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直击EASL 2026丨Cautar EL Maimouni医生:聚焦晚期MASLD管理痛点,揭示代谢因素管控不足与肝纤维化进展关联

国际肝病 发表时间:2026/6/16 23:01:13 浏览量:119

2026年欧洲肝病学会年会(EASL 2026)在巴塞罗那顺利召开,这场国际肝病领域的顶级盛会,持续聚焦代谢相关脂肪性肝病(MASLD)这一临床重点议题。目前针对晚期MASLD合并慢性肝病患者的心脏代谢危险因素研究仍存在数据缺口,也是临床诊疗的棘手难题。本次大会上,西班牙巴塞罗那医院(Hospital Clinic Barcelona)Cautar EL Maimouni医生带来了相关多中心前瞻性研究。《国际肝病》特邀Maimouni教授接受专访,分享研究设计思路、临床探索方向与学术见解,探讨此项研究对晚期MASLD慢病管理的意义,现将访谈内容整理如下。


研究简介


摘要号:TOP-097-YI

晚期代谢相关脂肪性肝病患者的心代谢共病现状,以及血糖、体重管控对肝脏硬度的影响研究

Assessment of cardiometabolic comorbidities and the impact of glycemic and weight control on liver stiffness in advanced metabolic dysfunction associated steatotic liver disease


背景与目的

心代谢危险因素会推动MASLD的病情进展,但目前针对该病晚期阶段危险因素的患病情况、管控现状及临床影响的相关数据仍较为有限。本研究旨在:(1)分析合并MASLD的晚期慢性肝病(ACLD)患者的心代谢危险因素负荷与管控情况;(2)探究血糖控制水平及体重变化对疾病进展的影响。


研究方法

本研究为前瞻性、观察性、多中心临床试验。纳入标准:肝脏硬度值(LSM)≥10 kPa、肝纤维化分期F3~F4期,或影像学提示存在晚期肝脏病变的MASLD相关晚期慢性肝病患者。分别采集患者基线及随访阶段的临床资料、实验室检查与影像学数据。

本研究对肝脏硬度变化作出明确定义:肝脏硬度进展指LSM由<10 kPa升至≥10 kPa,或LSM升高幅度≥30%;肝脏硬度改善指LSM由≥10 kPa降至<10 kPa,或LSM下降幅度≥30%。


研究结果

本研究共纳入635例患者,女性占比50.2%;患者中位年龄66岁(IQR:59~72岁)。患者基线中位肝脏硬度值为17.3 kPa(12~25.7 kPa),中位受控衰减参数(CAP)为309 dB/m(269~351 dB/m)。

73%的患者合并2型糖尿病,其中12.5%患者血糖控制不佳;64.7%的患者存在肥胖,中位体质指数为32 kg/m²(29~36 kg/m²),仅有16.5%的患者使用胰高糖素样肽-1(GLP-1)受体激动剂治疗。整体人群中,82%的患者心血管风险为高危或极高危;55.9%的患者低密度脂蛋白胆固醇(LDL-C)未达到控制目标,56.5%的患者未接受他汀类药物治疗。

共有284例患者完成至少2次肝脏弹性检测(两次检测间隔≥1年),中位随访时长26个月(17~45个月)。其中14.8%的患者出现肝脏硬度进展,38.4%的患者肝脏硬度得到改善。随访期间,患者糖化血红蛋白(HbA1c)由6.7%显著降至6.4%(P=0.009),体重由86 kg显著降至83 kg(P=0.001)。

血糖控制不佳者的肝脏硬度进展发生率显著更高(47.6% vs 5.3%,P=0.002);血糖控制达标者的肝脏硬度改善比例明显更高(44.7% vs 19%,P=0.002)。体重增加或体重维持不变的患者更易出现肝脏硬度进展:两类人群进展占比分别为28%、17.6%,而体重下降≥5%的患者仅为8.3%(P=0.03)。体重降幅与肝脏硬度改善呈正相关:体重下降≥10%、下降5%~9.9%、下降<5%的患者中,肝脏硬度改善比例依次为58%、43%、33%(P=0.028)。

研究未发现他汀类药物使用与肝脏硬度变化存在关联。肝脏硬度进展会显著升高肝脏相关不良事件的发生风险(OR=4.3,95%CI:1.5~12.8,P=0.013)。


研究结论

MASLD相关晚期慢性肝病患者普遍存在心代谢危险因素管控不达标的问题。改善血糖控制、积极减重可明显降低肝脏硬度,提示优化代谢状态能够有效延缓本病的病情进展。


研究者访谈


《国际肝病》

既往针对代谢相关脂肪性肝病的研究多聚焦普通患者人群,关于晚期MASLD合并慢性肝病患者的心脏代谢危险因素数据相对匮乏。能否请您介绍一下,您团队开展这项多中心前瞻性研究的初衷是什么?


Maimouni医生:我们开展此项研究,首要目的是统计各类代谢因素的患病率。其中我们重点关注2型糖尿病与肥胖,二者是疾病进展最主要的驱动因素。现阶段仅得出初步研究结果,后续我们也会进一步分析其他代谢相关因素。此外,我们还希望评估这类代谢异常的控制水平,并探究其是否会影响晚期MASLD患者的病情发展,重点观察肝纤维化的进展、逆转与改善情况。


Hepatology Digest: Most previous studies on MASLD focus on general patients, while data on cardiometabolic risk factors in patients with advanced MASLD-related chronic liver disease are limited. Could you introduce the core original intention of this prospective multicenter study?

Dr. Cautar EL Maimouni, MD: Our primary objective for conducting this study was to calculate the prevalence of various metabolic factors. We placed particular emphasis on type 2 diabetes and obesity, as they are the major drivers of disease progression. We have only obtained preliminary results so far, and we will further analyze other related metabolic factors in follow-up work. In addition, we aimed to assess how well these metabolic abnormalities are controlled, and explore whether such abnormalities affect disease progression in patients with advanced MASLD. Our key observation focuses on the progression, regression and improvement of liver fibrosis.


《国际肝病》

本次研究纳入了635例晚期MASLD患者,能否为我们分享该研究人群的心脏代谢共病整体患病现状、血糖体重管控情况,以及GLP-1受体激动剂、他汀类药物的临床应用现状?这些数据反映了晚期MASLD患者目前存在哪些诊疗短板?


Maimouni医生:从患病情况来看,超半数患者合并至少一项心血管或心脏代谢危险因素。其中,2型糖尿病患病率达73%,高血压患病率高达75%,血脂异常的患病比例也超过半数,整体心脏代谢共病的患病风险极高。针对GLP-1受体激动剂、他汀类药物及其他相关治疗药物,我们目前仅完成了研究基线数据的分析。后续我们将在随访阶段开展更深入、详尽的数据分析,同时探究启动上述药物治疗是否会对晚期MASLD患者的病情进展产生影响,并依托FibroScan检测结果完成相关评估分析。


Hepatology Digest: Your study included 635 patients with advanced MASLD. Could you share the overall prevalence of cardiometabolic comorbidities, the status of glycemic and weight control, and the clinical application of GLP-1 receptor agonists and statins in this cohort? What clinical shortcomings do these data reflect in the management of advanced MASLD patients?

Dr. Cautar EL Maimouni, MD: In terms of disease prevalence, more than half of the patients had at least one cardiovascular or cardiometabolic risk factor. Specifically, the prevalence of type 2 diabetes reached 73%, hypertension 75%, and dyslipidemia also affected over half of the participants. Overall, these patients faced an extremely high risk of cardiometabolic comorbidities.

So far, we have only completed the analysis of baseline data regarding GLP-1 receptor agonists, statins and other related medications. We will conduct more in-depth and detailed data analysis during the follow-up period. Meanwhile, we will explore whether initiating treatment with the above drugs impacts disease progression in patients with advanced MASLD, and carry out relevant evaluation and analysis based on FibroScan test results.


《国际肝病》

请您分享本次研究最核心、最有价值的关键发现?整体而言,这项研究成果对目前晚期MASLD的临床诊疗和慢病管理,具备怎样的创新价值与指导意义?


Maimouni医生:本研究的核心目标之一是进一步提升临床对晚期MASLD患者代谢因素患病现状的认知。目前临床已知这类代谢危险因素的整体患病率较高,但往往忽视了患者是否接受了规范、有效的针对性治疗。因此,我们一方面旨在系统核查此类代谢危险因素的临床管控现状,验证其管控的规范性与有效性。另一方面,现有充足研究证据证实,各类代谢因素会显著升高肝纤维化及肝脏相关不良事件的发生风险,但这一关联在晚期MASLD人群中尚未得到充分、明确的论证。目前多数相关研究,仅阐明了代谢因素在普通分期MASLD患者中的作用。基于此,我们专门聚焦晚期MASLD人群开展研究,旨在明确代谢因素与晚期MASLD病情进展之间的内在关联。


Hepatology Digest: Could you share the most valuable and core key findings of this study? Overall, what innovative value and guiding significance do these results bring to the current clinical diagnosis, treatment and chronic disease management of advanced MASLD?

Dr. Cautar EL Maimouni, MD: One of the core goals of this study is to deepen clinical understanding of the prevalence of metabolic factors among patients with advanced MASLD. Clinicians are generally aware that these metabolic risk factors are highly prevalent in this population, yet they often overlook whether patients have received standardized and effective targeted treatment. Therefore, we intend to systematically investigate the current status of clinical management for these metabolic risk factors, and verify the standardization and effectiveness of relevant interventions.

Furthermore, substantial existing evidence has proven that metabolic factors significantly raise the risks of liver fibrosis and liver-related adverse events. However, this correlation has not been fully and clearly demonstrated in patients with advanced MASLD. Most relevant existing studies only illustrate the impacts of metabolic factors on patients with MASLD at earlier stages. Given this background, we specifically targeted patients with advanced MASLD in this research, to clarify the intrinsic correlation between metabolic factors and disease progression in this patient group.


(来源:《国际肝病》编辑部)

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