1990年至2021年全球MAFLD、MAFLD相关肝硬化和MASH相关肝癌的负担-动脉网

Global burden of MAFLD, MAFLD related cirrhosis and MASH related liver cancer from 1990 to 2021

Nature 等信源发布 2025-02-27 07:06

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Abstract

摘要

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease globally, driven by rising obesity, metabolic syndrome (MetS), and type 2 diabetes mellitus (T2DM). This study evaluates the global, regional, and national burden of MAFLD-related diseases from 1990 to 2021 and projects future trends.

代谢功能障碍相关脂肪肝病（MAFLD）是全球最常见的慢性肝病，其驱动因素包括日益增加的肥胖、代谢综合征（MetS）和2型糖尿病（T2DM）。本研究评估了1990年至2021年全球、区域及国家级别与MAFLD相关疾病的负担，并预测未来趋势。

Data were sourced from the Global Burden of Disease (GBD) 2021 database, including estimates for the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) associated with MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer. Countries were classified into 21 regions and five socio-demographic index (SDI) quintiles to analyze health disparities.

数据来源于《2021年全球疾病负担（GBD）》数据库，包括与MAFLD、MAFLD相关肝硬化和MASH相关肝癌相关的发病率、患病率、死亡率和伤残调整生命年（DALYs）的估计值。各国按21个地区和五个社会人口指数（SDI）五分位数进行分类，以分析健康差异。

Decomposition analyses assessed the contributions of population growth, aging, and epidemiological shifts. Future trends were modeled using the Bayesian Age-Period-Cohort (BAPC) framework. In 2021, approximately 1.27 billion MAFLD cases were reported globally, with an age-standardized prevalence rate (ASPR) of 15,018 per 100,000.

分解分析评估了人口增长、老龄化和流行病学变化的贡献。未来趋势使用贝叶斯年龄-时期-队列（BAPC）框架建模。2021年，全球报告了大约12.7亿MAFLD病例，年龄标化患病率（ASPR）为每10万人中15,018例。

The highest incidence occurred in South and East Asia. Mortality reached 138,328 cases for MAFLD and 97,403 for MAFLD-related cirrhosis. Decomposition analyses highlighted population growth and aging as key drivers. BAPC projections indicate a continued rise in MAFLD burden, particularly in low- and middle-income countries.

南亚和东亚的发病率最高。MAFLD的死亡病例达到138,328例，而与MAFLD相关的肝硬化死亡病例为97,403例。分解分析强调人口增长和老龄化是主要驱动因素。BAPC预测表明，MAFLD的负担将持续增加，尤其是在低收入和中等收入国家。

This study underscores the increasing global burden of MAFLD and its complications. Targeted public health interventions focusing on prevention and early management are urgently needed to mitigate future impacts..

本研究强调了MAFLD及其并发症日益加重的全球负担。迫切需要有针对性的公共卫生干预措施，重点关注预防和早期管理，以减轻未来的影响。

Introduction

简介

Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive liver disease caused by over nutrition and insulin resistance (IR) in genetically susceptible individuals, with a spectrum of diseases including non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH) and its associated fibrosis and cirrhosis.

非酒精性脂肪性肝病（NAFLD）是一种慢性进行性肝病，由遗传易感个体因营养过剩和胰岛素抵抗（IR）引起，其疾病谱包括非酒精性脂肪肝（NAFL）、非酒精性脂肪性肝炎（NASH）及其相关的纤维化和肝硬化。

，

. Currently, it is the most common chronic liver disease worldwide, and its incidence and prevalence are rapidly increasing worldwide, making it a growing and underestimated global public health problem

目前，它是全球最常见的慢性肝病，其发病率和患病率正在全球范围内迅速增加，成为一个日益严重且被低估的全球公共卫生问题。

，

. NAFLD is causally associated with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM), and together they contribute to the development of atherosclerotic cardiovascular disease (CVD), chronic kidney disease (CKD), liver failure, and malignant tumors such as hepatocellular carcinoma (HCC).

非酒精性脂肪性肝病（NAFLD）与代谢综合征（MetS）和2型糖尿病（T2DM）存在因果关联，并且它们共同促进了动脉粥样硬化性心血管疾病（CVD）、慢性肾病（CKD）、肝衰竭以及诸如肝细胞癌（HCC）等恶性肿瘤的发展。

，

。

In recent years, the Delphi Consensus has renamed NAFLD several times and modified the definition, with NAFLD designations ranging from metabolic dysfunction-associated fatty liver disease (MAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) in 2023

近年来，德尔菲共识多次对NAFLD的名称进行更改并修改定义，NAFLD的命名从代谢功能障碍相关脂肪肝病（MAFLD）到2023年的代谢功能障碍相关脂肪性肝病（MASLD）不等。

，

.Among other things, in this new definition, MAFLD is no longer a diagnosis of exclusion but is based on the presence of metabolic dysfunction, and as such, can now be diagnosed in conjunction with other liver disorders (e.g., alcoholic liver disease, chronic hepatitis B virus infection and chronic hepatitis C virus infection, primary biliary cholangitis and primary hemochromatosis etc.) coexisting with other liver diseases, especially in Asian populations.

在这一新定义中，MAFLD 不再是一个排他性诊断，而是基于代谢功能障碍的存在，因此现在可以与其他肝脏疾病（例如酒精性肝病、慢性乙型肝炎病毒感染、慢性丙型肝炎病毒感染、原发性胆汁性胆管炎和原发性血色病等）同时诊断，尤其是亚洲人群中常与其他肝脏疾病共存。

.This change in terminology better reflects the pathophysiology and impact on cardiometabolism of this common and burdensome liver disease. Retrospective analysis of data from epidemiologic surveys showed that more than 95% of patients with NAFLD met the diagnostic criteria for MAFLD, and the epidemiologic data for NAFLD can be used analogously for MAFLD.

术语的这一变化更好地反映了这种常见且负担沉重的肝病的病理生理学及其对心脏代谢的影响。对流行病学调查数据的回顾性分析显示，超过95%的非酒精性脂肪肝病（NAFLD）患者符合代谢相关脂肪肝病（MAFLD）的诊断标准，并且NAFLD的流行病学数据可以类比用于MAFLD。

.In addition, although the Global Burden of Disease (GBD) database was updated to 2021 and has not yet changed the terminology of MAFLD, the present study harmonized the name change to the terminology of MAFLD, MAFLD-associated cirrhosis, and MASH-associated liver cancer in accordance with the most recent Guideline for the Prevention and Treatment of Metabolic Dysfunction-associated Fatty Liver Disease (Version 2024) from China.

此外，尽管全球疾病负担（GBD）数据库已更新至2021年，且尚未更改MAFLD的术语，但本研究根据中国最新发布的《代谢功能障碍相关脂肪肝病预防与治疗指南（2024版）》，将名称调整为MAFLD、MAFLD相关肝硬化和MASH相关肝癌的术语。

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Epidemiologic studies have shown gender, racial and regional differences in the prevalence and incidence of MAFLD. The global prevalence of MAFLD is estimated to be 32.4%, with a higher prevalence in males (39.7%) than in females (25.6%). The prevalence is expected to be as high as 37.8% after 2016

流行病学研究表明，MAFLD 的患病率和发病率存在性别、种族和地区差异。据估计，MAFLD 的全球患病率为 32.4%，其中男性患病率（39.7%）高于女性（25.6%）。预计 2016 年后患病率将高达 37.8%。

; Latin America has the highest pooled prevalence (44.4%), followed by the Middle East, North Africa, South Asia, South-East Asia, North America, East Asia, and the lowest in Western Europe (25.1%)

；拉丁美洲的综合患病率最高（44.4%），其次是中东、北非、南亚、东南亚、北美、东亚，最低的是西欧（25.1%）。

. Globally, about 20–30% of patients with MAFLD are likely to progress to MASH, and 2–5% of these patients will further develop cirrhosis. In addition, MASH has emerged as one of the most prominent etiologic factors leading to HCC

在全球范围内，大约20-30%的MAFLD患者可能会进展为MASH，其中2-5%的患者会进一步发展为肝硬化。此外，MASH已成为导致HCC的最突出的病因因素之一。

. A systematic review and meta-analysis published in 2022 showed that approximately 3–6% of patients with MASH globally will ultimately develop HCC

2022年发表的一项系统评价和荟萃分析显示，全球大约有3-6%的MASH患者最终会发展为HCC。

, and notably, the GBD database in 2021 showed that mortality due to MASH-related liver cancer has progressively surpassed that due to alcoholic liver disease-associated HCC

，特别是2021年GBD数据库显示，由于MASH相关的肝癌导致的死亡率已逐步超过因酒精性肝病相关的HCC导致的死亡率。

. The incidence of MAFLD and MAFLD-related cirrhosis and MASH-related liver cancer is expected to increase further globally in the next decade as obesity and T2DM become more prevalent worldwide

预计在未来十年中，随着肥胖和2型糖尿病在全球范围内日益普遍，MAFLD及其相关的肝硬化和MASH相关的肝癌发病率将进一步增加。

，

。

The GBD study offers an invaluable platform for assessing the health impacts of a plethora of diseases and injuries

GBD研究为评估众多疾病和伤害的健康影响提供了一个宝贵的平台。

，

.In this study, we aims to present the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of MAFLD, MAFLD-related cirrhosis and MASH-related liver cancer as well as their evolving trends from 1990 to 2021. Our objective is to delineate the burden and trends of these diseases globally, regionally, and nationally, by socio-demographic index (SDI), age, sex.

本研究旨在分析1990年至2021年间MAFLD、MAFLD相关肝硬化和MASH相关肝癌的发病率、患病率、死亡率以及伤残调整生命年（DALYs）及其变化趋势。我们的目标是通过社会人口指数（SDI）、年龄和性别，描绘这些疾病在全球、区域和国家层面的负担与趋势。

In addition, we conducted global health inequality analyses for 3 diseases and made projections of future trends in disease..

此外，我们对3种疾病的全球健康不平等进行了分析，并预测了疾病未来的趋势。

Methods

方法

Data source and sociodemographic index

数据来源和社会人口指数

(

SDI)

The study used anonymized data from GBD 2021, a comprehensive database that measured the impact of 371 diseases, 88 risk factors, and injuries across 5 SDI and 204 countries and territories

该研究使用了GBD 2021的匿名数据，这是一个全面的数据库，衡量了371种疾病、88个风险因素和伤害在5个SDI和204个国家和地区的影响。

，

. This information, accessible at

. 这些信息，可在

https://vizhub.healthdata.org/gbd-results

, was overseen by the Institute for Health Metrics and Evaluation at the University of Washington in the USA

，由美国华盛顿大学的健康指标与评估研究所监督进行

. The GBD 2021 findings were crucial for policymakers, public health professionals, and researchers as they facilitated the identification of health disparities within and between populations, monitoring changes over time, gauging health advancements, and shaping strategies to address post-COVID-19 health inequalities.

GBD 2021 的研究结果对政策制定者、公共卫生专业人士和研究人员至关重要，因为它们有助于识别不同人群内部和之间的健康差异，监测随时间的变化，评估健康进展，并制定策略以应对后新冠疫情的健康不平等问题。

。

In our study, we obtained the incidence, prevalence, mortality, and DALYs estimates for 3 diseases involving MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer. Our analysis covered 204 countries and territories, grouped into 21 GBD regions based on geographic proximity and further classified into 5 categories according to the SDI.

在我们的研究中，我们获得了涉及MAFLD、MAFLD相关肝硬化和MASH相关肝癌的3种疾病的发病率、患病率、死亡率和DALYs估计值。我们的分析涵盖了204个国家和地区，根据地理邻近性分为21个GBD区域，并进一步按照SDI分为5类。

The SDI is a composite measure of per capital income, total fertility rate (age < 25 years), and average educational attainment (age ≥ 15 years), reflecting a country’s overall social and economic development.

SDI 是人均收入、总生育率（年龄 < 25 岁）和平均受教育年限（年龄 ≥ 15 岁）的综合衡量指标，反映了一个国家的整体社会和经济发展水平。

，

。

Cross-country inequality analysis

跨国家不平等分析

The slope index of inequality (SII) and the Concentration Index (CI) are standardized measures of absolute and relative gradient inequality, respectively

不平等的斜率指数（SII）和集中指数（CI）分别是绝对梯度不平等和相对梯度不平等的标准化衡量指标。

. They quantify inequalities in the distribution of the disease burden of MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer across countries. The SII is obtained through regression analysis, relating a country’s DALYs rates to its SDI relative position, defined by the population’s midpoint in a cumulative distribution ranked by SDI.

他们量化了MAFLD、MAFLD相关肝硬化和MASH相关肝癌在各国之间的疾病负担分布不平等。SII通过回归分析获得，将一个国家的DALYs率与其SDI相对位置联系起来，该位置由在按SDI排名的累积分布中的人口中点定义。

Heteroscedasticity is examined using a weighted regression model. The CI is calculated by numerically integrating the area under the Lorenz Curve, aligning the cumulative proportion of DALYs with the population’s cumulative distribution sorted by SDI.

使用加权回归模型检验异方差性。通过数值积分计算洛伦兹曲线下的面积来得到CI，将DALYs的累积比例与按SDI排序的人口累积分布对齐。

，

。

Decomposition analysis

分解分析

To elucidate the principal factors influencing the changes in the burden of MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer between 1990 and 2021, a decomposition analysis was performed. This analysis sought to quantify the separate impacts of population growth, aging, and epidemiological shifts.

为了阐明影响1990年至2021年间MAFLD、MAFLD相关肝硬化和MASH相关肝癌负担变化的主要因素，进行了分解分析。该分析旨在量化人口增长、老龄化和流行病学转变的各自影响。

The methodology entailed assessing the contribution of each factor in isolation, with the other two factors remaining fixed.

该方法包括单独评估每个因素的贡献，同时保持其他两个因素不变。

。

Bayesian age-period-cohort

贝叶斯年龄-时期-队列模型

(

BAPC) model prediction

BAPC）模型预测

To project future trends in MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer burden, we employed the Bayesian Age-Period-Cohort (BAPC) model, which incorporates demographic data and considers age, period, and cohort effects. This model allows us to estimate how disease incidence and mortality will evolve, taking into account shifts in population structure, changes in healthcare practices, and broader societal influences.

为了预测MAFLD、MAFLD相关肝硬化以及MASH相关肝癌负担的未来趋势，我们采用了贝叶斯年龄-时期-队列（BAPC）模型，该模型结合了人口统计数据并考虑了年龄、时期和队列效应。这一模型使我们能够估算疾病发病率和死亡率将如何演变，同时考虑到人口结构的变化、医疗实践的改变以及更广泛的社会影响。

。

The BAPC model uses a Bayesian framework that integrates prior knowledge and observed data. For this study, demographic projections were downloaded from the GBD 2021 database, and the model was implemented using R software (version 4.3.3) with the “BAPC” and “INLA” packages

BAPC模型使用了一个贝叶斯框架，该框架整合了先验知识和观测数据。在本研究中，人口预测数据从GBD 2021数据库下载，并使用R软件（版本4.3.3）通过“BAPC”和“INLA”包实现了该模型。

，

. The priors of the model were specified based on historical trends observed from 1990 to 2021, and the projections were validated against known disease dynamics. This approach provides robust estimates of future trends in age-standardized incidence rates (ASIR) and age-standardized mortality rate (ASMR), which are beneficial for long-term health planning and resource allocation..

模型的先验参数基于1990年至2021年间观察到的历史趋势进行设定，预测结果已通过已知的疾病动态进行了验证。这种方法对未来年龄标化发病率（ASIR）和年龄标化死亡率（ASMR）的趋势提供了可靠的估计，有助于长期卫生规划和资源分配。

Statistical analysis

统计分析

Joinpoint regression is a statistical method used to analyze trend changes in time series data by identifying “joinpoints”, splitting the time series into multiple phases, and calculating the annual percent change (APC) for each segment. The rate trend was assessed using a joinpoint regression model that calculated the APC with its 95% confidence interval (CI) to depict the trend over the delineated time frame.

加入点回归是一种统计方法，用于通过识别“连接点”来分析时间序列数据中的趋势变化，将时间序列划分为多个阶段，并计算每个阶段的年度百分比变化（APC）。使用加入点回归模型评估了趋势变化，该模型计算了APC及其95%置信区间（CI），以描绘划定时间范围内的趋势。

. The average annual percentage change (AAPC), derived from APC, provided a comprehensive overview of 3 diseases trends, aiding in understanding its temporal dynamics. DALYs rates are presented as estimates per 100,000 population, accompanied by their 95% uncertainty intervals (UIs)

. 平均年度百分比变化（AAPC）由APC推导而来，全面概述了三种疾病的趋势，有助于理解其时间动态。DALYs比率以每10万人口的估计值表示，并附有其95%的不确定性区间（UIs）。

，

. The analyses and visualizations in this study were conducted using the World Health Organization Health (WHO) Equity Assessment Toolkit along with R software (version4.3.3).

本研究中的分析和可视化是使用世界卫生组织健康（WHO）公平性评估工具包以及R软件（版本4.3.3）进行的。

Results

结果

Global incidence, prevalence, mortality and dalys

全球发病率、患病率、死亡率和伤残调整生命年

Globally, in 2021, there were an estimated 1,267,867,997 global cases of MAFLD (95%UI 1,157,934,071 to 1,380,435,423), with an age-standardized prevalence rate (ASPR) of 15,018.07 (95% UI 13,756.47 to 16,361.44) per 100,000 persons, surpassing the rates for MAFLD-related cirrhosis and MASH-related liver cancer (Table .

2021年，全球约有1,267,867,997例MAFLD病例（95%不确定区间[UI] 1,157,934,071至1,380,435,423），年龄标化患病率（ASPR）为每10万人15,018.07例（95% UI 13,756.47至16,361.44），超过了与MAFLD相关的肝硬化和MASH相关的肝癌的患病率（表。

). From 1990 to 2021, the ASPR for MAFLD (AAPC = 0.71, 95% CI 0.68 to 0.74), MAFLD-related cirrhosis (AAPC = 0.71, 95% CI 0.68 to 0.74) and NASH-related liver cancer (AAPC = 1.36, 95% CI 1.32 to 1.41) exhibited a significant increasing trend (Fig.

). 从1990年到2021年，MAFLD（AAPC = 0.71，95% CI 0.68 至 0.74）、MAFLD相关肝硬化（AAPC = 0.71，95% CI 0.68 至 0.74）和NASH相关肝癌（AAPC = 1.36，95% CI 1.32 至 1.41）的ASPR呈现显著上升趋势（图。

A-C; Table

A-C；表格

）。

Table 1 Global prevalence, incidence, mortality, and disability-adjusted life years (DALYs) for MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer from 1990 to 2021.

表1 1990年至2021年MAFLD、MAFLD相关肝硬化和MASH相关肝癌的全球患病率、发病率、死亡率和伤残调整生命年（DALYs）。

Full size table

全尺寸表格

In 2021, the global incidence was 48,353,272 cases (95%UI 44,229,139 to 52,358,017), MAFLD-related cirrhosis was 48,310,981 (95%UI 44,191,374 to 52,313,165), and MASH-related liver cancer was 42,291 (95%UI 34,033 to 51,129). ASIR for MAFLD was the highest at 593.28 per 100,000 persons (95%UI 542.72 to 643.7) (Table .

2021年，全球发病率为48,353,272例（95%不确定区间 44,229,139至52,358,017），与MAFLD相关的肝硬化为48,310,981例（95%不确定区间 44,191,374至52,313,165），与MASH相关的肝癌为42,291例（95%不确定区间 34,033至51,129）。MAFLD的年龄标化发病率最高，为每10万人593.28例（95%不确定区间 542.72至643.7）（表。

). From 1990 to 2021, the ASIR for MAFLD (AAPC = 0.71, 95% CI 0.70 to 0.73), MAFLD-related cirrhosis (AAPC = 0.71, 95% CI 0.69 to 0.73) and MASH-related liver cancer (AAPC = 0.99, 95% CI 0.95 to 1.03) exhibited a significant increasing trend (Table

). 从1990年到2021年，MAFLD的ASIR（AAPC = 0.71，95% CI 0.70至0.73）、MAFLD相关肝硬化（AAPC = 0.71，95% CI 0.69至0.73）和MASH相关肝癌（AAPC = 0.99，95% CI 0.95至1.03）呈现显著增加趋势（表

）。

In 2021, an estimated 138,328 (95%UI 108,288 to 173,905) mortality cases was attributed to MAFLD, and approximately 97,403 (95%UI 69,530 to 130,168) cases died from MAFLD-related cirrhosis globally. The ASMR for MAFLD (AAPC = 0.99, 95% CI 0.95 to 1.03) and MASH-related liver cancer (AAPC = 0.82, 95% CI 0.72 to 0.92) exhibited a positive trend, while the ASMR for MAFLD-related cirrhosis showed a declining pattern (AAPC = − 0.05, 95% CI to 0.20 to 0.11) over recent decades (Fig. .

2021年，约有138,328例（95%不确定区间[UI] 108,288至173,905）死亡病例归因于MAFLD，其中约97,403例（95% UI 69,530至130,168）死于与MAFLD相关的肝硬化。近几十年来，MAFLD的年龄标化死亡率（ASMR；AAPC = 0.99，95%置信区间[CI] 0.95至1.03）和MASH相关肝癌（AAPC = 0.82，95% CI 0.72至0.92）呈现上升趋势，而与MAFLD相关的肝硬化的ASMR则呈下降趋势（AAPC = -0.05，95% CI -0.20至0.11）（图X）。

D-F; Table

D-F；表

）。

For the DALYs, globally, MAFLD accounted for the highest number of DALYs among the 3 diseases in 2021 (3,667,267, 95%UI: 2,903,576 to 4,607,307), and MASH-related liver cancer exhibited the highest positive AAPC of the age-standardized DALYs rate (AAPC = 0.60, 95% CI 0.43 to 0.77) (Table

在全球范围内，就DALYs而言，2021年MAFLD在三种疾病中占DALYs数量最高（3,667,267，95%UI：2,903,576至4,607,307），而MASH相关肝癌的年龄标化DALYs率表现出最高的正AAPC（AAPC=0.60，95%CI 0.43至0.77）（表）。

）。

Fig. 1

图1

Global distribution of 3 diseases burden in 2021. (

2021年全球三种疾病负担的分布。

) Age-standardized prevalence rates of MAFLD. (

）MAFLD的年龄标化患病率。（

) Age-standardized prevalence rates of MAFLD-related cirrhosis. (

）与MAFLD相关的肝硬化年龄标化患病率。（

C语言

) Age-standardized prevalence rates of MASH-related liver cancer. (

）与MASH相关的肝癌的年龄标准化患病率。（

) Age-standardized mortality rates of MAFLD. (

年龄标准化的MAFLD死亡率。

) Age-standardized mortality rates of MAFLD-related cirrhosis. (

）与MAFLD相关的肝硬化年龄标准化死亡率。（

) Age-standardized mortality rates of MASH-related liver cancer.

年龄标准化的MASH相关肝癌死亡率。

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Regional incidence and mortality

地区发病率和死亡率

When analyzed by geographic regions, South Asia and East Asia exhibited the highest number of incidence of MAFLD in 2021. Specifically, South Asia had the highest incidence of MAFLD (10,765,351, 95%UI 9,758,064 to 11,817,449), while South Asia recorded the highest incidence of MAFLD-related cirrhosis (10,760,191, 95% UI 9,753,407 to 11,812,144) and East Asia had the highest incidence of NASH-related liver cancer (11,858, 95% UI 9,095 to 15,058) (Fig. .

按地理区域分析时，南亚和东亚在2021年表现出最高的MAFLD发病率。具体而言，南亚的MAFLD发病率最高（10,765,351，95%UI 9,758,064至11,817,449），同时南亚的MAFLD相关肝硬化发病率最高（10,760,191，95% UI 9,753,407至11,812,144），而东亚的NASH相关肝癌发病率最高（11,858，95% UI 9,095至15,058）（图。

A-C; Table

A-C；表格

）。

Table 2 Incidence, mortality, ASIR, and ASMR of MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer by global, SDI, and GBD regions in 2021.

表2 2021年全球、SDI和GBD地区中MAFLD、MAFLD相关肝硬化和MASH相关肝癌的发病率、死亡率、ASIR和ASMR。

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In the year 2021, North Africa and Middle East exhibited the highest ASIR for MAFLD and MAFLD-related cirrhosis at a value of 1,037.64 per 100,000 persons (95% UI 963.01 to 1,109.65) and a value of 1,037 per 100,000 persons (95% UI 962.4 to 1,109.01) respectively, while Western Sub-Saharan Africa showed the highest ASIR for MASH-related liver cancer at a value of 1.11 per 100,000 persons (95% UI 0.83 to 1.48) (Table .

2021年，北非和中东的MAFLD和MAFLD相关肝硬化ASIR最高，分别为每10万人1,037.64例（95% UI 963.01至1,109.65）和每10万人1,037例（95% UI 962.4至1,109.01），而西撒哈拉非洲的MASH相关肝癌ASIR最高，为每10万人1.11例（95% UI 0.83至1.48）（表。

) .Moreover, South Asia also had the highest number of mortality of MAFLD (18,670, 95% UI 13,608 to 24,921) and MAFLD-related cirrhosis (13,201, 95% UI 8,323 to 19,248).In addition, East Asia exhibited the highest number of mortality of MASH-related liver cancer in 2021(10,936, 95% UI 8,458 to 13,798) (Table .

此外，南亚也是MAFLD（18,670例，95%不确定区间13,608至24,921）和MAFLD相关肝硬化（13,201例，95%不确定区间8,323至19,248）死亡人数最多的地区。此外，东亚在2021年MASH相关肝癌的死亡人数最高（10,936例，95%不确定区间8,458至13,798）（表。

).In terms of ASMR, from 1990 to 2021, Andean Latin America showed the highest ASMR of MAFLD (ASMR = 5.89,95% UI 4.03 to 8.07). For MAFLD-related cirrhosis and MASH-related liver cancer, Andean Latin America (ASMR = 5.52,95% UI 3.72 to 7.68) and Western Sub-Saharan Africa (ASMR = 1.23,95%UI 0.91 to 1.65) exhibited the highest ASMR respectively (Fig. .

在ASMR方面，从1990年到2021年，安第斯拉丁美洲显示出最高的MAFLD的ASMR（ASMR = 5.89，95% UI 4.03至8.07）。对于MAFLD相关的肝硬化和MASH相关的肝癌，安第斯拉丁美洲（ASMR = 5.52，95% UI 3.72至7.68）和西撒哈拉非洲（ASMR = 1.23，95% UI 0.91至1.65）分别表现出最高的ASMR（图。

D-F; Table

D-F；表

）。

National incidence, prevalence, mortality, and dalys

全国发病率、患病率、死亡率和伤残调整生命年

Nationally, for MAFLD, Kuwait reported the highest ASPR of 32,312.16 per 100,000 (95%UI 29,947.12 to 34,838.96), followed by Egypt (31,668.79 per 100,000; 95%UI 29,272.46 to 34,224.69), Qatar (31,327.54 per 100,000; 95%UI 29,078.53 to 33,790.93), and Iran (Islamic Republic of) (30,510.05 per 100,000; 95%UI 28,210.86 to 32,985.75).

全国范围内，科威特报告的MAFLD的ASPR最高，为每10万人32,312.16例（95%不确定区间：29,947.12至34,838.96），其次是埃及（每10万人31,668.79例；95%不确定区间：29,272.46至34,224.69）、卡塔尔（每10万人31,327.54例；95%不确定区间：29,078.53至33,790.93）和伊朗（伊斯兰共和国）（每10万人30,510.05例；95%不确定区间：28,210.86至32,985.75）。

In contrast, Japan (8,133.47 per 100,000; 95%UI 7,457.73 to 8,837.39) and Finland (8,358.51 per 100,000; 95%UI 7,620.01 to 9,180.55) had the lowest ASPRs (Fig. .

相比之下，日本（每10万人8,133.47例；95%UI 7,457.73至8,837.39）和芬兰（每10万人8,358.51例；95%UI 7,620.01至9,180.55）的ASPRs最低（图。

A-C; Supplementary Table S1).For MAFLD-related cirrhosis, Kuwait reported the highest ASPR of 32,311.95 per 100,000 (95%UI 29,946.9 to 34,838.75).For NASH-related liver cancer, Mongolia reported the highest ASPR of 5.04 per 100,000 (95%UI 3.14 to 7.77) (Fig.

A-C；补充表S1）。对于MAFLD相关的肝硬化，科威特报告的ASPR最高，为每10万人中32,311.95例（95%UI 29,946.9至34,838.75）。对于NASH相关的肝癌，蒙古报告的ASPR最高，为每10万人中5.04例（95%UI 3.14至7.77）（图。

A-C; Supplementary Table S1). In terms of ASIR for MAFLD, Egypt (1,188.56 per 100,000; 95%UI 1,107.17 to 1,268.66) and Kuwait (1,174.17 per 100,000; 95%UI 1,092.51 to 1,257.53) had the highest rates (Supplementary Table S2).

A-C；补充表S1）。在MAFLD的ASIR方面，埃及（每10万人中1,188.56人；95%UI 1,107.17至1,268.66）和科威特（每10万人中1,174.17人；95%UI 1,092.51至1,257.53）的发病率最高（补充表S2）。

In terms of ASIR for MAFLD-related cirrhosis, the same trend has been observed. In terms of ASIR for MAFLD-related liver cancer, Mongolia (5.26 per 100,000; 95%UI 3.27 to 8.13) and Gambia (3.65 per 100,000; 95% UI 2.03 to 5.88) had the highest rates. For more information about ASMR and DALYs of 3 diseases, see Fig. .

就MAFLD相关肝硬化而言，ASIR也观察到了相同的趋势。在MAFLD相关肝癌的ASIR方面，蒙古（每10万人5.26例；95%UI 3.27至8.13）和冈比亚（每10万人3.65例；95%UI 2.03至5.88）的发病率最高。有关这三种疾病的ASMR和DALYs的更多信息，请参见图。

D-F and Supplementary Tables S3-S4.

D-F和补充表S3-S4。

Age and sex patterns

年龄和性别模式

In 2021, for the numbers of prevalence, the global burden of MAFLD was the highest in the 75–79 age group in both sexes (

2021年，在患病率方面，全球MAFLD负担在75-79岁年龄组中男女均为最高（

Supplementary Figure S1A; Supplementary Tables S5

补充图S1A；补充表格S5

). The incidence rates of MAFLD was higher in females (1,036.11) compared to males (1,346.48) in the 20–24 age group (

). 20-24岁年龄组中，女性的MAFLD发病率（1,036.11）高于男性（1,346.48）（

Supplementary Figure S2A; Supplementary Tables S6

补充图S2A；补充表S6

). The mortality rates was highest in the 95 + age group, followed by the 90–94 and 85–89 age groups, with no significant gender differences across age groups. Notably, in the 95 + age group, the females mortality rates contribution per 100,000 was greater than that of males (25.07 vs. 22.9) (

）。死亡率在95岁及以上年龄组中最高，其次是90-94岁和85-89岁年龄组，各年龄组之间没有显著的性别差异。值得注意的是，在95岁及以上年龄组中，女性每10万人死亡率的贡献大于男性（25.07 vs. 22.9）（

Supplementary Figure S3A; Supplementary Tables S7

补充图S3A；补充表S7

).For the numbers of DALYs, the global burden of MAFLD was the highest in the 95 + age group in females, while the highest in the 90–94 age group in males (206.41 vs. 193.77) (

).对于DALYs的数量，全球MAFLD的负担在女性95岁及以上年龄组中最高，而在男性90-94岁年龄组中最高（206.41 vs. 193.77）(

Supplementary Figure S4A; Supplementary Tables S8

补充图S4A；补充表S8

).For more information about the numbers of prevalence, incidence, mortality, DALYs, ASPR, ASIR, ASMR of MAFLD-related cirrhosis and MASH-related liver cancer, see

).有关MAFLD相关肝硬化和MASH相关肝癌的患病率、发病率、死亡率、DALY、ASPR、ASIR、ASMR的更多数据信息，请参见

Supplementary Figure S1-S4; Supplementary Tables S5-S8

补充图S1-S4；补充表S5-S8

。

Burden of 3 diseases by SDI

三种疾病按SDI的负担

SDI, a measure derived from the GBD database, assesses the level of socioeconomic development in a country or region. In 2021, the middle and low-middle SDI quintile levels exhibited higher incidence of MAFLD and MAFLD-related cirrhosis. The high and middle SDI quintile levels showed higher incidence for MASH-related liver cancer (Fig. .

SDI是从GBD数据库衍生出的一项指标，用于评估一个国家或地区的社会经济发展水平。2021年，中等和中低SDI五分位水平的MAFLD和MAFLD相关肝硬化的发病率较高。高和中等SDI五分位水平的MASH相关肝癌发病率较高（图。

A-C). Nationally, similar associations were found between ASIR for MAFLD and MAFLD-related cirrhosis with SDI across 204 countries and territories in 2021. The burden of MAFLD and MAFLD-related cirrhosis in North Africa and Middle East was much higher than expected levels in 2021. Interestingly, a ‘M-shaped’ relationship between ASIR and SDI was observed (Fig. .

A-C). 在全国范围内，2021年在204个国家和地区中，MAFLD的年龄标化发病率（ASIR）与社会人口指数（SDI）之间发现了相似的关联。2021年，北非和中东的MAFLD及其相关肝硬化负担远高于预期水平。有趣的是，观察到ASIR与SDI之间存在“M型”关系（图.

A-D) for MAFLD and MAFLD-related cirrhosis. It’s worth noting that a ‘W-shaped’ relationship between ASIR and SDI was observed for MASH-related liver cancer (Fig.

A-D）用于MAFLD和MAFLD相关肝硬化。值得注意的是，对于MASH相关的肝癌，观察到ASIR与SDI之间存在“W型”关系（图。

E-F). The correlation between SDI and ASMR for MAFLD and MAFLD-related cirrhosis also showed a fluctuating trend (

E-F). MAFLD 和 MAFLD 相关肝硬化中 SDI 与 ASMR 的相关性也显示出波动趋势 (

Supplementary Figure S5A-B

补充图 S5A-B

). The‘W-shaped’ relationship between ASMR and SDI was still observed for MASH-related liver cancer (

). ASMR 与 SDI 之间的“W 形”关系在 MASH 相关肝癌中仍然存在 (

Supplementary Figure S5C

补充图 S5C

).For more information about the burden of 3 diseases by SDI, see

).有关SDI对三种疾病负担的更多信息，请参见

Supplementary Figure S5 and Supplementary Tables S9-S12

补充图S5和补充表S9-S12

。

The “M-shaped” and “W-shaped” relationships reveal complex non-linear associations between SDI and the incidence and mortality of MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer. Among them, the “M-shaped”relationship indicated that the incidence of MAFLD and related cirrhosis was highest in countries with moderate SDI levels and relatively low in countries with low and high SDI levels; In low SDI areas, the incidence of MAFLD may be relatively low despite inadequate health resources and a higher burden of malnutrition and infectious diseases, due to a lower prevalence of obesity and poor lifestyle.

“M型”和“W型”关系揭示了SDI与MAFLD、MAFLD相关肝硬化及MASH相关肝癌的发病率和死亡率之间复杂的非线性关联。其中，“M型”关系表明，中等SDI水平国家的MAFLD及相关肝硬化的发病率最高，而低SDI和高SDI水平国家相对较低；在低SDI地区，尽管卫生资源不足，营养不良和传染病负担较重，但由于肥胖率较低且生活方式不健康的影响较小，MAFLD的发病率可能仍然较低。

At this time, other liver diseases (e.g., hepatitis, parasitic infections, etc.) may predominate. In high SDI areas, although the prevalence of MAFLD is still high due to good healthcare systems and public health interventions, the condition is effectively controlled in some populations due to advanced early diagnosis and treatment, which may reduce the incidence of cirrhosis associated with MAFLD.

此时，其他肝脏疾病（如肝炎、寄生虫感染等）可能占主导地位。在高SDI地区，尽管由于良好的医疗体系和公共卫生干预措施，MAFLD的患病率仍然较高，但由于早期诊断和治疗的进步，部分人群的病情得到了有效控制，这可能会降低与MAFLD相关的肝硬化发病率。

The“W-shaped”relationship, on the other hand, shows that the prevalence of MASH-associated liver cancer is higher in low and high SDI countries, and relatively lower in intermediate SDI countries were relatively low, reflecting the complex dynamics of MASH-associated liver cancer in countries with different SDI levels.

另一方面，“W型”关系表明，在社会人口指数（SDI）较低和较高的国家中，与MASH相关的肝癌患病率较高，而在SDI中等的国家相对较低，这反映出在不同SDI水平的国家中，与MASH相关的肝癌存在着复杂的动态变化。

The above two patterns reflect the influence of lifestyle, medical resources and disease management levels at different stages of socioeconomic development, providing an important scientific basis for global liver disease prevention and control, and helping to formulate precise health policies for different countries and regions to reduce the global burden of MAFLD and its complications..

上述两种模式反映了不同经济社会发展阶段生活方式、医疗资源及疾病管理水平的影响，为全球肝脏疾病防治提供了重要的科学依据，有助于制定针对不同国家和地区的精准卫生政策，减轻MAFLD及其并发症的全球负担。

Fig. 2

图2

The burden of 3 diseases globally and in 204 countries and 21 regions, as shown by SDI. (

全球及204个国家和21个地区的三种疾病负担，按SDI显示。

) ASIR globally and in 21 GBD regions of MAFLD, 1990–2021. (

) ASIR 全球及 21 个 GBD 地区的 MAFLD，1990-2021。(

) MAFLD ASIR and SDI in 204 countries and regions, 2021. (

) 204个国家和地区的MAFLD ASIR和SDI，2021年。(

) ASIR globally and in 21 GBD regions of MAFLD-related cirrhosis, 1990–2021. (

) 1990年至2021年全球及21个GBD地区MAFLD相关肝硬化的ASIR（

) MAFLD-related cirrhosis ASIR and SDI in 204 countries and regions, 2021. (

) 204个国家和地区的MAFLD相关肝硬化ASIR和SDI，2021年。(

) ASIR globally and in 21 GBD regions of MASH-related liver cancer, 1990–2021.(

`) ASIR 全球及 21 个 GBD 地区的 MASH 相关肝癌，1990-2021。(`

) MASH-related liver cancer ASIR and SDI in 204 countries and regions, 2021.

) 2021年全球204个国家和地区的MASH相关肝癌ASIR和SDI。

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Cross-country inequality analysis

跨国不平等分析

The SII value is calculated through regression analysis and reflects the health gap between the lowest and highest socioeconomic groups. According to the results, the SII value of MAFLD has changed between 1990 and 2021. Specifically, the SII value was 18 in 1990 and − 17.85 in 2021, indicating a significant shift in the direction of health inequality from favoring the high socio-economic groups to favoring the low socio-economic groups during this time period.

通过回归分析计算得到的SII值反映了最低和最高社会经济群体之间的健康差距。根据结果，1990年至2021年期间，MAFLD的SII值发生了变化。具体而言，1990年的SII值为18，而2021年为−17.85，表明在此期间健康不平等的方向发生了显著变化，从有利于高社会经济群体转变为有利于低社会经济群体。

The presence of a negative SII is usually a noteworthy phenomenon as it implies that the health status of the previously dominant high socio-economic groups may have deteriorated in relative terms or that the low socio-economic groups’s health status has improved significantly or even surpassed that of the high socio-economic groups.

负的SII的存在通常是一个值得注意的现象，因为它意味着以前占主导地位的高社会经济群体的健康状况可能在相对意义上恶化，或者低社会经济群体的健康状况显著改善，甚至超过了高社会经济群体。

The CI for MAFLD increased from − 0.11 in 1990 to -0.03 in 2021, suggesting a reduction in health inequalities for MAFLD. Specifically, MAFLD was concentrated to a greater extent among lower socio-economic groups in 1990, suggesting that lower socio-economic groups accounted for a greater proportion of the MAFLD burden.

1990年至2021年，MAFLD的集中指数从-0.11上升到-0.03，表明MAFLD的健康不平等现象有所减少。具体而言，1990年MAFLD在较低社会经济群体中集中程度更高，表明较低社会经济群体承担了更大比例的MAFLD负担。

Although MAFLD is still more concentrated among lower socioeconomic groups in 2021, the extent of this inequality is decreasing (Fig. .

尽管在2021年，MAFLD仍然更集中于较低社会经济群体，但这种不平等的程度正在减少（图。

A-B). We observed the same trend in MAFLD-associated cirrhosis (Fig.

A-B). 我们在与MAFLD相关的肝硬化中观察到了相同的趋势（图。

C-D).

C-D）。

The results of the SDI-related health inequality analysis of DALYs for MASH-related liver cancer showed SII values of -2.56 in 1990 and − 1.72 in 2021, and although SII remained negative, indicating that the burden of MASH-related liver cancer is still concentrated in low socio-economic groups, the absolute difference in inequality has decreased, a change that reflects a health inequality mitigation.

与MASH相关肝癌的DALY健康不平等分析结果显示，1990年SII值为-2.56，2021年为-1.72，尽管SII仍为负值，表明MASH相关肝癌的负担仍然集中在低社会经济群体，但不平等的绝对差异已有所减少，这一变化反映出健康不平等的缓解。

In addition, the CI for MASH-associated liver cancer declined from 0.05 in 1990 (burden of disease concentrated in high socio-economic status groups) to -0.11 in 2021 (burden concentrated in low socio-economic status groups), indicating a significant change in the direction of health inequality. The burden of MASH-associated liver cancer has increased progressively in low-income groups over the past few decades, reflecting the higher risk of disease faced by people of lower socio-economic status (Fig. .

此外，MASH相关肝癌的集中指数（CI）从1990年的0.05（疾病负担集中在高社会经济地位群体）下降到2021年的-0.11（负担集中在低社会经济地位群体），表明健康不平等的方向发生了显著变化。在过去的几十年中，低收入群体中MASH相关肝癌的负担不断增加，反映出较低社会经济地位人群面临更高的患病风险（图。

E-F).

E-F）。

Fig. 3

图 3

Cross-country inequality analysis. (

跨国不平等分析。

) Absolute income-related healthy inequality in MAFLD burden, presented using regression lines, 1990 vs. 2021. (

与绝对收入相关的MAFLD负担的健康不平等，使用回归线表示，1990年对比2021年。

) Relative income-related healthy inequality in MAFLD burden, presented using concentration curves, 1990 vs. 2021. (

1990年与2021年按相对收入相关的MAFLD负担健康不平等，使用集中曲线表示。

) Absolute income-related healthy inequality in MAFLD-related cirrhosis burden, presented using regression lines, 1990 vs. 2021. (

与绝对收入相关的MAFLD相关肝硬化负担的健康不平等，使用回归线表示，1990年对比2021年。

) Relative income-related healthy inequality in MAFLD-related cirrhosis burden, presented using concentration curves, 1990 vs. 2021. (

1990年与2021年相对收入相关的MAFLD相关肝硬化负担的健康不平等，使用集中曲线表示。

) Absolute income-related healthy inequality in MASH-related liver cancer burden, presented using regression lines, 1990 vs. 2021. (

与绝对收入相关的MASH相关肝癌负担的健康不平等，使用回归线展示，1990年对比2021年。

) Relative income-related healthy inequality in MASH-related liver cancer burden, presented using concentration curves, 1990 vs. 2021.

) 1990年与2021年MASH相关肝癌负担中相对收入相关的健康不平等，使用集中曲线表示。

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Decomposition analysis

分解分析

For incidence decomposition analysis of MAFLD, the past 30 years have seen a significant global increase in both sexes. Of these, the increase in population growth (12,569,058.39 vs. 12,123,797.05) and epidemiological changes trends were greater in males than in females.

对于 MAFLD 的发病率分解分析，过去 30 年里，全球男女的发病率均显著增加。其中，男性的人口增长（12,569,058.39 对比 12,123,797.05）和流行病学变化趋势大于女性。

For mortality decomposition analysis of MAFLD, the past 30 years also have seen a significant global increase in both sexes. It is noteworthy that the number of deaths increased more among females than males (83,429.02 vs. 82,968.62). Decomposition analyses can therefore help us understand the extent to which these three factors individually influence the burden of disease in MAFLD.

对于MAFLD的死亡分解分析，过去30年全球男女两性的死亡人数均显著增加。值得注意的是，女性的死亡人数增长比男性更多（83,429.02 vs. 82,968.62）。因此，分解分析可以帮助我们了解这三种因素在多大程度上分别影响MAFLD的疾病负担。

We can thus infer that the number of MAFLD cases may increase with age. As the population grows, it may result in more people having MAFLD. The epidemiological changes trends (incidence), such as the emergence of new diseases or new treatments, may alter the incidence of MAFLD (.

因此，我们可以推断 MAFLD 的病例数量可能会随着年龄的增长而增加。随着人口的增长，可能会导致更多人患上 MAFLD。流行病学变化趋势（发病率），如新疾病或新治疗的出现，可能会改变 MAFLD 的发病率。

Supplementary Figure S6A-B and Supplementary Table S13-S14

补充图S6A-B和补充表S13-S14

). For more information about the decomposition analysis of MAFLD-related cirrhosis and MASH-related liver cancer, see

）。有关MAFLD相关肝硬化和MASH相关肝癌的分解分析的更多信息，请参见

Supplementary Figure S6C-F; Supplementary Tables S13-S14

补充图 S6C-F；补充表 S13-S14

。

Bayesian age‑period‑cohort

贝叶斯年龄-时期-队列模型

(

BAPC

)

model prediction

模型预测

Using the BAPC model, we projected the global burden of MAFLD from 2022 to 2036. The model accounts for age, period, and cohort effects and incorporates data from 1990 to 2021. By 2036, the ASIR for MAFLD is projected to increase to 91.28 per 100,000 for males and 91.94 per 100,000 for females. The growth rates were 4.73% and 16.39%, respectively, compared with 2021 (Fig. .

使用BAPC模型，我们预测了2022年至2036年全球MAFLD的负担。该模型考虑了年龄、时期和队列效应，并纳入了1990年至2021年的数据。到2036年，男性MAFLD的ASIR预计将增加到每10万人91.28例，女性为每10万人91.94例。与2021年相比，增长率分别为4.73%和16.39%（图。

A-B;

Supplementary Table S15 and S17

补充表 S15 和 S17

).Similarly, for MAFLD-related cirrhosis, the predicted results showed an increasing trend in ASIR, and the increase was more pronounced in females than in males (Fig.

同样，对于与MAFLD相关的肝硬化，预测结果显示ASIR呈上升趋势，且女性的上升幅度比男性更明显（图。

C-D;

Supplementary Table S15 and S17

补充表 S15 和 S17

).The predicted ASIR of MASH-related liver cancer to 2036 were illustrated in Fig.

). 图中展示了至2036年MASH相关肝癌的预测年龄标准化发病率（ASIR）。

E-F and

E-F 和

Supplementary Table S15 and S17

补充表 S15 和 S17

.The results showed an increasing trend in ASIR for NASH-related liver cancer in males and a decreasing trend in females by 2036.

结果表明，到2036年，男性NASH相关肝癌的ASIR呈上升趋势，而女性则呈下降趋势。

The model also accounts the global ASMR of 3 diseases. Global ASMR of MAFLD and MAFLD-related cirrhosis are both expected to continue declining. By 2036, the ASMR of MAFLD is forecasted to be 2.18 per 100,000 for males and 1.97 per 100,000 for females, reflecting a decrease of 6.43% and 10.85%, respectively, compared to 2021 (Fig. .

该模型还计算了三种疾病的全球年龄标化死亡率（ASMR）。代谢相关脂肪性肝病（MAFLD）及其相关肝硬化的全球ASMR均预计将继续下降。到2036年，男性MAFLD的ASMR预计为每10万人2.18例，女性为每10万人1.97例，相较于2021年分别下降了6.43%和10.85%（图。

A-B;

Supplementary Table S16 and S18

补充表 S16 和 S18

). Notably, the decline in MAFLD mortality is expected to be more pronounced among females, contributing significantly to the overall reduction in global MAFLD burden. The predicted ASMR of MAFLD-related cirrhosis to 2036 were illustrated in Fig.

）。值得注意的是，预计女性的MAFLD死亡率下降将更为显著，这将对全球MAFLD负担的整体减少做出重要贡献。预测至2036年MAFLD相关肝硬化的年龄标化死亡率（ASMR）如图所示。

C-D and

C-D 和

Supplementary Table S16 and S18

补充表 S16 和 S18

. Notably, the BAPC model showed an increasing trend in ASMR for MASH-related liver cancer in males compared to females from 2022 to 2026 (Fig.

特别是，BAPC模型显示，从2022年到2026年，男性与女性相比，MASH相关肝癌的年龄标化死亡率（ASMR）呈上升趋势（图。

E-F;

电子战；

Supplementary Table S16 and S18

补充表 S16 和 S18

）。

Fig. 4

图4

Projects the global age-standardized incidence of 3 diseases for both sexes from 2022 to 2036. (

预测2022年至2036年三种疾病在两性中的全球年龄标准化发病率。(

) Projected Incidence in males for MAFLD. (

男性MAFLD的预计发病率。

) Projected Incidence in females for MAFLD. (

女性MAFLD的预计发病率。

C语言

) Projected Incidence in males for MAFLD-related cirrhosis. (

男性MAFLD相关肝硬化预计发病率。

) Projected Incidence in females for MAFLD-related cirrhosis. (

女性MAFLD相关肝硬化预计发病率。

) Projected Incidence in males for MASH-related liver cancer. (

) 男性MASH相关肝癌的预计发病率。 (

) Projected Incidence in females for MASH-related liver cancer.

女性MASH相关肝癌的预计发病率。

Full size image

全尺寸图像

Fig. 5

图5

Projects the global age-standardized mortality of 3 diseases for both sexes from 2022 to 2036. (

预测2022年至2036年三种疾病在两性中的全球年龄标准化死亡率。(

) Projected mortality in males for MAFLD. (

男性MAFLD的预计死亡率。

) Projected mortality in females for MAFLD. (

女性MAFLD的预测死亡率。

) Projected mortality in males for MAFLD-related cirrhosis. (

) 男性MAFLD相关肝硬化预计死亡率。 (

) Projected mortality in females for MAFLD-related cirrhosis. (

) 女性 MAFLD 相关肝硬化预计死亡率。 (

) Projected mortality in males for MASH-related liver cancer. (

) 男性因MASH相关肝癌的预计死亡率。 (

) Projected mortality in females for MASH-related liver cancer.

女性MASH相关肝癌的预计死亡率。

Full size image

全尺寸图像

Discussion

讨论

The results of this study underscore the increasing global burden of MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer. The rising incidence, prevalence, and disability-adjusted life years (DALYs) associated with these conditions from 1990 to 2021 align with the global trends in obesity, metabolic syndrome, and type 2 diabetes, which are well-established risk factors for MAFLD and its progression.

这项研究的结果强调了MAFLD、MAFLD相关肝硬化和MASH相关肝癌的全球负担日益加重。从1990年到2021年，与这些疾病相关的发病率、患病率和伤残调整生命年（DALYs）的上升，与全球肥胖、代谢综合征和2型糖尿病的趋势一致，而这些都是MAFLD及其进展的公认风险因素。

This trend is consistent across multiple socio-demographic regions, although with notable regional variability, reflecting disparities in socioeconomic development and healthcare access..

这一趋势在多个社会人口统计区域中是一致的，尽管存在显著的区域差异，反映了社会经济发展和医疗保健获取方面的不平等。

Global epidemiological context

全球流行病学背景

MAFLD has rapidly become the most common liver disease globally and is currently estimated to affect 38% of the global population

MAFLD迅速成为全球最常见的肝脏疾病，目前估计影响全球38%的人口。

. Rapid urbanization, the transition towards more processed, calorie-dense diets, and the reduction in physical activity have become ubiquitous risk factors, especially in middle- and low-income countries

快速城市化、转向加工更多、热量更密集的饮食以及身体活动的减少已成为普遍的风险因素，尤其是在中低收入国家。

，

. Regions such as South Asia and East Asia, where rapid economic development has led to substantial lifestyle changes, are experiencing a disproportionate rise in MAFLD incidence. This phenomenon is particularly worrying given that these regions also have significant population sizes, thus amplifying the absolute burden of liver-related diseases globally..

南亚和东亚等地区由于经济快速发展导致生活方式发生重大变化，MAFLD（代谢相关脂肪性肝病）发病率正在不成比例地攀升。考虑到这些地区人口众多，这一现象尤其令人担忧，因为这会加剧全球肝脏相关疾病的绝对负担。

Further compounding the problem is the established association of MAFLD with cardiovascular disease (CVD), chronic kidney disease (CKD), and malignancies such as hepatocellular carcinoma (HCC)

更加复杂化的问题是，MAFLD与心血管疾病（CVD）、慢性肾病（CKD）以及诸如肝细胞癌（HCC）等恶性肿瘤之间已确立的关联。

，

. The interplay between metabolic dysfunction and liver health cannot be overstated

代谢功能障碍与肝脏健康之间的相互作用怎么强调都不为过。

. As MAFLD progresses to MASH, fibrosis, cirrhosis, and ultimately liver cancer, the demand on healthcare systems grows, often outpacing the capacity of low-resource settings to manage such cases effectively. The mortality rates linked to MASH-related liver cancer, which have already surpassed those due to alcohol-related HCC, are set to rise further, underscoring the need for preemptive healthcare interventions..

随着MAFLD进展为MASH、纤维化、肝硬化，并最终发展为肝癌，对医疗系统的需求不断增加，常常超出低资源环境有效管理此类病例的能力。与MASH相关的肝癌死亡率已经超过酒精相关HCC的死亡率，并且预计将进一步上升，凸显了采取预防性医疗干预措施的必要性。

Socioeconomic inequality and regional disparities

社会经济不平等和地区差异

One of the more profound observations from this study is the shift in the socioeconomic distribution of MAFLD and related conditions. Historically, MAFLD has been concentrated in high-income groups, where access to abundant food and more sedentary lifestyles predominated

这项研究中较为深刻的观察之一是MAFLD及相关疾病在社会经济分布上的变化。历史上，MAFLD主要集中在高收入群体，这些人群更容易获得丰富的食物，并以久坐的生活方式为主。

，

. However, the inequality analysis revealed a reversal of this trend, with MAFLD now disproportionately affecting lower-income groups. This transition suggests that while high-income nations have begun implementing preventive public health strategies, low- and middle-income countries (LMICs) are still grappling with rapidly worsening risk factors.

然而，不平等分析揭示了这一趋势的逆转，MAFLD 现在对低收入群体的影响不成比例。这种转变表明，虽然高收入国家已经开始实施预防性的公共卫生战略，但低收入和中等收入国家 (LMICs) 仍在努力应对迅速恶化的风险因素。

The continued rise of MAFLD among these populations is likely driven by increased consumption of processed foods, urbanization, and limited access to healthcare services.

这些人群中MAFLD的持续上升可能是由于加工食品消费增加、城市化以及医疗保健服务有限所致。

。

Regional differences in MAFLD burden further emphasize the importance of tailored public health approaches. Latin America, the Middle East, and South Asia currently exhibit the highest prevalence and incidence rates, while regions such as Western Europe show a relatively lower but still significant burden.

区域差异进一步凸显了采取针对性公共卫生方法的重要性。拉丁美洲、中东和南亚目前的MAFLD患病率和发病率最高，而西欧等地区的负担相对较低但仍显著。

The highest age-standardized prevalence rates (ASPR) are observed in countries such as Kuwait, Egypt, and Iran, while nations like Japan and Finland report much lower rates. These stark contrasts highlight the need for region-specific strategies that address local risk factors, healthcare capacity, and socioeconomic conditions.

科威特、埃及和伊朗等国的年龄标化患病率 (ASPR) 最高，而日本和芬兰等国的患病率则低得多。这些鲜明的对比凸显了针对当地风险因素、医疗能力和社会经济条件制定区域特定策略的必要性。

Without such targeted interventions, regions with already high burdens, such as South Asia, may face exponential increases in liver-related diseases in the coming years..

如果没有这样的针对性干预，南亚等已经负担沉重的地区在未来几年可能会面临肝病的指数级增长。

Gender and age-related considerations

性别和年龄相关考虑因素

Age and gender patterns also play a crucial role in shaping the MAFLD epidemic

年龄和性别模式也在塑造MAFLD流行病方面发挥着至关重要的作用。

，

. The present study showed significant gender differences in the prevalence and incidence of MAFLD in different age groups. The higher prevalence in young women (20–24 age) compared to men may be related to the protective effect of estrogen on fat metabolism and insulin sensitivity. However, the burden is higher in older women (75–79 age), primarily influenced by postmenopausal hormonal changes, increased abdominal obesity, and exacerbation of metabolic abnormalities.

本研究显示，在不同年龄组中，MAFLD的患病率和发病率存在显著的性别差异。年轻女性（20-24岁）相较于男性的较高患病率可能与雌激素对脂肪代谢和胰岛素敏感性的保护作用有关。然而，老年女性（75-79岁）的疾病负担更高，主要受到绝经后激素变化、腹部肥胖增加以及代谢异常加剧的影响。

In contrast, the overall MAFLD burden is higher in men and has increased more over the past 30 years, possibly due to higher visceral fat accumulation, insulin resistance, less healthy eating habits, and inadequate health management. The findings highlight the critical role of gender in the prevalence and incidence of MAFLD and suggest that gender-specific health management and prevention strategies should be personalized in the future to reduce the global burden of MAFLD and its complications..

相比之下，男性的总体MAFLD负担更高，并且在过去30年中增长更多，这可能是由于内脏脂肪积累较多、胰岛素抵抗、不健康的饮食习惯以及健康管理不足所致。研究结果强调了性别在MAFLD患病率和发病率中的关键作用，并建议未来应个性化制定针对性别的健康管理和预防策略，以减轻全球MAFLD及其并发症的负担。

Moreover, the increase in disease burden with advancing age is particularly concerning given the rapid aging of populations in many parts of the world. The intersection of aging populations with the rising incidence of metabolic diseases like MAFLD suggests that healthcare systems worldwide may soon face significant resource challenges.

此外，鉴于世界许多地区人口老龄化的加速，疾病负担随年龄增长而增加的问题尤其令人担忧。老龄化人口与MAFLD等代谢性疾病发病率上升的交汇点表明，全球医疗系统可能很快将面临严峻的资源挑战。

Aging populations also tend to have comorbidities that complicate liver disease progression, such as hypertension, diabetes, and CKD, further increasing the demand for specialized care.

老龄化人口通常也存在共病，这些共病会复杂化肝病的进展，例如高血压、糖尿病和慢性肾病（CKD），进一步增加了对专业护理的需求。

。

Future projections and public health implications

未来预测与公共卫生意义

The projections made using the Bayesian Age-Period-Cohort (BAPC) model are particularly troubling, as they predict a continued rise in the burden of MAFLD-related diseases through 2036. The model shows that age-standardized incidence rates (ASIR) for MAFLD will increase in both males and females, although the rise is expected to be more pronounced in females.

使用贝叶斯年龄-时期-队列（BAPC）模型做出的预测尤其令人担忧，因为它们预测到2036年MAFLD相关疾病的负担将持续增加。该模型显示，男性和女性的MAFLD年龄标准化发病率（ASIR）都将上升，尽管女性的上升幅度预计将更为显著。

Additionally, while the mortality rate (ASMR) for MAFLD is predicted to decline slightly due to advances in healthcare, the incidence and mortality associated with MASH-related liver cancer are expected to rise, particularly among males..

此外，虽然由于医疗保健的进步，MAFLD的死亡率（ASMR）预计将略有下降，但与MASH相关的肝癌的发病率和死亡率预计会上升，尤其是男性群体。

A number of interventions have been implemented to reduce the global burden of MAFLD, with high-income countries, such as the Nordic countries, showing significant results in lifestyle management, while low- and middle-income countries have limited interventions due to the proliferation of processed food consumption and the low availability of healthy diets.

为了减轻MAFLD的全球负担，已经实施了一系列干预措施。高收入国家（如北欧国家）在生活方式管理方面取得了显著成果，而低收入和中等收入国家由于加工食品消费的增加和健康饮食的可获得性较低，干预措施较为有限。

With regard to early detection and metabolic management, high-income countries have integrated them into their health-care systems, but screening rates are low in low-income countries, leading to diagnosis of the disease at a late stage. In terms of policy interventions, high-income countries have implemented health policies targeting low-income groups, while low-income countries lack targeted public health policies due to resource constraints.

对于早期发现和代谢管理，高收入国家已将其整合到医疗卫生系统中，但低收入国家筛查率较低，导致疾病晚期才得以诊断。在政策干预方面，高收入国家实施了针对低收入群体的健康政策，而低收入国家由于资源有限，缺乏针对性的公共卫生政策。

In terms of international cooperation, WHO and other organizations have promoted the prevention and control of MAFLD globally, but the implementation of transnational cooperation is still insufficient..

在国际合作方面，世界卫生组织和其他组织促进了全球对MAFLD的预防和控制，但跨国合作的实施仍然不足。

As a result, existing interventions have been effective in high-income countries, but low- and middle-income countries still face challenges. In the future, it is necessary to strengthen the regulation of healthy diets and promote healthy eating; promote low-cost screening, incorporate it into the primary health care system, and increase the rate of early diagnosis; optimize social health policies, reduce health inequalities, and provide health care subsidies; and promote international cooperation, share best practices, and support resource-poor countries, all of which will work together to curb the rising trend of the global burden of MAFLD..

因此，现有的干预措施在高收入国家有效，但低收入和中等收入国家仍面临挑战。未来需要加强对健康饮食的监管，推动健康饮食；推广低成本筛查，将其纳入初级卫生保健系统，提高早期诊断率；优化社会健康政策，减少健康不平等，提供医疗补贴；推动国际合作，分享最佳实践，支持资源匮乏国家，这些措施共同作用，才能遏制全球MAFLD负担不断上升的趋势。

Strengths and limitations

优势与局限性

The study utilizes the comprehensive GBD 2021 database, which includes data from 204 countries and territories, allowing for a detailed and global assessment of MAFLD and its complications. Compared with previous studies, this study has the following key strengths: In first place, most MAFLD studies have been limited to specific countries or regions, whereas this study reveals differences in the burden of MAFLD across regions and socioeconomic levels through global data analysis, providing a stronger scientific basis for the development of targeted interventions.

该研究利用了全面的GBD 2021数据库，其中包含来自204个国家和地区的数据，从而能够对MAFLD及其并发症进行详细且全球性的评估。与以往的研究相比，本研究具有以下几个关键优势：首先，大多数MAFLD研究局限于特定国家或地区，而本研究通过全球数据分析揭示了MAFLD负担在不同地区和社会经济水平上的差异，为制定针对性干预措施提供了更有力的科学依据。

In the second place, previous MAFLD-related studies have focused on lifestyle factors in high-income countries, this study reveals the socioeconomic drivers of the MAFLD burden through inequality analysis, emphasizing the rising problem of health inequality. In the third place, previous MAFLD-related studies have focused only on the prevalence of the disease, whereas this study provides detailed regional data and proposes precise public health intervention strategies by combining SDI analysis.

其次，以往的MAFLD相关研究多集中于高收入国家的生活方式因素，本研究则通过不平等分析揭示了MAFLD负担的社会经济驱动因素，强调了健康不平等问题的日益严重。再次，以往的MAFLD相关研究仅关注疾病的患病率，而本研究提供了详细的区域数据，并通过结合SDI分析提出了精准的公共卫生干预策略。

Lastly, whereas previous relevant MAFLD studies have only been analyzed retrospectively, this study uses the BAPC prediction model to enable policymakers to identify in advance high-risk areas of rising MAFLD burdens and to take effective measures to reduce future burdens..

最后，以往相关的MAFLD研究仅进行了回顾性分析，而本研究使用BAPC预测模型，使政策制定者能够提前识别MAFLD负担上升的高风险区域，并采取有效措施减轻未来负担。

Despite the aforementioned strengths of this study, there are several limitations, which are reflected in the quality of the data, risk factor analysis and predictive modelling. Firstly, the study relies on secondary data from the GBD database, which may have inherent limitations related to data collection and reporting accuracy, especially in low-income countries.

尽管本研究有上述优势，但也存在若干局限性，这些局限性反映在数据质量、风险因素分析和预测建模方面。首先，本研究依赖于GBD数据库的二手数据，这些数据可能存在与数据收集和报告准确性相关的固有限制，尤其是在低收入国家。

Second, the terminology of NAFLD has changed, with NAFLD recently being reclassified as MAFLD. This may limit the applicability of the findings to current clinical practice due to the lack of recent data on MAFLD. Thirdly, projections of future disease trends, while based on robust statistical models, may not fully account for unforeseen changes in healthcare practices, socioeconomic factors, or public health interventions that could alter the trajectory of these diseases..

其次，NAFLD的术语已发生变化，最近被重新分类为MAFLD。由于缺乏关于MAFLD的最新数据，这可能会限制研究结果在当前临床实践中的适用性。第三，尽管未来疾病趋势的预测基于可靠的统计模型，但可能无法充分考虑医疗实践、社会经济因素或公共卫生干预措施中不可预见的变化，而这些变化可能会改变这些疾病的进展轨迹。

Conclusion

结论

This study highlights the growing global burden of MAFLD, MAFLD-related cirrhosis, and MASH-related liver cancer, with significant regional disparities and shifting socioeconomic trends. Urgent action is required to address the rising incidence of these conditions, particularly in low- and middle-income countries, where the burden is expected to increase significantly.

本研究强调了MAFLD、MAFLD相关肝硬化和MASH相关肝癌的全球负担日益加重，且存在显著的地区差异和不断变化的社会经济趋势。迫切需要采取行动应对这些疾病发病率的上升，特别是在低收入和中等收入国家，这些国家的疾病负担预计会显著增加。

Effective public health strategies, including lifestyle interventions and improved access to healthcare, are crucial to mitigate the future impact of these diseases..

有效的公共卫生策略，包括生活方式干预和改善医疗保健的可及性，对于减轻这些疾病未来的影响至关重要。

Data availability

数据可用性

Availability of data and materials: Relevant data can be retrieved through the available website (https://vizhub.healthdata.org/gbd-results/).

数据和材料的可用性：相关数据可以通过以下网址获取（https://vizhub.healthdata.org/gbd-results/）。

Abbreviations

缩略语

MAFLD:

Metabolic dysfunction-associated fatty liver disease

代谢功能障碍相关脂肪肝病

MASLD:

Metabolic dysfunction-associated steatotic liver disease

代谢功能障碍相关的脂肪性肝病

IR:

红外线：

Insulin resistance

胰岛素抵抗

NAFL:

非酒精性脂肪肝：

Non-alcoholic fatty liver

非酒精性脂肪肝

NASH:

纳什：

Non-alcoholic steatohepatitis

非酒精性脂肪性肝炎

MetS:

代谢综合征：

Metabolic syndrome

代谢综合征

CVD:

心血管疾病（CVD）：

Cardiovascular disease

心血管疾病

T2DM:

2型糖尿病:

Type 2 diabetes mellitus

2型糖尿病 Mellitus

CKD:

慢性肾脏病：

Chronic kidney disease

慢性肾病

HCC:

肝细胞癌：

Hepatocellular carcinoma

肝细胞癌

DALYs:

伤残调整生命年（DALYs）：

Disability-adjusted life years

残疾调整生命年

SDI:

Socio-demographic index

社会人口指数

SII:

Slope index of inequality

斜率不平等指数

CI:

持续集成：

Concentration Index

浓度指数

BAPC:

Bayesian Age-Period-Cohort

贝叶斯年龄-时期-队列模型

ASIR:

Age-standardized incidence rates

年龄标准化发病率

ASMR:

Age-standardized mortality rate

年龄标准化死亡率

ASPR:

Age-standardized prevalence rate

年龄标化患病率

APC:

Annual percent change

年度百分比变化

AAPC:

Average annual percentage change

年均百分比变化

UIs:

用户界面：

Uncertainty intervals

不确定性区间

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Acknowledgements

致谢

We thank the Institute of Health Metrology and Evaluation for sharing valuable GBD data.

我们感谢健康计量与评估研究所分享宝贵的GBD数据。

Funding

资金筹集

This study was supported by Scientific and technological innovation project of China Academy of Chinese Medical Sciences (No.CI2021A00801, No.CI2021A00806 and No.CI2023C026YL) and Sanming Proiect of Medicine in Shenzhen (No.SZZYSM202311014).

本研究得到了中国中医科学院科技创新工程项目（编号：CI2021A00801、CI2021A00806 和 CI2023C026YL）以及深圳市三名医学项目（编号：SZZYSM202311014）的支持。

Author information

作者信息

Author notes

作者笔记

Ziwei Guo, Dongjie Wu and Runhan Mao contributed equally to this work.

郭紫薇、吴东杰和毛润涵对这项工作做出了同等贡献。

Authors and Affiliations

作者与所属机构

Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China

中国中医科学院广安门医院感染科，北京，100053，中国

Ziwei Guo, Dongjie Wu, Qingjuan Wu & Wenliang Lv

郭紫薇、吴东杰、吴青娟、吕文亮

Department of Medical Laboratory, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China

中国中医科学院广安门医院检验科，北京，100053，中国

Runhan Mao

毛润涵

Department of Traditional Chinese Medicine, Peking University People’s Hospital, Beijing, 100044, China

中国北京，北京大学人民医院中医科，邮编100044

Ziang Yao

姚子昂

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Ziwei Guo

郭紫薇

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Dongjie Wu

吴东杰

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Runhan Mao

毛润涵

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Ziang Yao

姚子昂

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Qingjuan Wu

吴青娟

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Wenliang Lv

吕文亮

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Contributions

贡献

ZW G, DJ W and RH M had full access to all data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. ZW G, RH M, DJ W, QJ W and WL L planned the concept of this study. ZW G and DJ W conducted data extraction and analysis. ZW G, DJ W and RH M carried out data cleaning and material support.

ZW G、DJ W 和 RH M 完全掌握了研究中的所有数据，并对数据的完整性和数据分析的准确性负责。ZW G、RH M、DJ W、QJ W 和 WL L 规划了本研究的概念。ZW G 和 DJ W 进行了数据提取和分析。ZW G、DJ W 和 RH M 负责数据清理和材料支持。

All authors critically reviewed, revised and contributed to the final manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted..

所有作者都对最终稿件进行了严格审阅、修订并作出了贡献。通讯作者证实，所有列出的作者均符合作者资格标准，且没有其他符合标准的人被遗漏。

Corresponding authors

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Correspondence to

联系方式：

Qingjuan Wu

吴青娟

或

Wenliang Lv

吕文亮

。

Ethics declarations

伦理声明

Consent for publication

同意发表

All participants in this study consented to publication.

本研究的所有参与者均同意发表。

Competing interests

竞争利益

The authors declare no competing interests.

作者声明不存在竞争性利益。

Ethical approval and consent to participate

伦理批准与参与同意

For the GBD, which is publicly available, and no identifiable information was included in the analyses, the ‘Ethical approval and Ethics Approval and Consent to Participate’ was not applicable.

对于公开可用的GBD，且分析中不包含可识别信息，“伦理批准和参与同意”不适用。

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Springer Nature 对已发布地图中的管辖权声明和机构隶属关系保持中立。

Electronic supplementary material

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Below is the link to the electronic supplementary material.

以下是电子补充材料的链接。

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根据本许可，您无权分享从本文或其部分内容衍生的改编材料。本文中的图像或其他第三方材料包含在文章的 Creative Commons 许可中，除非材料的署名行另有说明。如果材料未包含在文章的 Creative Commons 许可中，并且您的预期用途不被法律规定允许或超出了允许的使用范围，您需要直接从版权持有人处获得许可。

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Guo, Z., Wu, D., Mao, R.

郭，Z.，吴，D.，毛，R.