与代谢功能障碍相关的脂肪性肝病和代谢功能障碍和酒精相关的脂肪性肝病相关的肝脏和肝外结局的风险：一项系统回顾和荟萃分析

IF 38.6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Lancet Gastroenterology & Hepatology Pub Date : 2025-09-12 DOI:10.1016/s2468-1253(25)00188-8

Ciro Celsa, Grazia Pennisi, Adele Tulone, Giacinta Ciancimino, Marco Vaccaro, Fabiana Pecorella, Gabriele Di Maria, Marco Enea, Federico Midiri, Alessandro Mantovani, Giovanni Targher, Aleksander Krag, Mary E Rinella, Calogero Cammà, Salvatore Petta

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引用次数: 0

摘要

代谢功能障碍相关的脂肪变性肝病（MASLD）和代谢功能障碍和酒精相关的脂肪变性肝病（MetALD）是脂肪变性肝病谱系中两个独立的实体。我们的目的是在一项综合荟萃分析中比较MASLD和MetALD患者的肝脏和肝外预后风险。方法在本系统评价和荟萃分析中，我们系统地检索了PubMed、Scopus和Cochrane中央对照试验注册库中截至2025年3月1日发表的观察性队列研究，并以英文撰写。我们纳入了比较成人（18岁）MASLD和MetALD的临床结果的研究，如果这些研究纳入了已知危险因素和潜在混杂因素的适当统计调整。我们排除了没有区分MASLD和MetALD的研究、病例报告、病例系列、评论、横断面研究或病例对照研究。我们对每项研究进行评估，以评估其合格性并提取数据。主要终点是肝脏相关事件；次要结局包括肝细胞癌、肝脏相关死亡率、心血管事件、肝外癌和全因死亡率。我们使用随机效应模型计算95% ci的合并风险比（hr）。该研究已在PROSPERO注册（CRD420251003928）。在鉴定的5579份记录中，我们纳入了24项队列研究，涉及11 575 558名个体。MASLD 9 801 312例（平均年龄55.7岁[SD 4.55]，男性~62%，女性~38%），MetALD 1 774 246例（平均年龄48.6岁[SD 4.91]，男性~82%，女性~18%）。与MASLD患者相比，MetALD患者发生肝脏相关事件（HR 1.62, 95% CI 1.16 - 2.25; p= 0.0086）、肝细胞癌（HR 1.33, CI 1.00 - 1.77; p= 0.048）和肝外癌（HR 1.03, CI 1.01 - 1.06; p< 0.0001）的风险显著高于MASLD患者。两种肝病的心血管事件发生率（HR 0.96, 95% CI 0.85 - 0.09; p= 0.48）、肝外癌相关死亡率（1.44,0.97 - 2.15;p= 0.065）和全因死亡率（1.08,0.97 - 1.19;p= 0.14）无显著差异。在大多数分析中观察到大量异质性（I2= 76-93%），只有肝外癌发生率显示低异质性（I2=0%）。Egger的回归检验表明，除了肝外癌相关死亡率外，所有结果都不太可能存在发表偏倚。与MASLD相比，metald可能与肝脏相关事件、肝细胞癌和肝外癌的高风险相关，而两种情况下的全因死亡率、肝外癌相关死亡率和心血管事件似乎相似。这些发现强调了对脂肪变性肝病谱系中这些相关但不同的实体需要不同的临床策略，并强调了在此背景下进行药理学临床试验的重要性。意大利教育、大学和研究部（MIUR）。

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Risk of hepatic and extrahepatic outcomes associated with metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction and alcohol-associated steatotic liver disease: a systematic review and meta-analysis

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD) are two separate entities within the spectrum of steatotic liver disease. We aimed to compare the risks of hepatic and extrahepatic outcomes between individuals with MASLD and MetALD in a comprehensive meta-analysis.

Methods

In this systematic review and meta-analysis, we systematically searched PubMed, Scopus, and the Cochrane Central Register of Controlled Trials for observational cohort studies published up to March 1, 2025, and written in English. We included studies comparing clinical outcomes between adults (>18 years) with MASLD and MetALD, if the studies incorporated appropriate statistical adjustments for known risk factors and potential confounding factors. We excluded studies that did not differentiate between MASLD and MetALD, case reports, case series, commentaries, cross-sectional or case-control studies. We evaluated each study to assess its eligibility and extracted the data. The primary outcome was liver-related events; secondary outcomes included hepatocellular carcinoma, liver-related mortality, cardiovascular events, extrahepatic cancers, and all-cause mortality. We used random-effect models to calculate pooled hazard ratios (HRs) with 95% CIs. The study was registered with PROSPERO (CRD420251003928).

Findings

Of 5579 records identified, we included 24 cohort studies involving 11 575 558 individuals in the analysis. 9 801 312 individuals had MASLD (mean age 57·0 years [SD 4·55], ~62% male, and ~38% female) and 1 774 246 had MetALD (mean age 48·6 years [SD 4·91], ~82% male, and ~18% female). Individuals with MetALD had significantly higher risks of liver-related events (HR 1·62, 95% CI 1·16–2·25; p=0·0086), hepatocellular carcinoma (1·33, 1·00–1·77; p=0·048), and extrahepatic cancers (1·03, 1·01–1·06; p<0·0001) compared with those with MASLD. The rates of cardiovascular events (HR 0·96, 95% CI 0·85–1·09; p=0·48), extrahepatic cancer-related mortality (1·44, 0·97–2·15; p=0·065), and all-cause mortality (1·08, 0·97–1·19; p=0·14) did not differ between the two liver conditions. Substantial heterogeneity was observed across most analyses (I²=76–93%), with only extrahepatic cancer incidence showing low heterogeneity (I²=0%). Egger's regression tests suggested that publication bias was unlikely for all outcomes except extrahepatic cancer-related mortality.

Interpretation

MetALD might be associated with a higher risk of liver-related events, hepatocellular carcinoma, and extrahepatic cancers than MASLD, whereas all-cause mortality, extrahepatic cancer-related mortality, and cardiovascular events seem similar between the two conditions. These findings emphasise the need for distinct clinical strategies for these related yet different entities within the steatotic liver disease spectrum and highlight the importance of conducting pharmacological clinical trials in this context.

Funding

The Italian Ministry of Education, University, and Research (MIUR).

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来源期刊

Lancet Gastroenterology & Hepatology Medicine-Hepatology

CiteScore

50.30

自引率

1.10%

发文量

期刊介绍： The Lancet Gastroenterology & Hepatology is an authoritative forum for key opinion leaders across medicine, government, and health systems to influence clinical practice, explore global policy, and inform constructive, positive change worldwide. The Lancet Gastroenterology & Hepatology publishes papers that reflect the rich variety of ongoing clinical research in these fields, especially in the areas of inflammatory bowel diseases, NAFLD and NASH, functional gastrointestinal disorders, digestive cancers, and viral hepatitis.