Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: results from two prospective cohort studies
Open accessAbstract
Type 2 diabetes (T2D) is a risk factor for hepatocellular carcinoma (HCC). However, it is unknown whether T2D duration or additional metabolic comorbidities further contribute to HCC risk. From the Nurses' Health Study (NHS), 120,826 women were enrolled in 1980, and from the Health Professionals Follow‐up Study (HPFS), 50,284 men were enrolled in 1986 and followed through 2012. Physician‐diagnosed T2D was ascertained at baseline and updated biennially. Cox proportional hazards regression models were used to calculate age‐ and multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident HCC. Over 32 years of follow‐up (4,488,410 person‐years), we documented 112 cases of HCC (69 women, 43 men). T2D was associated with an increased HCC risk (multivariable HR, 4.59; 95% CI, 2.98‐7.07), as was an increasing T2D duration (P trend < 0.001). Compared to nondiabetics, the multivariable HRs for HCC were 2.96 (95% CI, 1.57‐5.60) for 0‐<2 years; 6.08 (95% CI, 2.96‐12.50) for 2‐<10 years; and 7.52 (95% CI, 3.88‐14.58) for ≥10 years. Increasing number of metabolic comorbidities (T2D, obesity, hypertension, and dyslipidemia) was associated with increased HCC risk (P trend < 0.001); compared to individuals without metabolic comorbidity, those with four metabolic comorbidities had an 8.1‐fold increased HCC risk (95% CI, 2.48‐26.7). In T2D, neither insulin use nor oral hypoglycemic use was significantly associated with HCC risk (HR, 2.04 [95% CI, 0.69‐6.09] and HR, 1.45 [95% CI, 0.69‐3.07], respectively). Conclusion: T2D is independently associated with increased risk for HCC in two prospective cohorts of U.S. men and women. This risk is enhanced with prolonged diabetes duration and with comorbid metabolic conditions, suggesting the importance of insulin resistance in the pathogenesis of HCC. (Hepatology 2018;67:1797‐1806)
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Metabolic syndrome itself and T2D have been reported to be associated with an increased risk of HCC in large cohort studies, but the increase in absolute HCC risk attributable to metabolic factors or genetic factors in individuals with non-cirrhotic MASLD is very small.
“Metabolic syndrome itself and T2D have also been reported to be associated with an increased risk of HCC in large cohort studies, 46,245 but the increase in absolute HCC risk attributable to metabolic factors ( e.g. T2D, obesity) or genetic factors in individuals with non-cirrhotic MASLD is very small.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [245]
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- Authors
- Simon, T. G., King, L. Y., Chong, D. Q., Nguyen, L. H., Ma, Y., VoPham, T., Giovannucci, E. L., Fuchs, C. S., Meyerhardt, J. A., Corey, K. E., Khalili, H., Chung, R. T., Zhang, X., & Chan, A. T.
- Affiliations
- Harvard University (US)
- Duke University (US)
- National Cancer Centre Singapore (SG)
- Brigham and Women's Hospital (US)
- Yale Cancer Center (US)
- Corresponding author
- Chan, Andrew T.
- ORCID
- Venue
- Hepatology
- Published
- 2018-03-26
- Volume
- 67
- Issue
- 5
- Pages
- 1797-1806
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC5906170
- OpenAlex
- W2770703028
- Cited by
- 160
- References
- 55
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 20 · 2023: 20 · 2022: 19 · 2021: 29 · 2020: 18 · 2019: 18 · 2018: 7 · 2017: 1
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Brigham and Women's Hospital
- American Gastroenterological Association (K24 DK078772)
- Crohn's and Colitis Foundation (563526)
- National Institutes of Health (NIH K24, UM1-CA167552, CA-167552)
- National Cancer Institute (K07CA188126, P01CA087969, UM1CA186107, UM1CA167552, T32CA009001, U01CA167552)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK099422, K23DK099681, K24DK098311, K24DK078772, P30DK043351, T32DK007191)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- type 2 diabetes, hepatocellular carcinoma, metabolic comorbidities, diabetes duration, obesity, hypertension, dyslipidemia, insulin use, oral antidiabetic drugs, cancer risk
- MeSH terms
- Adult, Aged, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Prospective Studies, Risk Factors, United States, Cohort Studies, Comorbidity, Metabolic Syndrome
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