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 201–300 of 644
Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration
Patel, Y. A., Gifford, E. J., Glass, L. M., Turner, M. J., Han, B., Moylan, C. A., Choi, S. S., Suzuki, A., Provenzale, D., & Hunt, C. M. (2018) · Digestive Diseases and Sciences · doi:10.1007/s10620-018-5123-3 · Cited by 39
“AUROC Area under the ROC ALT Alanine aminotransferase AST Aspartate aminotransferase APRI AST-to-platelet ratio index BARD score Body mass index, AST/ALT ratio, and diabetes AUDIT-C Alcohol Use Disorders Identification Test Alcohol Consumption Questions BMI Body mass index FIB-4 Fibrosis-4 calculator HCC Hepatocellula…”
BackgroundAgarwal, L., Sahu, A. K., Baksi, A., Agarwal, A., & Aggarwal, S. (2020) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2020.11.004 · Cited by 39
Moreno‐Vedia, J., Girona, J., Ibarretxe, D., Masana, L., & Rodríguez‐Calvo, R. (2022) · Biomedicines · doi:10.3390/biomedicines10010197 · Cited by 40
“NASH can irreversibly progress to end-stage liver disease, leading to liver transplantation [10–13], including cirrhosis and hepatocellular carcinoma [14].”
BackgroundSynergistic and Detrimental Effects of Alcohol Intake on Progression of Liver Steatosis
Ciaula, A. D., Bonfrate, L., Krawczyk, M. J., Frühbeck, G., & Portincasa, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052636 · Cited by 37
“008 per 100 person-years of follow-up [46].”
BackgroundRedman, J. S., Natarajan, Y., Hou, J. K., Wang, J., Hanif, M., Feng, H., Kramer, J. R., Desiderio, R., Xu, H., El‐Serag, H. B., et al. (2017) · Digestive Diseases and Sciences · doi:10.1007/s10620-017-4721-9 · Cited by 38
Non-invasive tests for the prediction of primary hepatocellular carcinoma
Marasco, G., Colecchia, A., Silva, G. F., Rossini, B., Eusebi, L. H., Ravaioli, F., Dajti, E., Alemanni, L. V., Colecchia, L., Renzulli, M., et al. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i24.3326 · Cited by 38
Comprehensive Analysis of NAFLD and the Therapeutic Target Identified
Wen, W., Wu, P., Zhang, Y., Chen, Z., Sun, J. M., & Chen, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.704704 · Cited by 39
Farah, M., Anugwom, C. M., Ferrer, J. D., Baca, E. L., de Mattos, Â. Z., Possebon, J. P. P., Arrese, M. A., Prieto, J. E., Balderramo, D. C., Carrera, E., et al. (2022) · Annals of Hepatology · doi:10.1016/j.aohep.2022.100876 · Cited by 40
Lipid droplets disrupt mechanosensing in human hepatocytes
Chin, L., Theise, N. D., Loneker, A. E., Janmey, P. A., & Wells, R. G. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00098.2020 · Cited by 38
Lin, H., Li, G., Delamarre, A., Ahn, S. H., Zhang, X., Kim, B. K., Liang, L. Y., Lee, H. W., Wong, G. L., Yuen, P. C., et al. (2023) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2023.11.005 · Cited by 37
Hepatocellular carcinoma: Present and future
Armengol, C., Sarrias, M., & Sala, M. (2018) · Medicina Clínica (English Edition) · doi:10.1016/j.medcle.2017.08.024 · Cited by 37
Taniai, M., Hashimoto, E., Tobari, M., Kodama, K., Tokushige, K., Yamamoto, M., Takayama, T., Sugitani, M., Sano, K., Kondo, F., et al. (2018) · Hepatology Research · doi:10.1111/hepr.13203 · Cited by 38
Tu, C., Xiong, H. Y., Hu, Y., Wang, W., Mei, G., Wang, H., Li, Y., Zhou, Z., Meng, F., Zhang, P., et al. (2020) · Hepatology · doi:10.1002/hep.31202 · Cited by 37
“(2) As an expanding health problem, NASH has been projected to become the primary cause of liver transplantation in the next decade because of its potentially fatal pathology, leading to increased risks of cirrhosis, hepatocellular carcinoma, and liver failure.(3) Although extensive clinical and basic research has bee…”
BackgroundLi, W., Deng, R., Liu, S., Wang, K., & Sun, J. (2020) · Liver International · doi:10.1111/liv.14607 · Cited by 37
Sinn, D., Kang, D., Cho, S., Paik, S., Guallar, E., Cho, J., & Gwak, G. (2020) · International Journal of Epidemiology · doi:10.1093/ije/dyaa089 · Cited by 28
Zhang, H., Léveillé, M., Courty, É., Güneş, A., Nguyen, B., & Estall, J. L. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00321.2020 · Cited by 35
Kalyesubula, M., Mopuri, R., Asiku, J., Rosov, A., Yosefi, S., Edery, N., Bocobza, S. E., Moallem, U., & Dvir, H. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.048355 · Cited by 39
“Despite the increasing prevalence of MAFLD, and the accompanying rise in end-stage liver disease requiring liver transplantation (Goldberg et al., 2017; Wong et al., 2015) and in hepatocellular carcinoma (Mittal et al., 2016), there is as yet no approved drug therapy for the disorder.”
NAFLD-Related Hepatocarcinoma: The Malignant Side of Metabolic Syndrome
Michelotti, A., de Scordilli, M., Palmero, L., Guardascione, M., Masala, M., Roncato, R., Foltran, L., Ongaro, E., & Puglisi, F. (2021) · Cells · doi:10.3390/cells10082034 · Cited by 40
“Moreover, NAFLD and metabolic syndrome are also associated with a higher incidence of HCC independently from a cirrhotic evolution [63].”
BackgroundPrecision Medicine for Hepatocellular Carcinoma: Clinical Perspective
Galun, D. A., Mijac, D. D., Filipović, A., Bogdanović, A., Zivanovic, M., & Mašulović, D. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12020149 · Cited by 39
“Interestingly, the absence of cirrhosis is more frequently associated with HCC in NAFLD than other etiologies, suggesting that NAFLD-specific mechanisms of carcinogenesis are not necessarily dependent on hepatic fibrosis [66].”
BackgroundHepatocellular carcinoma in the post-hepatitis C virus era: Should we change the paradigm?
Meringer, H., Shibolet, O., & Deutsch, L. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i29.3929 · Cited by 36
Hepatic Fibrosis and Cancer: The Silent Threats of Metabolic Syndrome
Friedman, S. L. (2024) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2023.0240 · Cited by 37
“Roughly one-third of MASH-HCC cases arise in non-cirrhotic livers, whereas 95% of HCC cases associated with viral hepatitis occur in cirrhotic livers [3,66,67].”
BackgroundCarr, B., Giannelli, G., Guerra, V., Giannini, E., Farinati, F., Rapaccini, G., di Marco, M. D., Zoli, M., Caturelli, E., Masotto, A., et al. (2018) · International Journal of Biological Markers · doi:10.1177/1724600818776838 · Cited by 34
The Mexican consensus on nonalcoholic fatty liver disease
Bernal-Reyes, R., Castro‐Narro, G., Malé-Velázquez, R., Carmona-Sánchez, R., González-Huezo, M. S., García-Juárez, I., Chávez-Tapia, N. C., Aguilar-Salinas, C., Aiza-Haddad, I., Ballesteros-Amozurrutia, M. A., et al. (2019) · Revista de Gastroenterología de México (English Edition) · doi:10.1016/j.rgmxen.2019.02.003 · Cited by 35
“Fasting glucose, mg/dl, median (IQR) 130 (100-181) 94 (87-113) < 0.”
Ciaula, A. D., Calamita, G., Shanmugam, H., Khalil, M., Bonfrate, L., Wang, D. Q. ‐., Baffy, G., & Portincasa, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147702 · Cited by 34
“NAFLD is now the second leading indication for liver transplantation in the US, including a growing number of cases with NASH-related HCC [44].”
BackgroundInfluentialType 2 Diabetes Mellitus and Liver Disease: Across the Gut–Liver Axis from Fibrosis to Cancer
Manilla, V., Santopaolo, F., Gasbarrini, A., & Ponziani, F. R. (2023) · Nutrients · doi:10.3390/nu15112521 · Cited by 37
“However, even risk assessment by grading liver fibrosis could be insufficient; in fact, in the NAFLD population, HCC could be found in absence of advanced fibrosis [31,32] and, in this case, diabetes represents the strongest independent risk factor [25,26].”
BackgroundShim, C. W., Park, J., Kim, S., Kim, J. S., Kim, B. H., Kim, S. H., & Hong, E. K. (2017) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x17710247 · Cited by 34
Hoki, T., Katsuta, E., Yan, L., Takabe, K., & Ito, F. (2018) · Journal of Surgical Research · doi:10.1016/j.jss.2018.11.008 · Cited by 36
Nishina, S., & Hino, K. (2022) · Cancers · doi:10.3390/cancers14020454 · Cited by 34
“4-fold in patients with NAFLD and 5-fold in patients with metabolic syndrome compared to patients with hepatitis C virus infection [75].”
BackgroundKaminsky-Kolesnikov, Y., Rauchbach, E., Abu-Halaka, D., Hahn, M., García-Ruiz, C., Fernandez-Checa, J. C., Madar, Z., & Tirosh, O. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/5393761 · Cited by 39
“Recent studies reported that around 50% of all NAFLD cases may progress to HCC without fibrosis [29, 30].”
BackgroundZhang, Z., Yang, H., Han, F., & Guo, P. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47060464 · Cited by 37
Berkan‐Kawińska, A., & Piekarska, A. (2019) · Current Medical Research and Opinion · doi:10.1080/03007995.2019.1683817 · Cited by 32
Pan, M., Zheng, C., Deng, Y., Tang, K., Nie, H., Xie, J., Liu, D., Tu, G.-F., Yang, Q.-H., & Zhang, Y. (2021) · Journal of Chinese Integrative Medicine · doi:10.1016/j.joim.2021.07.004 · Cited by 32
Hepatocellular carcinoma in the non-cirrhotic liver
Dong, Y., Wang, W.-P., Lee, W. J., Meloni, M. F., Clevert, D.-A., Chammas, M. C., Tannapfel, A., Forgione, A., Piscaglia, F., & Dietrich, C. F. (2021) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-211309 · Cited by 32
“Although cirrhosis is the precursor lesion for most HCCs, an estimated 0.1 % of CHB patients without cirrhosis develop HCC annually [20], presumably through the direct carcinogenic effect of hepatitis B virus (HBV) [21].”
InfluentialBiological Activity of Natural and Synthetic Peptides as Anticancer Agents
Bauso, L. V., Fauci, V. L., Munaò, S., Bonfiglio, D., Armeli, A., Maimone, N., Longo, C., & Calabrese, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137264 · Cited by 33
“HCC is more developed in men than women, probably due to the higher frequency of risk factors such as alcohol abuse and chronic HBV and HCV infections [96].”
BackgroundLiu, T., Wang, P., Cong, M., Zhao, X., Zhang, D., Xu, H., Liu, L., Jia, J., & You, H. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14503 · Cited by 31
Wei, D., Wu, S., Liu, J., Zhang, X., Guan, X., Gao, L., & Xu, Z. (2020) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2020-0259 · Cited by 32
Distinctive features of hepatocellular carcinoma in non-alcoholic fatty liver disease.
Valenti, L., Pedica, F., & Colombo, M. (2021) · Digestive and Liver Disease · doi:10.1016/j.dld.2021.06.023 · Cited by 25
Advances in postoperative adjuvant therapy for primary liver cancer
Zeng, Z., Mo, N., Zeng, J., Ma, F., Jiang, Y., Huang, H.-S., Liao, X., Zhu, G., Ma, J., & Peng, T. (2022) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v14.i9.1604 · Cited by 31
Shi, Y., Taherifard, E., Saeed, A., & Saeed, A. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46060356 · Cited by 33
Jaber, F. S., Cholankeril, G. T., & El‐Serag, H. B. (2024) · Journal of the Canadian Association of Gastroenterology · doi:10.1093/jcag/gwae025 · Cited by 33
Lai, J. C., Yang, B., Lee, H. W., Lin, H., Tsochatzis, E. A., Petta, S., Bugianesi, E., Yoneda, M., Zheng, M., Hagström, H., et al. (2025) · Gut · doi:10.1136/gutjnl-2025-334981 · Cited by 32
Public health strategies for hepatocellular carcinoma: from risk factors to prevention and control
Lee, M.-H. (2025) · Journal of Liver Cancer · doi:10.17998/jlc.2025.07.25 · Cited by 31
“35 Longitudinal cohort studies have confirmed that MASLD significantly elevates the risk of cirrhosis and HCC. 36-38 Notably, MASLD also confers elevated HCC risk among patients with viral hepatitis who have achieved virological suppression, underscoring its growing importance in the post-antiviral…”
Ludwig, D., Fraum, T. J., Cannella, R., Tsai, R., Naeem, M., LeBlanc, M., Salter, A., Tsung, A., Fleckenstein, J., Shetty, A. S., et al. (2019) · HPB · doi:10.1016/j.hpb.2019.04.007 · Cited by 21
HIV RNA, CD4+ Percentage, and Risk of Hepatocellular Carcinoma by Cirrhosis Status
Torgersen, J., Kallan, M. J., Carbonari, D. M., Park, L. S., Mehta, R. L., D’Addeo, K., Tate, J. P., Lim, J. K., Goetz, M. B., Rodriguez‐Barradas, M. C., et al. (2019) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djz214 · Cited by 30
Role of epigenetic alterations in aflatoxin‐induced hepatocellular carcinoma
Mungamuri, S. K., & Mavuduru, V. A. (2020) · Liver Cancer International · doi:10.1002/lci2.20 · Cited by 30
Epidemiology and aetiology of hepatocellular carcinoma in Sub-Saharan Africa
Mak, D., & Kramvis, A. (2021) · Hepatoma Research · doi:10.20517/2394-5079.2021.15 · Cited by 32
Serum Bile Acid Profiles Improve Clinical Prediction of Nonalcoholic Fatty Liver in T2DM patients
Wu, T., Yang, M. S., Xu, H., Wang, L., Wei, H., & Ji, G. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00104 · Cited by 31
Hepatocellular carcinoma surveillance in patients with non-alcoholic fatty liver disease
Dahan, K. S. E., Daher, D., & Singal, A. (2022) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2022.0247 · Cited by 25
Zhang, C., Teng, Y., Bai, X., Tang, M., Stewart, W., Chen, J., Xu, X., & Zhang, X. (2024) · ACS Nano · doi:10.1021/acsnano.4c13404 · Cited by 36
Li, J., Chen, Q., Yi, J., Lan, X., Lu, K., Du, X., Guo, Z., Guo, Y., Geng, M., Li, D., et al. (2021) · Molecular Immunology · doi:10.1016/j.molimm.2021.03.005 · Cited by 30
Kudo, M. (2021) · Cancers · doi:10.3390/cancers13215475 · Cited by 29
Non-alcoholic steatohepatitis and risk of hepatocellular carcinoma
Rios, R. S., Zheng, K. I., & Zheng, M.-H. (2021) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001888 · Cited by 29
“[122-124] Sahil et al[125] reports that, in the absence of cirrhosis, NAFLD and metabolic syndrome are the most common causes of HCC, when compared with viral hepatitis and other causes.”
BackgroundWang, J., Zhu, W., Huang, S., Xu, L., Miao, M., Wu, C., Yu, C., Li, Y., & Xu, C. (2017) · Liver International · doi:10.1111/liv.13363 · Cited by 30
NAFLD and NAFLD Related HCC: Emerging Treatments and Clinical Trials
Khare, T., Liu, K., Chilambe, L. O., & Khare, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26010306 · Cited by 28
Comparisons between non-alcoholic steatohepatitis and alcohol-related hepatocellular carcinoma
Kumar, R., Goh, G. B., Kam, J. W., Chang, J. P.-E., & Tan, C. (2020) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2019.0012 · Cited by 28
“1% of ALD-related HCC as not having cirrhosis at diagnosis.(43) This is consistent with the results of our study.”
ResultGuan, M.-C., Ouyang, W., Liu, S.-Y., Sun, L.-Y., Chen, W.-Y., Tong, X.-M., Zhu, H., & Yang, T. (2022) · Hepatobiliary & Pancreatic Diseases International · doi:10.1016/j.hbpd.2022.05.003 · Cited by 23
Antwi, S. O., Craver, E. C., Nartey, Y. A., Sartorius, K., & Patel, T. C. (2022) · Cancers · doi:10.3390/cancers14246234 · Cited by 30
“, viral hepatitis and alcohol abuse), and this may be explained by a complex interaction between nutrition, lifestyle, genetics, and epigenetic mechanisms [8,53,55,56].”
BackgroundAdvances in Extracellular Matrix-Associated Diagnostics and Therapeutics
Karsdal, M. A., Cox, T. R., Parker, A. L., Willumsen, N., Sand, J. M. B., Jenkins, G. R., Hansen, H. H., Oldenburger, A., Geillinger‐Kästle, K. E., Larsen, A. T., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14061856 · Cited by 29
“Interestingly, unlike cancers associated with viral hepatitis, at least one-third of patients with MASH-associated HCCs had not developed cirrhosis by the time of their HCC diagnosis [97].”
Pinyopornpanish, K., Al-Yaman, W. A., Dasarathy, S., Romero‐Marrero, C., & McCullough, A. J. (2021) · Digestive Diseases and Sciences · doi:10.1007/s10620-021-07048-5 · Cited by 27
“Prior studies included small number of participants and reported fibrosis distribution on a single liver disease etiology [17, 18], while other large studies did not report on the fibrosis distribution [12, 13].”
BackgroundResultInfluentialCancer Etiology and Prevention Principle: “1 + X”
Liu, H., & Dong, Z. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1862 · Cited by 29
“In a cohort study, NAFLD increased the risk of thyroid cancer andHCC inmenwith higher levels of alanine aminotransferase, colorectal and lung cancer in smokers, and kidney cancer in men without diabetes (102).”
BackgroundInfluentialGiannakoulis, V. G., Dubovan, P., Papoutsi, E., Kataki, A., & Koskinas, J. S. (2021) · Cancers · doi:10.3390/cancers13184732 · Cited by 27
“This abnormal liver state actually represents the hepatic manifestation of insulin resistance and is strongly associated with obesity [72], while current evidence suggests that it constitutes an independent risk factor for HCC, even in the absence of cirrhosis [73].”
BackgroundDumitru, A., Matei, E., Cozaru, G. C., Chisoi, A., Alexandrescu, L., Popescu, R. C., Pundiche, M. B., Dumitru, E., Rugină, S., & Tocia, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052472 · Cited by 26
Romeo, M., Silvestrin, A., Senese, G., Nardo, F. D., Napolitano, C., Vaia, P., Coppola, A., Federico, P., Dallio, M., & Federico, A. (2025) · Biomedicines · doi:10.3390/biomedicines13082004 · Cited by 29
“This phenomenon strongly suggests the existence of distinct carcinogenic mechanisms, possibly independent of the classical fibrotic pathway, warranting a deeper exploration of alternative pathogenic routes [3].”
Safety and Efficacy of Bariatric Surgery in Cirrhosis Patients With Extreme Obesity
Vuppalanchi, R., McCabe, M. E., Tandra, S., Parcha, S. P., Ghafoor, A., Schuh, L., Inman, M. M., Selzer, D. J., Stefanidis, D., & Chalasani, N. (2020) · Annals of Surgery · doi:10.1097/sla.0000000000003891 · Cited by 26
Grattagliano, I., Ciaula, A. D., Baj, J., Molina‐Molina, E., Shanmugam, H., Garruti, G., Wang, D. Q. ‐., & Portincasa, P. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1433-4_12 · Cited by 28
Chapin, W. J., Hwang, W., Karasic, T. B., McCarthy, A. M., & Kaplan, D. E. (2022) · Cancer Medicine · doi:10.1002/cam4.4906 · Cited by 25
Yang, C., Yang, L., Yang, Y., Wan, M., Xu, D., Pan, D., & Sun, G. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114864 · Cited by 26
Phan, J., Ng, V., Sheinbaum, A. J., French, S., Choi, G., El-Kabany, M. M., Durazo, F. A., Saab, S., Tong, M. J., Busuttil, R. W., et al. (2018) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000001062 · Cited by 25
Yuan, X., Zhu, H., Pan, H., Chen, S., Liu, Z., Li, Y., Wang, L., Lü, L., Yang, H., & Gong, F. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i14.1741 · Cited by 25
Zhuge, B., & Li, G. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.10.149 · Cited by 25
Orabi, D., Berger, N. A., & Brown, J. M. (2021) · Cancers · doi:10.3390/cancers13143473 · Cited by 25
“related HCC often develops in the absence of cirrhosis [4,23,71,72], though this is unclear and may vary by population [20,70,73].”
BackgroundYilma, M., Saxena, V., & Mehta, N. J. (2022) · Current Gastroenterology Reports · doi:10.1007/s11894-022-00835-8 · Cited by 24
MAFLD in adults: non-invasive tests for diagnosis and monitoring of MAFLD
Chan, W., Wong, V. W., Adams, L. A., & Nguyen, M. H. (2024) · Hepatology International · doi:10.1007/s12072-024-10661-x · Cited by 24
“One distinct difference is that HCC in those with MAFLD can develop without the presence of cirrhosis [69].”
Changing Epidemiology of HCC: How to Screen and Identify Patients at Risk?
Lange, N. F., & Dufour, J. (2019) · Digestive Diseases and Sciences · doi:10.1007/s10620-019-05515-8 · Cited by 20
Non-alcoholic fatty liver disease (NAFLD) in non-obese individuals
Phipps, M. M., & Wattacheril, J. J. (2019) · Frontline Gastroenterology · doi:10.1136/flgastro-2018-101119 · Cited by 24
NAFLD-Related HCC: Focus on the Latest Relevant Preclinical Models
Fang, J., Celton‐Morizur, S., & Desdouets, C. (2023) · Cancers · doi:10.3390/cancers15143723 · Cited by 25
Nevola, R., Rinaldi, L., Giordano, M., Marrone, A., & Adinolfi, L. (2018) · Hepatoma Research · doi:10.20517/2394-5079.2018.38 · Cited by 25
“The IR, the cornerstone of the metabolic syndrome, is able to induce the onset of HCC by increasing the release of free fatty acids from the adipose tissue and subsequent accumulation in the hepatocytes on one hand and inducing the formation of ROS and subsequent oxidative stress with mitochondrial damage and endoplas…”
BackgroundResultInfluentialSmad3 Phospho-Isoform Signaling in Nonalcoholic Steatohepatitis
Yamaguchi, T., Yoshida, K., Murata, M., Suwa, K., Tsuneyama, K., Matsuzaki, K., & Naganuma, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116270 · Cited by 25
“of hepatic fibrosis [40,41], with 20% to 50% of NAFLD-related HCC occurring in patients”
BackgroundPathogenesis from Inflammation to Cancer in NASH-Derived HCC
Yu, S., Wang, J., Zheng, H., Wang, R., Johnson, N. L., Li, T., Li, P., Lin, J., Li, Y., Jin, Y., et al. (2022) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s377768 · Cited by 24
“6% of NASH-derived HCC patients did not have cirrhosis.(8) The prevalence of NASH has shown”
BackgroundRisk of nonalcoholic fatty liver disease and associations with gastrointestinal cancers
Mchenry, S. A., Zong, X., Shi, M., Fritz, C. D. L., Pedersen, K. S., Peterson, L. R., Lee, J. K., Fields, R. C., Davidson, N. O., & Cao, Y. (2022) · Hepatology Communications · doi:10.1002/hep4.2073 · Cited by 24
“[21] This differs from results from another VA cohort study of 1500 patients with HCC, in which NAFLD was the leading cause of HCC among patients without cirrhosis.[22] A recent meta- analysis showed that NAFLDrelated HCC was associated with a higher proportion of patients without cirrhosis (38.”
ResultChaudhary, S. P., Reyes, S., Chase, M. L., Govindan, A., Zhao, L., Luther, J., Bhan, I., Bethea, E., Franses, J., Walsh, E. P., et al. (2023) · The Oncologist · doi:10.1093/oncolo/oyac251 · Cited by 24
De Novo and Recurrence of Nonalcoholic Steatohepatitis After Liver Transplantation
Kappus, M. R., & Abdelmalek, M. F. (2017) · Clinics in Liver Disease · doi:10.1016/j.cld.2016.12.006 · Cited by 23
Hígado graso no alcohólico: una pandemia poco conocida
Augustín, S., Graupera, I., & Caballería, J. (2017) · Medicina Clínica · doi:10.1016/j.medcli.2017.06.026 · Cited by 23
Magnitude of Nonalcoholic Fatty Liver Disease: Eastern Perspective
Yu, B. C.-Y., Kwok, D., & Wong, V. W. (2019) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2019.01.007 · Cited by 24
“Although this may be partly due to misclassification with NASH-related cirrhosis counted as cryptogenic cirrhosis, subsequent studies confirmed that noncirrhotic HCC appeared to be more common in patients with NASH or idiopathic HCC than those with other liver diseases.(44) This means that the current recommendations…”
ResultHepatocellular carcinoma in the noncirrhotic liver: a literature review
Zhang, Y., Wang, C., Xu, H., Xiao, P., & Gao, Y. (2019) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000001419 · Cited by 23
Torres, M. C. P., Lai, Q., Piscaglia, F., Caturelli, E., Cabibbo, G., Biasini, E., Pelizzaro, F., Marra, F., Trevisani, F., & Giannini, E. G. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10153201 · Cited by 23
Hepatitis C virus genotype affects survival in patients with hepatocellular carcinoma
Park, H. K., Lee, S. S., Im, C. B., Im, C., Cha, R. R., Kim, W. S., Cho, H. C., Lee, J. M., Kim, H., Kim, T. H., et al. (2019) · BMC Cancer · doi:10.1186/s12885-019-6040-3 · Cited by 23
WNT–β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials
Lehrich, B. M., & Monga, S. P. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01127-y · Cited by 27
Known, new and emerging risk factors of hepatocellular carcinoma (review)
Trad, D., Bibani, N., Sabbah, M., Elloumi, H., Gargouri, D., Ouakaa, A., & Kharrat, J. (2017) · La Presse Médicale · doi:10.1016/j.lpm.2017.09.025 · Cited by 22
Banini, B. A., & Sanyal, A. J. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2020.11.001 · Cited by 21
NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF NON-ALCOHOLIC FATTY LIVER DISEASE.
Boursier, J., Guillaume, M., Bouzbib, C., Lannes, A., Pais, R., Smatti, S., Cariou, B., Bureau, C., Ganne-Carrié, N., Bourlière, M., et al. (2021) · Clinics And Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2021.101769 · Cited by 21
Fang, J., Sun, X., Xue, B., Fang, N., & Zhou, M. (2017) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2017/2945803 · Cited by 21
“At present, NAFLD has become the main cause for hepatocellular carcinoma in the United States [22, 23].”
BackgroundIdentifying High-Risk NASH Patients: What We Know so Far
Schulz, M., & Tacke, F. (2020) · Hepatic Medicine Evidence and Research · doi:10.2147/hmer.s265473 · Cited by 21
Epidemiology, mutational landscape and staging of hepatocellular carcinoma.
Fenton, S. E., Burns, M. C., & Kalyan, A. (2021) · Chinese Clinical Oncology · doi:10.21037/cco-20-162 · Cited by 18
“However, in the United States, NAFLD is the most frequent cause of HCC in the absence of cirrhosis or liver fibrosis (91).”
BackgroundRojas, Á., García-Lozano, M. D. R., Gil‐Gómez, A., Romero‐Gómez, M., & Ampuero, J. (2022) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2021.00247 · Cited by 21
Should we undertake surveillance for HCC in patients with MAFLD?
Norero, B., & Dufour, J. (2023) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188231160389 · Cited by 20
Overview of hepatocellular carcinoma: from molecular aspects to future therapeutic options
Panneerselvam, S., Wilson, C. M., Kumar, P., Abirami, D., Pamarthi, J., Reddy, M. S., & Varghese, J. (2023) · Cell Adhesion & Migration · doi:10.1080/19336918.2023.2258539 · Cited by 21
“There was 5.4-fold increased risk of HCC in the non-cirrhotic liver for NAFLD-related HCC and 5-fold for metabolic syndrome (MetS) related HCC [100].”
BackgroundInfluentialDiethylnitrosamine Induction of Hepatocarcinogenesis in Mice
Sotty, J., Bablon, P., Weiss, P.-H., & Soussan, P. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3694-7_2 · Cited by 21
D'Avola, D., Labgaa, I., & Villanueva, A. (2016) · Clinical Liver Disease · doi:10.1002/cld.579 · Cited by 21
The molecular basis for current targets of NASH therapies
Qureshi, K., & Neuschwander‐Tetri, B. A. (2019) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1703949 · Cited by 23
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
