2025年11月7日-11日，全球肝病领域顶级学术盛会-美国肝病研究学会(AASLD)年度大会 The Liver Meeting 2025 将在美国•华盛顿会议中心正式召开。本次会议将汇聚肝病研究领域的最新科研硕果与前沿探索方向，为全球参会者精心构筑一个深化肝病理论认知、拓展专业视野边界的学术交流殿堂。

为助力广大读者精准捕捉会议的学术精髓，及时洞悉领域前沿动态，肝胆相照平台特别甄选会议摘要中的热点研究内容，本篇专题报道聚焦“MASLD”这一关键领域，为广大同仁提供最新研究进展，展望其在临床实践中的广阔应用前景。

热点研究汇总

一

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Saroglitazar 改善合并 PCOS 与 MASLD 女性的肝脂肪变性：EVIDENCES VII 随机对照研究结果

萨罗格列净改善多囊卵巢综合征和代谢相关脂肪性肝病女性的肝脂肪变性：EVIDENCES VII 随机对照研究结果

作者：Niharika Samala¹，Monika Sarkar²，Sreemala Murthy³，Taufik Momin⁴，Sukanya Krishnan⁵，Farheen Shaikh⁵，Naga Chalasani⁶

¹印第安纳大学; ²加利福尼亚大学旧金山分校; ³印第安纳大学医学院; ⁴济德斯生活; ⁵济德斯; ⁶印第安纳大学医学中心

研究背景

代谢功能障碍相关脂肪性肝病（MASLD）在多囊卵巢综合征（PCOS）患者中十分常见，且常伴有更严重的肝组织学损伤。目前尚缺乏针对 PCOS合并MASLD的特异性治疗。基于此，本研究评估了Saroglitazar 4 mg/天对PCOS合并MASLD女性患者的疗效与安全性。

背景：代谢功能障碍相关的脂肪性肝病（MASLD）在多囊卵巢综合征（PCOS）中很常见，并且与更严重的组织学相关。目前缺乏专门针对PCOS患者MASLD的治疗方法。因此，我们研究了多囊卵巢综合征和MASLD女性中每天4毫克 saroglitazar的疗效和安全性.

研究方法

EVIDENCES VII 研究（NCT03617263）为一项多中心、随机、双盲、安慰剂对照试验。受试者为PCOS合并MASLD女性，随机分配接受 Saroglitazar 4 mg/天 或安慰剂，共24周。主要终点为治疗前后 MRI-PDFF（质子密度脂肪分数）的变化，在可评估人群（PPP）中进行分析，该人群包括基线及治疗结束时均有 MRI-PDFF 数据的个体。另评估预设的次要与探索性疗效、安全性及耐受性指标。

Methods：EVIDENCES VII (NCT03617263) is a multicenter, randomized, double-blind, placebo-controlled trial of saroglitazar 4 mg/day for 24 weeks in women with PCOS and MASLD. The primary endpoint was a change in MRI-PDFF from baseline to 24 weeks in the per-protocol population (PPP), which included individuals who had an evaluable MRI-PDFF at both baseline and at the end of treatment. Prespecified secondary and exploratory efficacy, safety, and tolerability endpoints were evaluated.

 研究结果

共评估155例疑似MASLD的 PCOS 女性，符合条件者60例，随机分配至Saroglitazar组（n=30）和安慰剂组（n=30）。PPP共包括25例Saroglitazar组及23例安慰剂组受试者。两组基线MRI-PDFF均值分别为22.02% ± 8.24%与22.66% ± 9.47%，总体匹配良好，除 Saroglitazar组的HbA1c略高（5.9% vs 5.5%，P = 0.035）。MRI-PDFF 从基线至24周的绝对变化（CFB）为Saroglitazar 组-3.13 ± 5.35，对照组-0.40 ± 4.98（p = 0.061）；MRI-PDFF 的百分比变化（%CFB）为Saroglitazar组 -14.67% ± 27.77%，安慰剂组1.89%±27.47%（P=0.041）。经HbA1c校正后，Saroglitazar的疗效更显著，MRI-PDFF的绝对变化（P=0.002）与百分比变化（P<0.001）均有统计学差异。

MRI-PDFF降低≥30%的受试者比例Saroglitazar组显著高于安慰剂组（36%vs8.7%，p=0.024）。此外，Saroglitazar组在多项代谢指标上表现更优：ALT（-37%vs4.8%，P=0.007）、碱性磷酸酶ALP（-28%vs-2.1%，P<0.001）、甘油三酯（-16%vs18%，P=0.009）、总胆固醇（-13%vs-1.5%，P<0.001）及sdLDL-C（-21%vs1.4%，P=0.027）。两组在HOMA-IR、性激素结合球蛋白（SHBG）、游离雄激素指数及其他性激素方面无显著差异。Saroglitazar耐受性良好，治疗组与对照组在体重、腰围及不良事件发生率方面均无差异。

Results：A total of 155 women with PCOS and suspected MASLD were assessed for eligibility. After applying eligibility criteria, 60 women were randomized to receive either 4 mg saroglitazar (n = 30) or placebo (n = 30). The PPP consisted of 25 saroglitazar and 23 placebo participants with baseline MRI-PDFF (mean ± SD) of 22.02% ± 8.24% and 22.66% ± 9.47%, respectively. The two groups were well matched except for higher HbA1c in the saroglitazar group (5.9% vs 5.5%, p = 0.035).

MRI-PDFF absolute change from baseline (CFB) to 24 weeks was -3.13 ± 5.35 with saroglitazar vs -0.40 ± 4.98 with placebo (p = 0.061). The %CFB of MRI-PDFF at 24 weeks was -14.67 ± 27.77 with saroglitazar vs 1.89 ± 27.47 with placebo (p = 0.041). The effect of saroglitazar was more pronounced after adjusting for HbA1c, demonstrating significant improvement based on both absolute CFB (p = 0.002) and %CFB (p < 0.001) in MRI-PDFF.

The proportion with ≥30% reduction in MRI-PDFF was significantly higher with saroglitazar than placebo (36% vs 8.7%, p = 0.024). Mean %CFB favored saroglitazar for ALT (-37% vs 4.8%, p = 0.007), ALP (-28% vs -2.1%, p < 0.001), triglycerides (-16% vs 18%, p = 0.009), total cholesterol (-13% vs -1.5%, p < 0.001), and sdLDL-C (-21% vs 1.4%, p = 0.027).

There were no significant changes between treatment groups for HOMA-IR, sex hormone-binding globulin, free androgen index, or other sex hormones. Saroglitazar was well tolerated, with no differences in body weight, waist circumference, or adverse events between groups.

研究结论

对于合并PCOS与MASLD的女性患者，Saroglitazar4mg/天可显著改善肝脂肪变性及血脂异常，且安全性与耐受性良好。

Conclusion：In patients with PCOS and MASLD, saroglitazar 4 mg/day significantly improved hepatic steatosis and dyslipidemia.

二

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专家组标准在预测高风险与非高风险 MASH 患者中的表现：来自大型多中心队列的数据

PERFORMANCE OF EXPERT PANEL CRITERIA IN PREDICTING AT-RISK AND NOT-AT-RISK MASH: DATA FROM A LARGE MULTI-CENTER COHORT

作者：Rashmee Patil¹, Jörn Schattenberg², Elizabeth Brombosz³, Gražina Binkauskiene³, Michelle Mazuranic³, Alma Laura Ladron de Guevara⁴, Marcelo Kugelmas⁵, Dimple Desai⁶, Aasim Sheikh⁷, John Poulos⁸, Edward Mena⁹, Mazen Noureddin¹⁰, Naim Alkhouri³

¹Pinnacle Clinical Research; ²Saarland University Medical Center, University of the Saarland; ³Summit Clinical Research; ⁴Centro de Investigacion y Gastroenterologia; ⁵South Denver Gastroenterology; ⁶South Texas Research Institute; ⁷Gastrointestinal Specialists of Georgia; ⁸Coastal Research Institute; ⁹California Liver Research Institute; ¹⁰Houston Methodist Hospital

研究背景

随着代谢功能障碍相关脂肪性肝病（MASLD）和代谢功能障碍相关脂肪性肝炎（MASH）发病率的上升，如何利用无创检测（NITs）区分具有肝脏相关并发症风险的患者与无风险人群显得尤为重要。2024年专家组共识（PMID39038768）及AASLD最新指南推荐了基于NITs的诊断算法，用于筛选可能从药物治疗中获益的高风险MASH患者，其依据包括肝酶水平、VCTECAP（用于评估脂肪变性）及LSM（用于评估纤维化）。本研究旨在验证这些算法在识别高风险与非高风险MASH患者中的有效性。

Background：As the incidence of MASLD and MASH rises, it is increasingly important to distinguish patients at risk of liver-related morbidity using non-invasive tests (NITs). A 2024 expert panel summary (PMID 39038768) and the updated AASLD practice guidance recommended NIT-based algorithms to identify patients with at-risk MASH who might benefit from pharmacologic treatment, based on liver enzymes, VCTE CAP for steatosis, and LSM for fibrosis. This study aimed to evaluate the performance of these algorithms in identifying at-risk versus not-at-risk MASH.

研究方法

研究回顾了大型数据库中接受MASH药物治疗临床试验筛选且有肝活检结果的患者资料。依据肝活检结果（NAS≥4且存在F2或F3期纤维化）将患者分为高风险与非高风险MASH两组。随后，利用肝活检结果评估各类常用NIT的诊断性能。所有统计分析使用SAS软件进行，P<0.05认为具有统计学意义。

Methods：A large database of patients evaluated for inclusion in MASH pharmacotherapy trials with available biopsy results was reviewed. Patients were classified as at-risk or not-at-risk MASH based on biopsy findings (NAS ≥ 4 and F2 or F3 fibrosis). Biopsy results were used to assess the diagnostic performance of the most frequently utilized NITs. Statistical analyses were performed using SAS software, with p < 0.05 considered statistically significant.

 研究结果

共纳入2,647例患者，其中1,408例（53%）为高风险MASH。与非高风险组相比，高风险组患者更常为女性（P=0.001）、非白人（P<0.001）及西班牙裔（P<0.001）。单项NIT在识别高风险MASH时的灵敏度介于14%–97%，特异度介于7%–89%（见表1）。

根据专家指南推荐的多指标联合评估结果显示，当CAP>280dB/m、LSM在8–15kPa且AST>17IU/L（女性）或>20IU/L（男性）时，灵敏度最高（60%）。而在联合模型中，CAP、LSM15.1–20kPa及相同AST阈值组合的特异度最高（93%）。CAP、LSM10–15kPa与AST>30IU/L的组合模型具有最高的曲线下面积（AUC=0.61），并能正确分类60%的高风险患者。在单项检测中，CAP单独识别高风险MASH的正确率最高（55%），其次为AST（53%）。

Results： Among 2,647 patients, 1,408 (53%) had at-risk MASH. Demographically, patients with at-risk MASH were more likely to be female (p = 0.001), non-White (p < 0.001), and Hispanic (p < 0.001). The performance of individual NITs in identifying at-risk MASH showed sensitivity ranging from 14% to 97% and specificity from 7% to 89% (Table 1).

When multiple NITs were applied, as recommended by expert guidelines, sensitivity was highest when CAP > 280 dB/m, LSM 8–15 kPa, and AST > 17 IU/L in females or > 20 IU/L in males (60%). In combined models, specificity was highest for CAP, LSM 15.1–20 kPa, and AST > 17 IU/L in females or > 20 IU/L in males (93%). The combination of CAP, LSM 10–15 kPa, and high AST (> 30 IU/L) yielded the highest AUC among all models (0.61) and correctly classified 60% of patients as at-risk.

The proportion of patients correctly identified as at-risk MASH was highest using CAP alone (55%), followed by AST alone (53%).

研究结论

研究结果表明，专家组推荐的无创检测算法能够较好地识别高风险MASH患者。然而，为进一步精确鉴别可能从药物治疗中获益的人群，仍需结合MRI-PDFF、MRE或综合评分（如MAST）等额外的确认性检测手段。

Conclusion：These findings suggest that expert-recommended algorithms can effectively identify high-risk patients using non-invasive tests. However, additional confirmatory methods—such as MRI-PDFF, MRE, or composite scores like MAST—may be necessary to more precisely identify patients who would benefit from pharmacologic therapy for at-risk MASH.

三

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减重手术、GLP-1受体激动剂与SGLT2抑制剂对MASLD患者复合性肝脏事件的比较疗效：一项多中心回顾性队列研究

COMPARATIVE EFFECTIVENESS OF BARIATRIC SURGERY, GLP-1 RA, AND SGLT2i ON COMPOSITE LIVER EVENTS IN MASLD PATIENTS: A MULTICENTER RETROSPECTIVE COHORT STUDY

作者：Diwanshu Soni¹, Leith Ghani¹, Majd Aboona¹, Pooja Rangan¹, Derek Scholes¹, Chih-Hua Chung², Mark Wong², Karn Wijarnpreecha³, Rohit Nathan¹, Moises Ruben¹, Michael Fallon¹, Farah Husain¹, Ma Ai Thanda Han⁴

¹University of Arizona College of Medicine – Phoenix; ²University of Arizona College of Medicine – Phoenix; ³University of Arizona College of Medicine – Phoenix; ⁴University of Arizona College of Medicine – Phoenix

背景

代谢功能障碍相关脂肪性肝病（MASLD）是全球最主要的慢性肝病原因，可进展为腹水、肝性脑病、食管静脉曲张、肝细胞癌（HCC）等严重并发症，并可能需要肝移植。

既往研究表明，减重手术、GLP-1受体激动剂（GLP-1RA）及SGLT2抑制剂（SGLT2i）均可延缓疾病进展，但尚缺乏直接比较其疗效的研究。本研究篇评估了上述不同干预措施对MASLD患者复合性肝脏事件发生率的影响。

Background：Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide and can progress to serious complications such as ascites, hepatic encephalopathy, esophageal varices, hepatocellular carcinoma (HCC), and liver transplantation. Bariatric surgery, GLP-1 receptor agonists (GLP-1 RA), and SGLT2 inhibitors (SGLT2i) have each been shown to slow disease progression, but their comparative effectiveness remains unclear. This study aimed to compare how these interventions affect the incidence of composite liver events in MASLD patients.

方法

本多中心回顾性队列研究在BannerHealth医疗体系开展，纳入依据ICD编码及代谢标准确诊为MASLD的患者。研究对象接受减重手术、GLP-1RA、SGLT2i或联合治疗，并随访至少12个月。复合性肝脏事件包括：肝相关事件（LREs：腹水、肝性脑病、食管静脉曲张）、肝移植及肝细胞癌（HCC），评估时间为干预后12个月。

药物使用经病历核实，减重手术经ICD编码确认，仅纳入由合格减重外科医生完成的病例。采用竞争风险分析比较不同治疗组复合性肝脏事件的发生率，以减重手术组为参照组，并对混杂因素进行校正。同时绘制Kaplan–Meier生存曲线，展示无肝脏事件生存率。

Methods：This multicenter retrospective cohort study conducted at Banner Health evaluated the impact of various interventions in MASLD patients identified through ICD codes and metabolic criteria. Patients received bariatric surgery, GLP-1 RA, SGLT2i, or combination therapy and were followed for at least 12 months.

Composite liver events included liver-related events (LREs: ascites, hepatic encephalopathy, or esophageal varices), liver transplantation, and hepatocellular carcinoma (HCC) within 12 months post-intervention. Medication use was confirmed, and bariatric procedures were validated using ICD codes and included only if performed by a certified bariatric surgeon.

Competing risk analysis was performed to assess the incidence of composite liver events across treatment groups, using the bariatric surgery group as the reference while adjusting for confounding variables. A Kaplan–Meier survival curve was generated to illustrate composite liver event–free survival.

 结果

共纳入14,589例患者，其中4.6%接受减重手术，45.4%使用GLP-1RA，27.2%使用SGLT2i，22.8%接受联合治疗。单变量与多变量分析均显示，减重手术组在干预后12个月内复合性肝脏事件（包括LREs、肝移植和HCC）发生率显著低于GLP-1RA组与SGLT2i组。然而，与联合治疗组比较，多变量分析未见统计学显著差异。Kaplan–Meier生存分析显示，减重手术组的无肝脏事件生存率明显优于其他治疗组。

Results：The cohort included 14,589 patients: 4.6% underwent bariatric surgery, 45.4% received GLP-1 RA, 27.2% received SGLT2i, and 22.8% received combination therapy..

Univariate and multivariate analyses showed that the bariatric surgery group had significantly lower rates of composite liver events — including LREs, liver transplantation, and HCC — at 12 months post-treatment compared with the GLP-1 RA and SGLT2i groups. However, multivariate analysis revealed no statistically significant difference when compared with the combination therapy group.

Kaplan–Meier survival analysis demonstrated superior liver event–free survival in the bariatric surgery group.

结论

在MASLD患者中，即使调整混杂因素后，减重手术在干预后12个月内仍较GLP-1RA与SGLT2i更有效地降低肝脏事件发生率。未来研究可进一步探讨在不同肝硬化状态下的MASLD亚组中，各干预措施的相对疗效。此外，仍需前瞻性研究以验证本研究结果，并系统评估这些干预对MASLD患者肝脏结局的长期影响。

Conclusion： Bariatric surgery was more effective than GLP-1 RA and SGLT2i in reducing liver events among MASLD patients within 12 months post-intervention, even after adjusting for confounding factors. Future studies should evaluate the comparative effectiveness of these interventions in MASLD subgroups with and without cirrhosis at the time of treatment. Moreover, prospective studies are warranted to validate these findings and to further assess the long-term impact of these interventions on liver-related outcomes in MASLD patients.

Tags： 2025 AASLD | “MASLD”领域三篇亮点研究提前看