模拟饮酒干预与肝脂肪变性：一项大型队列的纵向研究

张宁; 张圆; 魏君; 向毅; 胡逸凡; 肖雄

doi:10.12182/20240560503

模拟饮酒干预与肝脂肪变性：一项大型队列的纵向研究

四川大学华西公共卫生学院/四川大学华西第四医院流行病与卫生统计学系（成都 610041）

基金项目: 国家自然科学基金（No. 82273740）资助

详细信息

通讯作者:
肖雄: E-mail：xiaoxiong.scu@scu.edu.cn

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出版历程
- 收稿日期: 2023-12-04
- 修回日期: 2024-05-07
- 网络出版日期: 2024-06-16
- 发布日期: 2024-05-19
- 刊出日期: 2024-05-19

Hypothetical Alcohol Consumption Interventions and Hepatic Steatosis: A Longitudinal Study in a Large Cohort

Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China

More Information

Corresponding author:
XIAO Xiong: E-mail: xiaoxiong.scu@scu.edu.cn

摘要

摘要:
目的
基于一项大型队列的纵向研究数据，模拟评估饮酒干预（饮酒量和种类的改变）对肝脂肪变的影响。
方法
基于英国生物银行（UK Biobank, UKB），纳入同时接受了基线及重复调查的12687人。使用脂肪肝指数（fatty liver index, FLI）作为结局指标。参与者根据其饮酒量被分为不饮酒者、中度饮酒者和重度饮酒者。定义了以下干预措施：从基线到重复调查，酒精消费水平不变（如持续不饮酒、持续中度饮酒）；以及饮酒水平发生改变（如不饮酒到中度饮酒）。饮酒种类的干预类似于酒精量的干预。应用parametric g-formula模拟反事实场景下饮酒干预对FLI的影响。
结果
在UKB人群中，无论基线饮酒水平如何，相比于饮酒量恒定，饮酒量增加与更高的FLI水平有关。与其他饮酒种类相比，饮酒种类转变为红酒与较低的FLI水平有关。
结论
无论目前饮酒水平如何，饮酒量增加会增加肝脂肪变性的风险，如果戒酒具有挑战性，红酒可能是比其他类型更好的选择，本研究可为未来的实践指南和卫生政策提供信息支持。
- 饮酒量 /
- 饮酒种类 /
- 肝脏脂肪变性 /
- 目标试验 /
- 模拟干预
Abstract:
Objective
Non-alcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (ALD) are the most common chronic liver diseases. Hepatic steatosis is an early histological subtype of both NAFLD and ALD. Excessive alcohol consumption is widely known to lead to hepatic steatosis and subsequent liver damage. However, reported findings concerning the association between moderate alcohol consumption and hepatic steatosis remain inconsistent. Notably, alcohol consumption as a modifiable lifestyle behavior is likely to change over time, but most previous studies covered alcohol intake only once at baseline. These inconsistent findings from existing studies do not inform decision-making concerning policies and clinical guidelines, which are of greater interest to health policymakers and clinician-scientists. Additionally, recommendations on the types of alcoholic beverages are not available. Usually, assessing the effects of two or more hypothetical alcohol consumption interventions on hepatic steatosis provides answers to questions concerning the population risk of hepatic steatosis if everyone changes from heavy drinking to abstinence, or if everyone keeps on drinking moderately, or if everyone of the drinking population switches from red wine to beer? Thus, we simulated a target trial to estimate the effects of several hypothetical interventions, including changes in the amount of alcohol consumption or the types of alcoholic beverages consumed, on hepatic steatosis using longitudinal data, to inform decisions about alcohol-related policymaking and clinical care.
Methods
This longitudinal study included 12687 participants from the UK Biobank (UKB), all of whom participated in both baseline and repeat surveys. We excluded participants with missing data related to components of alcohol consumption and fatty liver index (FLI) in the baseline and the repeat surveys, as well as those who had reported liver diseases or cancer at the baseline survey. We used FLI as an outcome indicator and divided the participants into non-, moderate, and heavy drinkers. The surrogate marker FLI has been endorsed by many international organizations' guidelines, such as the European Association for the Study of the Liver. The calculation of FLI was based on laboratory and anthropometric data, including triglyceride, gamma-glutamyl transferase, body mass index, and waist circumference. Participants responded to questions about the types of alcoholic beverages, which were defined in 5 categories, including red wine, white wine/fortified wine/champagne, beer or cider, spirits, and mixed liqueurs, along with the average weekly or monthly amounts of alcohol consumed. Alcohol consumption was defined as pure alcohol consumed per week and was calculated according to the amount of alcoholic beverages consumed per week and the average ethanol content by volume in each alcoholic beverage. Participants were categorized as non-drinkers, moderate drinkers, and heavy drinkers according to the amount of their alcohol consumption. Moderate drinking was defined as consuming no more than 210 g of alcohol per week for men and 140 g of alcohol per week for women. We defined the following hypothetical interventions for the amount of alcohol consumed: sustaining a certain level of alcohol consumption from baseline to the repeat survey (e.g., none to none, moderate to moderate, heavy to heavy) and changing from one alcohol consumption level to another (e.g., none to moderate, moderate to heavy). The hypothetical interventions for the types of alcoholic beverages were defined in a similar way to those for the amount of alcohol consumed (e.g., red wine to red wine, red wine to beer/cider). We applied the parametric g-formula to estimate the effect of each hypothetical alcohol consumption intervention on the FLI. To implement the parametric g-formula, we first modeled the probability of time-varying confounders and FLI conditional on covariates. We then used these conditional probabilities to estimate the FLI value if the alcohol consumption level of each participant was under a specific hypothetical intervention. The confidence interval was obtained by 200 bootstrap samples.
Results
For the alcohol consumption from baseline to the repeat surveys, 6.65% of the participants were sustained non-drinkers, 63.68% were sustained moderate drinkers, and 14.74% were sustained heavy drinkers, while 8.39% changed from heavy drinking to moderate drinking. Regarding the types of alcoholic beverages from baseline to the repeat surveys, 27.06% of the drinkers sustained their intake of red wine. Whatever the baseline alcohol consumption level, the hypothetical interventions for increasing alcohol consumption from the baseline alcohol consumption were associated with a higher FLI than that of the sustained baseline alcohol consumption level. When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to moderate drinking, the mean ratio of FLI was 1.027 (95% confidence interval [CI]: 0.997-1.057). When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to heavy drinking, the mean ratio of FLI was 1.075 (95% CI: 1.042-1.108). When comparing sustained heavy drinking with the hypothetical intervention of changing from heavy drinking to moderate drinking, the mean ratio of FLI was 0.953 (95% CI: 0.938-0.968). The hypothetical intervention of changing to red wine in the UKB was associated with lower FLI levels, compared with sustained consumption of other types of alcoholic beverages. For example, when comparing sustaining spirits with the hypothetical intervention of changing from spirits to red wine, the mean ratio of FLI was 0.981 (95% CI: 0.948-1.014).
Conclusions
Regardless of the current level of alcohol consumption, interventions that increase alcohol consumption could raise the risk of hepatic steatosis in Western populations. The findings of this study could inform the formulation of future practice guidelines and health policies. If quitting drinking is challenging, red wine may be a better option than other types of alcoholic beverages in Western populations.
- Alcohol consumption /
- Alcoholic beverage type /
- Hepatic steatosis /
- Target trial /
- Hypothetical interventions

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图 1 在UKB中模拟的不同饮酒量干预下FLI的平均差异和平均比率

Figure 1. The mean differences and mean ratio of FLI under the different hypothetical interventions for alcohol consumption in the UKB

FLI: fatty liver index; MD: mean difference; MR: mean ratio. The blue box represents the hypothetical interventions of sustaining alcohol consumption, the green box represents the hypothetical interventions of reducing alcohol consumption, and the red box represents the hypothetical interventions of increasing alcohol consumption.

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图 2 在UKB中模拟的不同饮酒种类下FLI的平均差异和平均比率

Figure 2. The mean differences and mean ratios of FLI under the different hypothetical interventions for alcoholic beverage types in the UKB

FLI: fatty liver index; MD: mean difference; MR: mean ratio.

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表 1 UKB参与者的基线及重复调查特征 (n=12687)

Table 1 The baseline and repeat survey characteristics of the study participants in the UKB (n=12687)

Characteristic	Baseline survey	Repeat survey
Age/yr., mean (SD)	57.13 (7.36)	61.35 (7.35)
Female/case (%)	5926 (46.7)
White race/case (%)	12438 (98.0)
Low education level/case (%)	1031 (8.2)
Socioeconomic status (median [IQR])	−2.81 (−4.03, −0.93)
Menopausal status in female/case (%)
Pre-menopause	1253 (21.1)	597 (10.1)
Post-menopause	3765 (63.5)	4423 (74.6)
Not sure	904 (15.3)	902 (15.2)
Family history/case (%)	9534 (75.1)
Self-reported hypertension/case (%)	2834 (22.3)	3300 (26.0)
Self-reported diabetes/case (%)	471 (3.7)	651 (5.1)
Current smoking/case (%)	822 (6.5)	575 (4.5)
Dietary score (median [IQR])	4.00 (3.00, 5.00)	4.00 (3.00, 5.00)
Total physical activity/(MET h/d), median [IQR]	4.13 (1.91, 7.96)	4.24 (2.03, 7.87)
Insomnia symptoms/case (%)	9352 (73.7)	9526 (75.1)
Depressive symptoms/case (%)	402 (3.3)	380 (3.1)
Anxiety symptoms/case (%)	359 (2.9)	291 (2.3)
BMI/(kg/m²), mean (SD)	26.74 (4.28)	26.79 (4.34)
FLI (mean [SD])	44.84 (29.23)	46.27 (28.66)
FLI: fatty liver index, BMI: body mass index. The data are expressed as mean (standard deviation), median (interquartile range), or percentage. Low education level is defined as none of advanced (A/AS) levels, ordinary level (O-level), general certificate of secondary education, and the other equivalent or higher levels. Socioeconomic status is defined on the basis of the Townsend deprivation index. Family history refers to self-reported history of hypertension, stroke, or CVD from at least one first-degree relative (biological parents and siblings) in the baseline survey. The dietary score is based on the consumption of 7 dietary components ranging from 0 to 7^[35].

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表 2 UKB参与者基线及重复调查的饮酒量特征 (n=12687)

Table 2 Characteristics of alcohol consumption in UKB baseline and repeated surveys (n=12687)

Alcohol consumption	Baseline survey		Repeat survey
Capacity for alcohol/(g/week), mean (SD)	126.43 (119.15)		109.52 (108.12)
Level of drink/case (%)
None	963 (7.6)		1069 (8.4)
Moderate	8768 (69.1)		9256 (73.0)
Heavy	2956 (23.3)		2362 (18.6)
Changes in the level of alcohol consumption/case (%)
None to none		844 (6.65)
None to moderate		114 (0.90)
None to heavy		5 (0.04)
Modest to none		202 (1.59)
Moderate to moderate		8079 (63.68)
Moderateto heavy		487 (3.84)
Heavy to none		23 (0.18)
Heavy to moderate		1063 (8.39)
Heavy to heavy		1870 (14.74)
Moderate drinking is defined as ≤210 g/week for men and ≤140 g/week for women in the UKB. Levels exceeding those mentioned above are defined as heavy drinking.

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表 3 UKB饮酒人群基线及重复调查饮酒种类特征 (n=11499)

Table 3 Characteristics of the types of alcoholic beverages among the drinkers in the UKB baseline and repeated surveys (n=11499)

Alcoholic beverages type	Baseline survey		Repeat survey
Type/case (%)
Red wine	4205 (36.6)		4158 (36.2)
Other wines	2188 (19.0)		2261 (19.7)
Beer/cider	2793 (24.3)		2817 (24.5)
Spirits	482 (4.2)		535 (4.7)
Mixed	1831 (15.9)		1728 (15.0)
Changes in the alcoholic beverages type among drinkers 　from baseline to repeat survey/case (%)
Red wine to red wine		3112 (27.06)
Red wine to other wines		363 (3.16)
Red wine to beer/cider		197 (1.71)
Red wine to spirits		79 (0.69)
Red wine to mixed		454 (3.95)
Other wines to red wine		304 (2.64)
Other wines to other wines		1550 (13.48)
Other wines to beer/cider		90 (0.78)
Other wines to spirits		58 (0.50)
Other wines to mixed		186 (1.62)
Beer/cider to red wine		213 (1.85)
Beer/cider to other wines		90 (0.78)
Beer/cider to beer/cider		2200 (19.13)
Beer/cider to spirits		48 (0.42)
Beer/cider to mixed		242 (2.10)
Spirits to red wine		60 (0.52)
Spirits to other wines		48 (0.42)
Spirits to beer/cider		51 (0.44)
Spirits to spirits		279 (2.43)
Spirits to mixed		44 (0.38)
Mixed to red wine		469 (4.08)
Mixed to other wines		210 (1.83)
Mixed to beer/cider		279 (2.43)
Mixed to spirits		71 (0.62)
Mixed to mixed		802 (6.97)
In the UKB, other wines refer to white wine/fortified wine/champagne in our study. We showed the changes in the alcoholic beverages among drinkers in both baseline and repeated surveys.

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表 4 基于固定效应模型估计的饮酒量变化和FLI间的关联

Table 4 FEM analysis of the association between changes in alcohol consumption and changes in FLI in the UKB

Alcohol consumption	Point estimate	95% CI
Sustained non-drinking	Reference	−
Sustained modest drinking	0.72	−0.65, 2.10
Sustained heavy drinking	1.94	0.39, 3.49
Increased alcohol consumption	2.98	1.03, 4.94
Decreased alcohol consumption	−1.00	−2.65, 0.65
CI: confidence interval.

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参考文献(47)

[1]	POWELL E E, WONG V W, RINELLA M. Non-alcoholic fatty liver disease. Lancet, 2021, 397(10290): 2212–2224. doi: 10.1016/S0140-6736(20)32511-3.
[2]	YOUNOSSI Z M. Non-alcoholic fatty liver disease--a global public health perspective. J Hepatol, 2019, 70(3): 531–544. doi: 10.1016/j.jhep.2018.10.033.
[3]	ASRANI S K, MELLINGER J, ARAB J P, et al. Reducing the global burden of alcohol-associated liver disease: a blueprint for action. Hepatology, 2021, 73(5): 2039–2050. doi: 10.1002/hep.31583.
[4]	DEVARBHAVI H, ASRANI S K, ARAB J P, et al. Global burden of liver disease: 2023 update. J Hepatol, 2023, 79(2): 516-537. doi: 10.1016/j.jhep.2023.03.017.
[5]	RIAZI K, AZHARI H, CHARETTE J H, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol, 2022, 7(9): 851–861. doi: 10.1016/S2468-1253(22)00165-0.
[6]	WU X, FAN X, MIYATA T, et al. Recent advances in understanding of pathogenesis of alcohol-associated liver disease. Annu Rev Pathol, 2023, 18: 411–438. doi: 10.1146/annurev-pathmechdis-031521-030435.
[7]	ABDELMALEK M F. Nonalcoholic fatty liver disease: another leap forward. Nat Rev Gastroenterol Hepatol, 2021, 18(2): 85–86. doi: 10.1038/s41575-020-00406-0.
[8]	CRABB D W, IM G Y, SZABO G, et al. Diagnosis and treatment of alcohol-associated liver diseases: 2019 practice guidance From the American association for the study of liver diseases. Hepatology, 2020, 71(1): 306–333. doi: 10.1002/hep.30866.
[9]	YOU M, ARTEEL G E. Effect of ethanol on lipid metabolism. J Hepatol, 2019, 70(2): 237–248. doi: 10.1016/j.jhep.2018.10.037.
[10]	YOUNOSSI Z, HENRY L. Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology, 2016, 150(8): 1778–1785. doi: 10.1053/j.gastro.2016.03.005.
[11]	SINGAL A K, BATALLER R, AHN J, et al. ACG clinical guideline: alcoholic liver disease. Am J Gastroenterol, 2018, 113(2): 175–194. doi: 10.1038/ajg.2017.469.
[12]	CHOI J H, SOHN W, CHO Y K. The effect of moderate alcohol drinking in nonalcoholic fatty liver disease. Clin Mol Hepatol, 2020, 26(4): 662–669. doi: 10.3350/cmh.2020.0163.
[13]	SOOKOIAN S, CASTAÑO G O, PIROLA C J. Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals. Gut, 2014, 63(3): 530–532. doi: 10.1136/gutjnl-2013-305718.
[14]	AJMERA V H, TERRAULT N A, HARRISON S A. Is moderate alcohol use in nonalcoholic fatty liver disease good or bad? A critical review. Hepatology, 2017, 65(6): 2090–2099. doi: 10.1002/hep.29055.
[15]	DREYER N A, TUNIS S R, BERGER M, et al. Why observational studies should be among the tools used in comparative effectiveness research. Health Aff (Millwood), 2010, 29(10): 1818–1825. doi: 10.1377/hlthaff.2010.0666.
[16]	HERNáN M A, ROBINS J M. Using big data to emulate a target trial when a randomized trial is not available. Am J Epidemiol, 2016, 183(8): 758–764. doi: 10.1093/aje/kwv254.
[17]	HAN A L. Validation of fatty liver index as a marker for metabolic dysfunction-associated fatty liver disease. Diabetol Metab Syndr, 2022, 14(1): 44. doi: 10.1186/s13098-022-00811-2.
[18]	ARONSON J K, FERNER R E. Biomarkers--a general review. Curr Protoc Pharmacol, 2017, 76: 9.23.1-9.23.17. doi: 10.1002/cpph.19.
[19]	MANTHEY J, SHIELD K D, RYLETT M, et al. Global alcohol exposure between 1990 and 2017 and forecasts until 2030: a modelling study. Lancet, 2019, 393(10190): 2493–2502. doi: 10.1016/S0140-6736(18)32744-2.
[20]	CONROY M, SELLORS J, EFFINGHAM M, et al. The advantages of UK Biobank's open-access strategy for health research. J Intern Med, 2019, 286(4): 389–397. doi: 10.1111/joim.12955.
[21]	INNES H, CROOKS C J, ASPINALL E, et al. Characterizing the risk interplay between alcohol intake and body mass index on cirrhosis morbidity. Hepatology, 2022, 75(2): 369–378. doi: 10.1002/hep.32123.
[22]	European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol, 2016, 64(6): 1388-1402. doi: 10.1016/j.jhep.2015.11.004.
[23]	O'SHEA R S, DASARATHY S, MCCULLOUGH A J. Alcoholic liver disease. Hepatology, 2010, 51(1): 307–328. doi: 10.1002/hep.23258.
[24]	JANI B D, MCQUEENIE R, NICHOLL B I, et al. Association between patterns of alcohol consumption (beverage type, frequency and consumption with food) and risk of adverse health outcomes: a prospective cohort study. BMC Med, 2021, 19(1): 8. doi: 10.1186/s12916-020-01878-2.
[25]	ESLAM M, SARIN S K, WONG V W, et al. The Asian Pacific Association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease. Hepatol Int, 2020, 14(6): 889–919. doi: 10.1007/s12072-020-10094-2.
[26]	SIAFI E, ANDRIKOU I, THOMOPOULOS C, et al. Fatty liver index and cardiovascular outcomes in never-treated hypertensive patients: a prospective cohort. Hypertens Res, 2023, 46(1): 119–127. doi: 10.1038/s41440-022-01015-x.
[27]	CALORI G, LATTUADA G, RAGOGNA F, et al. Fatty liver index and mortality: the Cremona study in the 15th year of follow-up. Hepatology, 2011, 54(1): 145–152. doi: 10.1002/hep.24356.
[28]	BEDOGNI G, BELLENTANI S, MIGLIOLI L, et al. The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol, 2006, 6: 33. doi: 10.1186/1471-230X-6-33.
[29]	FERGUSON K D, MCCANN M, KATIKIREDDI S V, et al. Evidence synthesis for constructing directed acyclic graphs (ESC-DAGs): a novel and systematic method for building directed acyclic graphs. Int J Epidemiol, 2020, 49(1): 322–329. doi: 10.1093/ije/dyz150.
[30]	MANSOURNIA M A, ETMINAN M, DANAEI G, et al. Handling time varying confounding in observational research. BMJ, 2017, 359: j4587. doi: 10.1136/bmj.j4587.
[31]	NAIMI A I, COLE S R, KENNEDY E H. An introduction to g methods. Int J Epidemiol, 2017, 46(2): 756–762.
[32]	DOOSTI-IRANI A, MANSOURNIA M A, COLLINS G. Use of G-methods for handling time-varying confounding in observational research. Lancet Glob Health, 2019, 7(1): e35. doi: 10.1016/S2214-109X(18)30471-6.
[33]	VANDERWEELE T J, DING P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med, 2017, 167(4): 268–274. doi: 10.7326/M16-2607.
[34]	ROHRER J M, MURAYAMA K. These are not the effects you are looking for: causality and the within-/between-persons distinction in longitudinal data analysis. Adv Method Pract Psychol Sci, 2023, 6(1): 25152459221140842.
[35]	ZHANG Y, YANG H, LI S, et al. Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: a cohort study in the UK Biobank. PLoS Med, 2021, 18(11): e1003830. doi: 10.1371/journal.pmed.1003830.
[36]	ROERECKE M, VAFAEI A, HASAN O S M, et al. Alcohol consumption and risk of liver cirrhosis: a systematic review and meta-analysis. Am J Gastroenterol, 2019, 114(10): 1574–1586. doi: 10.14309/ajg.0000000000000340.
[37]	MORIYA A, IWASAKI Y, OHGUCHI S, et al. Alcohol consumption appears to protect against non-alcoholic fatty liver disease. Aliment Pharmacol Ther, 2011, 33(3): 378–388. doi: 10.1111/j.1365-2036.2010.04520.x.
[38]	DUNN W, SANYAL A J, BRUNT E M, et al. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J Hepatol, 2012, 57(2): 384–391. doi: 10.1016/j.jhep.2012.03.024.
[39]	IM P K, MILLWOOD I Y, KARTSONAKI C, et al. Alcohol drinking and risks of liver cancer and non-neoplastic chronic liver diseases in China: a 10-year prospective study of 0.5 million adults. BMC Med, 2021, 19(1): 216. doi: 10.1186/s12916-021-02079-1.
[40]	BLOMDAHL J, NASR P, EKSTEDT M, et al. Moderate alcohol consumption is associated with advanced fibrosis in non-alcoholic fatty liver disease and shows a synergistic effect with type 2 diabetes mellitus. Metabolism, 2021, 115: 154439. doi: 10.1016/j.metabol.2020.154439.
[41]	YOO J E, HAN K, SHIN D W, et al. Association between changes in alcohol consumption and cancer risk. JAMA Netw Open, 2022, 5(8): e2228544. doi: 10.1001/jamanetworkopen.2022.28544.
[42]	ROJAS-SAUNERO L P, HILAL S, MURRAY E J, et al. Hypothetical blood-pressure-lowering interventions and risk of stroke and dementia. Eur J Epidemiol, 2021, 36(1): 69–79. doi: 10.1007/s10654-020-00694-5.
[43]	FARRELL G C, CHITTURI S, LAU G K, et al. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J Gastroenterol Hepatol, 2007, 22(6): 775–777. doi: 10.1111/j.1440-1746.2007.05002.x.
[44]	FURTWAENGLER N A, De VISSER R O. Lack of international consensus in low-risk drinking guidelines. Drug Alcohol Rev, 2013, 32(1): 11–18. doi: 10.1111/j.1465-3362.2012.00475.x.
[45]	ROMEO J, GONZÁLEZ-GROSS M, WÄRNBERG J, et al. Effects of moderate beer consumption on blood lipid profile in healthy Spanish adults. Nutr Metab Cardiovasc Dis, 2008, 18(5): 365–372. doi: 10.1016/j.numecd.2007.03.007.
[46]	ASKGAARD G, GRØNBÆK M, KJÆR M S, et al. Alcohol drinking pattern and risk of alcoholic liver cirrhosis: a prospective cohort study. J Hepatol, 2015, 62(5): 1061–1067. doi: 10.1016/j.jhep.2014.12.005.
[47]	ZHOU Y, HUA J, HUANG Z. Effects of beer, wine, and baijiu consumption on non-alcoholic fatty liver disease: Potential implications of the flavor compounds in the alcoholic beverages. Front Nutr, 2022, 9: 1022977. doi: 10.3389/fnut.2022.1022977.

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模拟饮酒干预与肝脂肪变性：一项大型队列的纵向研究

通讯作者:
肖雄: E-mail：xiaoxiong.scu@scu.edu.cn

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Hypothetical Alcohol Consumption Interventions and Hepatic Steatosis: A Longitudinal Study in a Large Cohort

Corresponding author:
XIAO Xiong: E-mail: xiaoxiong.scu@scu.edu.cn

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模拟饮酒干预与肝脂肪变性：一项大型队列的纵向研究

通讯作者: 肖雄: E-mail：xiaoxiong.scu@scu.edu.cn

计量

出版历程

Hypothetical Alcohol Consumption Interventions and Hepatic Steatosis: A Longitudinal Study in a Large Cohort

Corresponding author: XIAO Xiong: E-mail: xiaoxiong.scu@scu.edu.cn

计量

出版历程

目录

数据库收录

友情链接

通讯作者:
肖雄: E-mail：xiaoxiong.scu@scu.edu.cn

Corresponding author:
XIAO Xiong: E-mail: xiaoxiong.scu@scu.edu.cn