虚弱与多种疾病有关。然而，它对慢性肝病的影响在很大程度上仍未被探索。这项研究评估了虚弱与代谢功能障碍相关的脂肪性肝病 (MASLD)、肝硬化、肝癌和肝脏相关死亡率的风险之间的关联。英国生物银行总共纳入了 339,298 名既往无肝病的参与者。通过使用身体虚弱和虚弱指数来评估基线虚弱，将参与者分类为非虚弱、虚弱前或虚弱。主要结局是 MASLD，次要结局包括肝硬化、肝癌和肝脏相关死亡率，通过入院记录和死亡登记确认。在中位随访 11.6 年期间，4,667 例 MASLD，1,636 例肝硬化，257 例肝癌，并确定了 646 例与肝脏相关的死亡病例。经过多变量调整后，发现患有前期衰弱（身体衰弱：HR = 1.66，95% CI = 1.40-1.97；衰弱指数：HR = 2.01，95% CI = 1.67-2.42）和衰弱的参与者发生MASLD的风险较高（身体虚弱：HR = 3.32，95% CI = 2.54-4.34；虚弱指数：HR = 4.54，95% CI = 3.65-5.66）高于非虚弱者。肝硬化、肝癌和肝脏相关死亡率也观察到类似的结果。此外，与非虚弱组相比，虚弱组发生 MASLD 的风险更高，MASLD 的定义是磁共振成像得出的肝脏质子密度脂肪分数 > 5%（身体虚弱：OR = 1.64，95% CI = 1.32-2.04；虚弱指数：OR = 1.48，95% CI = 1.30-1.68）。虚弱与慢性肝病风险增加相关。公共卫生策略应以降低体弱个体的慢性肝病风险为目标。虽然体弱很常见，并且与 MASLD 和晚期慢性肝病患者的不良预后相关，但其对这些结果的后续风险的影响在很大程度上仍未被探索。我们的研究表明，虚弱与 MASLD、肝硬化、肝癌和肝脏相关死亡率的风险增加有关。这一发现表明，评估虚弱可能有助于识别易患慢性肝病的高危人群。实施针对虚弱的策略可能会对肝脏相关疾病的预防产生重大的公共卫生益处。版权所有 © 2024 欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。

Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality.A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by using physical frailty and the frailty index, categorizing participants as nonfrail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries.During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: HR = 1.66, 95% CI = 1.40-1.97; frailty index: HR = 2.01, 95% CI = 1.67-2.42) and frailty (physical frailty: HR = 3.32, 95% CI = 2.54-4.34; frailty index: HR = 4.54, 95% CI = 3.65-5.66) than in those with nonfrailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as magnetic resonance imaging-derived liver proton density fat fraction > 5%, than the nonfrail group (physical frailty: OR = 1.64, 95% CI = 1.32-2.04; frailty index: OR = 1.48, 95% CI = 1.30-1.68).Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals.While frailty is common and associated with a poor prognosis in people with MASLD and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with the increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.