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Advances in Clinical Medicine
Vol. 13  No. 12 ( 2023 ), Article ID: 77935 , 11 pages
10.12677/ACM.2023.13122772

中国地区近10年非酒精性脂肪肝病的贝叶斯单臂Meta分析

文永昊1,2，樊海宁2*

1青海大学研究生院，青海 西宁

2青海大学附属医院，肝胆胰外科，青海 西宁

收稿日期：2023年11月25日；录用日期：2023年12月19日；发布日期：2023年12月26日

摘要

目的：系统评价中国近10年来的NAFLD的流行特征。方法：计算机检索PubMed、Embase、知网、万方等数据库2012年1月1日至2022年10月31日NAFLD的发病率的横断面研究。由2名研究者独立筛选文献后提取数据资料并评价纳入研究的偏倚风险，利用R软件(4.1.2)进行Meta分析。结果：共纳入141项研究，总人数1,218,241人。贝叶斯荟萃分析结果显示我国NAFLD的总体患病率为27.61% (95% CI 25.79~29.48)，其中，男性患病率为31.63% (95% CI 29.71-33.57)，在40~49岁之间达到高峰。女性患病率为19.02% (95% CI 17.01~21.19)，在60~69岁之间达到高峰。在BMI < 18.5、18.5 ≤ BMI < 24、24 ≤ BMI < 28和28 ≤ BMI的人群NAFLD患病率分别为3.54% (95% CI 1.73~6.22)、11.52% (95% CI 8.94~ 14.57)、38.56% (95% CI 34.50~42.74)和60.82% (95% CI 55.65~65.81)。在正常血糖、空腹血糖受损和糖尿病人群的NAFLD患病率分别为23.77% (95% CI 16.02~33.13)、43.18% (95% CI 36.93~ 49.68)和51.64% (95% CI 48.08~55.15)。代谢综合征和高脂血症患者NAFLD患病率分别为43.62% (95% CI 36.69~50.82)和44.13% (95% CI 39.92~48.50)。NAFLD合并糖尿病、超重、肥胖、代谢综合征及高脂血症的患病率分别为22.68% (95% CI 19.14~26.59)、48.35% (95% CI 44.59~52.14)、45.55% (95% CI 36.91~54.53)、43.62% (95% CI 36.69~50.82)和65.61% (95% CI 59.95~71.02)。结论：我国近10年来NAFLD的患病率在各个地区差异大，以沿海发达地区和西北地区较为严重。患病率和年龄、性别等因素相关联，绝经后的老年女性患病率增加，这一荟萃分析为2型糖尿病和肥胖患者中NAFLD的高患病率提供了证据。需要根据疾病的特点对重点人群进行NAFLD的管理，预防其进展，管理共病。

关键词

非酒精性脂肪肝，患病率，贝叶斯方法

Bayesian Single-Arm Meta-Analysis of Nonalcoholic Fatty Liver Disease in China in Recent 10 Years

Yonghao Wen1,2, Haining Fan2*

1Graduate School of Qinghai University, Xining Qinghai

2Department of Hepatobiliary and Pancreatic Surgery, Qinghai University Affiliated Hospital, Xining Qinghai

Received: Nov. 25th, 2023; accepted: Dec. 19th, 2023; published: Dec. 26th, 2023

ABSTRACT

Objective: To systematically evaluate the prevalence of NAFLD in China in the past 10 years. Methods: A cross-sectional study of the incidence of NAFLD was conducted in PubMed, Embase, CNJI, Wanfang and other databases from January 1, 2012 to October 31, 2022. After literature screening independently, two researchers extracted data and evaluated the risk of bias in the included studies. A meta-analysis was performed using R software (4.1.2). Results: A total of 141 studies with a total of 1,218,241 participants were included. Bayesian meta-analysis showed that the overall prevalence of NAFLD in China was 27.61% (95% CI 25.79~29.48), among which the prevalence in males was 31.63% (95% CI 29.71~33.57), peaking between the ages of 40 and 49. The prevalence in females was 19.02% (95% CI 17.01~21.19), peaking between 60 and 69 years of age. The prevalence of NAFLD in BMI < 18.5, 18.5 ≤ BMI < 24, 24 ≤ BMI < 28 and 28 ≤ BMI groups was 3.54% (95% CI 1.73~6.22), 11.52% (95% CI 8.94~14.57) and 38.56% (95% CI 34.50~42.74) and 60.82% (95% CI 55.65~65.81). The prevalence of NAFLD in patients with normal glucose, impaired fasting glucose and diabetes was 23.77% (95% CI 16.02~33.13), 43.18% (95%CI 36.93~ 49.68) and 51.64% (95% CI 48.08-55.15), respectively. The prevalence of NAFLD in patients with metabolic syndrome and hyperlipidemia was 43.62% (95% CI 36.69~ 50.82) and 44.13% (95% CI 39.92~ 48.50), respectively. The prevalence rates of NAFLD combined with diabetes, overweight, obesity, metabolic syndrome and hyperlipidemia were 22.68% (95% CI 19.14~26.59), 48.35% (95% CI 44.59~52.14) and 45.55% (95% CI 36.91~54.53), 43.62% (95% CI 36.69~50.82) and 65.61% (95% CI 59.95~71.02). Conclusion: The prevalence of NAFLD in China in recent 10 years is different in different regions, especially in the developed coastal areas and northwest areas. The prevalence is associated with age, sex and other factors, increasing in older postmenopausal women, and this meta-analysis provides evidence for the high prevalence of NAFLD in patients with type 2 diabetes and obesity. NAFLD needs to be managed in key populations according to the characteristics of the disease, to prevent its progression, and to manage comorbidity.

Keywords:Nonalcoholic Fatty Liver Disease, Prevalence, Bayesian Method

Copyright © 2023 by author(s) and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

http://creativecommons.org/licenses/by/4.0/

1. 引言

非酒精性脂肪性肝病(Nonalcoholic Fatty Liver Disease, NAFLD)是指除外酒精和其他明确的损肝因素所致的肝细胞脂肪过度堆积，进而导致门静脉、小叶炎症以及肝细胞损伤为特征的进展性疾病，包括单纯性脂肪肝、非酒精性脂肪性肝炎及其相关肝硬化。全球近三分之一的人口患有NAFLD [1] [2] ，肝癌和心血管并发症被证明是NAFLD危及生命的共病 [3] 。营养过剩和胰岛素抵抗是NAFLD发生和发展的主要危险因素 [4] 。目前没有药物被批准专门用于NAFLD的治疗，通过饮食控制和运动是NAFLD治疗的基石，两者都可以预防进展和改善疾病状态 [5] [6] [7] [8] 。

在过去的十年里，我国的城市化导致了久坐不动的生活方式和营养过剩，并为肥胖的流行奠定了基础，受肥胖及其相关疾病的影响，NAFLD已成为中国常见的肝脏疾病，但尚未得到足够的重视 [9] [10] [11] 。

为了更好地了解中国目前NAFLD的疾病负担，本研究通过汇总关于中国地区各省份近10年的流行病学资料，通过基于贝叶斯模型的单臂荟萃分析，分析10年来的NAFLD的流行趋势，为疾病的防控、地区诊疗计划的制订提供参考。

2. 材料与方法

2.1. 文献检索策略

计算机检索PubMed、Embase、知网、万方等数据库2012年1月1日至2022年10月31日NAFLD的发病率的横断面研究。英文检索词关键词：Non-alcoholic Fatty Liver Disease、Non alcoholic Fatty Liver Disease、NAFLD、Fatty Liver，Nonalcoholic、Nonalcoholic Fatty Livers、cross-sectional study、incidence rate、epidemiology、prevalence、China、Chinese。中文检索关键词：非酒精性脂肪肝、非酒精性脂肪肝病、患病率、流行病学等。

2.2. 文献纳入与排除标准

纳入标准：研究对象为中国人群；研究类型为横断面研究；结局指标报道了NAFLD的发病率，关于NAFLD的合并症及特殊人群中NAFLD的发生率也一并纳入分析。

排除标准：文献研究类型为病例对照研究；重复发表、数据缺失或统计学方法明显错误的研究。

2.3. 文献的质量评价

本研究纳入文献的质量采用美国医疗保健质量与研究机构推荐的横断面研究评价标准进行评价。

2.4. 统计学方法

本研究通过基于贝叶斯方法的单臂荟萃分析，对NAFLD的发病率进行合并分析 [12] 。使用马尔可夫链–蒙特卡罗(MCMC)模拟后验分布进行完整的贝叶斯分析，链数设置为：2，初始值设置为：2.5，退火次数设置50,000，迭代次数设置为200,000，步长为10。所有分析均在Rstudio和R(4.1.2)下运用“xlsx”“mcmcplots”“R2jags”“meta”“dplyr”以及“forestplot”包进行。通过τ2对研究结果之间的异质性进行评估。为了客观评价纳入文献的发表偏倚，我们还进行了Begger检验，当P < 0.05时认为研究结果存在发表偏倚。

3. 结果

3.1. 文献检索结果

经过筛选，最终共有141篇文献，文献筛选流程见图1。纳入文献的基本特征和文献的质量评价见表1。

Figure 1. Literature screening flow chart

图1. 文献筛选流程图

Table 1. Basic features of the included literature

表1. 纳入文献的基本特征

3.2. 不同人群NAFLD患病率、NAFLD人群合并症的发生率

本研究对不同特征人群的NAFLD患病率进行了汇总，主要根据性别、年龄段、糖代谢水平、BMI、代谢综合征、血脂异常人群进行分组。不同特征人群NAFLD患病率呈现出明显的差距，详见表2。本研究对NAFLD人群合并并发症的患病率进行了汇总，具体结果详见表2。

Table 2. Prevalence of NAFLD in different populations and incidence of complications in NAFLD populations

表2. 不同人群NAFLD患病率与NAFLD人群合并症的发生率

MS (Metabolic Syndrome)：代谢综合征；HLP (Hyperlipidaemia)：高脂血症。

3.3. 中国各省份患病率

本研究对各省份患病率和各年龄段患病率趋势进行了汇总见表3。

Table 3. Prevalence rates by province in China

表3. 中国各省份患病率

3.4. 中国各省份患病率

关于男女各年龄段的NAFLD患病率趋势，见图2。

Figure 2. Trends in the prevalence of NAFLD in men and women by age group

图2. 关于男女各年龄段的NAFLD患病率趋势

4. 讨论

本研究基于贝叶斯荟萃分析，包括来自141项研究的1,218,241名参与者，对2012年至2022年中国人群NAFLD的流行病学、不同糖代谢水平人群不同BMI人群的发病情况进行概述。

性别和年龄都可能是NAFLD的危险因素，本研究中不同人群之间NAFLD的患病率存在着明显的差异，一方面男性NAFLD的患病率明显高于女性；另一方面，绝经后的女性NAFLD的患病明显增加。动物实验通过对BCL6和雌激素介导的FPR2表达水平的研究阐述了男性相较于绝经期前女性更加容易罹患肝脏脂肪异常堆积和NAFLD的原因 [13] [14] ，这部分结果在本研究中得到了证实。代谢综合征、血脂异常、二型糖尿病人群NAFLD患病率接近半数，NAFLD已经成为这类代谢性疾病最主要的并发症 [15] 。NAFLD和2型糖尿病是一种常见的定期共存的疾病，可协同作用导致不良结果，二型糖尿病与NAFLD密切相关，相互促进，相互发展 [16] [17] [18] 。二型糖尿病患者的胰岛素抵抗导致循环中游离脂肪酸水平升高，从而增加肝脏的脂毒性和代谢负荷 [19] 。此类病人占比已经超过了半数，这将为糖尿病的治疗提出新的挑战，近年来研究者们的研究重点也更偏向此类病人，胰高血糖素样肽-1受体激动剂和钠–葡萄糖协同转运蛋白2抑制剂表现出了极大的潜力 [20] [21] 。因为不同糖代谢异常下NAFLD的患病率较高，NAFLD患者可能受益于糖代谢水平的早期筛查，以防止高血糖的长期并发症和发展为NASH和肝硬化，我们应当提高对糖尿病患者NAFLD重要性的认识，也要对糖尿病前期引起足够的重视 [22] [23] [24] 。因此，当非肥胖患者的在确诊后因积极处理。NAFLD成为一个日益严重的健康问题，但临床医生或普通人群的意识并没有同时提高 [25] ，提高公众对NAFLD的认识对其本身和并发症的控制至关重要 [26] 。另一方面，NAFLD中代谢性疾病合并症的患病率较高，这意味着对越来越多的NAFLD患者进行管理可能会给卫生系统带来更大的压力。

5. 研究局限性与展望

本研究仍存在一定的局限性：NAFLD的诊断主要以超声为主，而不是金标准肝活检 [27] [28] ，超声在轻度脂肪变性或肥胖患者中诊断NAFLD的可靠性和准确性会降低 [29] 。合并的结果存在一定的异质性，我们也未能发现异质性来源。在各省份患病率的分析中，部分省份只纳入1~2项研究。

综上所述，NAFLD是一种常见的肝病，现有证据表明，我国近10年的NAFLD总体患病率为27.61%，各个地区存在差异，以沿海发达地区和西北地区较为严重，重庆、四川和贵州等地NAFLD患病率较低。患病率和年龄、性别等因素相关联，绝经后的老年女性患病率增加。这一荟萃分析为2型糖尿病和肥胖患者中NAFLD的高患病率提供了证据。需要根据疾病的特点对重点人群进行NAFLD的管理，预防其进展，管理共病。

文章引用

文永昊,樊海宁. 中国地区近10年非酒精性脂肪肝病的贝叶斯单臂Meta分析
Bayesian Single-Arm Meta-Analysis of Nonalcoholic Fatty Liver Disease in China in Recent 10 Years[J]. 临床医学进展, 2023, 13(12): 19692-19702. https://doi.org/10.12677/ACM.2023.13122772

参考文献

  1. 1. Brunt, E.M., Wong, V.W., Nobili, V., Day, C.P., Sookoian, S., Maher, J.J., Bugianesi, E., Sirlin, C.B., Neuschwander- Tetri, B.A. and Rinella, M.E. (2015) Nonalcoholic Fatty Liver Disease. Nature Reviews Disease Primers, 1, Article No. 15080. https://doi.org/10.1038/nrdp.2015.80

  2. 2. Riazi, K., Azhari, H., Charette, J.H., Underwood, F.E., King, J.A., Afshar, E.E., Swain, M.G., Congly, S.E., Kaplan, G.G. and Shaheen, A.A. (2022) The Prevalence and Incidence of NAFLD Worldwide: A Systematic Review and Meta-Analysis. The Lancet Gastroenterology and Hepatology, 7, 851-861. https://doi.org/10.1016/S2468-1253(22)00165-0

  3. 3. Adams, L.A., Lymp, J.F., St Sauver, J., Sanderson, S.O., Lindor, K.D., Feldstein, A. and Angulo, P. (2005) The Natural History of Nonalcoholic Fatty Liver Disease: A Popula-tion-Based Cohort Study. Gastroenterology, 129, 113-121. https://doi.org/10.1053/j.gastro.2005.04.014

  4. 4. Jou, J., Choi, S.S. and Diehl, A.M. (2008) Mechanisms of Dis-ease Progression in Nonalcoholic Fatty liver Disease. Seminars in Liver Disease, 28, 370-379. https://doi.org/10.1055/s-0028-1091981

  5. 5. Wang, X.J. and Malhi, H. (2018) Nonalcoholic Fatty Liver Disease. Annals of Internal Medicine, 169, C65-C80. https://doi.org/10.7326/IsTranslatedFrom_AITC201811060_Japanese

  6. 6. Zhou, J., Zhou, F., Wang, W., et al. (2020) Epidemiological Features of NAFLD from 1999 to 2018 in China. Hepatology, 71, 1851-1864. https://doi.org/10.1002/hep.31150

  7. 7. 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版) [J]. 临床肝胆病杂志, 2018, 34(5): 947-957. https://doi.org/10.3969/j.issn.1001-5256.2018.05.007

  8. 8. 颜士岩, 范建高. 非酒精性脂肪性肝病相关肝细胞癌的诊断和治疗[J]. 临床肝胆病杂志, 2021, 37(8): 1748-1752. https://doi.org/10.3969/j.issn.1001-5256.2021.08.002

  9. 9. Loney, P.L., Chambers, L.W., Bennett, K.J., et al. (1998) Critical Appraisal of the Health Research Literature: Prevalence or Incidence of a Health Problem. Chronic Dis-eases in Canada, 19, 170-176.

  10. 10. Zhou, J., Zhou, F., Wang, W., Zhang, X.J., Ji, Y.X., Zhang, P., She, Z.G., Zhu, L., Cai, J. and Li, H. (2020) Epidemiological Features of NAFLD from 1999 to 2018 in China. Hepatology, 71, 1851-1864. https://doi.org/10.1002/hep.31150

  11. 11. Wong, V.W., Chan, W.K., Chitturi, S., Chawla, Y., Dan, Y.Y., Duseja, A., Fan, J., Goh, K.L., Hamaguchi, M., Hashimoto, E., Kim, S.U., Lesmana, L.A., Lin, Y.C., Liu, C.J., Ni, Y.H., Sollano, J., Wong, S.K., Wong, G.L., Chan, H.L. and Farrell, G. (2018) Asia-Pacific Working Party on Non-Alcoholic Fatty Liver Disease Guidelines 2017-Part 1: Definition, Risk Factors and Assessment. Journal of Gastroenterology and Hepatology, 33, 70-85. https://doi.org/10.1111/jgh.13857

  12. 12. 张天嵩. 基于二项式-正态层次模型框架下比例的贝叶斯Meta分析方法及实现[J]. 中国循证儿科杂志, 2019, 14(2): 123-128. https://doi.org/10.3969/j.issn.1673-5501.2019.02.009

  13. 13. Lee, C., Kim, J., Han, J., et al. (2022) Formyl Peptide Receptor 2 Determines Sex-Specific Differences in the Progression of Nonalcoholic Fatty Liver Disease and Steatohepa-titis. Nature Communications, 13, Article No. 578. https://doi.org/10.1038/s41467-022-28138-6

  14. 14. Nikkanen, J., Leong, Y.A., Krause, W.C., et al. (2022) An Evo-lutionary Trade-Off between Host Immunity and Metabolism Drives Fatty Liver in Male Mice. Science, 378, 290-295. https://doi.org/10.1126/science.abn9886

  15. 15. 中华医学会内分泌学分会. 非酒精性脂肪性肝病与相关代谢紊乱诊疗共识(第二版) [J]. 临床肝胆病杂志, 2018, 34(10): 2103-2108. https://doi.org/10.3969/.issn.1001-5256.2018.10.010

  16. 16. Younossi, Z.M., Golabi, P., de Avila, L., et al. (2019) The Global Epidemiology of NAFLD and NASH in Patients with Type 2 Diabetes: A Systematic Review and Me-ta-Analysis. Journal of Hepatology, 71, 793-801. https://doi.org/10.1016/j.jhep.2019.06.021

  17. 17. Hazlehurst, J.M., Woods, C., Marjot, T., et al. (2016) Non-Alcoholic Fatty Liver Disease and Diabetes. Metabolism: Clinical and Experimental, 65, 1096-1108. https://doi.org/10.1016/j.metabol.2016.01.001

  18. 18. Guo, K.F., et al. (2017) Non-Alcoholic Fatty Liver Disease Is Associated with Late But Not Early Atherosclerotic Lesions in Chinese Inpatients with Type 2 Diabetes. Journal of Dia-betes and Its Complications, 31, 80-85. https://doi.org/10.1016/j.jdiacomp.2016.09.008

  19. 19. Vatner, D.F., Majumdar, S.K., Kumashiro, N., et al. (2015) Insulin-Independent Regulation of Hepatic Triglyceride Synthesis by Fatty Acids. Proceedings of the National Academy of Sciences of the United States of America, 112, 1143-1148. https://doi.org/10.1073/pnas.1423952112

  20. 20. Ng, C.H., Lin, S.Y., Chin, Y.H., et al. (2022) Antidiabetic Medications for Type 2 Diabetics with Nonalcoholic Fatty Liver Disease: Evidence from a Network Meta-Analysis of Randomized Controlled Trials. Endocrine Practice, 28, 223-230. https://doi.org/10.1016/j.eprac.2021.09.013

  21. 21. 中华医学会内分泌学分会, 中华医学会糖尿病学分会. 中国成人2型糖尿病合并非酒精性脂肪性肝病管理专家共识[J]. 中华内分泌代谢杂志, 2021, 37(7): 589-598. https://doi.org/10.3760/cma.j.cn311282-20210105-00016

  22. 22. Smith, G.I., Shankaran, M., Yoshino, M., et al. (2020) Insulin Resistance Drives Hepatic De Novo Lipogenesis in Nonalcoholic Fatty Liver Disease. Journal of Clinical Investigation, 130, 1453-1460. https://doi.org/10.1172/JCI134165

  23. 23. Ortiz-Lopez, C., Lomonaco, R., Orsak, B., et al. (2012) Prevalence of Pre-diabetes and Diabetes and Metabolic Profile of Patients with Nonalcoholic Fatty Liver Disease (NAFLD). Diabetes Care, 35, 873-878. https://doi.org/10.2337/dc11-1849

  24. 24. Hagström, H., Nasr, P., Ekstedt, M., et al. (2018) Risk for Development of Severe Liver Disease in Lean Patients with Nonalcoholic Fatty Liver Disease: A Long-Term Follow-Up Study. Hepatol-ogy Communications, 2, 48-57. https://doi.org/10.1002/hep4.1124

  25. 25. Patel, P.J., Banh, X., Horsfall, L.U., et al. (2018) Underappreciation of Non-Alcoholic Fatty Liver Disease by Primary Care Clinicians: Limited Awareness of Surrogate Markers of Fibrosis. Internal Medicine Journal, 48, 144-151. https://doi.org/10.1111/imj.13667

  26. 26. Valery, P.C. and Powell, E.E. (2019) Engaging Primary Care Clinicians in the Assessment of NAFLD. Nature Reviews Gastroenterology & Hepatology, 16, 458-460. https://doi.org/10.1038/s41575-019-0164-4

  27. 27. Ratziu, V., Charlotte, F., Heurtier, A., et al. (2005) Sampling Variability of Liver Biopsy in Nonalcoholic Fatty Liver Disease. Gastroenterology, 128, 1898-1906. https://doi.org/10.1053/j.gastro.2005.03.084

  28. 28. Nalbantoglu, I.L. and Brunt, E.M. (2014) Role of Liver Biopsy in Nonalcoholic Fatty Liver Disease. World Journal of Gastroenterology, 20, 9026-9037.

  29. 29. Hernaez, R., Lazo, M., Bonekamp, S., et al. (2011) Diagnostic Accuracy and Reliability of Ultrasonography for the Detection of Fatty Liver: A Meta-Analysis. Hepatology, 54, 1082-1090. https://doi.org/10.1002/hep.24452

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