南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (4): 770-784.doi: 10.12122/j.issn.1673-4254.2026.04.06
陈浩1,2,3(
), 李振汉4,5, 纪梦佳6, 汪鑫诚7, 陈博峰6, 管谦1, 武嫚4, 卢林明1()
收稿日期:2025-10-23
出版日期:2026-04-20
发布日期:2026-04-24
通讯作者:
卢林明
E-mail:ha0chen@wnmc.edu.cn;llm7172@sina.com
作者简介:陈 浩，博士后，副教授，E-mail: ha0chen@wnmc.edu.cn
基金资助:
Hao CHEN1,2,3(), Zhenhan LI4,5, Mengjia JI6, Xincheng WANG7, Bofeng CHEN6, Qian GUAN1, Man WU4, Linming LU1()
Received:2025-10-23
Online:2026-04-20
Published:2026-04-24
Contact:
Linming LU
E-mail:ha0chen@wnmc.edu.cn;llm7172@sina.com
Supported by:摘要：
目的 分析非酒精性脂肪性肝病（NAFLD）的全球负担趋势、驱动因素及健康不平等，利用可解释机器学习识别关键死亡风险因素，并通过孟德尔随机化验证其潜在因果关联。 方法 基于全球疾病负担（GBD）2021数据，提取1990~2021年NAFLD的发病率、患病率、死亡率、残疾调整生命年（DALYs）等指标。运用Joinpoint回归分析趋势，分解分析法量化人口增长、老龄化和流行病学变化的贡献，集中指数评估健康不平等，XGBoost-SHAP机器学习识别死亡预测因子，并使用双样本孟德尔随机化对关键因子进行因果验证；分析按性别和社会人口指数（SDI）分层。 结果 全球NAFLD年龄标准化DALY率在男性（平均年度百分比变化［AAPC］=+0.34%）和女性（AAPC=+0.05%）中均呈上升趋势。分解分析显示，人口增长是全球DALYs增加的主要驱动力，而在高SDI地区，人口老龄化对男性死亡的贡献度达52.37%。健康不平等分析显示，2021年DALYs的集中指数为-0.05，负担向低SDI人群集中。机器学习识别吸烟（相对重要性=100%）和高龄（70~74岁：60%）为最关键死亡预测因素，模型测试集拟合优度良好（R²=0.98）。SDI分层分析显示吸烟和老龄化在不同SDI区域均位列前两位。孟德尔随机化进一步验证了吸烟起始（OR=1.35，P<0.05）与衰老（以衰弱指数代理，OR=2.01，P<0.05）与NAFLD风险间的正向因果关联。 结论 NAFLD负担沉重，存在性别与社会经济不平等。吸烟和高龄是关键风险因素，需制定整合烟草控制、老年健康管理与健康公平促进的针对性干预策略。
陈浩, 李振汉, 纪梦佳, 汪鑫诚, 陈博峰, 管谦, 武嫚, 卢林明. 全球非酒精性脂肪性肝病负担的关键决定因素：基于GBD数据的机器学习联合孟德尔随机化验证[J]. 南方医科大学学报, 2026, 46(4): 770-784.
Hao CHEN, Zhenhan LI, Mengjia JI, Xincheng WANG, Bofeng CHEN, Qian GUAN, Man WU, Linming LU. Key determinants of global burden of non-alcoholic fatty liver disease: machine learning combined with Mendelian randomization analysis based on GBD data[J]. Journal of Southern Medical University, 2026, 46(4): 770-784.
图1 全球NAFLD年龄标准化DALY率、YLDs和YLLs趋势(1990~2021年)按性别分层
Fig.1 Global trends in age-standardized disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) rates of NAFLD (1990-2021) stratified by sex. A: Age-standardized DALYs rate; B: Age-standardized YLDs rate; C: Age-standardized YLLs rate.
图2 全球NAFLD年龄标准化患病率、发病率和死亡率趋势(1990~2021)按性别分层
Fig.2 Global trends in age-standardized prevalence (A), incidence (B), and mortality rates (C) of NAFLD (1990-2021) stratified by sex.
| Location | DALYs | Deaths | Incidence | Prevalence | YLDs | YLLs | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | Male | Female | Male | Female | Male | Female | Male | Female | Male | Female | Male | |
| Global | 0.05 (0.02 to 0.08) | 0.34 (0.31 to 0.37) | 0.07 (0.04 to 0.1) | 0.35 (0.31 to 0.38) | 0.75 (0.73 to 0.76) | 0.7 (0.69 to 0.71) | 0.77 (0.75 to 0.79) | 0.65 (0.64 to 0.66) | 0.46 (0.45 to 0.46) | 0.72 (0.7 to 0.73) | 0.04 (0.01 to 0.07) | 0.34 (0.31 to 0.37) |
| High SDI | 0.1 (0.06 to 0.13) | -0.07 (-0.11 to -0.04) | 0.13 (0.09 to 0.16) | 0.09 (0.06 to 0.12) | 0.95 (0.94 to 0.96) | 0.82 (0.81 to 0.83) | 1.01 (1 to 1.03) | 0.92 (0.91 to 0.93) | 0.55 (0.53 to 0.57) | 0.56 (0.54 to 0.58) | 0.09 (0.05 to 0.12) | -0.08 (-0.12 to -0.04) |
| High-middle SDI | 0.09 (0 to 0.2) | 0.06 (-0.01 to 0.15) | -0.11 (-0.22 to -0.01) | -0.12 (-0.18 to -0.05) | 0.88 (0.84 to 0.92) | 0.72 (0.69 to 0.74) | 0.88 (0.85 to 0.92) | 0.64 (0.61 to 0.67) | 0.38 (0.35 to 0.41) | 0.41 (0.39 to 0.44) | 0.08 (0 to 0.2) | 0.06 (-0.02 to 0.15) |
| Middle SDI | -0.09 (-0.13 to -0.04) | 0.6 (0.56 to 0.63) | 0.01 (-0.03 to 0.05) | 0.62 (0.58 to 0.68) | 0.63 (0.61 to 0.66) | 0.7 (0.69 to 0.72) | 0.61 (0.59 to 0.64) | 0.57 (0.54 to 0.58) | 0.68 (0.66 to 0.69) | 1.04 (1.03 to 1.05) | -0.09 (-0.14 to -0.05) | 0.59 (0.56 to 0.63) |
Low- middle SDI | 0.08 (0.04 to 0.1) | 0.8 (0.78 to 0.83) | -0.08 (-0.12 to -0.06) | 0.87 (0.83 to 0.9) | 0.54 (0.54 to 0.55) | 0.62 (0.61 to 0.62) | 0.42 (0.41 to 0.42) | 0.54 (0.53 to 0.55) | 1.04 (1.01 to 1.06) | 1.49 (1.47 to 1.5) | 0.07 (0.04 to 0.09) | 0.8 (0.77 to 0.82) |
| Low-SDI | -0.32 (-0.33 to -0.3) | -0.36 (-0.37 to -0.34) | -0.25 (-0.27 to -0.22) | -0.31 (-0.34 to -0.29) | 0.43 (0.43 to 0.43) | 0.46 (0.45 to 0.46) | 0.35 (0.34 to 0.35) | 0.39 (0.38 to 0.39) | 0.15 (0.13 to 0.16) | 0.14 (0.13 to 0.16) | -0.32 (-0.34 to -0.3) | -0.36 (-0.38 to -0.34) |
表1 按性别和SDI分层的NAFLD相关负担指标AAPC（1990~2021）
Tab.1 Average annual percentage change （AAPC） of NAFLD-related burden indicators by sex and SDI （1990-2021）
| Location | DALYs | Deaths | Incidence | Prevalence | YLDs | YLLs | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | Male | Female | Male | Female | Male | Female | Male | Female | Male | Female | Male | |
| Global | 0.05 (0.02 to 0.08) | 0.34 (0.31 to 0.37) | 0.07 (0.04 to 0.1) | 0.35 (0.31 to 0.38) | 0.75 (0.73 to 0.76) | 0.7 (0.69 to 0.71) | 0.77 (0.75 to 0.79) | 0.65 (0.64 to 0.66) | 0.46 (0.45 to 0.46) | 0.72 (0.7 to 0.73) | 0.04 (0.01 to 0.07) | 0.34 (0.31 to 0.37) |
| High SDI | 0.1 (0.06 to 0.13) | -0.07 (-0.11 to -0.04) | 0.13 (0.09 to 0.16) | 0.09 (0.06 to 0.12) | 0.95 (0.94 to 0.96) | 0.82 (0.81 to 0.83) | 1.01 (1 to 1.03) | 0.92 (0.91 to 0.93) | 0.55 (0.53 to 0.57) | 0.56 (0.54 to 0.58) | 0.09 (0.05 to 0.12) | -0.08 (-0.12 to -0.04) |
| High-middle SDI | 0.09 (0 to 0.2) | 0.06 (-0.01 to 0.15) | -0.11 (-0.22 to -0.01) | -0.12 (-0.18 to -0.05) | 0.88 (0.84 to 0.92) | 0.72 (0.69 to 0.74) | 0.88 (0.85 to 0.92) | 0.64 (0.61 to 0.67) | 0.38 (0.35 to 0.41) | 0.41 (0.39 to 0.44) | 0.08 (0 to 0.2) | 0.06 (-0.02 to 0.15) |
| Middle SDI | -0.09 (-0.13 to -0.04) | 0.6 (0.56 to 0.63) | 0.01 (-0.03 to 0.05) | 0.62 (0.58 to 0.68) | 0.63 (0.61 to 0.66) | 0.7 (0.69 to 0.72) | 0.61 (0.59 to 0.64) | 0.57 (0.54 to 0.58) | 0.68 (0.66 to 0.69) | 1.04 (1.03 to 1.05) | -0.09 (-0.14 to -0.05) | 0.59 (0.56 to 0.63) |
Low- middle SDI | 0.08 (0.04 to 0.1) | 0.8 (0.78 to 0.83) | -0.08 (-0.12 to -0.06) | 0.87 (0.83 to 0.9) | 0.54 (0.54 to 0.55) | 0.62 (0.61 to 0.62) | 0.42 (0.41 to 0.42) | 0.54 (0.53 to 0.55) | 1.04 (1.01 to 1.06) | 1.49 (1.47 to 1.5) | 0.07 (0.04 to 0.09) | 0.8 (0.77 to 0.82) |
| Low-SDI | -0.32 (-0.33 to -0.3) | -0.36 (-0.37 to -0.34) | -0.25 (-0.27 to -0.22) | -0.31 (-0.34 to -0.29) | 0.43 (0.43 to 0.43) | 0.46 (0.45 to 0.46) | 0.35 (0.34 to 0.35) | 0.39 (0.38 to 0.39) | 0.15 (0.13 to 0.16) | 0.14 (0.13 to 0.16) | -0.32 (-0.34 to -0.3) | -0.36 (-0.38 to -0.34) |
图3 按SDI分层的NAFLD负担驱动因素分解
Fig.3 Decomposition of NAFLD burden drivers stratified by SDI. A: DALYs. B: Deaths. C: Incident cases. D: Prevalent cases. E: YLDs. F: YLLs.
| Location | Aging | Population | Epidemiological change | |||
|---|---|---|---|---|---|---|
| Female | Male | Female | Male | Female | Male | |
| Global | 14419.67 (36.2%) | 13433.21 (34.48%) | 24454.98 (61.39%) | 21239.63 (54.52%) | 958.31 (2.41%) | 4286.05 (11%) |
| High SDI | 3662.74 (47.31%) | 3535.45 (52.37%) | 3289.18 (42.48%) | 2890.79 (42.82%) | 790.68 (10.21%) | 324.23 (4.8%) |
| High-middle SDI | 3965.7 (60.49%) | 3928.67 (62.65%) | 3143.9 (47.95%) | 2996.16 (47.78%) | -553.23 (-8.44%) | -654.46 (-10.44%) |
| Middle SDI | 7052.4 (49.81%) | 6559.51 (40.23%) | 7146.98 (50.48%) | 7015.22 (43.03%) | -40.46 (-0.29%) | 2730.11 (16.74%) |
| Low-middle SDI | 2452.8 (28.15%) | 1214.64 (15.51%) | 6260.62 (71.86%) | 4682.7 (59.78%) | -1.24 (-0.01%) | 1936.13 (24.72%) |
| Low SDI | -42.7 (-1.62%) | -193.15 (-10.97%) | 3031.76 (115.34%) | 2274.03 (129.2%) | -360.44 (-13.71%) | -320.85 (-18.23%) |
表2 按SDI和性别分层的NAFLD归因死亡数驱动因素分解
Tab.2 Decomposition of NAFLD-attributable deaths by SDI and sex
| Location | Aging | Population | Epidemiological change | |||
|---|---|---|---|---|---|---|
| Female | Male | Female | Male | Female | Male | |
| Global | 14419.67 (36.2%) | 13433.21 (34.48%) | 24454.98 (61.39%) | 21239.63 (54.52%) | 958.31 (2.41%) | 4286.05 (11%) |
| High SDI | 3662.74 (47.31%) | 3535.45 (52.37%) | 3289.18 (42.48%) | 2890.79 (42.82%) | 790.68 (10.21%) | 324.23 (4.8%) |
| High-middle SDI | 3965.7 (60.49%) | 3928.67 (62.65%) | 3143.9 (47.95%) | 2996.16 (47.78%) | -553.23 (-8.44%) | -654.46 (-10.44%) |
| Middle SDI | 7052.4 (49.81%) | 6559.51 (40.23%) | 7146.98 (50.48%) | 7015.22 (43.03%) | -40.46 (-0.29%) | 2730.11 (16.74%) |
| Low-middle SDI | 2452.8 (28.15%) | 1214.64 (15.51%) | 6260.62 (71.86%) | 4682.7 (59.78%) | -1.24 (-0.01%) | 1936.13 (24.72%) |
| Low SDI | -42.7 (-1.62%) | -193.15 (-10.97%) | 3031.76 (115.34%) | 2274.03 (129.2%) | -360.44 (-13.71%) | -320.85 (-18.23%) |
| Location | Aging | Population | Epidemiological change | |||
|---|---|---|---|---|---|---|
| Female | Male | Female | Male | Female | Male | |
| Global | 44483771.87 (16.58%) | 44269747.11 (14.95%) | 205531485.28 (76.6%) | 218539970.47 (73.8%) | 97676566.68 (36.4%) | 92934328.25 (31.38%) |
| High SDI | 5184817.85 (14.13%) | 6663980.9 (13.43%) | 13923637.39 (37.95%) | 21393081.71 (43.12%) | 15520327.55 (42.3%) | 19927730.42 (40.17%) |
| High-middle SDI | 14607816.21 (22.8%) | 13232909.37 (19.71%) | 27866316.58 (43.5%) | 29817746.28 (44.42%) | 24563543.43 (38.34%) | 19671925.7 (29.3%) |
| Middle SDI | 30028010.02 (31.74%) | 24644902.37 (25.09%) | 77231967 (81.64%) | 72694788.04 (74.01%) | 28171016.9 (29.78%) | 28023053.32 (28.53%) |
| Low-middle SDI | 7638124.99 (14.18%) | 6025521.11 (10.11%) | 58970988.08 (109.49%) | 61405554.89 (103.06%) | 11723202.04 (21.77%) | 16684909.61 (28%) |
| Low SDI | -118112.99 (-0.63%) | -640813.47 (-3.01%) | 28417047.9 (151.17%) | 31321397.28 (147.11%) | 3724985.49 (19.82%) | 4642147.02 (21.8%) |
表3 按SDI和性别分层的NAFLD患病病例数驱动因素分解
Tab.3 Decomposition of NAFLD prevalent cases by SDI and sex
| Location | Aging | Population | Epidemiological change | |||
|---|---|---|---|---|---|---|
| Female | Male | Female | Male | Female | Male | |
| Global | 44483771.87 (16.58%) | 44269747.11 (14.95%) | 205531485.28 (76.6%) | 218539970.47 (73.8%) | 97676566.68 (36.4%) | 92934328.25 (31.38%) |
| High SDI | 5184817.85 (14.13%) | 6663980.9 (13.43%) | 13923637.39 (37.95%) | 21393081.71 (43.12%) | 15520327.55 (42.3%) | 19927730.42 (40.17%) |
| High-middle SDI | 14607816.21 (22.8%) | 13232909.37 (19.71%) | 27866316.58 (43.5%) | 29817746.28 (44.42%) | 24563543.43 (38.34%) | 19671925.7 (29.3%) |
| Middle SDI | 30028010.02 (31.74%) | 24644902.37 (25.09%) | 77231967 (81.64%) | 72694788.04 (74.01%) | 28171016.9 (29.78%) | 28023053.32 (28.53%) |
| Low-middle SDI | 7638124.99 (14.18%) | 6025521.11 (10.11%) | 58970988.08 (109.49%) | 61405554.89 (103.06%) | 11723202.04 (21.77%) | 16684909.61 (28%) |
| Low SDI | -118112.99 (-0.63%) | -640813.47 (-3.01%) | 28417047.9 (151.17%) | 31321397.28 (147.11%) | 3724985.49 (19.82%) | 4642147.02 (21.8%) |
图4 NAFLD负担的社会经济不平等分析(1990年与2021年)
Fig.4 Socioeconomic inequality analysis of NAFLD burden (1990 and 2021). A: Lorenz curve for DALYs. B: Scatter plot of DALYs rate against SDI rank. C: Lorenz curve for deaths. D: Scatter plot of death rate against SDI rank. E: Lorenz curve for incidence. F: Scatter plot of incidence rate against SDI rank. G: Lorenz curve for prevalence. H: Scatter plot of prevalence rate against SDI rank.
图5 基于XGBoost-SHAP的NAFLD死亡风险预测模型特征解析
Fig.5 Feature interpretation of the XGBoost-SHAP model for predicting NAFLD mortality risk: feature importance, model diagnostics, and ternary decomposition. A: Feature importance; B: Model diagnostics; C: Ternary decomposition of importance metrics.
图6 基于XGBoost-SHAP的NAFLD死亡风险预测模型特征解析:SHAP摘要图与依赖图
Fig.6 Feature interpretation of the XGBoost-SHAP model for predicting NAFLD mortality risk: SHAP summary plot (A) and dependence plot (B).
图7 基于孟德尔随机化的衰老(衰弱指数)与吸烟对NAFLD风险的因果效应分析
Fig.7 Mendelian randomization analysis of the causal effects of aging (frailty index) and smoking on NAFLD risk. A: Forest plot for frailty index. B: Forest plot for smoking initiation. C: Funnel plot for frailty index. D: Funnel plot for smoking initiation.E: Scatter plot for frailty index. F: Scatter plot for smoking initiation.
图8 孟德尔随机化留一法敏感性分析: 衰弱指数
Fig.8 Leave-one-out sensitivity analysis of Mendelian randomization: Frailty index.
图9 孟德尔随机化留一法敏感性分析: 吸烟起始
Fig.9 Leave-one-out sensitivity analysis of Mendelian randomization: smoking initiation.
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