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Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease
Open accessAbstract
Diabetes increases the risk of liver disease progression and cirrhosis development in patients with nonalcoholic steatohepatitis (NASH). The association between diabetes and the risk of hepatocellular carcinoma (HCC) in NASH patients with cirrhosis is not well quantified. All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between January 2006 and December 2015 were identified. All adult liver transplant registrants with NASH between 2004 and 2017 were identified using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation registry for external validation. Cox proportional hazard analysis was performed to investigate the association between diabetes and HCC risk. Among 354 Mayo Clinic patients with NASH cirrhosis, 253 (71%) had diabetes and 145 (41%) were male. Mean age at cirrhosis evaluation was 62. During a median follow-up of 47 months, 30 patients developed HCC. Diabetes was associated with an increased risk of developing HCC in univariate (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 1.1-11.9; P = 0.04) and multivariable analysis (HR = 4.2; 95% CI = 1.2-14.2; P = 0.02). In addition, age (per decade, HR = 1.8; 95% CI = 1.2-2.6; P < 0.01) and low serum albumin (HR = 2.1; 95% CI = 1.5-2.9; P < 0.01) were significantly associated with an increased risk of developing HCC in multivariable analysis. Other metabolic risk factors, including body mass index, hyperlipidemia, and hypertension, were not associated with HCC risk. Among UNOS NASH registrants (N = 6,630), 58% had diabetes. Diabetes was associated with an increased risk of developing HCC in univariate (HR = 1.4; 95% CI = 1.1-1.8; P < 0.01) and multivariable (HR = 1.3; 95% CI = 1.0-1.7; P = 0.03) analysis. Conclusion: Diabetes is associated with an increased risk of HCC in patients with NASH cirrhosis.
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“Another study reported a 4-fold increased risk of HCC in individuals with T2D and MASH-related cirrhosis followed for 47 months.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [55]
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“potential temporal causal relationship between diabetes and HCC among NASH cirrhosis patients.(38)”
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Wong, R. J., Colombo, M. G., Pinto, E., & Burra, P. (2026) · Clinics in Liver Disease · doi:10.1016/j.cld.2026.01.005
Hepatocellular Carcinoma in the Setting of Metabolic Dysfunction Associated Steatotic Liver Disease
Su, A., Clark, J. M., & Kim, A. K. (2026) · Current Hepatology Reports · doi:10.1007/s11901-025-00707-5
Rationale Diagnostik bei metabolischen Lebererkrankungen (MASLD)
Barton, A., & Schattenberg, J. M. (2026) · Die Diabetologie · doi:10.1007/s11428-026-01456-9
Medina‐Morales, E., Shah, Y., Xynogala, A., Trivedi, H. D., Ochoa‐Allemant, P., Saberi, B., Bonder, A., Tafesh, Z., Amin, A., Lingiah, V. A., et al. (2026) · Liver Transplantation · doi:10.1097/lvt.0000000000000888
Erkennung und Unterscheidung von atypischen hepatozellulären Karzinomen
Ben-Salah, C., Mayer, P., Longerich, T., & Klauß, M. (2026) · Die Radiologie · doi:10.1007/s00117-026-01623-5
Chang, S., Chen, W., Chen, Y., Yu, S., Yu, H., & Chai, C. (2026) · The Analyst · doi:10.1039/d6an00267f
Yang, X., Fu, P., & Liu, H. L. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1865521
Metadata
- Authors
- Yang, J. D., Ahmed, F., Mara, K. C., Addissie, B. D., Allen, A. M., Gores, G. J., & Roberts, L. R.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Mayo Clinic (US)
- Geisinger Medical Center (US)
- Corresponding author
- Roberts, Lewis R.
- Venue
- Hepatology
- Published
- 2019-10-21
- Volume
- 71
- Issue
- 3
- Pages
- 907-916
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC6960360
- OpenAlex
- W2957370227
- Cited by
- 209
- References
- 41
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 40 · 2023: 31 · 2022: 38 · 2021: 29 · 2020: 30 · 2019: 4
- FWCI
- 19.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA186566, U54CA221205, CA210964, CA165076, R01CA165076, CA186566, CA 221205, P50CA210964)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- hepatocellular carcinoma, diabetes mellitus, nonalcoholic steatohepatitis, liver cirrhosis, non-alcoholic fatty liver disease, liver transplantation, serum albumin, age, HCC risk factors, liver disease progression, metabolic risk factors, body mass index, hyperlipidemia, hypertension, liver cancer incidence, Mayo Clinic Rochester, UNOS registry, external validation
- MeSH terms
- Adult, Age Factors, Aged, Female, Carcinoma, Hepatocellular, Humans, Liver Cirrhosis, Liver Neoplasms, Male, Middle Aged, Registries, Risk, Serum Albumin, Diabetes Complications, Non-alcoholic Fatty Liver Disease
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