Prognostic and predictive effects of new steatotic liver disease nomenclatures: a large population-based study

Huixian Zeng; Letian Fang; Zhiyu Yang; Xinyu Zhao; Hongsen Chen; Puyi Xing; Zheyun Niu; Zheng Li; Zishuai Li; Jiayi Zhao; Wenbin Liu; Chunxia Jing; Hong You; Guangwen Cao

doi:10.1002/mco2.70087

MedComm ›› 2025, Vol. 6 ›› Issue (2) : e70087 DOI: 10.1002/mco2.70087

ORIGINAL ARTICLE

Prognostic and predictive effects of new steatotic liver disease nomenclatures: a large population-based study

Huixian Zeng ¹^,²^,³^,⁴^,⁵
, Letian Fang ²^,³^,⁴
, Zhiyu Yang ¹^,²^,³^,⁴^,⁶
, Xinyu Zhao ⁷
, Hongsen Chen ²^,³^,⁴
, Puyi Xing ¹^,²^,³^,⁴
, Zheyun Niu ⁸
, Zheng Li ²^,³^,⁴
, Zishuai Li ²^,³^,⁴
, Jiayi Zhao ²^,³^,⁴
, Wenbin Liu ²^,³^,⁴
, Chunxia Jing ¹
, Hong You ⁹^,^†
, Guangwen Cao ²^,³^,⁴^,^†

Author information +

¹. Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China

². Key Laboratory of Biological Defense, Ministry of Education, Second Military Medical University, Shanghai, China

³. Shanghai Key Laboratory of Medical Bioprotection, Second Military Medical University, Shanghai, China

⁴. Department of Epidemiology, Second Military Medical University, Shanghai, China

⁵. Jiading District Center for Disease Control and Prevention, Shanghai, China

⁶. Department of Vitral Statistics, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China

⁷. Clinical Epidemiology & EBM Unit, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China

⁸. Shanghai East Hospital, Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Tongji University, Shanghai, China

⁹. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing, China

youhongliver@ccmu.edu.cn

gcao@smmu.edu.cn

Show less

History +

PDF

Abstract

We aimed to compare the association of metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), metabolic dysfunction and ALD (MetALD), and MASLD with viral hepatitis (MASLD-Viral) with risks of cirrhosis, liver cancer, and mortality. The data of 464,556 adults from the UK Biobank (UKB), 13,526 adults from the National Health and Nutrition Examination Survey (NHANES), and 2554 adults from BeijngFH Health Cohort Study (FHCS) were included. Adjusted hazard ratios (aHR) and odds ratios were calculated using Cox and Logistic regression models, respectively. Compared with non-SLD, the risk of liver cancer increased from MetALD (aHR 1.70 [95% CI 1.37, 2.09]), MASLD (1.91 [1.66, 2.21]), MAFLD (2.01 [1.76, 2.29]), ALD (3.16 [2.54, 3.93]), to MASLD-Viral (22.0 [10.8, 44.4]) in a stepwise manner in the UKB; the risk of all-cause mortality increased from MetALD, MASLD, MAFLD, ALD, to MASLD-Viral in the NHANES. The odds ratio of liver fibrosis increased from MASLD, MAFLD, to MASLD-Viral in the FHCS. In patients with diabetes, metformin plus other drugs were associated with higher risks of cirrhosis, liver cancer, and all-cause mortality in MASLD or MAFLD. Prevention rather than antiglycemic treatment is important for patients with diabetic MASLD or MAFLD.

Keywords

antiglycemic medication / diabetes / metabolic dysfunction-associated fatty liver disease / metabolic dysfunction-associated steatotic liver disease / prognosis

Cite this article

Download citation ▾

Huixian Zeng, Letian Fang, Zhiyu Yang, Xinyu Zhao, Hongsen Chen, Puyi Xing, Zheyun Niu, Zheng Li, Zishuai Li, Jiayi Zhao, Wenbin Liu, Chunxia Jing, Hong You, Guangwen Cao. Prognostic and predictive effects of new steatotic liver disease nomenclatures: a large population-based study. MedComm, 2025, 6(2): e70087 DOI:10.1002/mco2.70087

登录浏览全文

4963

注册一个新账户忘记密码

References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Powell EE, Wong VWS, Rinella M. Non-alcoholic fatty liver disease. Lancet Lond Engl. 2021; 397(10290): 2212-2224.

[2]	Desjonqueres E, Gigante E. Hepatocellular carcinoma on the background of nonalcoholic fatty liver disease: epidemiological update. Hepatoma Res. 2022; 8: 16.

[3]	Kim GA, Moon JH, Kim W. Critical appraisal of metabolic dysfunction-associated steatotic liver disease: implication of janus-faced modernity. Clin Mol Hepatol. 2023; 29(4): 831-843.

[4]	Eslam M, Sanyal AJ, George J, International Consensus Panel. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020; 158(7): 1999-2014.e1.

[5]	Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol. 2020; 73(1): 202-209.

[6]	Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023; 79(6): 1542-1556.

[7]	Yang A, Zhu X, Zhang L, Ding Y. Transitioning from NAFLD to MAFLD and MASLD: consistent prevalence and risk factors in a Chinese cohort. J Hepatol. 2024; 80(4): e154-e155.

[8]	Hagström H, Vessby J, Ekstedt M, Shang Y. 99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical. J Hepatol. 2024; 80(2): e76-e77.

[9]	Song SJ, Lai JCT, Wong GLH, Wong VWS, Yip TCF. Can we use old NAFLD data under the new MASLD definition? J Hepatol. 2024; 80(2): e54-e56.

[10]	Perazzo H, Pacheco AG, Griep RH, Collaborators. Changing from NAFLD through MAFLD to MASLD: similar prevalence and risk factors in a large brazilian cohort. J Hepatol. 2024; 80(2): e72-e74.

[11]	Nguyen VH, Le MH, Cheung RC, Nguyen MH. Differential clinical characteristics and mortality outcomes in persons with NAFLD and/or MAFLD. Clin Gastroenterol Hepatol. 2021; 19(10): 2172-2181.e6.

[12]	Song R, Li Z, Zhang Y, Tan J, Chen Z. Comparison of NAFLD, MAFLD and MASLD characteristics and mortality outcomes in United States adults. Liver Int. 2024; 44(4): 1051-1060.

[13]	Younossi ZM, Paik JM, Al Shabeeb R, Golabi P, Younossi I, Henry L. Are there outcome differences between NAFLD and metabolic-associated fatty liver disease? Hepatol Baltim Md. 2022; 76(5): 1423-1437.

[14]	Zhao Q, Deng Y. Comparison of mortality outcomes in individuals with MASLD and/or MAFLD. J Hepatol. 2024; 80(2): e62-e64.

[15]	Fouad Y, Sanai F, Alboraie M, Zheng MH. What the new definition of MASLD left behind: dual etiology with viral hepatitis. Clin Gastroenterol Hepatol. 2024; 22(8): 1751-1752.

[16]	Lee BP, Dodge JL, Terrault NA. National prevalence estimates for steatotic liver disease and subclassifications using consensus nomenclature. Hepatol Baltim Md. 2024; 79(3): 666-673.

[17]	Villamil FG, Barbero M, Massenzio NE, et al. Prevalence of non-alcoholic fatty liver disease and liver fibrosis in a general population cohort from argentina. Ann Hepatol. 2023; 28(4): 101111.

[18]	Tan Z, Wu Y, Meng Y, et al. Trends in oxidative balance score and prevalence of metabolic dysfunction-associated steatotic liver disease in the united states: national health and nutrition examination survey 2001 to 2018. Nutrients. 2023; 15(23): 4931.

[19]	Colaci C, Gambardella ML, Scarlata GGM, et al. Dysmetabolic comorbidities and non-alcoholic fatty liver disease: a stairway to metabolic dysfunction-associated steatotic liver disease. Hepatoma Res. 2024; 10: 16.

[20]	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. Lancet Gastroenterol Hepatol. 2024; 9(3): 218-228.

[21]	Mao X, Cheung KS, Peng C, et al. Steatosis, HBV-related HCC, cirrhosis, and HBsAg seroclearance: a systematic review and meta-analysis. Hepatol Baltim Md. 2023; 77(5): 1735-1745.

[22]	Choi HSJ, Brouwer WP, Zanjir WMR, et al. Nonalcoholic steatohepatitis is associated with liver-related outcomes and all-cause mortality in chronic hepatitis B. Hepatol Baltim Md. 2020; 71(2): 539-548.

[23]	Chen K, Qu C. Impact of occult hepatitis B virus infection and high-fat diet on hepatocellular carcinoma development. Hepatoma Res. 2024; 10: 38.

[24]	Ajmera V, Cepin S, Tesfai K, et al. A prospective study on the prevalence of NAFLD, advanced fibrosis, cirrhosis and hepatocellular carcinoma in people with type 2 diabetes. J Hepatol. 2023; 78(3): 471-478.

[25]	Brodosi L, Musio A, Barbanti FA, Mita D, Marchesini G, Petroni ML. Diabetes and NAFLD: a high-risk cohort with definite therapeutic potential. Hepatoma Res. 2020; 6: 82.

[26]	Kim MN, Han K, Yoo J, Hwang SG, Zhang X, Ahn SH. Diabetic MAFLD is associated with increased risk of hepatocellular carcinoma and mortality in chronic viral hepatitis patients. Int J Cancer. 2023; 153(8): 1448-1458.

[27]	Schlesinger S, Aleksandrova K, Pischon T, et al. Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a european cohort. Ann Oncol. 2013; 24(9): 2449-2455.

[28]	Kramer JR, Natarajan Y, Dai J, et al. Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease. Hepatol Baltim Md. 2022; 75(6): 1420-1428.

[29]	Singh S, Singh PP, Singh AG, Murad MH, Sanchez W. Anti-diabetic medications and the risk of hepatocellular cancer: a systematic review and meta-analysis. Am J Gastroenterol. 2013; 108(6): 881-891; quiz 892.

[30]	Kaplan DE, Serper M, John BV, et al. Effects of metformin exposure on survival in a large national cohort of patients with diabetes and cirrhosis. Clin Gastroenterol Hepatol. 2021; 19(10): 2148-2160.e14.

[31]	Wu J, Zhu AX. Targeting insulin-like growth factor axis in hepatocellular carcinoma. J Hematol Oncol. 2011; 4: 30.

[32]	Alshehade S, Alshawsh MA, Murugaiyah V, et al. The role of protein kinases as key drivers of metabolic dysfunction-associated fatty liver disease progression: new insights and future directions. Life Sci. 2022; 305: 120732.

[33]	En Li Cho E, Ang CZ, Quek J, et al. Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Gut. 2023; 72(11): 2138-2148.

[34]	Ferguson D, Finck BN. Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus. Nat Rev Endocrinol. 2021; 17(8): 484-495.

[35]	Zhang X, Harmsen WS, Mettler TA, et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatol Baltim Md. 2014; 60(6): 2008-2016.

[36]	Nar A, Gedik O. The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Acta Diabetol. 2009; 46(2): 113-118.

[37]	Haukeland JW, Konopski Z, Eggesbø HB, et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol. 2009; 44(7): 853-860.

[38]	Unick JL, Beavers D, Jakicic JM, et al. Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the look AHEAD trial. Diabetes Care. 2011; 34(10): 2152-2157.

[39]

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.

[40]	American Diabetes Association. 8. Obesity management for the treatment of type 2 diabetes: standards of medical care in diabetes-2019. Diabetes Care. 2019; 42(Suppl 1): S81-S89.

[41]	Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia. 2012; 55(4): 885-904.

[42]

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 on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). Obes Facts. 2024; 17(4): 374-444.

[43]	Hydes TJ, Cuthbertson DJ, Palmer DH, et al. Ultrasonography in surveillance for hepatocellular carcinoma in patients with non-alcoholic fatty liver disease. Hepatoma Res. 2023; 9: 12.

[44]	Collins R. What makes UK Biobank special? Lancet Lond Engl. 2012; 379(9822): 1173-1174.

[45]	Plan and operation of the third national health and nutrition examination survey, 1988–94. Series 1: programs and collection procedures. Vital Health Stat Ser 1. 1994;(32): 1-407.

[46]	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.

[47]	Zhang YB, Pan XF, Lu Q, et al. Associations of combined healthy lifestyles with cancer morbidity and mortality among individuals with diabetes: results from five cohort studies in the USA, the UK and China. Diabetologia. 2022; 65(12): 2044-2055.

[48]	Sumida Y, Yoneda M, Hyogo H, et al. Validation of the FIB4 index in a japanese nonalcoholic fatty liver disease population. BMC Gastroenterol. 2012; 12: 2.

[49]	Li B, Chen L, Hu X, et al. Association of serum uric acid with all-cause and cardiovascular mortality in diabetes. Diabetes Care. 2023; 46(2): 425-433.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.