The DOI matches its Crossref record; 33 of the 34 references it cites were found in a registry or an index.
Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans Is Associated With Nonalcoholic Fatty Liver Disease
Open accessAbstract
Background & aims Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S.Methods We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features.Results A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC.Conclusions Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of 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
“In the same cohort, the risk of HCC in the absence of cirrhosis was 5-fold higher in individuals with MASLD than in those with chronic hepatitis C.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [123]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Although HCC may develop in non-cirrhotic MASLD, cirrhosis remains the key risk factor for HCC.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [123]
The cited source says what the claim attributes to it.
In the citing paper
“In a US Veterans Administration cohort 123 including 1,500 individuals with HCC from 2005 to 2010, metabolic syndrome was particularly prevalent in the subgroup who had no cirrhosis.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [123]
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
Toprak, Ö., Kurt, H., Sarı, Y., Şarkış, C., Us, H., & Kırık, A. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000468530 · Cited by 29,772
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944
Expert Panel on Detection, E. (2001) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.285.19.2486 · Cited by 26,011
Management of Hepatocellular Carcinoma: An Update Δσ
Bruix, J., & Sherman, M. (2011) · Hepatology · doi:10.1002/hep.24199 · Cited by 8,135
Hematological Problems in Pediatric Intensive Care
Revel‐Vilk, S., Cox, P. N., Robitaille, N., & Blanchette, V. S. (2013) · Pediatric and adolescent medicine · doi:10.1159/000350346 · Cited by 3,526
Sampling Variability of Liver Biopsy in Nonalcoholic Fatty Liver Disease
Ratziu, V., Charlotte, F., Heurtier, A., Gombert, S., Giral, P., Bruckert, E., Grimaldi, A., Capron, F., & Poynard, T. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.03.084 · Cited by 2,106
Rockey, D. C., Caldwell, S. H., Goodman, Z. D., Nelson, R. C., & Smith, A. D. (2008) · Hepatology · doi:10.1002/hep.22742 · Cited by 2,004
Ascha, 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
Epidemiology of Hepatocellular Carcinoma
Mittal, S., & El‐Serag, H. B. (2013) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e3182872f29 · Cited by 1,103
Lin, Z., Xin, Y., Dong, Q., Wang, Q., Jiang, X., Zhan, S.-H., Sun, Y. J., & Xuan, S. (2010) · Hepatology · doi:10.1002/hep.24105 · Cited by 1,071
Flagged first, then by citations
1 of the 34 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 601–644 of 644
Machado, M. V. (2024) · HepatoBiliary Surgery and Nutrition · doi:10.21037/hbsn-24-132
“HCC occurs in the context of liver disease, with around 85% of liver cancers developing in the set of liver cirrhosis (2).”
BackgroundJia, K., Gu, B., Saowakon, P., Kundrot, S., Palchuk, M. B., Warnick, J., Kaplan, I. D., Rinard, M., & Appelbaum, L. (2024) · medRxiv · doi:10.1101/2024.05.28.24307949
“Additionally, these models can identify individuals who are at risk but currently ineligible for screening, such as those with Nonalcoholic fatty liver disease (NAFLD) [35, 36, 13].”
BackgroundSpontaneously ruptured hepatocellular carcinoma on non-cirrhotic liver: A prospective case series
Romero-Gutiérrez, M., Pascual, S., Márquez, L., Rubio, M. G., Miquel, M., Alarcón, C., Ferrer, T., Aracil, C., Horta, D., Latorre, R., et al. (2024) · Gastroenterología y Hepatología (English Edition) · doi:10.1016/j.gastre.2024.04.032
Gavilán, P., Gavilán, J.-C., Arnedo, R., Clavijo, E., Viciana, I., & Correa, J. A. G. (2024) · Medicina Clínica (English Edition) · doi:10.1016/j.medcle.2024.07.018
Zhang, L., Liu, S., Zhao, Q., Liu, X.-Y., Liu, T., Zhang, Q., Liu, M.-H., & Zhao, W. (2025) · World Journal of Hepatology · doi:10.4254/wjh.v17.i2.102328
Alcohol Use Disorder Causes Profound Global Changes in Gene Expression and Splicing in the LiverPreprint
Wahlestedt, C., Blokhin, I. O., Booven, D. V., Argemí, J., Li, M., Rao, J. S., Barbier, E., Heilig, M. A., Cheng, J., Douaihy, A. B., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-6507570/v1
Chen, K., Feng, Q., & Liu, H. (2025) · Discover Oncology · doi:10.1007/s12672-025-02518-y
“In the same year, another study confirmed that NAFLD-HCC was frequently diagnosed at a more advanced tumor stage and could develop without cirrhosis, with patients experiencing significantly shorter survival times compared to those with HCV-related HCC [27].”
Hernáez, R., & Kanwal, F. (2025) · Springer eBooks · doi:10.1007/978-3-031-90225-3_3
Zhou, X., Qian, Y., Li, X., Jiang, C.-J., Feng, H., He, H.-Q., Zeng, H., Hui, Y., & Chen, W.-H. (2025) · Journal of Natural Products · doi:10.1021/acs.jnatprod.5c00279
Hepatocellular Carcinoma Epidemiology
Shaker, M. K., & Abdella, H. M. (2025) · Springer eBooks · doi:10.1007/978-981-96-3894-9_2
Al-Breedy, A. M., Shaker, M. K., & Elsahhar, M. (2025) · Springer eBooks · doi:10.1007/978-981-96-3894-9_10
Global changes in gene expression and splicing in alcoholic liver disease
Blokhin, I. O., Booven, D. V., Argemí, J., Li, M., Rao, J. S., Barbier, E., Heilig, M. A., Cheng, J., Douaihy, A. B., Bataller, R. A., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-52759-2
A contemporary review of care gaps in hepatocellular carcinoma surveillance
Duong, N., Nguyen, V., & Nguyen, M. H. (2025) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2025.2592105
“While there are no concrete recommendations for HCC surveillance in advanced fibrosis with MASLD, there is mounting data with concerns for increased risk of HCC in this patient population [32,33].”
Rates and Factors Associated With Hepatocellular Carcinoma Diagnosis, Stage, Treatment, and Survival
Ioannou, G. N., Yakovchenko, V., Taddei, T. H., Monto, A., Patton, H. M., Merante, M., Spoutz, P. M., Chia, L., Yudkevich, J., Aytaman, A., et al. (2025) · Gastro Hep Advances · doi:10.1016/j.gastha.2025.100859
Hu, C., Wang, T., Zhuang, X., Sun, Q., Wang, X., Lin, H., Feng, M., Zhang, J., Cao, Q., & Jiang, Y. (2021) · Figshare · doi:10.6084/m9.figshare.14431552
Tayyab, G. U. N., Rasool, S., Nasir, B., Rubi, G., Abou-Samra, A.-B., & Butt, A. A. (2020) · Figshare · doi:10.6084/m9.figshare.12096258
Hu, C., Wang, T., Zhuang, X., Sun, Q., Wang, X., Lin, H., Feng, M., Zhang, J., Cao, Q., & Jiang, Y. (2021) · Figshare · doi:10.6084/m9.figshare.14431555
D’Souza, E. A., Rosario, R. R. L., Tomasich, F., Ribeiro, M. A., Ferreira, F. G., Szutan, L. A., Abreu, P., & Gleisner, A. L. (2025) · Springer eBooks · doi:10.1007/978-3-031-79150-5_46
A consensus statement from the European Society for Clinical Investigation
Carbone, F., Després, J., Ioannidis, J. P. A., Neeland, I. J., Garruti, G., Busetto, L., Liberale, L., Ministrini, S., Vilahur, G., Schindler, T. H., et al. (2025) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Bissoondial, T. L., Reddi, R. C., Madugula, S. S., Shukla, M., Narayan, M., & Narayan, P. (2026) · bioRxiv · doi:10.64898/2026.01.06.698028
“Clinical data indicate that 20-30% of MASLD-related HCC cases occur in the absence of cirrhosis 8-12 .”
Saisa, D., Mustika, S., Fachrureza, M., Surya, S. C., Rampengan, D. D. C. H., Lele, J. A. J. M. N., Nojaid, A., & Hogipranata, M. O. (2025) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000003110
Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates
Weinfurtner, K. M., Amin, R., Skuli, N., Gade, T. P. F., & Kaplan, D. E. (2026) · Seminars in Liver Disease · doi:10.1055/a-2779-4984
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
Kim, N. J., Kim, H. N., McMahon, B. J., Kowalski, L., & Ioannou, G. N. (2026) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2026.2651251
“A study of U.S. Veterans with HCC found that compared to patients with HCV, those with MASLD were 5-times more likely to develop HCC in the absence of cirrhosis [54].”
Role of autophagy in liver sinusoidal endothelial cells on nonalcoholic steatohepatitis
Hammoutène, A. (2018) · theses.fr (ABES) · doi:10.70675/bce7a140z3574z43dbza40ez1cd3403ed525
Rôle des cellules endothéliales dans le carcinome hépatocellulaire associé au syndrome métabolique
Laouirem, S. (2019) · theses.fr (ABES) · doi:10.70675/8139d5c7zb3b1z466az837az2b9408b374a8
Diversité des macrophages dans un modèle murin de stéatohépatite non alcoolique
Tran, S. (2019) · theses.fr (ABES) · doi:10.70675/22efc884z2788z43fazabc1zaeb115ea6833
Rôle de l'isoforme A du récepteur de l'insuline dans l'homéostasie et la carcinogenèse hépatiques
Léandre, F. (2024) · theses.fr (ABES) · doi:10.70675/df1bc445z5d98z462dzbc59za0d4015bcf04
Lahtinen, E., Jia, K., Gu, B., Saowakon, P., Kundrot, S., Palchuk, M. B., Warnick, J., Kaplan, I. D., Curry, M. P., Sarwar, A., et al. (2026) · JHEP Reports · doi:10.1016/j.jhepr.2026.101859
Donald Barceloux MD, F., & Robert B. Palmer PhD, D. (2026) · Medical Toxicology · doi:10.1002/9781119872979.ch54
Barbosa, M. G., Vos, D. Y., Verzijl, C. R. C., Heida, A., Bakker, M., Kloosterhuis, N., Koster, M. H., Smit, M., Fajardo, A., Struik, D., et al. (2026) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2026.101788 · Cited by 1
Zhang, Z., Zheng, X., Dong, C., Li, P., Lin, Y., Sun, Z., Li, W., Liu, X., Li, J. J., Li, S., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c03220
Coimbra, F. J. F., de Godoy, A. L., Fernandes, P. H. D. S., Neto, H. F. E. C., Pinheiro, R. N., Boin, I. D. F. S. F., Andraus, W., Tustumi, F., AMARAL, P. C. G., Brandão‐Mello, C. E., et al. (2026) · ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) · doi:10.1590/0102-672020260000018e1947
Álvarez, P., Castaño‐García, A., & Varela-Calvo, M. (2026) · Revista Española de Enfermedades Digestivas · doi:10.17235/reed.2026.12053/2026
Seki, A., Chiba, T., Yagi, S., Horii, R., Takata, N., Nomura, H., Miyazawa, M., Hayashi, T., Terashima, T., Nakanuma, S., et al. (2026) · Hepatology Research · doi:10.1111/hepr.70230
Liang, B., Shi, H., Tie, X., Zeng, Q., & Long, K. (2026) · Medicine · doi:10.1097/md.0000000000049944
Peng, T., Wu, T., Lin, H.-H., Wu, C.-C., Hsu, S.-Y., & Hsu, C. C. (2026) · BMC Gastroenterology · doi:10.1186/s12876-026-05145-1
Selective Internal Radiation Therapy for Hepatocellular Malignancies: Existing Evidence and Advances
Yadav, P., & Shukla, J. (2026) · Indian Journal of Nuclear Medicine · doi:10.25259/ijnm_173_2026
Villani, R., & Serviddio, G. (2026) · Annals of Hepatology · doi:10.1016/j.aohep.2026.102434
Xu, W., Shi, Y., Liu, Z., Ma, H., Niu, J., Xie, Q., 谢建萍, Rao, H., Yang, S. T., Zhong, C., et al. (2026) · Liver International · doi:10.1111/liv.70936
“However, up to 30%–50% of MASLD-related HCC cases occur in the absence of cirrhosis, highlighting the need for effective risk stratification beyond fibrosis stage alone [6, 7].”
Kang, T. W., & Song, B. G. (2026) · Korean Journal of Radiology · doi:10.3348/kjr.2026.0168
BindingDB (2021) · UC San Diego · doi:10.7270/q2dj5jxg
Metadata
- Authors
- Mittal, S., El-Serag, H. B., Sada, Y. H., Kanwal, F., Duan, Z., Temple, S., May, S. B., Kramer, J. R., Richardson, P. A., & Davila, J. A.
- Affiliations
- Michael E. DeBakey VA Medical Center (US)
- Corresponding author
- Mittal, Sahil
- Venue
- Clinical Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 14
- Issue
- 1
- Pages
- 124-131.e1
- ISSN
- 1542-3565 (ISSN-L)
- PMC
- PMC4690789
- OpenAlex
- W1258381707
- Cited by
- 648
- References
- 34
- Citations by year
- 2026: 27 · 2025: 63 · 2024: 61 · 2023: 64 · 2022: 77 · 2021: 99 · 2020: 85 · 2019: 60 · 2018: 47 · 2017: 41 · 2016: 19
- FWCI
- 22.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Gastroenterology and Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA160738)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- hepatocellular carcinoma, non-alcoholic fatty liver disease, liver cirrhosis, metabolic syndrome, risk factors, veterans, hepatitis C virus, alcohol abuse, liver fibrosis markers
- MeSH terms
- Aged, Aged, 80 and over, Female, Carcinoma, Hepatocellular, Humans, Male, Middle Aged, Risk Factors, United States, Veterans, Cohort Studies, Metabolic Syndrome, 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
