代谢与酒精相关性肝病： 一个新的肝病实体

冯悦; 徐洪芹; 韩潘十力; 柳涛; 高沿航

doi:10.12449/JCH251106

代谢与酒精相关性肝病：一个新的肝病实体

DOI: 10.12449/JCH251106

吉林大学第一医院肝病科，感染病与病原生物学中心，吉林省代谢性肝病重点实验室，长春 130021

基金项目:

国家自然科学基金 (U24A20654);

国家自然科学基金 (82170602);

吉林省自然科学基金自由探索重点项目 (YDZJ202401427ZYTS);

吉林省肝脏代谢重点实验室 (YDZJ202502CXJD002)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：高沿航负责课题设计；高沿航、冯悦查阅文献并起草论文；高沿航、徐洪芹、韩潘十力、柳涛参与文章撰写及修改，校阅论文。

详细信息

通信作者:
高沿航， yanhang@mail.jlu.edu.cn （ORCID： 0000-0001-8590-6706）

计量
- 文章访问数: 6
- HTML全文浏览量: 4
- PDF下载量: 4
- 被引次数: 0
出版历程
- 收稿日期: 2025-09-16
- 录用日期: 2025-10-13
- 出版日期: 2025-11-25

Metabolic and alcohol-associated liver disease： A novel liver disease entity

Department of Hepatology，Center of Infectious Diseases and Pathogen Biology，Jilin Provincial Key Laboratory of Metabolic Liver Diseases，The First Hospital of Jilin University，Changchun 130021，China

Research funding:

National Natural Science Foundation of China (U24A20654);

National Natural Science Foundation of China (82170602);

Natural Science Foundation for Self-exploration Research of Jilin Province (YDZJ202401427ZYTS);

Jilin Provincial Key Laboratory of Metabolic Liver Diseases (YDZJ202502CXJD002)

More Information

Corresponding author: GAO Yanhang， yanhang@mail.jlu.edu.cn （ORCID： 0000-0001-8590-6706）

摘要

摘要: 近期提出的新术语“代谢与酒精相关性肝病”（MetALD），强调了代谢障碍与酒精暴露在肝损伤进程中的协同作用。尽管该理论框架深化了对肝病多病因复杂构成的理解，其临床应用仍面临诊断与治疗方面的诸多新挑战。本文综述了当前关于MetALD的流行现状、潜在发病机制、临床诊断标志物及治疗的最新证据，特别强调了开发能够精准模拟该疾病多因素致病过程的可靠临床前模型的紧迫性，并对粪菌移植和营养干预等新兴疗法进行了系统评估。最后，文章展望了未来MetALD药物创新的发展方向。
- 代谢与酒精相关性肝病 /
- 诊断 /
- 治疗学
Abstract: The term “metabolic and alcohol-related liver disease （MetALD）” recently proposed emphasizes the synergistic role of metabolic dysfunction and alcohol exposure in the progression of liver injury. Although this theoretical framework improves the understanding of the multifactorial and complex nature of liver disease， its clinical application still faces numerous new challenges in diagnosis and treatment. This article summarizes the latest evidence for the prevalence， potential pathogenesis， clinical diagnostic markers， and treatment of MetALD and particularly emphasizes the urgency to develop reliable preclinical models that can accurately simulate the intricate pathophysiology of this disease due to various factors. This article also provides a systematic evaluation of emerging therapies including fecal microbiota transplantation and nutritional interventions and proposes the future directions for drug innovation in MetALD.
- Metabolic and Alcohol-Associated Liver Disease /
- Diagnosis /
- Therapeutics

HTML全文

参考文献(41)

[1]	RINELLA ME, LAZARUS JV, RATZIU V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature[J]. J Hepatol, 2023, 79( 6): 1542- 1556. DOI: 10.1016/j.jhep.2023.06.003.
[2]	YOUNOSSI ZM, GOLABI P, PAIK JM, et al. The global epidemiology of nonalcoholic fatty liver disease(NAFLD) and nonalcoholic steatohepatitis(NASH): A systematic review[J]. Hepatology, 2023, 77( 4): 1335- 1347. DOI: 10.1097/hep.0000000000000004.
[3]	MANTHEY J, SHIELD KD, RYLETT M, et al. Global alcohol exposure between 1990 and 2017 and forecasts until 2030: A modelling study[J]. Lancet, 2019, 393( 10190): 2493- 2502. DOI: 10.1016/S0140-6736(18)32744-2.
[4]	SHI GX, QIAN YS, JIANG CM, et al. Prevalence of steatotic liver disease(MASLD, MetALD, ALD) and clinically significant fibrosis in US adolescents[J]. Sci Rep, 2024, 14: 25724. DOI: 10.1038/s41598-024-76922-9.
[5]	ISRAELSEN M, TORP N, JOHANSEN S, et al. Validation of the new nomenclature of steatotic liver disease in patients with a history of excessive alcohol intake: An analysis of data from a prospective cohort study[J]. Lancet Gastroenterol Hepatol, 2024, 9( 3): 218- 228. DOI: 10.1016/S2468-1253(23)00443-0.
[6]	JOHN BV, BASTAICH D, MEZZACAPPA C, et al. Identifying metabolic dysfunction-associated steatotic liver disease using natural language processing in a US national cohort[J]. Am J Gastroenterol, 2025, 120( 11): 2583- 2591. DOI: 10.14309/ajg.0000000000003321.
[7]	JEON S, CARR R. Alcohol effects on hepatic lipid metabolism[J]. J Lipid Res, 2020, 61( 4): 470- 479. DOI: 10.1194/jlr.r119000547.
[8]	FAN L, ZHU XZ, ZHANG XY, et al. Magnesium depletion score and mortality in individuals with metabolic dysfunction associated steatotic liver disease over a Median follow-up of 26 years[J]. Nutrients, 2025, 17( 2): 244. DOI: 10.3390/nu17020244.
[9]	GOMMERS LMM, HOENDEROP JGJ, BINDELS RJM, et al. Hypomagnesemia in type 2 diabetes: A vicious circle?[J]. Diabetes, 2016, 65( 1): 3- 13. DOI: 10.2337/db15-1028.
[10]	JOKINEN MJ, LUUKKONEN PK. Hepatic mitochondrial reductive stress in the pathogenesis and treatment of steatotic liver disease[J]. Trends Pharmacol Sci, 2024, 45( 4): 319- 334. DOI: 10.1016/j.tips.2024.02.003.
[11]	DING ZB, ERICKSEN RE, ESCANDE-BEILLARD N, et al. Metabolic pathway analyses identify proline biosynthesis pathway as a promoter of liver tumorigenesis[J]. J Hepatol, 2020, 72( 4): 725- 735. DOI: 10.1016/j.jhep.2019.10.026.
[12]	LUUKKONEN PK, DUFOUR S, LYU K, et al. Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease[J]. Proc Natl Acad Sci U S A, 2020, 117( 13): 7347- 7354. DOI: 10.1073/pnas.1922344117.
[13]	JEW MH, HSU CL. Alcohol, the gut microbiome, and liver disease[J]. J Gastro And Hepatol, 2023, 38( 8): 1205- 1210. DOI: 10.1111/jgh.16199.
[14]	RAYA TONETTI F, EGUILEOR A, MRDJEN M, et al. Gut-liver axis: Recent concepts in pathophysiology in alcohol-associated liver disease[J]. Hepatology, 2024, 80( 6): 1342- 1371. DOI: 10.1097/hep.0000000-000000924.
[15]	YUAN J, CHEN C, CUI JH, et al. Fatty liver disease caused by high-alcohol-producing Klebsiella pneumoniae[J]. Cell Metab, 2019, 30( 4): 675- 688. e 7. DOI: 10.1016/j.cmet.2019.08.018.
[16]	DUAN HY, GONG MM, YUAN G, et al. Sex hormone: A potential target at treating female metabolic dysfunction-associated steatotic liver disease?[J]. J Clin Exp Hepatol, 2025, 15( 2): 102459. DOI: 10.1016/j.jceh.2024.102459.
[17]	STAUFER K, HUBER-SCHÖNAUER U, STREBINGER G, et al. Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease[J]. J Hepatol, 2022, 77( 4): 918- 930. DOI: 10.1016/j.jhep.2022.04.040.
[18]	MORINAGA M, KON K, UCHIYAMA A, et al. Carbohydrate-deficient transferrin is a sensitive marker of alcohol consumption in fatty liver disease[J]. Hepatol Int, 2022, 16( 2): 348- 358. DOI: 10.1007/s12072-022-10298-8.
[19]	NGUYEN VL, PAULL P, HABER PS, et al. Evaluation of a novel method for the analysis of alcohol biomarkers: Ethyl glucuronide, ethyl sulfate and phosphatidylethanol[J]. Alcohol, 2018, 67: 7- 13. DOI: 10.1016/j.alcohol.2017.08.009.
[20]	TAVAGLIONE F, AMANGURBANOVA M, YANG AH, et al. Head-to-head comparison between phosphatidylethanol versus indirect alcohol biomarkers for diagnosis of MetALD versus MASLD: A prospective study[J]. Aliment Pharmacol Ther, 2025, 61( 6): 1043- 1054. DOI: 10.1111/apt.18506.
[21]	ARAB JP, DÍAZ LA, REHM J, et al. Metabolic dysfunction and alcohol-related liver disease(MetALD): Position statement by an expert panel on alcohol-related liver disease[J]. J Hepatol, 2025, 82( 4): 744- 756. DOI: 10.1016/j.jhep.2024.11.028.
[22]	FINANGER T, MELBY K, SPIGSET O, et al. Relationship between alcohol intake based on daily smartphone-reported consumption and PEth concentrations in healthy volunteers[J]. Alcohol Alcohol, 2024, 59( 4): agae040. DOI: 10.1093/alcalc/agae040.
[23]	GRANT BF, CHOU SP, SAHA TD, et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001-2002 to 2012-2013: Results from the national epidemiologic survey on alcohol and related conditions[J]. JAMA Psychiatry, 2017, 74( 9): 911- 923. DOI: 10.1001/jamapsychiatry.2017.2161.
[24]	RINELLA ME, NEUSCHWANDER-TETRI BA, SIDDIQUI MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease[J]. Hepatology, 2023, 77( 5): 1797- 1835. DOI: 10.1097/hep.0000000000000323.
[25]	SOOKOIAN S, PIROLA CJ. Resmetirom for treatment of MASH[J]. Cell, 2024, 187( 12): 2897- 2897. e 1. DOI: 10.1016/j.cell.2024.05.009.
[26]	HARRISON SA, BASHIR MR, GUY CD, et al. Resmetirom(MGL-3196) for the treatment of non-alcoholic steatohepatitis: A multicentre, randomised, double-blind, placebo-controlled, phase 2 trial[J]. Lancet, 2019, 394( 10213): 2012- 2024. DOI: 10.1016/S0140-6736(19)32517-6.
[27]	HARRISON SA, BEDOSSA P, GUY CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis[J]. N Engl J Med, 2024, 390( 6): 497- 509. DOI: 10.1056/nejmoa2309000.
[28]	YU ST, RAO S, REDDY JK. Peroxisome proliferator-activated receptors, fatty acid oxidation, steatohepatitis and hepatocarcinogenesis[J]. Curr Mol Med, 2003, 3( 6): 561- 572. DOI: 10.2174/1566524033479537.
[29]	RATZIU V, HARRISON SA, FRANCQUE S, et al. Elafibranor, an agonist of the peroxisome Proliferator-Activated receptor-α and-δ, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening[J]. Gastroenterology, 2016, 150( 5): 1147- 1159. e 5. DOI: 10.1053/j.gastro.2016.01.038.
[30]	KOIZUMI A, KAJI K, NISHIMURA N, et al. Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease[J]. World J Gastroenterol, 2024, 30( 28): 3428- 3446. DOI: 10.3748/wjg.v30.i28.3428.
[31]	ARMSTRONG MJ, HULL D, GUO K, et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis[J]. J Hepatol, 2016, 64( 2): 399- 408. DOI: 10.1016/j.jhep.2015.08.038.
[32]	NEWSOME PN, BUCHHOLTZ K, CUSI K, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis[J]. N Engl J Med, 2021, 384( 12): 1113- 1124. DOI: 10.1056/nejmoa20-28395.
[33]	SANYAL AJ, NEWSOME PN, KLIERS I, et al. Phase 3 trial of semaglutide in metabolic dysfunction–associated steatohepatitis[J]. N Engl J Med, 2025, 392( 21): 2089- 2099. DOI: 10.1056/nejmoa2413258.
[34]	MUDALIAR S, HENRY RR, SANYAL AJ, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease[J]. Gastroenterology, 2013, 145( 3): 574- 582. e 1. DOI: 10.1053/j.gastro.2013.05.042.
[35]	PATEL K, HARRISON SA, ELKHASHAB M, et al. Cilofexor, a nonsteroidal FXR agonist, in patients with noncirrhotic NASH: A phase 2 randomized controlled trial[J]. Hepatology, 2020, 72( 1): 58- 71. DOI: 10.1002/hep.31205.
[36]	BAJAJ JS, GAVIS EA, FAGAN A, et al. A randomized clinical trial of fecal microbiota transplant for alcohol use disorder[J]. Hepatology, 2021, 73( 5): 1688- 1700. DOI: 10.1002/hep.31496.
[37]	LI F, ZHANG ZY, BAI Y, et al. Glucosamine improves non-alcoholic fatty liver disease induced by high-fat and high-sugar diet through regulating intestinal barrier function, liver inflammation, and lipid metabolism[J]. Molecules, 2023, 28( 19): 6918. DOI: 10.3390/molecules28196918.
[38]	RYU T, CHANG Y, YOO JJ, et al. Glucosamine supplementation attenuates progression of metabolic dysfunction-associated steatotic liver disease and related comorbidities[J]. Clin Nutr, 2025, 47: 119- 128. DOI: 10.1016/j.clnu.2025.02.012.
[39]	NATARAJ K, SCHONFELD M, RODRIGUEZ A, et al. Protective role of 17β-estradiol in alcohol-associated liver fibrosis is mediated by suppression of integrin signaling[J]. Hepatol Commun, 2024, 8( 5): e0428. DOI: 10.1097/hc9.0000000000000428
[40]	BENEDÉ-UBIETO R, ESTÉVEZ-VÁZQUEZ O, GUO FF, et al. An experimental DUAL model of advanced liver damage[J]. Hepatol Commun, 2021, 5( 6): 1051- 1068. DOI: 10.1002/hep4.1698.
[41]	BABUTA M, MOREL C, DE CARVALHO RIBEIRO M, et al. A novel experimental model of MetALD in male mice recapitulates key features of severe alcohol-associated hepatitis[J]. Hepatol Commun, 2024, 8( 7): e0450. DOI: 10.1097/hc9.0000000000000450