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更新于：2026-10-07

Lenvatinib mesylate

甲磺酸仑伐替尼

更新于：2026-10-07

概要

基本信息

药物类型

小分子化药

别名

lenvatinib、lenvatinib mesilate、Lenvatinib mesilate (JAN)

+ [19]

靶点

FGFR1 x FGFR2 x FGFR3 x FGFR4 x PDGFRα x RET x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

作用方式

拮抗剂、抑制剂

作用机制

FGFR1拮抗剂(成纤维细胞生长因子受体-1拮抗剂)、FGFR2拮抗剂(成纤维细胞生长因子受体-2拮抗剂)、FGFR3拮抗剂(成纤维细胞生长因子受体-3拮抗剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [11]

在研适应症

晚期子宫内膜癌复发性子宫内膜癌胸腺肿瘤+ [85]

非在研适应症

晚期乳腺癌晚期胃癌甲状腺未分化癌+ [44]

原研机构

Eisai Co., Ltd.

在研机构

Eisai GmbH

Merck Sharp & Dohme Corp.Merck Sharp & Dohme LLC

+ [6]

非在研机构

Bristol Myers Squibb Co.

Merck & Co., Inc.

江苏先声药业有限公司

+ [2]

权益机构

Biotoscana Investments SA

Merck & Co., Inc.

Novartis AG

+ [3]

最高研发阶段批准上市

首次获批日期

美国 (2015-02-13),

甲状腺癌

最高研发阶段(中国)批准上市

特殊审评加速批准 (美国)、孤儿药 (美国)、孤儿药 (日本)、孤儿药 (澳大利亚)、优先审评 (澳大利亚)、附条件批准 (中国)、特殊审批 (中国)、优先审评 (中国)、突破性疗法 (美国)

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结构/序列

分子式C22H23ClN4O7S

InChIKeyHWLFIUUAYLEFCT-UHFFFAOYSA-N

CAS号857890-39-2

关联

809

项与甲磺酸仑伐替尼相关的临床试验

NCT05077215

/ Not yet recruiting临床3期

A Phase 3, Randomized, Open-Label, Active-Controlled, Superiority Trial of EG007, Added to the Combination of Lenvatinib Plus Pembrolizumab vs. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer

This is a Phase 3, multicenter, randomized, open-label trial to evaluate whether EG-007 plus Len+Pem is superior to Len+Pem alone in patients with advanced endometrial cancer (Stage III or IV). This trial will be preceded by a safety lead-in study with up to 28 patients (the safety lead-in is a separate, free-standing protocol).
Approximately 450 patients will be randomized equally (1:1) to receive EG-007 plus Len+Pem or Len+Pem alone. The randomization will be stratified by the following stratification factors:
* Diagnosis Classification (advanced Stage III/IV vs. recurrent endometrial cancer)
* ECOG score at baseline (0 vs 1)
* Geographic region (Asia vs ROW)

开始日期2026-12-01

申办/合作机构

Evergreen Therapeutics, Inc

NCT07256223

/ Not yet recruiting临床2期IIT

A Single-Arm, Multicenter, Prospective Clinical Study of Envafolimab Combined With Lenvatinib as First-Line Therapy in Renal Cell Carcinoma Patients With Liver Metastases

This is an open-label, single-arm, prospective, multicenter clinical study designed to evaluate the efficacy and safety of envafolimab in combination with lenvatinib for the treatment of patients with clear cell renal cell carcinoma (ccRCC) accompanied by liver metastases. The Department of Urology at Fudan University Shanghai Cancer Center serves as the primary research center.

开始日期2026-12-01

申办/合作机构

复旦大学

[+1]

NCT07843901

/ Not yet recruiting临床2期IIT

Phase II Study of Lenvatinib in Patients With Advanced Parathyroid Carcinoma(ALPS)

This is a multicenter, open-label, single-arm, phase II study evaluating the efficacy and safety of lenvatinib in patients with unresectable, advanced or metastatic parathyroid carcinoma.
Parathyroid carcinoma is a rare malignant tumor with limited systemic treatment options in patients with unresectable, recurrent, or metastatic disease. Excessive secretion of parathyroid hormone (PTH) and resulting hypercalcemia may cause significant morbidity and adversely affect prognosis and quality of life. Although complete surgical resection is considered the only potentially curative treatment for localized disease, no established standard systemic therapy is currently available for advanced or metastatic parathyroid carcinoma.
Lenvatinib is an oral multikinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), RET, and KIT. Inhibition of these signaling pathways may suppress tumor angiogenesis and tumor cell proliferation. Based on the potential role of angiogenic signaling in parathyroid carcinoma and the antitumor activity of lenvatinib demonstrated in various solid tumors, lenvatinib is being investigated as a potential treatment option for advanced or metastatic parathyroid carcinoma.
A total of 18 participants will be enrolled, including consideration of potential evaluability and dropout. Eligible participants must have histologically or cytologically confirmed parathyroid carcinoma that is unresectable, advanced, or metastatic, with at least one measurable lesion according to RECIST version 1.1. Participants must be at least 19 years of age and have an ECOG performance status of 0 or 1 with adequate bone marrow, renal, and hepatic function.
Lenvatinib will be administered orally once daily at a starting dose of 24 mg. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined reason for treatment discontinuation. Dose interruption or reduction to 20 mg, 14 mg, and 10 mg once daily may be implemented for treatment-related toxicities according to the protocol and applicable local prescribing information.
The primary objective is to evaluate the objective response rate (ORR), defined as the proportion of participants achieving a complete response (CR) or partial response (PR) according to RECIST version 1.1. Secondary objectives include evaluation of progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and the safety and tolerability of lenvatinib. Exploratory objectives include assessment of changes in corrected serum calcium and PTH levels and exploration of associations between biochemical changes and clinical outcomes such as ORR and PFS.
Tumor response will be assessed according to RECIST version 1.1. Baseline imaging will be performed within 28 days before the first dose of study treatment. Tumor assessments will be performed every 8 weeks (±7 days) through Week 48 and every 12 weeks (±14 days) thereafter. Safety assessments will include adverse events, clinical laboratory tests, vital signs, physical examinations, ECOG performance status, and electrocardiograms.
The overall study period is planned for 3 years, with participant enrollment from July 1, 2026, through June 30, 2028. Each participant will be followed for up to 12 months after treatment discontinuation, or until study completion, as applicable.
The study is designed to evaluate whether lenvatinib provides clinically meaningful antitumor activity and an acceptable safety profile in patients with advanced or metastatic parathyroid carcinoma, while also exploring potential changes in calcium and PTH levels as disease-related biochemical outcomes.

开始日期2026-11-01

申办/合作机构

Yonsei University

100 项与甲磺酸仑伐替尼相关的临床结果

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100 项与甲磺酸仑伐替尼相关的转化医学

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100 项与甲磺酸仑伐替尼相关的专利（医药）

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3,298

项与甲磺酸仑伐替尼相关的文献（医药）

2026-12-31·CANCER BIOLOGY & THERAPY

ABHD17C regulates the efficacy of lenvatinib in suppressing hepatocellular carcinoma

Article

作者: Wang, Wei ; Lin, Hongtan ; Zhang, Jiahui ; Sun, Yingming ; Shi, Chunfeng ; Li, Peng ; Wang, Jiawei ; Huang, Jinfa ; Ma, Xiaoqiu ; Xu, Hao ; Wang, Linpei

INTRODUCTION:

Lenvatinib is a first-line therapy for hepatocellular carcinoma (HCC), but its clinical efficacy is limited by drug resistance. ABHD17C, a depalmitoylation enzyme involved in HCC progression, has not been investigated in lenvatinib response. This study aimed to determine whether ABHD17C regulates the anti-tumor efficacy of lenvatinib in HCC.

METHODS:

Published single-cell RNA sequencing (scRNA-seq) data were analyzed to characterize ABHD17C expression in the HCC tumor microenvironment. Functional assays were performed in HCC cell lines to evaluate the effects of lenvatinib and ABHD17C modulation. The findings were validated using HCC xenograft mouse models and patient-derived tumor organoids.

RESULTS:

scRNA-seq analysis showed that ABHD17C is associated with an immunosuppressive tumor microenvironment characterized by reduced CD8⁺ T cell infiltration, increased T cell exhaustion, and abnormal intercellular communication. In vitro, lenvatinib inhibited proliferation, migration, and invasion while inducing apoptosis and cell cycle arrest in HCC cells. These effects were significantly attenuated by ABHD17C overexpression but enhanced by ABHD17C depletion. In vivo, ABHD17C-overexpressing xenografts were less responsive to lenvatinib, exhibiting increased tumor growth and reduced apoptosis. Similarly, in patient-derived organoids, ABHD17C overexpression diminished lenvatinib efficacy. Notably, lenvatinib reduced ABHD17C expression in organoids, suggesting potential feedback regulation.

CONCLUSION:

ABHD17C promotes an immunosuppressive tumor microenvironment and attenuates the anti-tumor effects of lenvatinib in HCC. Targeting ABHD17C may represent a potential strategy to enhance lenvatinib sensitivity and improve therapeutic outcomes.

2026-12-31·ANNALS OF MEDICINE

Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib

Review

作者: Liu, Huihui ; Cui, Chao ; Wang, Kai ; Li, Qingwei ; Sun, Yu ; Gao, Shuai ; Shi, Jingfei

BACKGROUND:

Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects.

OBJECTIVE:

This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and ≥3 grades for analysis.

PATIENTS/MATERIALS AND METHODS:

Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed.

RESULTS:

Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade ≥3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001.

CONCLUSION:

Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.

2026-12-31·CANCER BIOLOGY & THERAPY

Synchronizing immunity and angiogenesis in lung adenocarcinoma: bridging biological synergy and clinical translation

Article

作者: Peker, Pınar

The recent study by Liu et al. provided compelling preclinical evidence that lenvatinib enhances the efficacy of combined radiotherapy and PD-L1 blockade by modulating both angiogenesis and antitumor immunity in lung adenocarcinoma. In this correspondence, I discuss the translational implications of these findings and highlight several challenges that should be addressed before clinical implementation. These include the molecular heterogeneity of lung adenocarcinoma, interpatient variability in the temporal dynamics of vascular normalization and immune activation, and the limitations of relying solely on PD-L1 expression for patient selection. I further emphasize the need for biomarker-driven and adaptive clinical trial designs incorporating functional imaging, circulating biomarkers, and immune monitoring to optimize treatment timing and identify patients most likely to benefit from this therapeutic strategy. These considerations may facilitate the successful translation of promising preclinical observations into precision radioimmunotherapy for lung adenocarcinoma.

2,798

项与甲磺酸仑伐替尼相关的新闻（医药）

2026-10-06

·BioSpace

CatalYm to Present Updated GDFATHER-NEO Clinical Data and Highlight Ongoing Phase 2b Visugromab Trials at ESMO 2026

Rapid oral presentation will feature final pathological and radiological outcomes and event-free survival data from the Phase 2 GDFATHER-NEO trial in muscle-invasive bladder cancer Two additional presentations to highlight ongoing Phase 2b trials evaluating visugromab in non-small cell lung cancer and hepatocellular carcinoma MUNICH & SAN FRANCISCO--(BUSINESS WIRE)-- CatalYm today announced that updated clinical results from its Phase 2 GDFATHER-NEO trial will be presented in a rapid oral presentation at the European Society for Medical Oncology (ESMO) Congress 2026 , taking place October 23-27, 2026, in Madrid, Spain. The oral presentation will feature updated findings from the Phase 2 GDFATHER-NEO trial ( NCT06059547 ) and will include final pathological and radiological outcomes as well as event-free survival from the stratified, blinded trial evaluating visugromab versus placebo in combination with nivolumab as neoadjuvant treatment for patients with muscle-invasive bladder cancer (MIBC). These updated findings will provide further insights into the potential of GDF-15 inhibition in combination with immune checkpoint blockade. In addition, two Trial in Progress presentations will provide an overview of the ongoing GDFATHER-NSCLC-02 ( NCT07246863 ) and GDFATHER-HCC-01 ( NCT07219459 ) Phase 2b trials, which are evaluating visugromab in second-line metastatic non-squamous non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), respectively. Together, these studies reflect CatalYm's continued advancement of visugromab across multiple solid tumor indications. Presentation Details Rapid Oral Presentation – GDFATHER-NEO Abstract #9061 Title: Final pathological and radiological outcomes and initial EFS from a blinded, exploratory Phase 2 trial of nivolumab ± visugromab in MIBC (GDFATHER-NEO) Session: Rapid oral 1: Genitourinary tumours, renal and urothelial Presentation Date and Time: October 24, 2026; 10:15 - 11:45 am CEST Presenter: Andrea Necchi Location: Bilbao Auditorium - Hall 3 Trials in Progress Poster Presentation – GDFATHER-NSCLC-02 Abstract #4316 Title: Phase 2b randomized, blinded, placebo-controlled trial investigating the efficacy and safety of visugromab plus nivolumab with or without docetaxel in second line metastatic non-squamous NSCLC: GDFATHER-NSCLC-02 Presentation Date and Time: October 26, 2026; 12:00 - 12:45 pm CET Presenter: Martin Reck Presentation Number: 2725TiP Trials in Progress e-Poster Presentation – GDFATHER-HCC-01 Abstract #7627 Title: Phase 2b randomized, blinded trial to investigate the efficacy and safety of visugromab in combination with nivolumab and lenvatinib in unresectable or metastatic hepatocellular carcinoma after failure of first-line treatment including an anti-PD-(L)1 compound: GDFATHER-HCC-01 Presenter: Richard S. Finn Presentation Number: 1761eTiP About Visugromab Visugromab is a monoclonal antibody that neutralizes Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant produced by tumors which fosters immunotherapy resistance and drives cachexia in people with cancer. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by re-enabling immune cell activation, proliferation, and induction of interferon-γ. In addition, visugromab also mitigates cancer cachexia, a severe condition affecting a significant number of advanced cancer patients by inhibiting the activation of the GFRAL pathway in the brainstem, a key driver of weight loss and appetite suppression in cancer patients. About CatalYm CatalYm is developing visugromab, a first-in-class anti-GDF-15 antibody, in solid tumors and cachexia. In its first-in-human Phase 1/2a study, visugromab demonstrated deep and durable anti-tumor efficacy with long-lasting objective responses in relapsed and checkpoint refractory metastatic solid tumor patients in combination with anti-PD-1 treatment. In addition, data from the same study demonstrated that visugromab can significantly counteract the effects of cachexia in these patients. This data was published in Nature and presented at the International Conference on Sarcopenia, Cachexia & Wasting Disorders. CatalYm is now advancing visugromab into multiple Phase 2b studies including first-line metastatic non-squamous NSCLC ( NCT07098988 ), second-line metastatic non-squamous NSCLC ( NCT07246863 ), second-line hepatocellular carcinoma ( NCT07219459 ) and cachexia ( NCT07112196 ). Founded in 2016 and based in Munich, Germany, and San Francisco, USA, CatalYm is backed by leading international investors including Canaan Partners, Omega Funds, Bioqube Ventures, Forbion, Jeito Capital, Brandon Capital, Gilde Healthcare, Novartis Venture Fund, Vesalius, Bayern Kapital, BioGeneration Ventures, and Coparion. Contacts CatalYm GmbH Peter Garcia, CFO info@catalym.com Media Inquiries Trophic Communications Dr. Stephanie May or Anja Heuer Phone: +49 171 185 56 82 or +49 151 106 199 05 catalym@trophic.eu

临床2期免疫疗法临床结果ASCO会议

2026-10-05

·微信

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

2026-10-04

·今日头条

肾癌新双口服击败卡博替尼：《柳叶刀》III期数据解析

健幸之目｜国际生物医药前沿资讯晚期透明细胞肾细胞癌，最难的阶段往往不是一线治疗，而是免疫治疗失效之后。 2026年8月，《柳叶刀》刊发III期LITESPARK-011研究完整结果；该研究此前已于2026年2月在ASCO泌尿生殖系统肿瘤研讨会（ASCO GU 2026），以重磅摘要（LBA417）形式首次对外公布。研究结论：belzutifan联合仑伐替尼的双口服方案，在无进展生存期（PFS）和客观缓解率上优于卡博替尼；总生存期虽有改善趋势，但未达到统计学显著性。另一项重要进展：2026年9月24日，美国FDA正式批准belzutifan联合仑伐替尼，用于经PD-1/PD-L1抑制剂治疗后进展的晚期透明细胞肾细胞癌成人患者，审批完成时间较原定审评节点提前10天。这是全球首个获批的HIF-2α抑制剂联合VEGFR-TKI方案。先看这个适应症的分量：全球每年新发43万例，中国7.4万例依据GLOBOCAN 2020统计，全球肾癌年新发病例超43万，年死亡约18万，占成人恶性肿瘤的2%~3%，高发年龄段50至70岁，男女发病比例约2:1。国家癌症中心数据显示，2022年我国肾癌新发病例约7.37万例，死亡约2.4万例，发病率呈逐年上升态势。疾病特点值得重视：大约30%患者确诊时已出现转移；20%~40%局部进展期患者术后会发生远处转移，晚期肾癌5年生存率仅约20%。近十年，晚期肾癌一线治疗已经进入免疫联合时代，也就是PD-1/PD-L1联合抗VEGF或双免疫方案。但免疫治疗失败后的后续标准方案，全球尚未形成统一共识。卡博替尼这类药物的临床证据大多建立在免疫治疗普及之前；CONTACT-03等免疫再挑战相关研究也未取得成功，而LITESPARK-011正是瞄准这一临床空白开展。 LITESPARK-011研究做了什么？这是一项开放标签、随机、阳性对照III期试验，在25个国家的184个中心共纳入747例不可切除局部晚期或转移性透明细胞肾细胞癌患者。入组标准清晰：一线或二线接受过抗PD-1/PD-L1治疗后疾病进展，或是辅助治疗停药6个月内复发，受试者既往可以使用过VEGFR-TKI。受试者按1:1分组：试验组采用belzutifan 120 mg + lenvatinib 20 mg每日口服；对照组服用cabozantinib 60 mg每日口服。双重主要终点为盲态独立中心评估的无进展生存期（PFS）与总生存期（OS），关键次要终点为客观缓解率（ORR）。第二次期中分析时，中位随访时长29个月。结果：PFS和缓解全面胜出，OS未达统计学显著 • PFS（主要终点）：中位14.8个月 vs 10.7个月（HR 0.70，95%CI 0.59–0.84，单侧p<0.0001），进展或死亡风险降低约30%。12个月无进展生存率55% vs 41%，24个月36% vs 19%。 • ORR：52.6% vs 40.2%；完全缓解20例 vs 4例（5.4% vs 1.1%）。 • 缓解持续时间：中位23.0个月 vs 12.3个月，部分缓解病例中已有超过3年的长期应答，也是本研究最受关注的亮点。 • OS：中位34.9个月 vs 27.6个月（HR 0.85，95%CI 0.68–1.05，单侧p=0.061），未达到预设统计学界值。支撑FDA获批的最终分析数据：PFS为14.6个月 vs 10.6个月（HR 0.74），ORR为53% vs 40%；OS最终分析为33.7个月 vs 28.6个月（HR 0.85），依旧没有统计学显著差异。也就是说，FDA此次批准，依据是PFS和ORR带来的获益，而非总生存期获益。安全性：两组毒性发生率相当，谱型与药物机制一致 ≥3级治疗相关不良事件84% vs 83%。试验组最常见不良反应为腹泻、高血压、贫血（belzutifan特征性毒性）；对照组多见腹泻、高血压、手足综合征。试验组低氧事件发生率15.4%，对照组为0；≥3级高血压两组分别为31%与29%。两组因不良事件停药比例相近（11.1% vs 11.3%）。在患者报告结局上，疾病症状恶化情况与整体生活质量，两组基本持平。 FDA药品说明书保留belzutifan胚胎-胎儿毒性黑框警告，同时标注贫血、低氧风险警示；该联合方案额外增加心功能不全相关警示。为什么这个组合能赢？机制上的互补抑制透明细胞肾癌发病核心是VHL基因失活，引发HIF通路异常激活。belzutifan是首个HIF-2α抑制剂，可在转录因子层面阻断缺氧信号；仑伐替尼属于多靶点VEGFR-TKI，强力抑制肿瘤血管生成。二者作用环节互补、耐药谱不重叠，这是该组合优于单靶点TKI的理论基础，LITESPARK-011研究首次用III期随机临床数据证实这一点。突破在哪？免疫失败后的第一个"机制联合"标准这项研究是首个HIF-2α抑制剂联合VEGFR-TKI的III期试验，也是首个针对免疫治疗失败人群，对照当代VEGFR-TKI标准治疗取得阳性结果的III期试验。它把晚期肾癌后线治疗，从经验性更换TKI，推向按作用机制联合、结合毒性筛选患者的新模式。FDA获批后，该方案成为这一患者群体首个正式落地的全新机制联合疗法。对国内临床同样具备参考价值：我国晚期肾癌后线治疗目前仍以TKI单药为主，该联合方案国内获批时间尚未公布，现阶段患者仍需选用国内已获批的治疗方案，遵从医嘱治疗。仍需保持理性：三点不能忽视 1. OS获益尚未证实。PFS与ORR获益明确，但期中分析和最终分析的总生存期均未达到统计学显著，长期生存获益仍需持续随访验证。 2. 毒性需要筛选患者。双口服联合方案≥3级不良事件发生率超八成，更适合体能状态良好、脏器储备充足，能够完成密切监测的患者；贫血明显、低氧风险高、血压与蛋白尿控制不佳者需谨慎使用。 3. 开放标签设计。非盲的试验设计，会对症状评估与不良事件上报带来一定偏倚。总的来看，LITESPARK-011为晚期肾癌后线带来首个机制互补的口服联合方案，PFS与缓解率优势明确；总生存期的最终结论，还需要更长时间随访。搜索关键词：LITESPARK-011、belzutifan、lenvatinib、cabozantinib、晚期肾细胞癌、HIF-2α抑制剂、免疫治疗后进展、ASCO GU 2026 话题标签：#肾细胞癌 #透明细胞肾癌 #HIF2α抑制剂 #belzutifan #lenvatinib #柳叶刀 #健幸之目参考文献 [1] Motzer RJ, McDermott R, Park SH, et al. Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial. Lancet. 2026;408(10557):808-820. doi:10.1016/S0140-6736(26)01089-5. [2] Motzer RJ, Park SH, McDermott RS, et al. Belzutifan plus lenvatinib versus cabozantinib for advanced renal cell carcinoma after anti–PD-(L)1 therapy: open-label phase 3 LITESPARK-011 study. J Clin Oncol. 2026;44(suppl 7):LBA417. doi:10.1200/JCO.2026.44.7_suppl.LBA417. [3] Choueiri TK, Bauer TM, Papadopoulos KP, et al. Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med. 2021;27(5):802-805. doi:10.1038/s41591-021-01324-7. [4] U.S. Food and Drug Administration. FDA approves belzutifan in combination with lenvatinib for advanced renal cell carcinoma with a clear cell component. 2026-09-24. 免责声明：本文为医药科普，不构成诊断、用药或治疗建议。本文所用图片均有AI辅助设计完成，仅供科普使用，不作他用。健幸之目：把顶级期刊研究，翻译成患者能提问、家属能听懂、临床能讨论的证据要点。

100 项与甲磺酸仑伐替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09920	甲磺酸仑伐替尼	L01XE	DB09078

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
晚期子宫内膜癌	欧盟	Eisai GmbH	2023-07-25
晚期子宫内膜癌	冰岛	Eisai GmbH	2023-07-25
晚期子宫内膜癌	列支敦士登	Eisai GmbH	2023-07-25
晚期子宫内膜癌	挪威	Eisai GmbH	2023-07-25
复发性子宫内膜癌	欧盟	Eisai GmbH	2023-07-25
复发性子宫内膜癌	冰岛	Eisai GmbH	2023-07-25
复发性子宫内膜癌	列支敦士登	Eisai GmbH	2023-07-25
复发性子宫内膜癌	挪威	Eisai GmbH	2023-07-25
胸腺肿瘤	日本	Eisai Co., Ltd.	2021-03-23
晚期肾细胞癌	欧盟	Eisai GmbH	2016-08-25
晚期肾细胞癌	冰岛	Eisai GmbH	2016-08-25
晚期肾细胞癌	列支敦士登	Eisai GmbH	2016-08-25
晚期肾细胞癌	挪威	Eisai GmbH	2016-08-25
子宫内膜癌	澳大利亚	Eisai Co., Ltd.	2016-01-28
肾细胞癌	澳大利亚	Eisai Co., Ltd.	2016-01-28
晚期肝细胞癌	欧盟	Eisai GmbH	2015-05-28
晚期肝细胞癌	冰岛	Eisai GmbH	2015-05-28
晚期肝细胞癌	列支敦士登	Eisai GmbH	2015-05-28
晚期肝细胞癌	挪威	Eisai GmbH	2015-05-28
分化型甲状腺癌	欧盟	Eisai GmbH	2015-05-28

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
晚期非小细胞肺癌	临床3期	中国	江苏康宁杰瑞生物制药有限公司	2021-10-28
转移性食管癌	临床3期	美国	Merck Sharp & Dohme Corp.	2021-07-28
转移性食管癌	临床3期	美国	Eisai, Inc.	2021-07-28
转移性食管癌	临床3期	中国	Eisai, Inc.	2021-07-28
转移性食管癌	临床3期	中国	Merck Sharp & Dohme Corp.	2021-07-28
转移性食管癌	临床3期	日本	Merck Sharp & Dohme Corp.	2021-07-28
转移性食管癌	临床3期	日本	Eisai, Inc.	2021-07-28
转移性食管癌	临床3期	阿根廷	Merck Sharp & Dohme Corp.	2021-07-28
转移性食管癌	临床3期	阿根廷	Eisai, Inc.	2021-07-28
转移性食管癌	临床3期	加拿大	Merck Sharp & Dohme Corp.	2021-07-28

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临床结果

适应症

分期

评价

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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


NCT05078931 (WCLC2026)	临床2期	EGFR突变的非小细胞肺癌 EGFR-mutated \| PD-L1 Positive	33	Lenvatinib plus Pembrolizumab (PD-L1 positive (TPS ≥1%) + EGFR mutated (L858R or 19DEL) + TKI-resistant advanced NSCLC + Overall)	夢廠醖窪窪觸餘窪鏇鬱(淵獵範構鏇築窪構顧製) = 鹽淵築餘壓簾醖築簾願觸夢窪遞築壓選糧襯衊 (窪鬱範積窪艱觸築願憲 ) 更多	积极	2026-09-12
NCT04246177 (MK-7902-012 \| LEAP-012 \| LEAP-012 \| KEYNOTE-966 \| E7080-G000-318, CTgov)	临床3期	肝细胞癌	480	TACE+Pembrolizumab+Lenvatinib (Lenvatinib + Pembrolizumab + TACE)	網餘憲壓糧壓選窪積繭(襯鹽糧製蓋窪鹽積構構) = 獵憲製構淵築衊簾築鹽鹹蓋選繭顧淵觸選蓋鹹 (膚鏇積積窪淵夢鹹願夢, 衊範蓋鹽夢顧願顧蓋鏇 ~ 簾網網廠觸衊簾憲夢淵) 更多	-	2026-09-03
				Placebo+TACE (Placebo + TACE)	網餘憲壓糧壓選窪積繭(襯鹽糧製蓋窪鹽積構構) = 鹽醖壓網築廠膚糧獵壓鹹蓋選繭顧淵觸選蓋鹹 (膚鏇積積窪淵夢鹹願夢, 範選糧選醖夢鬱壓窪淵 ~ 選鏇遞齋網網製憲艱鹽) 更多
NCT04949256 (LEAP-014 \| E7080-G000-320 \| MK-7902-014, CTgov)	临床3期	转移性食管鳞状细胞癌 \| 转移性食管癌	863	Paclitaxel+cisplatin+pembrolizumab+Lenvatinib+5-FU (Part 1: Pembrolizumab + Lenvatinib + Chemotherapy)	鹹鹹壓繭築襯網鏇鹽獵 = 鬱壓觸選齋壓鬱鑰衊鹹廠築築膚齋構餘廠製蓋 (膚餘觸鏇鏇廠糧積壓衊, 蓋窪蓋蓋醖願遞繭餘壓 ~ 衊遞齋範糧顧衊壓顧製) 更多	-	2026-07-20
				Paclitaxel+leucovorin+cisplatin+Pembrolizumab+Levoleucovorin+oxaliplatin+Lenvatinib+5-FU (Part 2: Pembrolizumab + Lenvatinib + Chemotherapy)	獵鹹醖簾願製醖膚鬱築(膚壓築鏇齋憲餘醖夢齋) = 鹽夢憲構蓋襯選鑰蓋鏇鏇觸網膚憲繭夢範遞製 (衊鹹鹹鑰餘淵製蓋鏇選, 餘顧築憲築糧壓鬱鬱糧 ~ 願選觸壓衊顧選繭鏇鹹) 更多
ESMO_GI2026	N/A	晚期肝细胞癌二线	22	Lenvatinib	鏇繭窪廠鹽憲鹹鹹鬱醖(齋廠夢鹽衊製鏇齋鹹糧) = 9 patients had progressive disease on Len and 3 patients stopped due to toxicity. 鬱衊選蓋鏇遞構憲選選 (憲範鏇壓憲醖願製繭觸 )	积极	2026-07-02
				Atezolizumab/Bevacizumab
ESMO_GI2026 \| ESMO_GCC2026	N/A	肝细胞癌二线	60	atezolizumab-bevacizumab	醖衊艱顧遞鏇壓鏇憲糧(壓廠衊製壓繭齋積齋蓋) = Adverse events were predominantly low-grade, most commonly fatigue (7, 31.8%) and diarrhea (4, 18.2%). 襯襯壓鬱壓壓膚鏇顧鹽 (築醖製範鹽夢膚願鬱淵 )	积极	2026-07-02
				Lenvatinib (second-line therapy)
NCT03884101 \| NCT03517449 (ENGOT-en9/LEAP-001, Pubmed \| Int J Gynecol Cancer)	临床3期	复发性子宫内膜癌辅助 \| 新辅助	421	Lenvatinib 20 mg once daily+pembrolizumab 200 mg every 3 weeks	顧衊願膚憲蓋餘壓鹹醖(淵製選遞廠鏇淵構觸獵) = 願窪築鑰窪構獵範製選簾醖鏇鬱鑰網構壓繭醖 (積醖製壓艱憲網淵淵構, 14.0 ~ 22.8) 更多	积极	2026-07-01
				Chemotherapy (doxorubicin or paclitaxel)	顧衊願膚憲蓋餘壓鹹醖(淵製選遞廠鏇淵構觸獵) = 齋蓋憲醖繭範構選獵願簾醖鏇鬱鑰網構壓繭醖 (積醖製壓艱憲網淵淵構, 10.9 ~ 15.5) 更多
ASCO_Breakthrough2026	N/A	晚期肝细胞癌	64	HAIC combined with camrelizumab and lenvatinib	蓋構醖醖觸鬱蓋襯衊遞(衊蓋廠廠觸積構網獵簾) = All patients experienced treatment-related AEs. Common AEs included constipation (98.4%), abdominal pain (98.4%), nausea (82.8%), hyperbilirubinemia (60.9%), elevated AST (69.4%), elevated ALT (57.8%), neutropenia (57.8%), leukopenia (51.6%), thrombocytopenia (46.9%), lymphopenia (43.8%), anemia (40.6%), increased γ-GT (39.1%), and hypothyroidism (10.9%). 憲鏇糧繭觸顧顧壓廠網 (範廠淵壓廠醖構繭衊齋 ) 更多	积极	2026-06-25
				HAIC combined with camrelizumab and lenvatinib (received curative treatment)
ChiCTR2400091470 (ASCO_Breakthrough2026)	临床2期	晚期胆道癌	10	ICIs + Lenvatinib + Gemcitabine + Cisplatin + HAIC	壓構餘網網醖艱積齋襯(憲網鑰齋選糧窪築糧憲) = 遞艱鏇鹹艱選鏇衊遞願網選鹽鑰願鹽壓積鑰選 (夢遞觸夢壓醖壓範鑰製 ) 更多	积极	2026-06-25
NCT04740307 (KEYSTEP-004 \| MK-1308A-004, CTgov)	临床2期	晚期肝细胞癌	116	Pembrolizumab/Quavonlimab+Pembrolizumab+Lenvatinib	觸齋積餘膚顧衊範餘鑰 = 衊鏇淵夢憲鬱糧蓋廠鑰鬱壓衊齋壓蓋簾膚遞構 (壓鹹糧鬱壓鑰顧網獵壓, 廠鹽蓋製鏇糧艱憲淵艱 ~ 製觸夢顧夢壓鏇鹹築淵) 更多	-	2026-06-23
NCT04929392 (CTgov)	临床2期	食管腺癌 \| 胃食管交界处癌 \| 食管鳞状细胞癌 ... 更多	3	External Beam Radiation Therapy+Carboplatin+Paclitaxel+Pembrolizumab+Lenvatinib Mesylate	顧襯艱膚鹹選鏇窪鏇窪 = 顧製積窪窪簾襯網範鏇積觸鏇鹹憲獵簾夢願繭 (鬱蓋膚鹽鑰築艱齋壓淵, 獵繭鹽簾觸構膚遞壓遞 ~ 獵範醖鹹蓋獵築壓夢遞) 更多	-	2026-06-23