Celsa Ciro, Pennisi Grazia, Tulone Adele, Ciancimino Giacinta, Vaccaro Marco, Pecorella Fabiana, Di Maria Gabriele, Enea Marco, Midiri Federico, Mantovani Alessandro, Targher Giovanni, Krag Aleksander, Rinella Mary E, Cammà Calogero, Petta Salvatore
Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Palermo, Italy; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Palermo, Italy.
Lancet Gastroenterol Hepatol. 2025 Sep 12. doi: 10.1016/S2468-1253(25)00188-8.
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.
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).
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 (I=76-93%), with only extrahepatic cancer incidence showing low heterogeneity (I=0%). Egger's regression tests suggested that publication bias was unlikely for all outcomes except extrahepatic cancer-related mortality.
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.
The Italian Ministry of Education, University, and Research (MIUR).
代谢功能障碍相关脂肪性肝病（MASLD）和代谢功能障碍与酒精相关脂肪性肝病（MetALD）是脂肪性肝病谱系中的两个不同实体。我们旨在通过一项全面的荟萃分析比较MASLD和MetALD患者肝内和肝外结局的风险。
在这项系统评价和荟萃分析中，我们系统检索了截至2025年3月1日发表的、用英文撰写的观察性队列研究的PubMed、Scopus和Cochrane对照试验中央登记库。如果研究对已知风险因素和潜在混杂因素进行了适当的统计调整，我们纳入比较成人（>18岁）MASLD和MetALD临床结局的研究。我们排除了未区分MASLD和MetALD的研究、病例报告、病例系列、评论、横断面或病例对照研究。我们评估每项研究以评估其合格性并提取数据。主要结局是肝脏相关事件；次要结局包括肝细胞癌、肝脏相关死亡率、心血管事件、肝外癌症和全因死亡率。我们使用随机效应模型计算合并风险比（HRs）及95%置信区间（CIs）。该研究已在PROSPERO注册（CRD420251003928）。
在识别出的5579条记录中，我们纳入了24项队列研究，分析涉及11575558人。9801312人患有MASLD（平均年龄57.0岁[标准差4.55]，男性约62%，女性约38%），1774246人患有MetALD（平均年龄48.6岁[标准差4.91]，男性约82%，女性约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（1.3
