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
Chalasani, N., Younossi, Z., Lavine, J. E., Charlton, M., Cusi, K., Rinella, M., Harrison, S. A., Brunt, E. M., & Sanyal, A. J. (2018) · Hepatology · doi:10.1002/hep.29367 · Cited by 7,239
“This study confirms past small reports of HCC in NAFLD patients without cirrhosis.((62)) It is important to recognize that most patients with cryptogenic cirrhosis may have what is considered “burned out” NAFLD.”
ResultLlovet, J. M., Kelley, R. K., Villanueva, A., Singal, A. G., Pikarsky, E., Roayaie, S., Lencioni, R., Koike, K., Zucman-Rossi, J., & Finn, R. S. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-00240-3 · Cited by 7,055
Mechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354
A global view of hepatocellular carcinoma: trends, risk, prevention and management
Yang, J. D., Hainaut, P. L., Gores, G. J., Amadou, A., Plymoth, A., & Roberts, L. R. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0186-y · Cited by 4,290
MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.312 · Cited by 3,286
Non-alcoholic fatty liver disease - a global public health perspective
Younossi, Z. M. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2018.10.033 · Cited by 2,149
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
“The NASH epidemic has provoked a dramatic increase in HCC (Berkan-Kawi nska and Piekarska, 2020; Mittal et al., 2016; Negro, 2020).”
BackgroundEpidemiology and Management of Hepatocellular Carcinoma
Kulik, L., & El‐Serag, H. B. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.08.065 · Cited by 1,764
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
Epidemiology and surveillance for hepatocellular carcinoma: New trends
Singal, A. G., Lampertico, P., & Nahon, P. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.08.025 · Cited by 1,149
New trends on obesity and NAFLD in Asia
Fan, J.-G., Kim, S. U., & Wong, V. W. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.06.003 · Cited by 1,100
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
Clinical epidemiology and disease burden of nonalcoholic fatty liver disease
Perumpail, B. J., Khan, M. A., Yoo, E. R., Cholankeril, G. T., Kim, D., & Ahmed, A. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i47.8263 · Cited by 759
Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine
Fujiwara, N., Friedman, S. L., Goossens, N., & Hoshida, Y. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.09.016 · Cited by 659
Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives
Arab, J. P., Karpen, S. J., Dawson, P. A., Arrese, M., & Trauner, M. (2017) · Hepatology · doi:10.1002/hep.28709 · Cited by 634
“Moreover, emerging data suggest that the recent increase in the incidence of HCC is driven by NAFLD, particularly in Western countries.((6)) Currently, promotion of lifestyle changes in diet and exercise habits as well as control of comorbidities (i.”
BackgroundEpidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma
Massarweh, N. N., & El‐Serag, H. B. (2017) · Cancer Control · doi:10.1177/1073274817729245 · Cited by 637
“Additional data also indicate a small but important proportion of NAFLD/ NASH-related HCC develops in the absence of prior significant liver damage or cirrhosis.(62)”
BackgroundRecent insights into the pathogenesis of nonalcoholic fatty liver disease
Arab, J. P., Arrese, M., & Trauner, M. (2018) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043617 · Cited by 573
Complications, morbidity and mortality of nonalcoholic fatty liver disease
Mantovani, A., Scorletti, E., Mosca, A., Alisi, A., Byrne, C. D., & Targher, G. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154170 · Cited by 580
Ganesan, P., & Kulik, L. (2022) · Clinics in Liver Disease · doi:10.1016/j.cld.2022.08.004 · Cited by 489
(2024) · Obesity Facts · doi:10.1159/000539371 · Cited by 545
van der Windt, D. J., Sud, V., Zhang, H., Varley, P. R., Goswami, J., Yazdani, H. O., Tohme, S. T., Loughran, P., O'Doherty, R. M., Minervini, M. I., et al. (2018) · Hepatology · doi:10.1002/hep.29914 · Cited by 489
“A concerning observation is the relatively high incidence of HCC in NASH before the development of cirrhosis.((3)) This observation emphasizes the important role of inflammation in cancer development and progression in NASH.”
BackgroundEpidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis
Tang, A., Hallouch, O., Chernyak, V., Kamaya, A., & Sirlin, C. B. (2017) · Abdominal Radiology · doi:10.1007/s00261-017-1209-1 · Cited by 485
Non-alcoholic fatty liver disease
Neuschwander‐Tetri, B. A. (2017) · BMC Medicine · doi:10.1186/s12916-017-0806-8 · Cited by 470
“cirrhotic HCC occurs in patients with NAFLD compared to other causes of chronic liver disease [12].”
BackgroundArachidonic Acid Metabolites in Cardiovascular and Metabolic Diseases
Sonnweber, T., Pizzini, A., Nairz, M., Weiß, G., & Tancevski, I. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113285 · Cited by 452
Mechanisms of liver fibrosis and its role in liver cancer
Dhar, D., Baglieri, J., Kisseleva, T., & Brenner, D. A. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370219898141 · Cited by 449
Global epidemiology and burden of HCV infection and HCV-related disease
Thrift, A. P., El‐Serag, H. B., & Kanwal, F. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.176 · Cited by 382
Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment
Llovet, J. M., Willoughby, C. E., Singal, A. G., Greten, T. F., Heikenwälder, M., El-Serag, H. B., Finn, R. S., & Friedman, S. L. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00754-7 · Cited by 354
Non-alcoholic fatty liver disease
Maurice, J. B., & Manousou, P. (2018) · Clinical Medicine · doi:10.7861/clinmedicine.18-3-245 · Cited by 387
Chu, H., Duan, Y., Yang, L., & Schnabl, B. (2019) · Gut · doi:10.1136/gutjnl-2018-316307 · Cited by 354
Xu, X., Poulsen, K. L., Wu, L., Liu, S., Miyata, T., Song, Q., Wei, Q., Zhao, C., Lin, C., & Yang, J. B. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01119-3 · Cited by 387
“However, HCC can also develop in the absence of cirrhosis.(17,18) Fatty degeneration of the liver, as a pathological change, was first proposed by William Bowman who found that fat accumulation in the liver through observing human liver specimens under the microscope in 1842.”
BackgroundEpidemiology and risk-stratification of NAFLD-associated HCC
Ioannou, G. N. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.08.012 · Cited by 361
Younossi, Z., & Henry, L. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.03.005 · Cited by 334
“HCC Patients with NAFLD or ALD are at risk for developi ng HCC, which leads to death or liver transplantation [77-86].”
BackgroundAssociation between non-alcoholic fatty liver disease and cancer incidence rate.
Kim, G.-A., Lee, H.-C., Choe, J., Kim, M.-J., Lee, M. J., Chang, H.-S., Bae, I. Y., Kim, H., An, J., Shim, J., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.09.012 · Cited by 311
Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment
Hwang, S. Y., Danpanichkul, P., Agopian, V. G., Mehta, N., Parikh, N. D., Abou‐Alfa, G. K., Singal, A. G., & Yang, J. D. (2024) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0824 · Cited by 359
Alexander, M., Loomis, A. K., van der Lei, J., Duarte-Salles, T., Prieto-Alhambra, D., Ansell, D., Pasqua, A., Lapi, F., Rijnbeek, P., Mosseveld, M., et al. (2019) · BMC Medicine · doi:10.1186/s12916-019-1321-x · Cited by 317
Current treatment paradigms and emerging therapies for NAFLD/NASH
Raza, S. (2020) · Frontiers in bioscience · doi:10.2741/4892 · Cited by 329
The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease
Fujii, H., Kawada, N., & Japan Study Group of NAFLD (JSG-NAFLD) (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113863 · Cited by 308
The effects of physical exercise on fatty liver disease.
van der Windt, D. J., Sud, V., Zhang, H., Tsung, A., & Huang, H. (2018) · Gene Expression · doi:10.3727/105221617x15124844266408 · Cited by 294
Current epidemiology in hepatocellular carcinoma
Konyn, P., Ahmed, A., & Kim, D. (2021) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2021.1991792 · Cited by 283
KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease
Kang, S. H., Lee, H. W., Yoo, J., Cho, Y., Kim, S. U., Lee, T. H., Jang, B. K., Ahn, S. B., Ahn, S. B., Kim, H., et al. (2021) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2021.0178 · Cited by 276
A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis
Harrison, S. A., Goodman, Z., Jabbar, A., Vemulapalli, R., Younes, Z. H., Freilich, B., Sheikh, M. Y., Schattenberg, J. M., Kayali, Z., Zivony, A., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.11.024 · Cited by 260
Lin, H., Lee, H. W., Yip, T. C.-F., Tsochatzis, E., Petta, S., Bugianesi, E., Yoneda, M., Zheng, M.-H., Hagström, H., Boursier, J., et al. (2024) · JAMA · doi:10.1001/jama.2024.1447 · Cited by 250
NAFLD‐related hepatocellular carcinoma: The growing challenge
Shah, P. A., Patil, R., & Harrison, S. A. (2022) · Hepatology · doi:10.1002/hep.32542 · Cited by 270
“In a Veterans Affairs (VA) study, patients with MetS were found to have more than a fivefold risk of developing HCC in the absence of cirrhosis compared with patients with hepatitis‐related HCC.[81] Angulo et al.”
BackgroundWang, P., Ji, Y., Zhang, X., Zhao, L., Yan, Z.-Z., Zhang, P., Shen, L., Yang, X., Fang, J., Tian, S., et al. (2017) · Nature Medicine · doi:10.1038/nm.4290 · Cited by 221
Koda, Y., Teratani, T., Chu, P.-S., Hagihara, Y., Mikami, Y., Harada, Y., Tsujikawa, H., Miyamoto, K., Suzuki, T., Taniki, N., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24734-0 · Cited by 219
Intestinal Barrier and Permeability in Health, Obesity and NAFLD
Portincasa, P., Bonfrate, L., Khalil, M., Angelis, M. D., Calabrese, F. M., D’Amato, M., Wang, D. Q. ‐., & Ciaula, A. D. (2021) · Biomedicines · doi:10.3390/biomedicines10010083 · Cited by 219
Papatheodoridi, A., Chrysavgis, L., Koutsilieris, M., & Chatzigeorgiou, A. (2019) · Hepatology · doi:10.1002/hep.30834 · Cited by 210
“Unlike other chronic liver diseases, such as viral or alcoholic hepatitis, this may happen even in the absence of cirrhosis.(65,66) Indeed, Ertle et al.”
BackgroundNonalcoholic Fatty Liver Disease
Wang, X., & Malhi, H. (2018) · Annals of Internal Medicine · doi:10.7326/aitc201811060 · Cited by 212
Non-alcoholic fatty liver disease: A patient guideline
Francque, S. M., Marchesini, G., Kautz, A., Walmsley, M., Dorner, R., Lazarus, J. V., Zelber-Sagi, S., Hallsworth, K., Busetto, L., Frühbeck, G., et al. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100322 · Cited by 264
“Importantly, HCC has also been reported in patients with NASH who do not have cirrhosis, and even in patients with NAFL.(41,42) It is not clear how big this risk is exactly, but in general, the more severe the disease is, the higher the risk is.”
BackgroundZeng, X., Zhu, M., Liu, X., Chen, X., Yuan, Y., Li, L., Liu, J., Lu, Y., Cheng, J., & Chen, Y. (2020) · Nutrition & Metabolism · doi:10.1186/s12986-020-0434-8 · Cited by 187
Dysregulation of Nrf2 in Hepatocellular Carcinoma: Role in Cancer Progression and Chemoresistance
Raghunath, A., Sundarraj, K., Arfuso, F., Sethi, G., & Perumal, E. (2018) · Cancers · doi:10.3390/cancers10120481 · Cited by 187
“In Western societies, infl mmation with non-alcoholic fatty liver disease leads to the development of HCC, along with obesity nd type 2 diabetes mellitus [14,15].”
BackgroundMahmud, N., Kaplan, D. E., Taddei, T. H., & Goldberg, D. S. (2019) · Hepatology · doi:10.1002/hep.30494 · Cited by 190
“The VOCAL cohort has also been used for numerous prior studies focused on patients with chronic liver disease(13-16) and is very representative of the United Network for Organ Sharing (UNOS) liver transplant distribution from an etiology standpoint (Supporting Fig.”
MethodZheng, Y., Wang, S., Wu, J., & Wang, Y. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04367-1 · Cited by 197
Global Epidemiology of Nonalcoholic Fatty Liver Disease and Perspectives on US Minority Populations
Sherif, Z. A., Saeed, A., Ghavimi, S., Nouraie, M. S., Laiyemo, A. O., Brim, H., & Ashktorab, H. (2016) · Digestive Diseases and Sciences · doi:10.1007/s10620-016-4143-0 · Cited by 183
“USA 27–34 % [13, 41, 47, 114] 3–5 % [13] 10–20 % [48]”
Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma
Tümen, D., Heumann, P., Gülow, K., Demirci, C. N., Cosma, L.-S., Müller, M., & Kandulski, A. (2022) · Biomedicines · doi:10.3390/biomedicines10123202 · Cited by 192
“Especially in industrialized nations, the proportion of patients with an HCC based on the presence of NAFLD without cirrhosis is increasing [30].”
BackgroundYu, M., Lin, C., Liu, C., Yang, S.-H., Tseng, Y.-L., & Wu, C. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.07.001 · Cited by 176
Should we undertake surveillance for HCC in patients with NAFLD?
Younes, R., & Bugianesi, E. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.10.006 · Cited by 165
Chen, X., Li, L., Liu, X., Luo, R., Liao, G., Li, L., Liu, J., Cheng, J., Lu, Y., & Chen, Y. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.04.022 · Cited by 170
Ciaula, A. D., Baj, J., Garruti, G., Celano, G., Angelis, M. D., Wang, H. H., Palo, D. M. D., Bonfrate, L., Wang, D. Q. ‐., & Portincasa, P. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9082648 · Cited by 166
“Furthermore, hepatocellular carcinoma (HCC) can originate from cirrhosis [6,16–18] but also from NASH [19].”
BackgroundSingal, A. G., Hoshida, Y., Pinato, D. J., Marrero, J. A., Nault, J., Paradis, V., Tayob, N., Sherman, M., Lim, Y., Feng, Z., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.01.233 · Cited by 170
Alkhouri, N., Lawitz, E., Noureddin, M., DeFronzo, R., & Shulman, G. I. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1668374 · Cited by 162
Kaplan, D. E., Serper, M. A., Mehta, R., Fox, R., John, B., Aytaman, A., Baytarian, M., Hunt, K., Albrecht, J., Njei, B., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.01.026 · Cited by 145
Nonalcoholic Fatty Liver Disease
Bril, F., & Cusi, K. J. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2016.06.005 · Cited by 158
Nonalcoholic Fatty Liver Disease and Recent Guideline Updates
Ando, Y., & Jou, J. H. (2021) · Clinical Liver Disease · doi:10.1002/cld.1045 · Cited by 170
Mittal, S., Kanwal, F., Ying, J., Chung, R., Sada, Y. H., Temple, S., Davila, J. A., & El‐Serag, H. B. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.07.025 · Cited by 145
“HCC Surveillance Two hepatologists (HES, SM) manually reviewed the EMR including imaging reports, laboratory tests, and physician notes within the 2 years prior to the HCC diagnosis date to determine receipt of HCC surveillance, presence or absence of cirrhosis, and recognition of cirrhosis status by providers [20,21].”
MethodKhalaf, N. I., Ying, J., Mittal, S., Temple, S., Kanwal, F., Davila, J. A., & El‐Serag, H. B. (2016) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2016.07.033 · Cited by 138
“0.(16) Model for End-Stage Liver Disease (MELD) and ChildPugh scores were calculated from laboratory tests and clinical features obtained from progress notes.”
MethodThe microbiome and hepatobiliary-pancreatic cancers
Mima, K., Nakagawa, S., Sawayama, H., Ishimoto, T., Imai, K., Iwatsuki, M., Hashimoto, D., Baba, Y., Yamashita, Y., Yoshida, N., et al. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.05.001 · Cited by 136
“Experimental studies using a mouse model of diethylnitrosamine-induced HCC suggest that lipopolysaccharide from intestinal Gram-negative microbes can potentiate tumor progression through the activation of TLR4 expressed on hepatocytes and hepatic stellate cells [33,34].”
BackgroundInfluentialNonalcoholic Fatty Liver Disease (NAFLD). Mitochondria as Players and Targets of Therapies?
Ciaula, A. D., Passarella, S., Shanmugam, H., Noviello, M., Bonfrate, L., Wang, D. Q. ‐., & Portincasa, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105375 · Cited by 142
“Carriers of the variant p.I148M have an increased risk of developing NAFLD [7], liver fibrosis and cirrhosis [8], and hepatocellular carcinoma (HCC) [9–11]; - Membrane-bound O-acyltransferase domain-containing 7 gene (MBOAT7) has lysophosphatidylinositol acyltransferase activity with the regulation of arachidonic acid…”
BackgroundInfluentialNonalcoholic fatty liver disease and liver transplantation - Where do we stand?
Mikolašević, I., Filipec-Kanižaj, T., Mijić, M., Jakopčić, I., Milić, S., Hrstić, I., Sobočan, N., Štimac, D., & Burra, P. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i14.1491 · Cited by 131
Gawrieh, S., Dakhoul, L., Miller, E., Scanga, A., deLemos, A., Kettler, C., Burney, H., Liu, H., Abu-Sbeih, H., Chalasani, N., et al. (2019) · Alimentary Pharmacology and Therapeutics · doi:10.1111/apt.15464 · Cited by 118
Lonardo, A., & Suzuki, A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9051278 · Cited by 129
MASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges
Phoolchund, A. G. S., & Khakoo, S. I. (2024) · Cancers · doi:10.3390/cancers16020259 · Cited by 137
“As a result of this, they are less likely to be o ff ered curative surgical therapies, such as orthotopic liver transplantation (OLT) or resection [81], with fewer options for HCC-speci fi c treatment [55], and, hence, they have worse outcomes.”
BackgroundThe Race to Bash NASH: Emerging Targets and Drug Development in a Complex Liver Disease
Romero, F. A., Jones, C. T., Xu, Y., Fenaux, M., & Halcomb, R. L. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01701 · Cited by 126
Risk stratification and early detection biomarkers for precision HCC screening
Lee, Y., Fujiwara, N., Yang, J. D., & Hoshida, Y. (2022) · Hepatology · doi:10.1002/hep.32779 · Cited by 128
Cenicriviroc for the treatment of non-alcoholic steatohepatitis and liver fibrosis
Tacke, F. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1442436 · Cited by 124
“NASH represents a particular high-risk situation for HCC, and HCC can even arise in non-cirrhotic livers [68, 69].”
BackgroundRustgi, V. K., Li, Y., Gupta, K., Minacapelli, C. D., Bhurwal, A., Catalano, C., & Elsaid, M. I. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.03.021 · Cited by 125
Human biomimetic liver microphysiology systems in drug development and precision medicine
Gough, A., Soto-Gutierrez, A., Vernetti, L., Ebrahimkhani, M. R., Stern, A. M., & Taylor, D. L. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00386-1 · Cited by 117
Zhao, X., Yang, L., Chang, N., Hou, L., Zhou, X., Yang, L., & Li, L. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2582-1 · Cited by 116
Hepatokines and adipokines in NASH-related hepatocellular carcinoma
Kücükoglu, Ö., Sowa, J., Mazzolini, G. D., Syn, W., & Canbay, A. E. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.10.030 · Cited by 114
Hepatocellular Carcinoma: An Overview of the Changing Landscape of Treatment Options
Koulouris, A., Tsagkaris, C., Spyrou, V., Pappa, E. V., Troullinou, A., & Nikolaou, M. (2021) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s300182 · Cited by 111
“patients not only lacking signs of cirrhosis but also without histological evidence of hepatitis.(5,6) However, cirrhosis is still present at the time of diagnosis in the majority of cases.”
BackgroundA Practical Guideline for Hepatocellular Carcinoma Screening in Patients at Risk
Frenette, C. T., Isaacson, A., Bargellini, I., Saab, S., & Singal, A. G. (2019) · Mayo Clinic Proceedings Innovations Quality & Outcomes · doi:10.1016/j.mayocpiqo.2019.04.005 · Cited by 113
“In a retrospective cohort study among 1500 US veterans, 13% of HCC cases developed in the absence of cirrhosis, with NAFLD being the main risk factor.(36) Furthermore, it has been suggested that patients with noncirrhotic NAFLD have a higher mortality rate than patients with HCC at the background of cirrhotic NAFLD.”
BackgroundKasmari, A. J., Welch, A. R., Liu, G., LESLIE, D. L., McGarrity, T. J., & Riley, T. (2017) · The American Journal of Medicine · doi:10.1016/j.amjmed.2016.12.029 · Cited by 106
Singal, A. G., Lok, A. S.-F., Feng, Z., Kanwal, F., & Parikh, N. D. (2020) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.09.036 · Cited by 110
Progress in Nonalcoholic Fatty Liver Disease: SIRT Family Regulates Mitochondrial Biogenesis
Zeng, C., & Chen, M. (2022) · Biomolecules · doi:10.3390/biom12081079 · Cited by 108
Natural history of NASH and HCC
Negro, F. (2020) · Liver international (Print) · doi:10.1111/liv.14362 · Cited by 88
Paik, J. M., Golabi, P., Younossi, Y., Srishord, M. K., Mishra, A., & Younossi, Z. M. (2020) · Hepatology Communications · doi:10.1002/hep4.1599 · Cited by 129
“In this context, understanding the global burden of complications of CLD (cirrhosis and LC) according to etiology of CLD, geographic location, and trends over time will be important.(8) Although there are adequate data on the prevalence and mortality associated with CLD, data on morbidity and DALYs related to CLD are…”
BackgroundNASH and Hepatocellular Carcinoma: Immunology and Immunotherapy
Pinter, M., Pinato, D. J., Ramadori, P., & Heikenwalder, M. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1258 · Cited by 103
Nash, M. J., Frank, D. N., & Friedman, J. E. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00349 · Cited by 101
“In addition, NAFLD is one of the fastest growing causes for liver cancer in the USA (63).”
BackgroundInflammatory and fibrotic mechanisms in NAFLD—Implications for new treatment strategies
Lee, Y. A., & Friedman, S. L. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13380 · Cited by 104
Characteristics and outcome of hepatocellular carcinoma in patients with NAFLD without cirrhosis
Bengtsson, B., Stål, P., Wahlin, S., Björkström, N., & Hagström, H. (2019) · Liver international (Print) · doi:10.1111/liv.14087 · Cited by 84
Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease
Wong, C. R., Nguyen, M., & Lim, J. K. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i37.8294 · Cited by 98
Kanda, T., Goto, T., Hirotsu, Y., Masuzaki, R., Moriyama, M., & Omata, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041525 · Cited by 97
“Having NAFLD or metabolic syndrome was independently associated with HCC in the absence of cirrhosis [73].”
BackgroundStacchiotti, A., Grossi, I., García-Gómez, R., Patel, G. A., Salvi, A., Lavazza, A., Petro, G. D., Monsalve, M., & Rezzani, R. (2019) · Cells · doi:10.3390/cells8091053 · Cited by 93
Goedeke, L., & Shulman, G. I. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101178 · Cited by 102
“Liver-targeted uncoupling also leads to reduced hepatic VLDL production [4], reducing intramyocellular plasma membrane sn-1,2-DAG content and PKCq/PKCε activity and reversing muscle insulin resistance [5].”
BackgroundMAFLD enhances clinical practice for liver disease in the Asia-Pacific region
Kawaguchi, T., Tsutsumi, T., Nakano, D., Eslam, M., George, J., & Torimura, T. (2021) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2021.0310 · Cited by 93
Statins Are Underutilized in Patients with Nonalcoholic Fatty Liver Disease and Dyslipidemia
Blais, P., Lin, M. F., Kramer, J. R., El‐Serag, H. B., & Kanwal, F. (2015) · Digestive Diseases and Sciences · doi:10.1007/s10620-015-4000-6 · Cited by 93
“However, several studies have employed this approach to account for limitations of preexisting clinical data [13, 20].”
BackgroundEpigenetic remodelling in human hepatocellular carcinoma
Braghini, M. R., Re, O. L., Romito, I., Fernández‐Barrena, M. G., Barbaro, B., Pomella, S., Rota, R., Vinciguerra, M., Avila, M. A., & Alisi, A. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02297-2 · Cited by 93
The metabolic basis of nonalcoholic steatohepatitis
Chakravarthy, M. V., & Neuschwander‐Tetri, B. A. (2020) · Endocrinology Diabetes & Metabolism · doi:10.1002/edm2.112 · Cited by 93
Wijarnpreecha, K., Thongprayoon, C., Edmonds, P. J., & Cheungpasitporn, W. (2015) · QJM · doi:10.1093/qjmed/hcv172 · Cited by 87
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
