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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A study reported a 4-fold increased risk of HCC in individuals with T2D and MASH-related cirrhosis followed for 47 months.
“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]
The Mayo cohort Results report a significant association between diabetes and HCC in NASH-related cirrhosis, with median follow-up of 46 months for patients with diabetes and 47 months for those without. The study’s approximately fourfold estimate applies to diabetes as defined in its Methods, not specifically to type 2 diabetes; the Discussion also cautions that the estimate is imprecise and smaller in the validation cohort. Page numbers were not available in our copy. (LLM, conf=0.83)
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- 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 › Epidemiology › 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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