Cited by 267Alcohol Consumption and Health EffectsLiver Disease Diagnosis and TreatmentDiabetes, Cardiovascular Risks, and Lipoproteins

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Interaction between alcohol consumption and metabolic syndrome in predicting severe liver disease in the general population

Åberg, Fredrik, Helenius‐Hietala, Jaana, Puukka, Pauli, Färkkilä, Martti, Jula, Antti·2018·Hepatology

DOI 10.1002/hep.29631

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Abstract

The metabolic syndrome and alcohol risk use are both associated with a high prevalence of hepatic steatosis, but only a minority develop liver failure or liver cancer. Few general population studies have analyzed metabolic predictors of such severe liver complications. We studied which metabolic factors best predict severe liver complications, stratified by alcohol consumption, in 6732 individuals without baseline liver disease who participated in the Finnish population-based Health 2000 Study (2000-2001), a nationally representative cohort. Follow-up data from national registers until 2013 were analyzed for liver-related admissions, mortality, and liver cancer. Baseline alcohol use and metabolic factors were analyzed by backward stepwise Cox regression analysis. Eighty-four subjects experienced a severe liver event during follow-up. In the final multivariate model, factors predictive of liver events were age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.004-1.04), sex (women: HR, 0.55; 95% CI, 0.34-0.91), alcohol use (HR, 1.002; 95% CI, 1.001-1.002), diabetes (HR, 2.73; 95% CI, 1.55-4.81), low-density lipoprotein (LDL) cholesterol (HR, 0.74; 95% CI, 0.58-0.93), and homeostasis model assessment of insulin resistance (HOMA-IR) (HR, 1.01; 95% CI, 1.004-1.02). Among alcohol risk users (≥210 g/week for men, ≥ 140 g/week for women), diabetes (HR, 6.79; 95% CI, 3.18-14.5) was the only significant predictor. Among nonrisk drinkers, age, alcohol use, smoking, waist circumference, low LDL cholesterol and HOMA-IR were significant independent predictors. The total-to-LDL cholesterol ratio and waist circumference-to-body mass index ratio emerged as additional independent predictors. CONCLUSION: Multiple components of the metabolic syndrome independently affected the risk for severe liver disease. Alcohol was significant even when average alcohol consumption was within the limits currently defining nonalcoholic fatty liver disease. (Hepatology 2018;67:2141-2149).

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Background
Genetic and Environmental Susceptibility to Alcoholic Hepatitis
Morgan, M. Y., Sharma, M., & Atkinson, S. R. (2021) · Clinics in Liver Disease · doi:10.1016/j.cld.2021.04.001 · Cited by 11
Hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease with increased alcohol intake (MetALD)
John, B. V., Bastaich, D., Paulus, E., Spector, S. A., & Dahman, B. A. (2025) · JHEP Reports · doi:10.1016/j.jhepr.2025.101639 · Cited by 9
Impact of metabolic risk factors on hepatic and cardiac outcomes in patients with alcohol- and non-alcohol-related fatty liver disease
Lim, J. H., Sang, H., & Kim, H. I. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100721 · Cited by 10
Alkoholos májbetegség: a genetikai-epigenetikai tényezők szerepe és az absztinencia hatása
Pár, A., & Pár, G. (2019) · Orvosi Hetilap · doi:10.1556/650.2019.31352 · Cited by 9
The Mexican consensus on alcoholic hepatitis
Velasco, J. A. V.-R., la Tijera, F. H., Castro‐Narro, G., Zamarripa-Dorsey, F., Abdo-Francis, J. M., Haddad, I. A., Ledesma, J. M. A., Bielsa-Fernández, M. V., Reyes, E. C., Cisneros-Garza, L. E., et al. (2020) · Revista de Gastroenterología de México (English Edition) · doi:10.1016/j.rgmxen.2020.04.004 · Cited by 9
Alcohol‐related hepatocellular carcinoma is a heterogenous condition: Lessons from a latent class analysis
Costentin, C. E., Minovès, M., Kotzki, S., Farges, O., Goutté, N., Decaens, T., & Bailly, S. (2022) · Liver International · doi:10.1111/liv.15256 · Cited by 9
Diabetes, Liver Cancer, and Cirrhosis: What Next?
Yki‐Järvinen, H., & Luukkonen, P. K. (2018) · Hepatology · doi:10.1002/hep.30136 · Cited by 9
“79fold increase in severe liver events in persons with diabetes as compared with people without diabetes among alcohol risk users.(5) Although classification of the etiology of liver disease is often dichotomous (nonalcoholic versus alcoholic, HBsAg positive versus negative), in real life the patient might have double…”
Background
Alcohol associated liver disease and bariatric surgery: Current perspectives and future directions
Cooper, K. M., Colletta, A., Hebda, N., & Devuni, D. (2024) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v16.i3.650 · Cited by 8
Prevalence and Clinical Correlation of Cardiometabolic Risk Factors in Alcohol-Related Liver Disease and Metabolic Dysfunction and Alcohol Associated Liver Disease (MetALD)
Dixon, W., Corey, K. E., Luther, J., Goodman, R. P., & Schaefer, E. A. K. (2024) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2024.102492 · Cited by 8
The natural history of alcohol-related liver disease
Parker, R. (2020) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000627 · Cited by 8
Oral cytological changes in young adults related to alcohol consumption
Maidana, M. D. S., Varela, A. S., Corcini, C. D., Pereira, J. R., Pires, D. M., Tavella, R. A., Fernandes, C. L. F., dos Santos, M., Garcia, E. M., & Júnior, F. M. R. D. S. (2021) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2021.105127 · Cited by 8
Histopathology of Nonalcoholic Fatty Liver Disease
TINIAKOS, D. G., & Sakellariou, S. (2020) · Springer eBooks · doi:10.1007/978-3-319-95828-6_3 · Cited by 8
Fatty Liver Disease
TINIAKOS, D. G., Anstee, Q. M., Brunt, E. M., & Burt, A. D. (2023) · Elsevier eBooks · doi:10.1016/b978-0-7020-8228-3.00005-3 · Cited by 7
MetALD: Genetic Factors and Clinical Outcomes
Israelsen, M. E., Trépo, E., Krag, A. A., & Stender, S. (2025) · Seminars in Liver Disease · doi:10.1055/a-2630-0952 · Cited by 7
“82 – 84 As described above, several studies have shown that genetic risk variants modify the risk of developing decompensated cirrhosis among individuals with the same burden of cardiometabolic and alcohol-related risk factors.”
Austrian multisociety consensus on metabolic dysfunction-associated steatotic liver disease
Mandorfer, M., Semmler, G., Aigner, E. S., Bräuer, A., Brix, J. M., Clodi, M., Datz, C., Effenberger, M., Felsenreich, D. M., Ludvik, B. H., et al. (2025) · Wiener klinische Wochenschrift · doi:10.1007/s00508-025-02617-4 · Cited by 7
Role of Alcohol in Steatotic Liver Disease: Impact on Patients with Cardiometabolic Risk Factors
Capinha, F., Carvalhana, S. C., & Cortez‐Pinto, H. (2025) · Digestive Diseases and Sciences · doi:10.1007/s10620-025-08912-4 · Cited by 6
Response to semaglutide of non-drinker subjects with type 2 diabetes
Petralli, G., Raggi, F., Zoppo, A. D., Rovera, C., Salvati, A., Brunetto, M. R., & Solini, A. (2024) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-024-01344-6 · Cited by 6
“Alcohol use is regarded as a main responsible for the development of liver metabolic abnormalities in people with [22] and without T2D [23, 24].”
Background
Mild-moderate alcohol consumption and diabetes are associated with liver fibrosis in patients with biopsy-proven MASLD
Huang, A., Zou, C., Dai, Z., Sun, Y. H., Wang, J., Liu, S., Han, L., Chen, S., Liang, Q., Wang, C., et al. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1437479 · Cited by 6
Racial Disparities in Associations of Alcohol Consumption With Liver Disease Mortality in a Predominantly Low-Income Population: A Report From the Southern Community Cohort Study
Fan, L., Zhu, X., Shingina, A., Kabagambe, E. K., Shrubsole, M. J., & Dai, Q. (2022) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001768 · Cited by 6
Utility and prognostic value of diagnosing MAFLD in patients undergoing liver transplantation for alcohol‐related liver disease
Vanlerberghe, B. T. K., van Malenstein, H., Sainz‐Barriga, M., Jochmans, I., Cassiman, D. M., Monbaliu, D. R. L., der Merwe, V., Pirenne, J., Nevens, F., & Verbeek, J. (2023) · Clinical Transplantation · doi:10.1111/ctr.14965 · Cited by 6
Time to revise the definition of NAFLD: A purist vision
Mantovani, A. (2019) · Digestive and Liver Disease · doi:10.1016/j.dld.2018.12.018 · Cited by 6
Drug development of nonalcoholic fatty liver disease: challenges in research, regulatory pathways, and study endpoints
Do, A., Ilagan‐Ying, Y. C., Mehal, W. Z., & Lim, J. K. (2020) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2020.1811674 · Cited by 7
The effect of moderate alcohol consumption on nonalcoholic fatty liver disease
Park, J. W., & Suk, K. T. (2023) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2023.0085 · Cited by 6
MetALD: decoding the evolution of steatotic liver disease nomenclature and implications for clinical practice and beyond
Ghodrati, F., Zhang, A. B., & Mahmud, N. (2026) · Gastroenterology report · doi:10.1093/gastro/goag006 · Cited by 6
Prevalence of metabolic syndrome and its association with selected factors among people with psychiatric conditions in Ethiopia: a systematic review and meta-analysis
Tsega, S. S., Alemayehu, E., Dessie, A. M., Anley, D. T., Anteneh, R. M., Moges, N., Zemene, M. A., Gebeyehu, A. A., Belete, M. A., Asmare, Z. A., et al. (2025) · BMC Public Health · doi:10.1186/s12889-025-21571-4 · Cited by 5
“Worldwide, Alcohol consumption is one of the foremost risk factors for disability-adjusted life years and deaths [68].”
Non-metabolic causes of steatotic liver disease
Nasr, P., Jönsson, C., Ekstedt, M., & Kechagias, S. (2023) · Metabolism and Target Organ Damage · doi:10.20517/mtod.2023.20 · Cited by 5
Extent to which weight loss contributes to improving metabolic dysfunction-associated and metabolic and alcohol related/associated steatotic liver disease: a study on Japanese participants undergoing health checkups
Fukuda, T., Okamoto, T., Fukaishi, T., Kawakami, A., Tanaka, M., Yamada, T., & Monzen, K. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1392280 · Cited by 5
Chronic Viral Hepatitis Signifies the Association of Premixed Insulin Analogues with Liver Cancer Risks: A Nationwide Population-Based Study
Chiang, C., Kuo, C.-S., Lin, W., Su, J.-H., Chen, J.-D., & Huang, K. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16122097 · Cited by 5
Alcohol-Related Liver Disease
Krag, A. A., Åberg, F., Mellinger, J. L., Lee, B. P., & Israelsen, M. E. (2026) · JAMA · doi:10.1001/jama.2026.12038 · Cited by 7
Changes over time in the Chronic Liver Disease risk score predict liver-related outcomes: longitudinal analysis of the Whitehall II study
Åberg, F. O., Britton, A. R., & Luukkonen, P. K. (2022) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2022.2113130 · Cited by 4
Dual alcohol and metabolic‐related liver disease: Results from a population of liver transplant patients
Erard, D., Villeret, F., Chouik, Y., Guillaud, O., Scoazec, J., Caussy, C., Disse, E., Boillot, O., Hervieu, V., & Dumortier, J. (2023) · Liver International · doi:10.1111/liv.15779 · Cited by 4
“4,5 ALD and NAFLD are distinguished by average alcohol intake, since they share the same histological features.”
Background
Genetic Risk Factors for Steatotic Liver Disease After Liver Transplantation
Liukkonen, V., Semenova, M., Hyvärinen, K., Lauronen, J., Partanen, J., Arola, J. T., Nordin, A. J., Färkkilä, M. A., & Åberg, F. O. (2025) · Liver International · doi:10.1111/liv.70067 · Cited by 4
“syndrome and only 8% did not have any metabolic risk factors [2].”
Association between estimated glomerular filtration rate and reversion to normoglycemia in people with impaired fasting glucose: a 5-year retrospective cohort study
Tu, L., Hu, H., Zhou, X., Zhang, H., Liu, X., Yang, D., & He, Y. (2024) · European journal of medical research · doi:10.1186/s40001-024-01669-y · Cited by 4
“Previous studies have indicated that drinking is linked to insulin resistance and heightened susceptibility to diabetes [41, 54].”
Background
Alcohol Consumption in Patients with Non-alcoholic Fatty Liver Disease: Convenient vs. Inconvenient Truths
Armstrong, M. J., Mellinger, J. L., & Trivedi, P. J. (2018) · The American Journal of Gastroenterology · doi:10.1038/s41395-018-0237-y · Cited by 4
Hepatology through the crystal ball
Williams, R. L. (2019) · Hepatology International · doi:10.1007/s12072-019-09959-y · Cited by 4
Two drinks per day does not take your fatty liver away
Bellentani, S., Bedogni, G., & Tiribelli, C. (2017) · Hepatology · doi:10.1002/hep.29753 · Cited by 4
Editorial: looking for patients at risk of cirrhosis in the general population—many needles in a haystack
Ampuero, J., & Romero‐Gómez, M. (2018) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14517 · Cited by 4
Influence of Obesity Class on Clinical Outcomes in Alcoholic Hepatitis: A National Cohort Study of Mortality, Complications, and Resource Use
Jaan, A., Najim, M., Farooq, U., Dhawan, A., Nawaz, H., Jahagirdar, V., Ali, H., & Ahlawat, S. (2025) · JGH Open · doi:10.1002/jgh3.70166 · Cited by 3
“Moreover, there is growing evidence that obesity and alcohol have a synergistic detrimental effect on hepatic cells, resulting in an elevated risk of hepatocellular carcinoma [8, 9].”
Association between serum homocysteine levels and advanced hepatic fibrosis in alcohol-related liver disease: A cross-sectional study of NHANES
Ma, C., Zhang, X., Zhang, W., Duan, J., & Yang, H. (2025) · Medicine · doi:10.1097/md.0000000000043395 · Cited by 3
“…and alcohol exhibit synergistic effects on the onset and progression of liver injury, with important effects for hepatocellular lipid accumulation and damage, liver inflammation and fibrosis, [33,34] and obesity may be an independent predictor of liver-related mortality in patients with ALD.”
The nomenclature of fatty liver disease and its impact on obesity traits, insulin resistance, and hepatic fibrosis
Xiang, L., Li, X., Gong, J., He, L., Li, W., Chen, J., Feng, R., Du, S., & Ye, W. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02736-x · Cited by 3
“Furthermore, multiple elements of metabolic syndrome independently enhance the likelihood of serious liver disease, even when alcohol consumption remains within the threshold for NAFLD [42].”
Differential associations of cardiometabolic risk factors with liver-related events by alcohol consumption category: Results from a large population-based study
Xue, H., Wang, L., Wu, Y., Liao, Y., Wang, S., Chen, A., Chan, S. O., Ling, W., Chen, X., & Yu, C. (2025) · Hepatology · doi:10.1097/hep.0000000000001628 · Cited by 4
Alcohol Abstinence Is Associated with Regression of Non-Invasive Fibrosis Markers in Patients with Metabolic Syndrome: A 12-Month Prospective Study
Mihaila, D. F., Domnariu, H. P., Moga, D. F. C., & Domnariu, C. D. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15062257 · Cited by 3
Vi trenger en ny strategi for leversykdom
Vesterhus, M. N., Jørgensen, K. K., Frigstad, S. O., Haukeland, J. W., & Karlsen, T. H. (2022) · Tidsskrift for Den norske legeforening · doi:10.4045/tidsskr.21.0892 · Cited by 3

Authors: Åberg, F., Helenius‐Hietala, J., Puukka, P., Färkkilä, M., & Jula, A.
Affiliations: University of Helsinki (FI)
Department of Health,National Institute for Health and Welfare,Turku,Finland
Corresponding author: Åberg, Fredrik
ORCID: Åberg, Fredrik
Helenius‐Hietala, Jaana
Färkkilä, Martti
Jula, Antti
Venue: Hepatology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2018-04-16
Volume: 67
Issue: 6
Pages: 2141-2149
ISSN: 0270-9139 (ISSN-L)
1527-3350
DOI: 10.1002/hep.29631
OpenAlex: W2770566262
Cited by: 267
References: 32
Citations by year: 2026: 20 · 2025: 32 · 2024: 46 · 2023: 28 · 2022: 30 · 2021: 31 · 2020: 34 · 2019: 26 · 2018: 16
FWCI: 16.75
Type: journal article
Language: en
Open access: closed
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Hepatology (publishedVersion)
PubMed (publishedVersion)
Funders: Finska Läkaresällskapet
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: alcohol consumption, metabolic syndrome, severe liver disease, liver failure, liver cancer, non-alcoholic fatty liver disease, diabetes mellitus, insulin resistance, HOMA-IR, LDL cholesterol, waist circumference, smoking, risk factors, liver-related mortality, general population, Finland, sex differences
MeSH terms: Alcohol Drinking, Female, Humans, Liver Diseases, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Severity of Illness Index, Metabolic Syndrome

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Interaction between alcohol consumption and metabolic syndrome in predicting severe liver disease in the general population

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