Temporal trends, clinical patterns and outcomes of NAFLD‐related HCC in patients undergoing liver resection over a 20‐year period
Open accessAbstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) worldwide. NAFLD-HCC often occurs in noncirrhotic liver raising important surveillance issues. AIM: To determine the temporal trends for prevalence, clinical characteristics and outcomes of NAFLD-HCC in patients undergoing liver resection. METHODS: Consecutive patients with histologically confirmed HCC who underwent liver resection over a 20-year period (1995-2014). NAFLD was diagnosed based on past or present exposure to obesity or diabetes without other causes of chronic liver disease. RESULTS: A total of 323 HCC patients were included, 12% with NAFLD. From 1995-1999 to 2010-2014, the prevalence of NAFLD-HCC increased from 2.6% to 19.5%, respectively, P = .003, and followed the temporal trends in the prevalence of metabolic risk factors (28% vs 52%, P = .017), while hepatitis C-HCC decreased (from 43.6% to 19.5%, P = .003). NAFLD-HCC occurred more frequently in the absence of bridging fibrosis/cirrhosis (63% of cases, P < .001 compared to other aetiologies). Within the NAFLD group, tumour characteristics were similar between F0-F2 and F3-F4 patients, except for a higher proportion of single nodules (95% vs 54%, P < .01). A total of 53% patients had tumour recurrence and 40% died. NAFLD-HCC had similar time to recurrence and survival as HCCs of other aetiologies. Satellite nodules, tumour size, microvascular invasion and male sex but not the aetiology were independently associated with recurrence. CONCLUSION: Non-alcoholic fatty liver disease increased substantially over the past 20 years among resectable HCCs. It is now the leading cause of HCC occuring without/or with only minimal fibrosis. NAFLD patients are older, with larger tumours while survival and recurrence rates are as severe as in other aetiologies.
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Similar observations have been confirmed in a European study and two Japanese studies, where cirrhosis was absent in 38% and 49% of individuals with MASLD-related HCC, respectively.
“Similar observations have been con fi rmed in a European study 232 and two Japanese studies, where cirrhosis was absent in 38% and 49% of individuals with MASLD-related HCC, respectively. 233,234”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [232]
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Cites
Global cancer statistics, 2012
Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet‐Tieulent, J., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21262 · Cited by 26,858 · see citing works
Global Cancer Statistics, 2002
Parkin, D. M., Bray, F., Ferlay, J., & Pisani, P. (2005) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.55.2.74 · Cited by 18,573 · see citing works
EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma
European Association for the Study of the Liver, & European Organisation for Research and Treatment of Cancer (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2011.12.001 · Cited by 5,218 · see citing works
Vernon, G. C., Baranova, A. V., & Younossi, Z. M. (2011) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2011.04724.x · Cited by 3,067 · see citing works
Park, E. J., Lee, J. H., Yu, G.-Y., He, G., Ali, S. R., Holzer, R. G., Österreicher, C. H., Takahashi, H., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2009.12.052 · Cited by 1,764 · see citing works
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 · see citing works
Lambert, J. E., Ramos–Roman, M. A., Browning, J. D., & Parks, E. J. (2014) · Gastroenterology · doi:10.1053/j.gastro.2013.11.049 · Cited by 1,069 · see citing works
Hepatocellular carcinoma: Recent trends in the United States
El‐Serag, H. B. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.09.013 · Cited by 974 · see citing works
Hepatocellular carcinoma in non-alcoholic fatty liver disease: An emerging menace
Baffy, G., Brunt, E. M., & Caldwell, S. H. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2011.10.027 · Cited by 856 · see citing works
Younossi, Z. M., Otgonsuren, M., Henry, L., Venkatesan, C., Mishra, A., Erario, M., & Hunt, S. (2015) · Hepatology · doi:10.1002/hep.28123 · Cited by 802 · see citing works
Wong, R. J., Cheung, R. C., & Ahmed, A. (2013) · Hepatology · doi:10.1002/hep.26986 · Cited by 720 · see citing works
Davila, J. A., Morgan, R. O., Shaib, Y. H., McGlynn, K. A., & El‐Serag, H. B. (2005) · Gut · doi:10.1136/gut.2004.052167 · Cited by 703 · see citing works
Piscaglia, F., Svegliati‐Baroni, G., Barchetti, A., Pecorelli, A., Marinelli, S., Tiribelli, C., Bellentani, S., & on behalf of the HCC‐NAFLD Italian Study Group (2016) · Hepatology · doi:10.1002/hep.28368 · Cited by 604 · see citing works
Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team
Dyson, J., Jaques, B., Chattopadyhay, D., Lochan, R., Graham, J., Das, D., Aslam, T., Patanwala, I., Gaggar, S., Cole, M., et al. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2013.08.011 · Cited by 603 · cited 1× · see citing works
“NAFLD accounted for 35% of HCC cases in 2010 and metabolic risk factors were present in 66% of all HCC cases.(4) In the USA, an analysis of MarketScan Research Database between 2002 and 2008, revealed that NAFLD (alone or associated with other causes of chronic liver disease) was the leading risk factor for HCC in 59%…”
BackgroundCalvisi, D. F., Wang, C., Ho, C., Ladu, S., Lee, S. A., Mattu, S., Destefanis, G., Delogu, S., Zimmermann, A., Ericsson, J., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.12.006 · Cited by 598 · see citing works
Paradis, V., Zalinski, S., Chelbi, E., Guedj, N., Degos, F., Vilgrain, V., Bédossa, P., & Belghiti, J. (2008) · Hepatology · doi:10.1002/hep.22734 · Cited by 567 · see citing works
Ertle, J., Dechêne, A., Sowa, J., Penndorf, V., Herzer, K., Kaiser, G. M., Schlaak, J., Gerken, G., Syn, W., & Canbay, A. E. (2010) · International Journal of Cancer · doi:10.1002/ijc.25797 · Cited by 519 · see citing works
Obesity, inflammation, and liver cancer
Sun, B., & Karin, M. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.09.020 · Cited by 496 · see citing works
Bhala, N. B., Angulo, P., van der Poorten, D., Lee, E., Hui, J. M., Saracco, G. M., Adams, L. A., Charatcharoenwitthaya, P., Topping, J. H., Bugianesi, E., et al. (2011) · Hepatology · doi:10.1002/hep.24491 · Cited by 450 · see citing works
He, G., Yu, G.-Y., Temkin, V., Ogata, H., Kuntzen, C., Sakurai, T., Sieghart, W., Peck-Radosavljevic, M., Leffert, H. L., & Karin, M. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.048 · Cited by 427 · see citing works
Characteristics of Patients With Nonalcoholic Steatohepatitis Who Develop Hepatocellular Carcinoma
Yasui, K., Hashimoto, E., Komorizono, Y., Koike, K., Arii, S., Imai, Y., Shima, T., Kanbara, Y., Saibara, T., Mori, T., et al. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.01.023 · Cited by 420 · see citing works
Minireview: IGF, Insulin, and Cancer
Gallagher, E. J., & LeRoith, D. (2011) · Endocrinology · doi:10.1210/en.2011-0231 · Cited by 347 · see citing works
Population-based risk factors and resource utilization for HCC: US perspective
Sanyal, A. J., Poklepovic, A. S., Moyneur, É., & Barghout, V. E. (2010) · Current Medical Research and Opinion · doi:10.1185/03007995.2010.506375 · Cited by 312 · see citing works
Yang, S. Q., Lin, H. Z., Hwang, J., Chacko, V. P., & Diehl, A. M. (2001) · PubMed · Cited by 151 · see citing works
Surgical treatment of hepatocellular carcinoma associated with the metabolic syndrome
Cauchy, F., Zalinski, S., Dokmak, S., et al. (2012) · British journal of surgery · doi:10.1002/bjs.8963 · Cited by 125 · see citing works
Lee, T., Wu, J., Yu, S., Lin, J., Wu, M., & Wu, C. (2017) · International Journal of Cancer · doi:10.1002/ijc.30784 · Cited by 92 · see citing works
Shu-hui, S. (2012) · Infectious Disease Information · Cited by 86 · see citing works
Cirrhosis is under-recognised in patients subsequently diagnosed with hepatocellular cancer
Walker, M., El‐Serag, H. B., Sada, Y., Mittal, S., Ying, J., Duan, Z., Richardson, P., Davila, J. A., & Kanwal, F. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13505 · Cited by 84 · see citing works
Cullin7: a new gene involved in liver carcinogenesis related to metabolic syndrome
Paradis, V., Albuquerque, M., Mebarki, M., Hernandez, L., Zalinski, S., Quentin, S., Belghiti, J., Soulier, J., & Bédossa, P. (2012) · Gut · doi:10.1136/gutjnl-2012-302091 · Cited by 47 · see citing works
Obesity and hepatocellular carcinoma: Hype and reality
El‐Serag, H. B., & Kanwal, F. (2014) · Hepatology · doi:10.1002/hep.27172 · Cited by 45 · see citing works
Scatton, O., Goumard, C., Cauchy, F., et al. (2015) · Journal of Surgical Oncology · doi:10.1002/jso.23916 · Cited by 25 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Glo- bal cancer statistics, 2012. CA: A Cancer Journal for Clinicians. 2015;65:87-108.
Cited by
Sorted by citations
Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210 · see citing works
Self-citationFrom NASH to HCC: current concepts and future challenges
Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O., & Heikenwalder, M. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0145-7 · Cited by 1,392 · see citing works
Changing epidemiology, global trends and implications for outcomes of NAFLD
Wong, V. W.-S., Ekstedt, M., Wong, G. L.-H., & Hagström, H. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.04.036 · Cited by 765 · see citing works
Epidemiology 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 · see citing works
Stine, J. G., Wentworth, B. J., Zimmet, A., Rinella, M. E., Loomba, R., Caldwell, S. H., & Argo, C. K. (2018) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14937 · Cited by 336 · see citing works
Ebrahimi, F., Hagström, H., Sun, J., Bergman, D., Shang, Y., Yang, W., Roelstraete, B., & Ludvigsson, J. F. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.08.018 · Cited by 65 · see citing works
- Authors
- Pais, R., Fartoux, L., Goumard, C., Scatton, O., Wendum, D., Rosmorduc, O., & Ratziu, V.
- Affiliations
- Inserm (FR)
- Corresponding author
- Ratziu, V.
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2017-08-31
- Volume
- 46
- Issue
- 9
- Pages
- 856-863
- ISSN
- 0269-2813 (ISSN-L)
- 1365-2036
- OpenAlex
- W2750832778
- Cited by
- 129
- References
- 31
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 22 · 2023: 18 · 2022: 13 · 2021: 21 · 2020: 15 · 2019: 9 · 2018: 14 · 2017: 1
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Alimentary Pharmacology & Therapeutics (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- European Union's Horizon 2020 research
- EPoS (Elucidating Pathways of Steatohepatitis) (634413)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Keywords
- non-alcoholic fatty liver disease, hepatocellular carcinoma, hepatectomy, temporal trends, non-cirrhotic liver, tumor recurrence, survival, tumor characteristics, satellite nodules, microvascular invasion, tumor size, metabolic risk factors, obesity, diabetes mellitus, hepatitis C, fibrosis
- MeSH terms
- Aged, Female, Hepatectomy, Hepatitis C, Carcinoma, Hepatocellular, Humans, Liver, Liver Cirrhosis, Liver Neoplasms, Male, Middle Aged, Neoplasm Recurrence, Local, Risk Factors, Prevalence, Non-alcoholic Fatty Liver Disease
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