The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016) · Hepatology · doi:10.1002/hep.28431 · Cited by 10,781
Management of Hepatocellular Carcinoma: An Update Δσ
Bruix, J., & Sherman, M. (2011) · Hepatology · doi:10.1002/hep.24199 · Cited by 8,135
Inflammation and cancer: back to Virchow?
Balkwill, F., & Mantovani, A. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04046-0 · Cited by 7,746
Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms
Calle, E. E., & Kaaks, R. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1408 · Cited by 3,613
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
Estes, C., Razavi, H. A., Loomba, R. S., Younossi, Z. M., & Sanyal, A. J. (2017) · Hepatology · doi:10.1002/hep.29466 · Cited by 2,496
Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma
Ally, A., Balasundaram, M., Carlsen, R., Chuah, E., Clarke, A., Dhalla, N., Holt, R. A., Jones, S. J. M., Lee, D., Ma, Y., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.046 · Cited by 2,490
Estes, C., Anstee, Q. M., Arias, M., Bantel, H., Bellentani, S., Caballería, J., Colombo, M., Craxì, A., Crespo, J., Day, C. P., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.05.036 · Cited by 2,046
Altekruse, S. F., McGlynn, K. A., & Reichman, M. E. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.7753 · Cited by 1,695
Mann, C. J. (2003) · Emergency Medicine Journal · doi:10.1136/emj.20.1.54 · Cited by 1,558 · cited 1×
“potential temporal causal relationship between diabetes and HCC among NASH cirrhosis patients.(38)”
BackgroundAscha, M. S., Hanouneh, I. A., Lopez, R., Tamimi, T. A.-R., Feldstein, A. F., & Zein, N. N. (2010) · Hepatology · doi:10.1002/hep.23527 · Cited by 1,296
Fasting Serum Glucose Level and Cancer Risk in Korean Men and Women
Jee, S. H. (2005) · JAMA · doi:10.1001/jama.293.2.194 · Cited by 989
Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study
Tapper, E. B., & Parikh, N. D. (2018) · BMJ · doi:10.1136/bmj.k2817 · Cited by 858
El‐Serag, H. B., Hampel, H., & Javadi, F. (2006) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2005.12.007 · Cited by 831
Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease
Kanwal, F., Kramer, J. R., Mapakshi, S., Natarajan, Y., Chayanupatkul, M., Richardson, P. A., Li, L., Desiderio, R., Thrift, A. P., Asch, S. M., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.08.024 · Cited by 795
White, D. L., Kanwal, F., & El–Serag, H. B. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.10.001 · Cited by 766
Noureddin, M., Vipani, A., Bresee, C. J., Todo, T., Kim, I. K., Alkhouri, N., Setiawan, V. W., Tran, T. T., Ayoub, W. S., Lu, S. C.-L., et al. (2018) · The American Journal of Gastroenterology · doi:10.1038/s41395-018-0088-6 · Cited by 578
Sanyal, A. J., Banas, C. A., Sargeant, C., Luketic, V. A., Sterling, R. K., Stravitz, R. T., Shiffman, M. L., Heuman, D. M., COTTERELL, A. H., Fisher, R. A., et al. (2006) · Hepatology · doi:10.1002/hep.21103 · Cited by 521
Bhala, N. B., Angulo, P., van der Poorten, D., Lee, E., Hui, J. M., Saracco, G. M., Adams, L. A., Charatcharoenwitthaya, P., Topping, J. H., Bugianesi, E., et al. (2011) · Hepatology · doi:10.1002/hep.24491 · Cited by 450
Sakurai, T., Maeda, S., Chang, L., & Karin, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603499103 · Cited by 403
Chen, H.-P., Shieh, J., Chang, C., Chen, T.-T., Lin, J., Wu, M., Lin, J.-H., & Wu, C. (2012) · Gut · doi:10.1136/gutjnl-2011-301708 · Cited by 399
Obesity Drives STAT-1-Dependent NASH and STAT-3-Dependent HCC
Grohmann, M., Wiede, F., Dodd, G. T., Gurzov, E. N., Ooi, G. J., Butt, T., Rasmiena, A. A., Kaur, S., Gulati, T., Goh, P. K., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.053 · Cited by 373 · cited 1×
“(26) Diabetes promotes hepatocarcinogenesis through activation of inflammatory cascades with production of proinflammatory cytokines and reactive oxygen species, which cause genomic instability, promote cellular proliferation, and inhibit apoptosis of hepatocytes.(27-33) Diabetes may also be associated with hyperinsul…”
BackgroundPopulation-Attributable Fractions of Risk Factors for Hepatocellular Carcinoma in the United States
Welzel, T. M., Graubard, B. I., Quraishi, S. M., Zeuzem, S., Davila, J. A., El‐Serag, H. B., & McGlynn, K. A. (2013) · The American Journal of Gastroenterology · doi:10.1038/ajg.2013.160 · Cited by 326
Diabetes mellitus and risk of hepatocellular carcinoma: a systematic review and meta‐analysis
Wang, P., Kang, D., Cao, W., Wang, Y., & Liu, Z. (2011) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1291 · Cited by 316
Hui, L., Zatloukal, K., Scheuch, H., Stępniak-Konieczna, E., & Wagner, E. F. (2008) · Journal of Clinical Investigation · doi:10.1172/jci37156 · Cited by 313
Veldt, B. J., Chen, W., Heathcote, J., Wedemeyer, H. H., Reichen, J., Hofmann, P., de Knegt, R. J., Zeuzem, S., Manns, M. P., Hansen, B. E., et al. (2008) · Hepatology · doi:10.1002/hep.22251 · Cited by 281
Siddiqui, M. S., Fuchs, M. A., Idowu, M. O., Luketic, V. A., Boyett, S. L., Sargeant, C., Stravitz, R. T., Puri, P., Matherly, S. C., Sterling, R. K., et al. (2014) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2014.10.008 · Cited by 240
Yang, J. D., Larson, J. J., Watt, K. D. S., Allen, A. M., Wiesner, R. H., Gores, G. J., Roberts, L. R., Heimbach, J. K., & Leise, M. D. (2016) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2016.11.034 · Cited by 152
Self-citationFactors That Affect Risk for Hepatocellular Carcinoma and Effects of Surveillance
Yang, J. D., Harmsen, W. S., Slettedahl, S. W., Chaiteerakij, R., Enders, F., Therneau, T. M., Orsini, L. S., Kim, W. R., & Roberts, L. R. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.03.027 · Cited by 123
Self-citationIoannou, G. N., Green, P. K., Lowy, E., Mun, E. J., & Berry, K. (2018) · PLoS ONE · doi:10.1371/journal.pone.0204412 · Cited by 117
Role of Albumin in Growth Inhibition in Hepatocellular Carcinoma
Bağırsakçı, E., Şahin, E., Atabey, N., Erdal, E., Guerra, V., & Carr, B. I. (2017) · Oncology · doi:10.1159/000471807 · Cited by 105
Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle
Nojiri, S., & Joh, T. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15035163 · Cited by 103
Yang, J. D., Mohamed, H. A., Cvinar, J. L., Gores, G. J., Roberts, L. R., & Kim, W. R. (2016) · The American Journal of Gastroenterology · doi:10.1038/ajg.2016.330 · Cited by 82
Self-citationPelusi, S., Petta, S., Rosso, C., Borroni, V. N., Fracanzani, A. L., Dongiovanni, P., Craxı̀, A., Bugianesi, E., Fargion, S. R., & Valenti, L. V. C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163069 · Cited by 82
Incidence of altered glucose tolerance in liver cirrhosis
Gentile, S., Loguercio, C., Marmo, R., Carbone, L., & Blanco, C. D. V. (1993) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(93)90130-w · Cited by 58
Diabetes and Insulin Therapy, but Not Metformin, Are Related to Hepatocellular Cancer Risk
Miele, L., Bosetti, C., Turati, F., Rapaccini, G. L., Gasbarrini, A., Vecchia, C. L., Boccia, S., & Grieco, A. (2015) · Gastroenterology Research and Practice · doi:10.1155/2015/570356 · Cited by 47
Hepatocellular Carcinoma in Olmsted County, Minnesota, 1976-2008
Yang, J. D., Kim, B., Sanderson, S. O., Sauver, J. L. S., Yawn, B. P., Pedersen, R. A., Larson, J. J., Therneau, T. M., Roberts, L. R., & Kim, W. R. (2012) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2011.07.001 · Cited by 44
Self-citationRecent Trends in the Epidemiology of Hepatocellular Carcinoma in Olmsted County, Minnesota
Yang, J. D., Mohammed, H. A., Harmsen, W. S., Enders, F., Gores, G. J., & Roberts, L. R. (2017) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000000810 · Cited by 41
Self-citationBeyond apoptosis of JNK1 in liver cancer
Chen, F., & Castranova, V. (2009) · Cell Cycle · doi:10.4161/cc.8.8.8200 · Cited by 22
Metabolic factors affecting hepatocellular carcinoma in steatohepatitis
Zarrinpar, A., Faltermeier, C. M., Agopian, V. G., Naini, B. V., Harlander‐Locke, M. P., Kaldas, F. M., Farmer, D. G., & Busuttil, R. W. (2018) · Liver International · doi:10.1111/liv.14002 · Cited by 19
Kwong, A. J., Kim, W. R., & Flemming, J. A. (2018) · Hepatology · doi:10.1002/hep.30045 · Cited by 12
Cited by
Sorted by citations
Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002
Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention
Huang, D. Q., El-Serag, H. B., & Loomba, R. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00381-6 · Cited by 1,855
Global Epidemiology and Genetics of Hepatocellular Carcinoma
Toh, M. R., Wong, E. Y. T., Wong, S. H., Ng, A. W. T., Loo, L., Chow, P. K.-H., & Ngeow, J. Y. Y. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.01.033 · Cited by 622
A Global View of the Interplay between Non-Alcoholic Fatty Liver Disease and Diabetes
Stefan, N., & Cusi, K. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00003-1 · Cited by 593
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review