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Synergism Between Obesity and Alcohol in Increasing the Risk of Hepatocellular Carcinoma: A Prospective Cohort Study
Open accessAbstract
Obesity and alcohol interact to increase the risk of death from liver failure in men. In the present study, we aimed to examine whether obesity and alcohol were multiplicative or additive in increasing the risk of hepatocellular carcinoma (HCC) in both men and women. We conducted a prospective, population-based study of 23,712 Taiwanese residents (50.3% men) from 7 townships who underwent an evaluation for liver disease and were followed for 11.6 years for incident HCC. The mean age was 47 (standard deviation, 10) years and the mean body mass index (weight (kg)/height (m)(2)) was 24 (standard deviation, 3). Overall, 305 cases of HCC were identified over 275,126 person-years of follow-up. Age, male sex, alcohol drinking, cigarette smoking, elevated alanine aminotransferase, serum hepatitis B surface antigen, anti-hepatitis C virus positivity, and diabetes mellitus were each statistically significant predictors of incident HCC in univariate analyses (P < 0.05). Alcohol use and obesity (body mass index ≥30) showed a synergistic association with the risk of incident HCC in both unadjusted analyses (hazard ratio = 7.19, 95% confidence interval: 3.69, 14.00; P < 0.01) and multivariable-adjusted analyses (age, sex, smoking, serum alanine aminotransferase, serum hepatitis B surface antigen, anti-hepatitis C virus antibody, and diabetes mellitus) (hazard ratio = 3.82, 95% confidence interval: 1.94, 7.52; P < 0.01). Relative excess risks due to interaction, attributable proportion, and synergy index were 4.83, 0.67, and 4.53, respectively, suggesting a multiplicative interaction between alcohol use and obesity. Obesity and alcohol synergistically increase the risk of incident HCC.
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“Alcohol consumption may also increase the risk of HCC in persons with obesity, with a synergistic interaction even after adjustment for multiple carcinogenic confounders.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [96]
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“To test whether the interaction is additive or multiplicative, we examined the combined impact of alcohol and obesity on HCC risk by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI) and their respective confidence intervals, as previously described (30, 31).”
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Metadata
- Authors
- Loomba, R., Yang, H.-I., Su, J., Brenner, D., Barrett-Connor, E., Iloeje, U., & Chen, C.-J.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Loomba, Rohit
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-01-24
- Volume
- 177
- Issue
- 4
- Pages
- 333-342
- ISSN
- 0002-9262 (ISSN-L)
- 1476-6256
- PMC
- PMC3626057
- OpenAlex
- W2116448477
- Cited by
- 221
- References
- 37
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 17 · 2023: 21 · 2022: 18 · 2021: 23 · 2020: 17 · 2019: 20 · 2018: 11 · 2017: 12 · 2016: 17 · 2015: 20 · 2014: 13 · 2013: 9
- FWCI
- 14.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Epidemiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30CA23100-27, P30CA023100)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK090303)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- hepatocellular carcinoma, obesity, alcohol consumption, synergistic interaction, multiplicative interaction, body mass index, liver cancer risk factors, hepatitis B, hepatitis C, diabetes mellitus, smoking, alanine aminotransferase, Taiwanese population
- MeSH terms
- Adult, Alanine Transaminase, Alcohol Drinking, Algorithms, Analysis of Variance, Female, Follow-Up Studies, Hepatitis B Surface Antigens, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Obesity, Prospective Studies, Risk Factors, Smoking, Taiwan, Biomarkers, Tumor, Cohort Studies, Body Mass Index, Incidence, Multivariate Analysis, Confidence Intervals, Odds Ratio, Hepatitis C Antibodies, Hepatitis B, Chronic, Diabetes Complications
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