代谢功能障碍相关脂肪性肝炎 （MASH） ，是 代谢功能障碍相关脂肪性肝病 （MASLD） 进展至终末期 肝病的重要阶段，对全球公众健康构成日益严重的威胁，且治疗选择非常有限。 MASLD/MASH 表现出明显的 性别差异 ，绝经期前女性的发病率低于男性及绝经后女性，这提示了 雌激 素信号 可能在肝脏中发挥着重要的保护作用。然而，肝脏雌激素信号的具体调控机制，仍有待阐明。 2026 年 1 月 5 日，上海交通大学 黄哲 团队联合 南京中医药大学 蒋卫民 团队、复旦大学 附属上海市第 五人民医院 臧淑妃 团队及 东部战区总医院 顾萍 团队 （ 杨芳 、 王魏 为论文共同第一作者 ） ，在 Nature 子刊 Nature Metabolism 上 发表了题为 ： Hepatic GPR110 contributes to sex disparity in the development of MASH through oestrogen receptor α-dependent signalling 的研究论文。 该研究表明，肝脏中的 G 蛋白偶联受体 GPR110 通过调控肝脏 雌激素受体 α （ER α ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 真核细胞含有多种 无膜细胞器 ，包括细胞核内的核仁、PML 小体、卡哈尔小体、核斑和核应激体，以及细胞质中的应激颗粒 （SG） 、P-body、肌球蛋白颗粒 和神经元运输颗粒。这些无膜细胞器是细胞内多种生物过程时空协调的执行者。例如，应激颗粒 （SG） 会在各种应激压力下迅速聚集，以隔离未翻译的mRNA 以防止异常翻译，并促进应激压力后的恢复，P-body 参与 mRNA 的修饰和降解，它们的失调与多种疾病有关。发现新的无膜细胞器仍是一个活跃研究领域，备 受研究人员的关注。 2026 年 1 月 9 日，海军军医大学免疫与炎症全国重点实验室 侯晋 、 曹雪涛 院士等 （ 李云晖 、 雷婷 、 聂雯 、 马明睿 、 赵伟 、 周烨 为论文共同第一作 者） ， 在 Cell Metabolism 期刊 发表 了 题为： Lipid-induced granules in hepatocytes alleviate liver fibrosis 的研究论文。 发现了在 肝细胞 中由 脂质累积 诱导形成的 一种 新型 无膜细胞器 ，将其命名为 脂质诱导 颗粒 （Lipid-in ...

格隆汇1月7日丨信立泰(002294.SZ)公布，收到国家药品监督管理局核准签发的受理通知书，公司自主 研发的创新药SAL0145注射液（项目代码：SAL0145）临床试验申请获得受理。代谢功能障碍相关脂肪 性肝炎（MASH）是代谢功能障碍相关脂肪性肝病（MASLD）的进展形式之一，后者累及全球约30% 成年人口。若不加以干预或治疗，MASH会进一步发展为肝硬化甚至肝癌，对患者的生命健康造成威 胁。临床前研究显示，SAL0145具有治疗MASH的潜力，若能研发成功并获批上市，将有望为患者提供 新的用药选择，满足未被满足的临床需求，并进一步丰富公司慢病领域的创新产品管线。 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 代谢功能障碍相关脂肪性肝病 （MASLD） ，之前称为非酒精性脂肪性肝病 （NAFLD） ，是一个日益严重的全球健康问题。MASLD 可从单纯脂肪变性 （MASL） 进展为代谢功能障碍相关脂肪性肝炎 （MASH） ，其特征为肝细胞气球样变和小叶炎症。 在 MASH 中，轻度至重度炎症活动 （≥I2） 和显著纤维化 （≥F2） 的存在与发病率和死亡率增加相关。因此，I≥2 或 F≥2 的患者被认为处于有风险的 MASH 状态。尽管纤维化逆转仍是关键的治疗终点，但显著纤维化和轻度至重度炎症活动是启动临床干预的关键时期。因此，迫切需要识别出疾病进展风险更高且可能 从临床干预中获益的 MASH 患者。 近日，上海交通大学医学院附属瑞金医院 谢青 教授、 曹竹君 研究员， 中国科学院上海药物研究所 谢岑 研究员、 郭小珍 副研究员作为共同通讯作者 （ 黄燕 、 李嘉琦 、 宋舒瑛 、 杜冰莹 、 曹愈堂 为共同第一作者 ） ，在 Cell 子刊 Cell Reports Medicine 上发表了题为： Blood metabolic panels for identifying ...

Core Insights - Altimmune, Inc. announced positive topline results from the IMPACT Phase 2b trial of pemvidutide, a dual receptor agonist, in patients with metabolic dysfunction-associated steatohepatitis (MASH) at 48 weeks [2][3] Group 1: Trial Results - Statistically significant improvements in key non-invasive markers of fibrosis, including Enhanced Liver Fibrosis (ELF) and Liver Stiffness Measurement (LSM), were observed across treatment arms compared to placebo [3][5] - The 1.2 mg and 1.8 mg doses of pemvidutide achieved mean reductions in ELF of -0.49 and -0.58 respectively, versus +0.16 in placebo (p<0.0001) [5] - The 1.2 mg and 1.8 mg doses achieved mean reductions in LSM of -3.04 (p<0.05) and -3.97 (p<0.001) respectively, compared to -0.03 in placebo [5] - Participants receiving pemvidutide also showed significant reductions in liver fat content, alanine aminotransferase (ALT), and corrected T1 (cT1) [5] - Weight loss was observed with the 1.2 mg and 1.8 mg doses at 4.5% and 7.5% respectively, compared to 0.2% in placebo (p<0.0001) [13] Group 2: Tolerability and Safety - The tolerability profile of pemvidutide was favorable at 48 weeks, with low treatment-related discontinuation rates of 0% and 1.2% for the 1.2 mg and 1.8 mg doses respectively, compared to 3.5% for placebo [13] - No serious or severe adverse events related to treatment were reported [13] Group 3: Regulatory Progress - The company held a productive End-of-Phase 2 meeting with the FDA, aligning on parameters for a registrational Phase 3 trial for pemvidutide in MASH patients with moderate to advanced liver fibrosis [6][7] - The FDA's qualification of AIM-MASH AI Assist was noted, which aims to standardize histologic assessment in the Phase 3 trial [6] Group 4: Future Plans - The company plans to initiate the Phase 3 program for pemvidutide in 2026, leveraging the strong evidence of antifibrotic improvements and favorable tolerability [7]

Core Insights - The article discusses the increasing public health burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and its progression to Metabolic Dysfunction-Associated Steatohepatitis (MASH), highlighting limited treatment options [2] - A study published in Cell Metabolism reveals that the diene acid analog 326E alleviates MASH by dual targeting ACLY and PPARα, demonstrating its therapeutic potential and good tolerability in human clinical trials [2][5] Group 1: Mechanism and Efficacy - The diene acid ATP-citrate lyase (ACLY) inhibitor 326E significantly reduces liver lipid accumulation and alleviates MASH symptoms in mouse models [3] - 326E works by inhibiting ACLY to decrease de novo lipogenesis (DNL) and acts as an allosteric modulator of PPARα to enhance fatty acid oxidation (FAO), thus addressing MASH [3][8] - The study confirmed the preventive effects of 326E on MASH in non-human primates, further supporting its potential as a treatment [4] Group 2: Clinical Trials and Results - A randomized 1b/2a phase clinical trial in human MASH patients (NCT06491576) showed that 326E has good tolerability and lowers levels of γ-glutamyl transferase (γ-GGT), a key biomarker for liver disease [5][9] - The results from preclinical studies in mice and non-human primates, along with human clinical trials, indicate that 326E has therapeutic potential for MASH through its unique mechanisms of action [8]

Core Viewpoint - Novo Nordisk has reached a final agreement to acquire Akero Therapeutics for up to $5.2 billion, with a cash offer of $54 per share and an additional contingent value right of $6 per share, pending regulatory approval of Akero's drug efruxifermin [1][2] Group 1: Acquisition Details - The total acquisition price is up to $5.2 billion, consisting of $4.7 billion in cash and a $500 million contingent value right [1] - The deal has been unanimously approved by Akero's board and is expected to close by the end of the year [1] - Following the announcement, Akero's stock surged nearly 18%, while Novo Nordisk's stock fell over 1% [1] Group 2: Akero Therapeutics and Efruxifermin - Akero is a clinical-stage biopharmaceutical company focused on developing therapies for patients with severe metabolic diseases [1] - Efruxifermin is currently undergoing late-stage trials aimed at treating patients with moderate to advanced liver fibrosis due to metabolic dysfunction-associated steatohepatitis (MASH) [1] - MASH can progress from metabolic dysfunction-associated steatotic liver disease (MASLD) and is characterized by steatosis, inflammation, and fibrosis, potentially leading to cirrhosis [1] Group 3: Strategic Implications - Novo Nordisk's CEO emphasized the potential of efruxifermin to reverse liver damage and become a cornerstone therapy, either alone or in combination with Wegovy [2] - Akero believes that Novo Nordisk's global leadership in metabolic diseases will accelerate the evaluation and commercialization of efruxifermin [2] - A contingent payment of $6 per share will be made to Akero shareholders if efruxifermin receives full approval from U.S. regulators by June 30, 2031 [2]

Core Viewpoint - Roche is strengthening its position in the cardiovascular, renal, and metabolic diseases (CVRM) sector through the acquisition of 89bio for $3.5 billion, securing the innovative MASH drug Pegozafermin, which is currently in Phase III clinical trials [1][10]. Group 1: Acquisition Details - Roche's acquisition of 89bio focuses on Pegozafermin, which has the potential to generate peak sales exceeding $5 billion, as the global MASH drug market is projected to reach $35 billion by 2030 [1][2]. - The acquisition agreement includes a base price of $14.50 per share plus up to $6 per share in contingent value rights (CVR), potentially bringing the total deal value to $3.5 billion [4][8]. - The CVR stipulates additional payments based on Pegozafermin achieving specific sales milestones, potentially adding up to $1 billion for 89bio's shareholders [5][6][7]. Group 2: Market Potential and Demand - MASH affects an estimated 5%-7% of the adult population globally, with significant unmet clinical needs, particularly in China and the U.S., where the number of patients is expected to rise substantially by 2032 [2][4]. - The MASH treatment landscape has seen numerous failures, making Pegozafermin's potential as a first-in-class therapy particularly promising [4][19]. Group 3: Roche's CVRM Strategy - Roche's CEO emphasized that the acquisition enhances the company's CVRM product portfolio and opens opportunities for combination therapies with existing projects [11]. - Roche has a diverse pipeline in the CVRM space, including several promising candidates such as GLP-1 drugs and RNAi therapies, indicating a strategic focus on this area for future growth [14][16][17]. - The company has invested in multiple potential blockbuster drugs, including Petrelintide and Zilebesiran, to solidify its position in the metabolic and cardiovascular markets [17][19]. Group 4: Competitive Landscape - The MASH treatment field is highly competitive, with over 60 active clinical trials and multiple candidates from major pharmaceutical companies, highlighting the intense research activity in this area [19][22]. - Roche's strategic investments and acquisitions are aimed at building a comprehensive network in the CVRM sector, positioning the company for significant growth in this rapidly evolving market [22][23].

Core Viewpoint - Novo Nordisk's weight loss drug Wegovy has recently received FDA approval for a new indication, allowing it to be used for the treatment of metabolic dysfunction-associated steatotic liver disease (MASH), which has positively impacted the company's stock price, increasing it by up to 5% [1][3]. Group 1 - The approval signifies that Novo Nordisk has gained a first-mover advantage in the lucrative GLP-1 drug market by expanding the indication from weight loss to liver disease [5][7]. - Wegovy's application now includes treatment for adults with moderate to severe liver fibrosis associated with MASH, providing new treatment options for patients suffering from this serious liver condition [9]. - Analysts believe that this approval could help Novo Nordisk reverse its declining market performance, which has seen its market value nearly halved due to intense competition in the obesity market [6][8]. Group 2 - Wegovy is well-known for its significant weight loss effects, which have contributed to a rapidly growing market, and expanding its application will enhance its competitive position [7]. - The company faces pressure from cheaper generics and more effective competitors like Eli Lilly's Zepbound, making the expansion of Wegovy's uses a crucial step to support demand for its flagship product [8]. - The approval is seen as a critical development for Novo Nordisk, especially after a challenging start to the year [6].

Core Viewpoint - The article discusses the significant role of GLP-1 receptor agonists, particularly semaglutide, in treating metabolic dysfunction-associated steatohepatitis (MASH) and its mechanisms beyond weight loss [6][12]. Group 1: Mechanism of Action - Semaglutide shows a strong effect on blood sugar control and weight loss, rapidly gaining recognition as a "miracle drug" for weight management [6]. - A recent study published in *Nature Medicine* reveals that semaglutide not only aids in weight loss but also has direct effects on liver tissue, indicating multiple pathways of action [6][12]. - Mediation analysis indicates that approximately 69.3% of the total effect on MASH relief can be attributed to weight loss, while the contribution to combating liver fibrosis drops to only 25.1%, suggesting other mechanisms are at play [7][12]. Group 2: Protein Analysis - The study identified 72 proteins associated with MASH relief and semaglutide treatment, many of which are linked to metabolic, fibrotic, or inflammatory pathways [9]. - In a separate cohort, these proteins were found to be abnormally expressed in MASH patients, and their levels normalized after semaglutide treatment, indicating a "reset" of pathological protein profiles [9][11]. Group 3: Animal Studies - Animal models demonstrated that semaglutide can inhibit fibrosis independently of weight loss, with significant reductions in liver fibrosis markers observed even in models that did not gain weight [10][11]. - The gene expression profiles in liver tissues showed downregulation of genes related to inflammation and collagen synthesis, confirming direct anti-fibrotic mechanisms [10][11]. Group 4: Future Implications - The research presents a comprehensive view of semaglutide's action against MASH, highlighting that while weight loss is a crucial mechanism, there are additional molecular effects that contribute to its efficacy [12][14]. - If future trials validate the predictive value of the identified protein markers, they could serve as dynamic biomarkers for early identification, personalized treatment, and efficacy monitoring in MASH patients [12][14].