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
Cited by
Sorted by citations
Items 101–200 of 644
Endocrine Disruptors and Developmental Origins of Nonalcoholic Fatty Liver Disease
Treviño, L. S., & Katz, T. A. (2017) · Endocrinology · doi:10.1210/en.2017-00887 · Cited by 88
“The last stage in NAFLD progression is hepatocellular carcinoma (HCC), and in the absence of cirrhosis, the main risk factors for HCC are NAFLD and metabolic syndrome (6).”
BackgroundCai, Z., Chen, G., Zeng, Y., Dong, X., Lin, M., HUANG, X.-H., Zhang, D., Liu, X., & Liu, J. (2017) · International Journal of Cancer · doi:10.1002/ijc.30798 · Cited by 84
“Unlike most other solid tumors, majority of HCC cases were developed with a history of cirrhosis due to chronic HBV or HCV infections.(2,3) Surgical resection was demonstrated to be the first choice for HCC treatment according to the clinical experiences of the past 50 years.”
BackgroundLiver Inflammation and Hepatobiliary Cancers
Leone, V., Ali, A., Weber, A., Tschaharganeh, D. F., & Heikenwälder, M. F. (2021) · Trends in cancer · doi:10.1016/j.trecan.2021.01.012 · Cited by 88
Esfeh, J. M., Hajifathalian, K., & Ansari‐Gilani, K. (2019) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2019.0039 · Cited by 82
Epidemic of non-alcoholic fatty liver disease and hepatocellular carcinoma
Said, A., & Ghufran, A. (2017) · World Journal of Clinical Oncology · doi:10.5306/wjco.v8.i6.429 · Cited by 81
Chrysavgis, L., Giannakodimos, I., Diamantopoulou, P., & Cholongitas, Ε. (2022) · World Journal of Gastroenterology · doi:10.3748/wjg.v28.i3.310 · Cited by 84
Pοlyzos, S. A., Chrysavgis, L., Vachliotis, I. D., Chartampilas, E., & Cholongitas, Ε. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.04.010 · Cited by 84
Fatty Liver Disease: Diagnosis and Stratification
Saiman, Y., Duarte‐Rojo, A., & Rinella, M. E. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-042220-020407 · Cited by 78
Cancer-Associated Thrombosis in Cirrhotic Patients with Hepatocellular Carcinoma
Zanetto, A., Campello, E., Spiezia, L., Burra, P., Simioni, P., & Russo, F. P. (2018) · Cancers · doi:10.3390/cancers10110450 · Cited by 77
“Additionally, among new HCC cases without advanced fibrosis or cirrhosis in the United States, non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome accounted for the majority of cases [11].”
BackgroundCardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease
Hadi, H. E., Vincenzo, A. D., Vettor, R., & Rossato, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092215 · Cited by 97
“The risk of neoplastic degeneration in NAFLD patients is different according to the different population study [9].”
BackgroundHepatocellular carcinoma and non-alcoholic fatty liver disease
Golabi, P., Rhea, L. P., Henry, L. L., & Younossi, Z. M. (2019) · Hepatology International · doi:10.1007/s12072-019-09995-8 · Cited by 73
The hepatic lipidome: From basic science to clinical translation
ten Hove, M., Pater, L. V., Storm, G., Weiskirchen, S., Weiskirchen, R., Lammers, T., & Bansal, R. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.027 · Cited by 73
The Role of Innate Immune Cells in Nonalcoholic Fatty Liver Disease
Nati, M., Chung, K., & Chavakis, T. (2021) · Journal of Innate Immunity · doi:10.1159/000518407 · Cited by 73
Pinyopornpanish, K., Khoudari, G., Saleh, M. A., Angkurawaranon, C., Pinyopornpanish, K., Mansoor, E., Dasarathy, S., & McCullough, A. J. (2021) · BMC Gastroenterology · doi:10.1186/s12876-021-01978-0 · Cited by 75
Autophagy as a molecular target of quercetin underlying its protective effects in human diseases
Ashrafizadeh, M., Ahmadi, Z., Farkhondeh, T., & Samarghandian, S. (2019) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2019.1671458 · Cited by 71
“Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder responsible for affecting a high population worldwide (Tiniakos et al. 2010, Mittal et al. 2016, Engin 2017, Younossi 2018).”
BackgroundExosomal microRNAs as Biomarkers and Therapeutic Targets for Hepatocellular Carcinoma
Sorop, A., Constantinescu, D., Cojocaru, F., Dinischiotu, A., Cucu, D., & Dima, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094997 · Cited by 68
Crudele, L., Matteis, C. D., Piccinin, E., Gadaleta, R. M., Cariello, M., Buduo, E. D., Piazzolla, G., Suppressa, P., Berardi, E., Sabbà, C., et al. (2022) · JHEP Reports · doi:10.1016/j.jhepr.2022.100627 · Cited by 72
“However, several studies have demonstrated that liver cancer can also arise in individuals with NAFLD/NASH without cirrhosis.(6,7) Therefore, since metabolic alterations are now recognized as an important hallmark of cancer, healthy lifestyle habits may not only improve MetS and NAFLD conditions, but also have an impa…”
Trends in hepatocellular carcinoma due to non-alcoholic fatty liver disease
Bertot, L. C., & Adams, L. A. (2018) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2019.1549989 · Cited by 68
“A higher prevalence of metabolic features (type 2 diabetes, obesity, hypertension, coronary artery disease, and dyslipidemia) is seen among non-cirrhotic NAFLD patients with HCC compared to non-cirrhotic HCC patients of other etiologies [63], whereas no significant differences regarding metabolic conditions are noted…”
BackgroundBurden of Disease due to Nonalcoholic Fatty Liver Disease.
Muthiah, M., & Sanyal, A. (2020) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2019.09.007 · Cited by 57
Reddy, K. R., McLerran, D., Marsh, T. L., Parikh, N. D., Roberts, L. R., Schwartz, M., Nguyen, M. H., Befeler, A. S., Page-Lester, S., Tang, R., et al. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.06.027 · Cited by 71
Neutrophil Extracellular Traps and Liver Disease
Hilscher, M. B., & Shah, V. H. (2019) · Seminars in Liver Disease · doi:10.1055/s-0039-3399562 · Cited by 66
Geh, D., Manas, D., & Reeves, H. L. (2021) · HepatoBiliary Surgery and Nutrition · doi:10.21037/hbsn.2019.08.08 · Cited by 66
“Although HCC can develop in other etiologies of chronic liver disease in the absence of cirrhosis, NAFLD has a higher risk of non-cirrhotic HCC when compared to HCV and ALD (23).”
ResultTobari, M., & Hashimoto, E. (2019) · Gut and Liver · doi:10.5009/gnl19236 · Cited by 63
“Experimental studies have shown that estrogen decreases the generation of reactive oxygen species, down-regulates the expression of transforming growth factor beta-1, and inhibits activation and fibrogenesis by stellate cells.86,87 Accordingly, women are protected from the development and progression of NAFLD/NASH by…”
BackgroundInfluentialSchumacher, J. D., & Guo, G. L. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_228 · Cited by 64
Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma
Zenlander, R., Havervall, S., Magnusson, M., Engstrand, J., Ågren, A., Thålin, C., & Stal, P. I. (2021) · Scientific Reports · doi:10.1038/s41598-021-97233-3 · Cited by 65
Hu, L., Gu, Y., Liang, J., Ning, M., Yang, J., Zhang, Y., Qu, H. Y., Yang, Y., Leng, Y., & Zhou, B. N. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01669 · Cited by 63
Chan, T. T., Chan, W., Wong, G. L., Chan, A. W. H., Mustapha, N. R. N., Chan, S. L., Chong, C. C. N., Mahadeva, S., Shu, S. S., Lai, P. B. S., et al. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000588 · Cited by 62
Gutiérrez‐Cuevas, J., Lucano‐Landeros, S., López-Cifuentes, D., Santos, A., & Armendáriz‐Borunda, J. (2022) · Cancers · doi:10.3390/cancers15010023 · Cited by 64
The Potential Mechanisms of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease
Zhu, X., Bian, H., & Gao, X. (2016) · Molecules · doi:10.3390/molecules21101336 · Cited by 63
“Recent studies showed that NAFLD is becoming a major cause of hepatocellular carcinoma (HCC) in the United States [5], and some of HCC cases can occur in the absence of cirrhosis [6,7].”
BackgroundRemodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC
Longo, M., Paolini, E., Meroni, M., & Dongiovanni, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084173 · Cited by 61
“that NASH patients with advanced fibrosis (F3–F4) were seven times more likely to develop HCC and, in a small proportion, HCC arises in NAFLD individuals without fibrosis [3,4].”
BackgroundNAFLD-Associated HCC: Progress and Opportunities
Geh, D., Anstee, Q. M., & Reeves, H. L. (2021) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s272213 · Cited by 64
“18 24 Published series indicate that patients with NAFLD-HCC generally have a worse prognosis compared to HCC of other etiologies.”
Changing Epidemiology of Hepatocellular Carcinoma Within the United States and Worldwide
Rich, N. E. (2023) · Surgical Oncology Clinics of North America · doi:10.1016/j.soc.2023.06.004 · Cited by 60
Shahini, E., Pasculli, G., Solimando, A. G., Tiribelli, C., Cozzolongo, R., & Giannelli, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054286 · Cited by 59
“Furthermore, surveillance allows for earlier detection of HCC and more frequent curative treatments, as revealed by a retrospective analysis of 887 cases of HCC diagnosed between 2005 and 2010 in the United States National Veterans Administration [194].”
BackgroundMoore, J. B. (2019) · Proceedings of The Nutrition Society · doi:10.1017/s0029665119000570 · Cited by 60
Jiang, C., Cheng, G., Liao, M., & Huang, J. (2021) · World Journal of Surgical Oncology · doi:10.1186/s12957-021-02188-4 · Cited by 59
Zhang, Y., Wang, H., & Xiao, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22095016 · Cited by 57
“It should be noted that NASH-related HCC can develop in the absence of cirrhosis or fibrosis [4].”
BackgroundOgresta, D., Mrzljak, A., Berković, M. C., Bilić-Čurčić, I., Stojsavljević, S., & Virović-Jukić, L. (2022) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2021.00268 · Cited by 58
A Molecular Insight into the Role of Antioxidants in Nonalcoholic Fatty Liver Diseases
Ezhilarasan, D., & Thangavelu, L. P. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/9233650 · Cited by 63
“%) in individuals with type 2 diabetes, obesity, and older age [13, 14].”
Zhang, C., Teng, Y., Li, F., Ho, W., Bai, X., Xu, X., & Zhang, X. (2023) · ACS Nano · doi:10.1021/acsnano.3c03217 · Cited by 63
Hester, C. A., Rich, N. E., Singal, A. G., & Yopp, A. C. (2019) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2018.7105 · Cited by 58
Lipid droplets are intracellular mechanical stressors that impair hepatocyte function
Loneker, A. E., Alisafaei, F., Kant, A., Li, D., Janmey, P. A., Shenoy, V. B., & Wells, R. G. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2216811120 · Cited by 54
Grgurević, I., Božin, T., Mikuš, M., Kukla, M., & O’Beirne, J. P. (2021) · Cancers · doi:10.3390/cancers13225844 · Cited by 58
“Similarly, a multicentric study from the USA demonstrated a fivefold higher incidence of HCC amongst non-cirrhotic NAFLD patients as compared with patients with non-cirrhotic chronic hepatitis C [29].”
BackgroundOsteopontin is a proximal effector of leptin-mediated non-alcoholic steatohepatitis (NASH) fibrosis
Coombes, J. D., Choi, S. S., Swiderska‐Syn, M., Manka, P. P., Reid, D. T., Palma, E., Briones-Orta, M. A., Xie, G., Younis, R. L., Kitamura, N., et al. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.10.028 · Cited by 59
Lefebvre, E. A., Gottwald, M. D., Lasseter, K. C., Chang, W., Willett, M. S., Smith, P. F., Somasunderam, A., & Utay, N. S. (2016) · Clinical and Translational Science · doi:10.1111/cts.12397 · Cited by 57
Tobari, M., Hashimoto, E., Taniai, M., Kodama, K., Kogiso, T., Tokushige, K., Yamamoto, M., Nishino, T., Katagiri, S., & Tatsuo, A. (2020) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.14867 · Cited by 51
Wang, Y., & Liu, Y. (2021) · Inflammation · doi:10.1007/s10753-021-01442-x · Cited by 66
Augmenter of liver regeneration: Mitochondrial function and steatohepatitis
Verma, A. K., Sharma, A., Nithyananthan, S., & Gandhi, C. R. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.06.019 · Cited by 56
Hepatocellular Carcinoma: Prevention, Diagnosis, and Treatment
Feng, F., & Zhao, Y. (2024) · Medical Principles and Practice · doi:10.1159/000539349 · Cited by 62
Management of metabolic-associated fatty liver disease: The diabetology perspective
Jeeyavudeen, M. S., Khan, S. K., Fouda, S., & Pappachan, J. M. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i1.126 · Cited by 54
Pennisi, G., Celsa, C., Giammanco, A., Spatola, F., & Petta, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225613 · Cited by 52
“The development of HCC in patients with NAFLD without cirrhosis suggests a NAFLD-specific mechanism of carcinogenesis that is probably independent of hepatic fibrosis [68].”
BackgroundPrepaid versus traditional Medicaid plans: lack of effect on pregnancy outcomes and prenatal care.
The University of North Carolina at Chapel Hill University Libraries (2020) · Europe PMC (PubMed Central) · doi:10.17615/9ymf-xe92 · Cited by 55
Yang, M., Wang, J., Xiao, W., & Fan, X. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1410668 · Cited by 61
Tayob, N., Christie, I. C., Richardson, P., Feng, Z., White, D. L., Davila, J. A., Corley, D. A., Kanwal, F., & El‐Serag, H. B. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.12.005 · Cited by 53
Li, H., Xi, Y., Xin, X., Tian, H., & Hu, Y. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.109915 · Cited by 53
Torres, M. C. P., Bodini, G., Furnari, M., Marabotto, E., Zentilin, P., Strazzabosco, M., & Giannini, E. G. (2020) · Cancers · doi:10.3390/cancers12061422 · Cited by 54
“More recently, a study performed among 354 Mayo Clinic patients with NAFLD-cirrhosis, showed that diabetes (HR: 4.2, 95% CI 1.2–14.2, p = 0.02), age and low albumin significantly predicted the development of HCC, whereas other metabolic risk factors, such as increased Body Mass Index (BMI), hyperlipidemia and hyperten…”
BackgroundResultInfluentialEpidemiology of Hepatocellular Carcinoma
El‐Serag, H. B. (2020) · Wiley eBooks · doi:10.1002/9781119436812.ch59 · Cited by 53
Cachexia is Prevalent in Patients With Hepatocellular Carcinoma and Associated With Worse Prognosis
Rich, N. E., Phen, S., Desai, N., Mittal, S., Yopp, A. C., Yang, J. D., Marrero, J. A., Iyengar, P., Infante, R. E., & Singal, A. G. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.09.022 · Cited by 52
Jian-yong, M., Wang, B., Shao, H., Zhang, S., Chen, X., Li, F., & Liang, W. (2022) · Drug Delivery · doi:10.1080/10717544.2022.2070299 · Cited by 52
“HCC has also been reported in patients who did not have any signs of cirrhosis and had no histological evidence of hepatitis (Mittal et al., 2016; Pennisi et al., 2019).”
NASH: The Emerging Most Common Form of Chronic Liver Disease.
Tesfay, M., Goldkamp, W., & Neuschwander‐Tetri, B. A. (2018) · Europe PMC (PubMed Central) · Cited by 53
Radiologic Imaging in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.
Esterson, Y. B., & Grimaldi, G. (2018) · Clinical Liver Disease · doi:10.1016/j.cld.2017.08.005 · Cited by 43
Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014
Saracco, G. M., Evangelista, A., Fagoonee, S., Ciccone, G., Bugianesi, E., Caviglia, G. P., Abate, M. L., Rizzetto, M., Pellicano, R., & Smedile, A. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i36.8187 · Cited by 50
Goldberg, D. S., Ross‐Driscoll, K., & Lynch, R. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.11.016 · Cited by 50
Mindikoglu, A. L., Opekun, A. R., Gagan, S. K., & Devaraj, S. (2017) · Gastroenterology Research and Practice · doi:10.1155/2017/3932491 · Cited by 49
“These mechanisms are modulated, and like NAFLD, a multifactorial premalignant condition [6] appears to be under the influence of multiple circadian processes [41, 42].”
BackgroundJeong, S., Kim, K., Chang, J., Choi, S., Kim, S. M., Son, J., Lee, G., Kim, W., & Park, S. M. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-2951 · Cited by 46
“Compared to other etiologic factors of HCC, NAFLDassociated HCC occasionally occurs without cirrhotic liver when routine screening for HCC is yet conducted, thus presenting with more advanced stage and less amenable to curative approaches (5,6).”
BackgroundOverdiagnosis of hepatocellular carcinoma: Prevented by guidelines?
Rich, N. E., & Singal, A. G. (2021) · Hepatology · doi:10.1002/hep.32284 · Cited by 48
“For HCC, there can be competing risks of mortality from liver- related and non- liver- related causes given that 80%– 90% of HCC occur in the setting of cirrhosis.[96,97] Liver function is an important determinant of eligibility for HCC- directed therapy and cirrhosisrelated mortality and is therefore reflected in the…”
BackgroundBerberine prevents NAFLD and HCC by modulating metabolic disorders
Lin, X., Zhang, J., Chu, Y., Nie, Q., & Zhang, J. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108593 · Cited by 56
Ding, J., Liu, H., Zhang, X., Zhao, N., Peng, Y., Shi, J., Chen, J., Chi, X., Li, L., Zhang, M., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adh9940 · Cited by 55
Metabolic‐associated fatty liver disease (MAFLD) in coeliac disease
Rispo, A., Imperatore, N., Guarino, M., Tortora, R., Alisi, A., Cossiga, V., Testa, A., Ricciolino, S., Fiorentino, A., & Morisco, F. (2020) · Liver International · doi:10.1111/liv.14767 · Cited by 49
Petrelli, F., Manara, M., Colombo, S., Santi, G. D., Ghidini, M., Mariani, M., Iaculli, A., Rausa, E., Rampulla, V., Arru, M., et al. (2022) · Neoplasia · doi:10.1016/j.neo.2022.100809 · Cited by 49
Stroffolini, T., & Stroffolini, G. (2023) · Cancers · doi:10.3390/cancers15082388 · Cited by 50
“Conversely, NAFLD is generally defined as having fatty liver disease in the absence of known causes such as alcohol, HBV or HCV; it is now the leading cause of HCC occurring in the absence of significant fibrosis [70].”
BackgroundEmerging Roles of Liver Sinusoidal Endothelial Cells in Nonalcoholic Steatohepatitis
Furuta, K., Guo, Q., Hirsova, P., & Ibrahim, S. H. (2020) · Biology · doi:10.3390/biology9110395 · Cited by 49
Hu, C., Wang, T., Zhuang, X., Sun, Q., Wang, X., Lin, H., Feng, M., Zhang, J., Cao, Q., & Jiang, Y. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-02820-7 · Cited by 50
Ahmed, E., El-Derany, M. O., Anwar, A. M., Saied, E. M., & Magdeldin, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010210 · Cited by 47
“In two large studies in the Veterans Health Administration, 20% to 36% of non-cirrhotic NASH patients were diagnosed with HCC [5,6].”
BackgroundYang, T., Hu, L.-Y., Li, Z., Liu, K., Wu, H., Xing, H., Lau, W.-Y., Pawlik, T., Zeng, Y.-Y., Zhou, Y., et al. (2019) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-018-04071-2 · Cited by 43
Fouad, Y. M., Esmat, G., Elwakil, R., Zakaria, S., Yosry, A., Waked, I. A., El-Razky, M., Doss, W. H., El‐Serafy, M., Mostafa, E., et al. (2022) · Saudi Journal of Gastroenterology · doi:10.4103/sjg.sjg_357_21 · Cited by 49
“Recommendations • Patients cured of HCV or having profound HBV virological suppression with MAFLD need monitoring because of the increased risk for progression to cirrhosis, development of HCC, as well as extrahepatic‑related complications.”
BackgroundInfluentialXu, Z., Hu, W., Wang, B., Xu, T., Wang, J., & Wei, D. (2022) · Yonsei Medical Journal · doi:10.3349/ymj.2022.63.7.619 · Cited by 47
“This increasing prevalence of NAFLD will be accompanied by an increasing number of patients with liver fibrosis, cirrhosis and hepatocellular carcinoma.(2,3) Although the global health and economic burden of NAFLD is inCanagliflozin Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism and Inhibi…”
BackgroundSamy, A. M., Kandeil, M. A., Sabry, D., Abdel-Ghany, A. A., & Mahmoud, M. O. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e30387 · Cited by 55
“%) of tumors arise before cirrhosis in people with NASH [109].”
BackgroundType 2 Diabetes and Hepatocellular Carcinoma: Risk Factors and Pathogenesis
Wainwright, P., Scorletti, E., & Byrne, C. D. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0851-x · Cited by 41
Pal, P., Palui, R., & Ray, S. (2021) · World Journal of Hepatology · doi:10.4254/wjh.v13.i11.1584 · Cited by 51
NAFLD and Increased Aortic Stiffness: Parallel or Common Physiopathological Mechanisms?
Villela‐Nogueira, C. A., Leite, N. C., Cardoso, C. R. L., & Salles, G. F. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17040460 · Cited by 45
“Type 2 diabetes mellitus, an increasingly prevalent disease worldwide, is currently regarded as one of NAFLD‘s main risk factors, and it correlates with the severest histological aspects of NAFLD, with a growing prevalence of hepatocellular carcinoma [6–9].”
BackgroundPhipps, M. M., Livanos, A. E., Guo, A., Pomenti, S. F., Yeh, J., Dakhoul, L., Burney, H. N., Kettler, C. D., Liu, H., Miller, E., et al. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000643 · Cited by 45
Consenso mexicano de la enfermedad por hígado graso no alcohólico
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 · doi:10.1016/j.rgmx.2018.11.007 · Cited by 52
“Glucosa en ayunas, mg/dl, mediana (RIQ) 130 (100-181) 94 (87-113) < 0.”
Fouad, Y. M., Lazarus, J. V., Negro, F., Peck‐Radosavljevic, M., Sarin, S. K., Ferenci, P., Esmat, G., Ghazinian, H., Nakajima, A., Silva, M., et al. (2021) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16346 · Cited by 44
The role of microbiota in nonalcoholic fatty liver disease
Ciaula, A. D., Bonfrate, L., & Portincasa, P. (2022) · European Journal of Clinical Investigation · doi:10.1111/eci.13768 · Cited by 44
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) · European Journal of Clinical Investigation · doi:10.1111/eci.70059 · Cited by 46
Pennisi, G., Enea, M., Romero‐Gomez, M., Viganò, M., Bugianesi, E., Wong, V. W. ‐., Fracanzani, A. L., Sebastiani, G., Boursier, J., Berzigotti, A., et al. (2022) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16763 · Cited by 43
“Notably, our data from F2 patients add further insights regarding the risk of developing HCC in patients with NASH but without cirrhosis,30-33 even if systematic screening in these patients cannot be suggested.34-36 A recent multicentre study18 used a competitive risks model to evaluate the…”
BackgroundShi, C., de Wit, S., Učambarlić, E., Markousis‐Mavrogenis, G., Screever, E. M., Meijers, W. C., de Boer, R. A., & Aboumsallem, J. P. (2023) · Cancers · doi:10.3390/cancers15030729 · Cited by 51
Non-alcoholic fatty liver disease-related hepatocellular carcinoma
Daher, D., Dahan, K. S. E., & Singal, A. G. (2023) · Journal of Liver Cancer · doi:10.17998/jlc.2022.12.30 · Cited by 45
“Patients with NASH cirrhosis have an annual HCC incidence of 1-2%, although more than one-fourth of NASH-related HCC occur without underlying cirrhosis.(11,12) In fact, NASH is the leading cause of non-cirrhotic HCC.”
BackgroundCarcinoma hepatocelular: presente y futuro
Armengol, C., Sarrias, M., & Sala, M. (2017) · Medicina Clínica · doi:10.1016/j.medcli.2017.08.010 · Cited by 42
Patel, Y. A., Gifford, E. J., Glass, L. M., McNeil, R. B., Turner, M. J., Han, B., Provenzale, D., Choi, S. S., Moylan, C. A., & Hunt, C. M. (2017) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14411 · Cited by 42
“As the leading cause of chronic liver disease in the US, NAFLD is of increasing clinical concern in the VHA.3 In our national VHA study, we characterised NAFLD and identified risk factors for advanced fibrosis.”
BackgroundResultInfluentialTAZ-induced Cybb contributes to liver tumor formation in non-alcoholic steatohepatitis
Wang, X., Zeldin, S. M., Shi, H., Zhu, C., Saito, Y., Corey, K. E., Osganian, S. A., Remotti, H. E., Verna, E. C., Pajvani, U. B., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.11.031 · Cited by 41
Treatment Candidacy for Pharmacologic Therapies for NASH
Rowe, I. A., Wong, V. W.-S., & Loomba, R. (2022) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.03.005 · Cited by 41
Nonalcoholic fatty liver disease
Sotiropoulou, M. G., Katsaros, I., Vailas, M. G., Lidoriki, I., Papatheodoridis, G., Kostomitsopoulos, N. G., Valsami, G. N., Tsaroucha, A. K., & Schizas, D. (2021) · Saudi Journal of Gastroenterology · doi:10.4103/sjg.sjg_249_21 · Cited by 43
“disease entity can occur at the onset of NASH even in the absence of cirrhosis.[9] Thus, NAFLD has an increasing economic and clinical burden worldwide.”
BackgroundLabeur, T. A., van Vugt, J. L. A., ten Cate, D. W. G., Takkenberg, R. B., IJzermans, J. N. M., Koerkamp, B. G., de Man, R. A., van Delden, O. M., Eskens, F. A. L. M., & Klümpen, H. (2018) · Liver Cancer · doi:10.1159/000493586 · Cited by 40
Dakhoul, L., Gawrieh, S., Jones, K. R., Ghabril, M., McShane, C., Orman, E. S., Vilar‐Gómez, E., Chalasani, N., & Nephew, L. D. (2018) · Hepatology Communications · doi:10.1002/hep4.1277 · Cited by 41
Yen, Y.-H., Cheng, Y.-F., Wang, J.-H., Lin, C.-C., & Wang, C.-C. (2021) · PLoS ONE · doi:10.1371/journal.pone.0244939 · Cited by 37
“defined NAFLD as the presence of metabolic syndrome [21].”
BackgroundMagnitude of Nonalcoholic Fatty Liver Disease: Western Perspective
Samji, N. S., Verma, R., & Satapathy, S. K. (2019) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2019.05.001 · Cited by 45
“health system in Texas, United States, involving 1500 patients showed a strong association of NASH without cirrhosis with hepatocellular carcinoma.(110)”
BackgroundShetty, A., & Syn, W. (2019) · Europe PMC (PubMed Central) · Cited by 40
Confounding factors of non-invasive tests for nonalcoholic fatty liver disease
Wai, J. W., Fu, C., & Wong, V. W. (2020) · Journal of Gastroenterology · doi:10.1007/s00535-020-01686-8 · Cited by 41
“Although hepatocellular carcinoma has been well reported in non-cirrhotic patients with NAFLD [59], cirrhosis remains one of the most important risk factors for hepatocellular carcinoma [60, 61], and the absolute incidence of hepatocellular carcinoma in the non-cirrhotic population is very low [62].”
BackgroundLupșor‐Platon, M., Serban, T., Silion, A. I., Tirpe, G. R., Tirpe, A., & Florea, M. (2021) · Cancers · doi:10.3390/cancers13040790 · Cited by 42
“[11] reported that NAFLD individuals are fivefold more likely to develop HCC without underlying cirrhosis, compared to patients suffering from other chronic liver diseases.”
Background
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
