapestry: Lessons from multi-omics and spatial biology in hepatocellular cancer 破解肿瘤图谱：肝细胞癌多组学与空间生物学研究启示 Dawiyat Massoudi, Ankit Srivastava, Renumathy Dhanasekaran Hepatology. October 2026: 84(4):1229-1245

临床结果

2026-10-05

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EASD2026丨未来肥胖管理的挑战：从唯体重论转向以患者为中心，重构减重治疗新格局

编者按：当地时间9月28日~10月2日，第62届欧洲糖尿病研究协会年会（EASD2026）在意大利米兰盛大召开。会议期间的“未来肥胖管理的挑战”专题异彩纷呈，3位学者分别围绕脑胰岛素抵抗机制、药物疗效与耐受性、治疗应答异质性与减重管理三大维度进行分享，系统剖析了肥胖治疗的现状与演变方向。本文为您整理该专题的精彩观点，并荟萃各位教授对肥胖管理未来方向的临床洞见与学术思考。一、肥胖中的脑胰岛素抵抗：治疗障碍还是靶点？德国乌尔姆大学医院Martin Heni教授阐述了脑胰岛素抵抗在肥胖代谢异质性中的驱动作用。他指出，“肥胖并不等于肥胖”：不同肥胖亚型的并发症风险迥异。其团队利用全身MRI精准量化脂肪分布，在23 548名受试者中筛选单脂肪库蓄积的少见表型，聚焦肝、胰腺、骨骼肌、内脏四个脂肪库。结果显示，各组糖尿病风险均升高，肝脂肪变性者糖尿病风险最高，肌肉脂肪变性也会显著增加糖尿病的发生风险（即使无其他部位脂肪堆积）。各脂肪库对应特异疾病谱，如肝脂肪变性组发生肝病风险最高，且存在明确乳腺癌关联信号；肌肉脂肪变性组心房颤动与膝骨关节炎风险均最高，且该组不少人BMI处于正常范围，提示疾病风险并非仅由体重公斤数决定。图1. 不同脂肪蓄积表型的并发症风险与BMI分布差异脂肪去向的调控关键在大脑。不同脂肪分布组的脑结构存在差异，关联脑区多为胰岛素受体高表达的人胰岛素敏感区，参与全身稳态、摄食奖赏与认知调控[1-2]。研究人员通过正糖钳夹联合鼻内胰岛素选择性激活脑胰岛素信号，发现瘦者肝糖生成受抑、外周葡萄糖摄取增加，存在脑胰岛素抵抗的超重/肥胖者则无上述效应[3-4]。该效应单次微弱，却随每餐反复累积，长期可改变整体代谢。脑胰岛素信号经自主神经下传至肝、脂肪、胰腺等外周器官[5]。横断面研究显示，脑胰岛素抵抗者内脏脂肪更多。在为期2年的生活方式干预中，脑胰岛素敏感者内脏脂肪显著减少，且干预结束后9年体重仍低于基线，而抵抗者获益甚微[6]。此外，胰高血糖素（GCG）也可作用于人脑，提示进食后存在多激素协同信号[7]。 Heni教授总结道，脑胰岛素抵抗参与肥胖代谢异质性并影响治疗应答，既是治疗障碍，也是克服治疗抵抗的潜在新靶点。二、减重药物疗效已至上限？创新多靶点药物研发攻克瓶颈德国慕尼黑亥姆霍兹中心糖尿病与肥胖研究所Timo Müller教授围绕减重药物疗效瓶颈，解析了非GLP-1依赖的多靶点多肽激动剂在实现有效减重的同时提升耐受性的药理学策略。 Müller教授强调，摄食与能量代谢并非由单一肠激素调控，而是多种肠激素协同作用的结果，因此优化减重药物需同时靶向多重机制；替尔泊肽等药物的临床成功，正是对这一思路的有力验证[8]。目前，在不合并2型糖尿病（T2DM）的肥胖患者中，药物治疗的减重疗效呈阶梯式提升：司美格鲁肽平均可减重14.9%（2.4 mg，68周），替尔泊肽达20.9%（15 mg，72周），瑞他鲁肽可达24.2%（12 mg，48周）。但疗效之外，胃肠道反应和心率增快等耐受性问题仍是主要瓶颈。 Müller等人提出了多肽靶向递送核受体药物策略，即：将核激素类药物共价偶联于肠促胰岛素肽，借助肽受体实现靶细胞内精准递送。PPARα/γ共激动剂Tesaglitazar经GLP-1递送后，在3 nmol/kg低剂量时仍可改善糖耐量[9]；经GLP-1:GIP递送PPARα/γ/δ三重激动剂Lanifibranor所构建的GLP-1:GIP:Lani减重幅度约40%，显著优于物理混合给药[10]，同时约80%减重来自脂肪，瘦体重保留良好。该分子维持正常的肠促胰岛素受体信号传导，钳夹试验显示其胰岛素敏感性更优，并可减轻肝脏炎症、通过下调丙酮酸羧化酶抑制肝糖生成以及改善射血分数等。此外，这一“五重”分子不引起贫血、液体潴留或肾损害，也不影响瘦小鼠的体重与血糖。图2. GLP-1:GIP:Lani可显著增强疗效且保留瘦体重良好为优化耐受性，团队进一步在GLP-1受体（GLP-1R）敲除小鼠中验证：常规剂量瑞他鲁肽（一种GLP-1R/GIPR/GCGR三激动剂）无减重作用，提高剂量后则可实现非GLP-1R依赖的减重[11]，表明GLP-1R并非实现强效减重的必需靶点。此外，GCG与GIP协同可使摄食减少78%而不恶化糖耐量；低剂量GCG联合递增剂量GIP可发挥协同减重作用，获得与司美格鲁肽相当甚至更优的减重效果，为非GLP-1R依赖的治疗策略提供了药效学依据。针对“GCG可能诱发心动过速”的顾虑，研究团队证实，瑞他鲁肽所致心率增快主要由GLP-1R介导，GCGR并不主导该效应；结合前述“强效减重可不依赖GLP-1R”的发现，Bluewater生物科学公司开发了每周1次皮下注射的GIPR:GCGR双激动剂BWB3054，旨在为不耐受GLP-1R激动剂的人群提供替代方案；相较瑞他鲁肽，该分子对GLP-1的受体激动效力下降100倍以上。食蟹猴实验显示，给予5倍于瑞他鲁肽剂量的BWB3054仍耐受性良好，未见心率增快，提示GIPR:GCGR共激动可在不诱发胃肠道不良反应与心动过速的前提下实现有效减重。该分子即将进入首次临床研究。三、超越减重，改善整体代谢健康爱尔兰都柏林大学学院Carel le Roux教授深入探讨了临床减重中的低应答机制，提出肥胖管理目标亟须从单一的体重降幅百分比转向器官功能与整体健康获益。他以《丑小鸭》开场，强调低应答者虽与众不同，但不应被污名化。瑞典肥胖受试者研究（SOS）、胃旁路术以及袖状胃切除术数据显示[12-13]，减重应答始终呈现近似正态的连续谱。这一异质性规律同样适用于药物治疗：SURMOUNT-5研究[14]第72周数据显示替尔泊肽组有13%的患者减重＜10%，22%患者减重≥30%，应答跨度显著。图3. 减重手术后最大减重百分比呈正态分布目前，术前暂无可靠的应答预测指标，仅明确糖尿病患者与男性应答较弱，但治疗后3~6个月的早期应答可较好预测长期减重效果。遗传学证据显示[15]，同住夫妇的应答差异与一般人群相似，而一级亲属及同卵双胞胎的疗效应答高度一致，提示低应答有其生物学基础。有效肥胖药物可帮助建立新的“低脂肪稳态”，这与单纯热量限制后身体主动回弹的代偿机制有本质区别[16]。为寻找预测因子，欧盟SOPHIA项目开发了免费减重手术轨迹预测模型，下载超百万次；整合ABOS队列（N=1602，最终分析N=250）多组学数据后发现，其预测效能并未超越体重、身高、年龄、是否吸烟、是否患T2DM、糖尿病病程及干预方式等简单临床变量。Carel le Roux教授进而提出，应以“健康目标”替代“减重百分比”——正如血脂与血糖管理关注的是治疗后残余风险——STEP-UP研究显示[17]，BMI达到27 kg/m2或腰围/身高比达到0.53，较减重百分比更能预测心血管低风险状态。未来，肥胖管理应正视疾病的生物学基础，针对不同亚型患者实施分层治疗，更应避免因应答不佳而责备患者。结语从“大脑如何调控脂肪分布”，到“药物还能更强、更安全吗”，再到“为何患者对治疗低应答”，本专题的3场报告共同指向一个趋势：肥胖管理正在从单一减重指标，转向以生物学异质性为基础、以健康获益为目标、以分层治疗为路径的全新范式。可以预见，临床将迎来更多机制各异的创新疗法，以满足不同人群的个体化治疗需求；同时，对于应答不佳的患者，少一分责备、多一分探索，亦是这场变革的应有之义。参考文献：上下滑动可查看 [1] Kullmann S, Heni M, et al.Physiol Rev 2016.[2] Kullmann S, Heni M, et al. The Lancet Diabetes Endocrinol 2020.[3] Heni M, et al. Diabetes 2017.[4] Hummel J, Heni M, et al.Nat Metab 2023.[5] Wangler N, Heni M, et al.Nat Rev Endocrinol 2026.[6] Kullmann S, Heni M, et al.Nat Commun 2020.[7] Wagner R, Heni M, et al. Diabetes Obes Metab 2026.[8] Müller TD, et al. Nat Rev Drug Discov 2022.[9] Quarta C, et al. Nat Metab 2022.[10] Liskiewicz&Novikoff, et al. Nature 2026.[11] Perez-Tilve, et al. Mol Metab 2026.[12] Sjöström L, et al JAMA 2012.[13] Manning S, et al. Surg Endosc 2015.[14] Aronne LJ,Le Roux CW. et al. N Engl J Med 2025.[15] Hatoum NJ, et al. J Clin Endocrinol Metab 2011.[16] Purnell JQ,le Roux CW. J Intern Med 2026.[17] le Roux C, et al. ObesityWeek 2025. 声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！（来源：《国际糖尿病》编辑部）版权声明版权属《国际糖尿病》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。

2026-10-05

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EASD2026丨未来肥胖管理的挑战：从唯体重论转向以患者为中心，重构减重治疗新格局

编者按：当地时间9月28日~10月2日，第62届欧洲糖尿病研究协会年会（EASD2026）在意大利米兰盛大召开。会议期间的“未来肥胖管理的挑战”专题异彩纷呈，3位学者分别围绕脑胰岛素抵抗机制、药物疗效与耐受性、治疗应答异质性与减重管理三大维度进行分享，系统剖析了肥胖治疗的现状与演变方向。本文为您整理该专题的精彩观点，并荟萃各位教授对肥胖管理未来方向的临床洞见与学术思考。一、肥胖中的脑胰岛素抵抗：治疗障碍还是靶点？德国乌尔姆大学医院Martin Heni教授阐述了脑胰岛素抵抗在肥胖代谢异质性中的驱动作用。他指出，“肥胖并不等于肥胖”：不同肥胖亚型的并发症风险迥异。其团队利用全身MRI精准量化脂肪分布，在23 548名受试者中筛选单脂肪库蓄积的少见表型，聚焦肝、胰腺、骨骼肌、内脏四个脂肪库。结果显示，各组糖尿病风险均升高，肝脂肪变性者糖尿病风险最高，肌肉脂肪变性也会显著增加糖尿病的发生风险（即使无其他部位脂肪堆积）。各脂肪库对应特异疾病谱，如肝脂肪变性组发生肝病风险最高，且存在明确乳腺癌关联信号；肌肉脂肪变性组心房颤动与膝骨关节炎风险均最高，且该组不少人BMI处于正常范围，提示疾病风险并非仅由体重公斤数决定。图1. 不同脂肪蓄积表型的并发症风险与BMI分布差异脂肪去向的调控关键在大脑。不同脂肪分布组的脑结构存在差异，关联脑区多为胰岛素受体高表达的人胰岛素敏感区，参与全身稳态、摄食奖赏与认知调控[1-2]。研究人员通过正糖钳夹联合鼻内胰岛素选择性激活脑胰岛素信号，发现瘦者肝糖生成受抑、外周葡萄糖摄取增加，存在脑胰岛素抵抗的超重/肥胖者则无上述效应[3-4]。该效应单次微弱，却随每餐反复累积，长期可改变整体代谢。脑胰岛素信号经自主神经下传至肝、脂肪、胰腺等外周器官[5]。横断面研究显示，脑胰岛素抵抗者内脏脂肪更多。在为期2年的生活方式干预中，脑胰岛素敏感者内脏脂肪显著减少，且干预结束后9年体重仍低于基线，而抵抗者获益甚微[6]。此外，胰高血糖素（GCG）也可作用于人脑，提示进食后存在多激素协同信号[7]。Heni教授总结道，脑胰岛素抵抗参与肥胖代谢异质性并影响治疗应答，既是治疗障碍，也是克服治疗抵抗的潜在新靶点。二、减重药物疗效已至上限？创新多靶点药物研发攻克瓶颈德国慕尼黑亥姆霍兹中心糖尿病与肥胖研究所Timo Müller教授围绕减重药物疗效瓶颈，解析了非GLP-1依赖的多靶点多肽激动剂在实现有效减重的同时提升耐受性的药理学策略。Müller教授强调，摄食与能量代谢并非由单一肠激素调控，而是多种肠激素协同作用的结果，因此优化减重药物需同时靶向多重机制；替尔泊肽等药物的临床成功，正是对这一思路的有力验证[8]。目前，在不合并2型糖尿病（T2DM）的肥胖患者中，药物治疗的减重疗效呈阶梯式提升：司美格鲁肽平均可减重14.9%（2.4 mg，68周），替尔泊肽达20.9%（15 mg，72周），瑞他鲁肽可达24.2%（12 mg，48周）。但疗效之外，胃肠道反应和心率增快等耐受性问题仍是主要瓶颈。Müller等人提出了多肽靶向递送核受体药物策略，即：将核激素类药物共价偶联于肠促胰岛素肽，借助肽受体实现靶细胞内精准递送。PPARα/γ共激动剂Tesaglitazar经GLP-1递送后，在3 nmol/kg低剂量时仍可改善糖耐量[9]；经GLP-1:GIP递送PPARα/γ/δ三重激动剂Lanifibranor所构建的GLP-1:GIP:Lani减重幅度约40%，显著优于物理混合给药[10]，同时约80%减重来自脂肪，瘦体重保留良好。该分子维持正常的肠促胰岛素受体信号传导，钳夹试验显示其胰岛素敏感性更优，并可减轻肝脏炎症、通过下调丙酮酸羧化酶抑制肝糖生成以及改善射血分数等。此外，这一“五重”分子不引起贫血、液体潴留或肾损害，也不影响瘦小鼠的体重与血糖。图2. GLP-1:GIP:Lani可显著增强疗效且保留瘦体重良好为优化耐受性，团队进一步在GLP-1受体（GLP-1R）敲除小鼠中验证：常规剂量瑞他鲁肽（一种GLP-1R/GIPR/GCGR三激动剂）无减重作用，提高剂量后则可实现非GLP-1R依赖的减重[11]，表明GLP-1R并非实现强效减重的必需靶点。此外，GCG与GIP协同可使摄食减少78%而不恶化糖耐量；低剂量GCG联合递增剂量GIP可发挥协同减重作用，获得与司美格鲁肽相当甚至更优的减重效果，为非GLP-1R依赖的治疗策略提供了药效学依据。针对“GCG可能诱发心动过速”的顾虑，研究团队证实，瑞他鲁肽所致心率增快主要由GLP-1R介导，GCGR并不主导该效应；结合前述“强效减重可不依赖GLP-1R”的发现，Bluewater生物科学公司开发了每周1次皮下注射的GIPR:GCGR双激动剂BWB3054，旨在为不耐受GLP-1R激动剂的人群提供替代方案；相较瑞他鲁肽，该分子对GLP-1的受体激动效力下降100倍以上。食蟹猴实验显示，给予5倍于瑞他鲁肽剂量的BWB3054仍耐受性良好，未见心率增快，提示GIPR:GCGR共激动可在不诱发胃肠道不良反应与心动过速的前提下实现有效减重。该分子即将进入首次临床研究。三、超越减重，改善整体代谢健康爱尔兰都柏林大学学院Carel le Roux教授深入探讨了临床减重中的低应答机制，提出肥胖管理目标亟须从单一的体重降幅百分比转向器官功能与整体健康获益。他以《丑小鸭》开场，强调低应答者虽与众不同，但不应被污名化。瑞典肥胖受试者研究（SOS）、胃旁路术以及袖状胃切除术数据显示[12-13]，减重应答始终呈现近似正态的连续谱。这一异质性规律同样适用于药物治疗：SURMOUNT-5研究[14]第72周数据显示替尔泊肽组有13%的患者减重＜10%，22%患者减重≥30%，应答跨度显著。图3. 减重手术后最大减重百分比呈正态分布目前，术前暂无可靠的应答预测指标，仅明确糖尿病患者与男性应答较弱，但治疗后3~6个月的早期应答可较好预测长期减重效果。遗传学证据显示[15]，同住夫妇的应答差异与一般人群相似，而一级亲属及同卵双胞胎的疗效应答高度一致，提示低应答有其生物学基础。有效肥胖药物可帮助建立新的“低脂肪稳态”，这与单纯热量限制后身体主动回弹的代偿机制有本质区别[16]。为寻找预测因子，欧盟SOPHIA项目开发了免费减重手术轨迹预测模型，下载超百万次；整合ABOS队列（N=1602，最终分析N=250）多组学数据后发现，其预测效能并未超越体重、身高、年龄、是否吸烟、是否患T2DM、糖尿病病程及干预方式等简单临床变量。Carel le Roux教授进而提出，应以“健康目标”替代“减重百分比”——正如血脂与血糖管理关注的是治疗后残余风险——STEP-UP研究显示[17]，BMI达到27 kg/m2或腰围/身高比达到0.53，较减重百分比更能预测心血管低风险状态。未来，肥胖管理应正视疾病的生物学基础，针对不同亚型患者实施分层治疗，更应避免因应答不佳而责备患者。结语从“大脑如何调控脂肪分布”，到“药物还能更强、更安全吗”，再到“为何患者对治疗低应答”，本专题的3场报告共同指向一个趋势：肥胖管理正在从单一减重指标，转向以生物学异质性为基础、以健康获益为目标、以分层治疗为路径的全新范式。可以预见，临床将迎来更多机制各异的创新疗法，以满足不同人群的个体化治疗需求；同时，对于应答不佳的患者，少一分责备、多一分探索，亦是这场变革的应有之义。参考文献：上下滑动可查看[1] Kullmann S, Heni M, et al.Physiol Rev 2016.[2] Kullmann S, Heni M, et al. The Lancet Diabetes Endocrinol 2020.[3] Heni M, et al. Diabetes 2017.[4] Hummel J, Heni M, et al.Nat Metab 2023.[5] Wangler N, Heni M, et al.Nat Rev Endocrinol 2026.[6] Kullmann S, Heni M, et al.Nat Commun 2020.[7] Wagner R, Heni M, et al. Diabetes Obes Metab 2026.[8] Müller TD, et al. Nat Rev Drug Discov 2022.[9] Quarta C, et al. Nat Metab 2022.[10] Liskiewicz&Novikoff, et al. Nature 2026.[11] Perez-Tilve, et al. Mol Metab 2026.[12] Sjöström L, et al JAMA 2012.[13] Manning S, et al. Surg Endosc 2015.[14] Aronne LJ,Le Roux CW. et al. N Engl J Med 2025.[15] Hatoum NJ, et al. J Clin Endocrinol Metab 2011.[16] Purnell JQ,le Roux CW. J Intern Med 2026.[17] le Roux C, et al. ObesityWeek 2025.声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。（来源：《国际糖尿病》编辑部）

100 项与辛酸拉尼米韦相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09547	辛酸拉尼米韦	J05AH04	DB11888

研发状态

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10 条最早获批的记录,

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适应症	国家/地区	公司	日期
甲型流感病毒感染	日本	Daiichi Sankyo Co., Ltd.	2019-06-18
乙型流感病毒感染	日本	Daiichi Sankyo Co., Ltd.	2019-06-18

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适应症	最高研发状态	国家/地区	公司	日期
慢性哮喘	临床1期	英国	Biota Scientific Management Pty Ltd.	2013-10-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02014649 (FROSTY, CTgov)	临床1/2期	甲型流感病毒感染	15	Placebo+20 mg laninamivir octanoate (20mg Laninamivir Octanoate)	願鏇網膚顧糧積簾齋壓(夢艱鏇壓網衊鹹淵夢窪) = 廠糧壓蓋襯夢鹽壓艱淵遞簾構鹹齋積蓋糧遞窪 (構鹹積積選鑰衊襯糧獵, 34.2) 更多	-	2025-01-13
				40 mg laninamivir octanoate (40mg Laninamivir Octanoate)	願鏇網膚顧糧積簾齋壓(夢艱鏇壓網衊鹹淵夢窪) = 遞範餘鏇選積衊齋繭顧遞簾構鹹齋積蓋糧遞窪 (構鹹積積選鑰衊襯糧獵, 29.8) 更多
NCT01793883 (Igloo, CTgov)	临床2期	乙型流感病毒感染 \| 甲型流感病毒感染	639	Placebo+40 mg Laninamivir Octanoate (40 mg Laninamivir Octanoate DPI)	壓範築衊鬱襯遞鬱夢選(製範範願餘網築壓淵簾) = 鹹鬱顧蓋壓憲淵願選觸淵獵築觸構選窪範蓋鏇 (蓋衊獵蓋觸糧製壓積製, 廠觸壓鏇範夢鹹鏇網鏇 ~ 醖糧簾構窪壓廠窪糧範) 更多	-	2017-09-01
				80 mg Laninamivir Octanoate (80 mg Laninamivir Octanoate DPI)	壓範築衊鬱襯遞鬱夢選(製範範願餘網築壓淵簾) = 憲遞積憲餘醖網膚範窪淵獵築觸構選窪範蓋鏇 (蓋衊獵蓋觸糧製壓積製, 範衊構構顧觸願積範範 ~ 夢窪選網窪憲蓋鬱窪壓) 更多
NCT00803595 (MARVEL, CTgov)	临床3期	甲型流感病毒感染	1,002	CS-8958 (CS-8958 High Dose 40 mg)	構艱簾壓繭鹹醖蓋遞壓(繭餘繭壓簾憲憲範簾積) = 網構壓範襯窪憲構願鬱淵艱積糧顧繭顧構廠壓 (衊廠鑰窪窪簾醖鬱膚選, 顧衊顧鹽憲獵廠糧膚積 ~ 糧蓋範淵衊鹽衊範糧齋) 更多	-	2011-11-22
				CS-8958 (CS-8958 Low Dose 20 mg)	構艱簾壓繭鹹醖蓋遞壓(繭餘繭壓簾憲憲範簾積) = 選鑰獵壓艱鏇網鏇繭築淵艱積糧顧繭顧構廠壓 (衊廠鑰窪窪簾醖鬱膚選, 艱鏇遞範糧蓋蓋鑰鏇簾 ~ 鑰願願淵鏇齋鹹觸築壓) 更多
NCT00803595 (Pubmed \| Clin Infect Dis)	临床3期	流感病毒感染	1,003	40 mg laninamivir octanoate	窪鬱襯壓遞鏇鏇觸鏇淵(餘製簾簾衊遞餘遞壓簾) = 襯選鏇鑰網窪鹽遞願顧簾觸製選選網膚構構餘 (齋鹽衊醖簾鑰衊積膚顧 )	积极	2010-11-15
				20 mg laninamivir octanoate	窪鬱襯壓遞鏇鏇觸鏇淵(餘製簾簾衊遞餘遞壓簾) = 餘鏇餘網選膚鬱蓋窪襯簾觸製選選網膚構構餘 (齋鹽衊醖簾鑰衊積膚顧 )