Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team
Open accessAbstract
Background & aims Hepatocellular cancer (HCC) commonly complicates chronic liver disease and increases in incidence have been reported despite falling prevalences of viral hepatitis.Methods Following the introduction of centralised specialist teams to manage patients with cancer in England, we characterised the demographics of patients with HCC referred to the Newcastle-upon-Tyne Hospitals NHS Foundation Trust between 2000 and 2010. Regional HCC mortality data was from Public Health England.Results HCC related mortality in the region rose 1.8 fold in 10 years, from 2.0 to 3.7 per 100,000. 632 cases were reviewed centrally, with 2-3 fold increases in referrals of patients with associated hepatitis C, alcoholic liver disease or no chronic liver disease and a >10 fold increase in HCC associated with non-alcoholic fatty liver disease (NAFLD). By 2010 NAFLD accounted for 41/118 (34.8%) cases. Irrespective of associated etiologies, metabolic risk factors were present in 78/118 (66.1%) cases in 2010, associated with regional increases in obesity and diabetes. Median overall survival was just 10.7 months. Although patients with NAFLD associated HCC were older (71.3 yr vs. 67.1 yr; p<0.001) and their cancers less often detected by surveillance, their survival was similar to other etiologies. This was attributed to significantly higher incidental presentation (38.2%) and lower prevalence of cirrhosis (77.2%).Conclusions HCC related mortality is increasing, with typical patients being elderly with metabolic risk factors. The prognosis for most of the cases is poor, but older patients with co-morbidities can do well, managed, within a specialist multidisciplinary team if their cancer is detected pre-symptomatically.
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In a tertiary centre for HCC referral in Northern England, individuals with HCC due to MASLD had a lower prevalence of cirrhosis (77.2%) than those with other aetiologies.
“In a tertiary centre for HCC referral in Northern England, 231 individuals with HCC due to MASLD had a lower prevalence of cirrhosis (77.2%) than those with other aetiologies.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [231]
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“This picture makes NAFLD as the most common cause of chronic liver disease((1)) as a dramatically growing risk factor for hepatocellular carcinoma,((2)) as a leading indication for liver transplantation,((3)) and as a condition leaving individuals at increased risk of extrahepatic—mostly cardiovascular—morbidity and m…”
BackgroundMethodImmunotherapy for hepatocellular carcinoma: Current and future
Johnston, M. P., & Khakoo, S. I. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i24.2977 · Cited by 196 · see citing works
Petta, S., Sebastiani, G., Viganò, M., Ampuero, J., Wai-Sun Wong, V., Boursier, J., Berzigotti, A., Bugianesi, E., Fracanzani, A. L., Cammà, C., et al. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.06.045 · Cited by 197 · see citing works
Management of non-alcoholic fatty liver disease
Petroni, M. L., Brodosi, L., Bugianesi, E., & Marchesini, G. (2021) · BMJ · doi:10.1136/bmj.m4747 · Cited by 181 · see citing works
Yu, 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 · see citing works
Should we undertake surveillance for HCC in patients with NAFLD?
Younes, R., & Bugianesi, E. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.10.006 · Cited by 174 · see citing works
Granito, A., Muratori, L., Lalanne, C., Quarneti, C., Ferri, S., Guidi, M., Lenzi, M., & Muratori, P. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i22.2994 · Cited by 172 · see citing works
Vitale, A., Svegliati‐Baroni, G., Ortolani, A., Cucco, M., Riva, G. V. D., Giannini, E. G., Piscaglia, F., Rapaccini, G., Marco, M. D., Caturelli, E., et al. (2021) · Gut · doi:10.1136/gutjnl-2021-324915 · Cited by 171 · see citing works
Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes?
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“(47) have further assessed the risk of incident T2DM at 5 years of follow-up in the following three subgroups of subjects: (1) in those in whom there was resolution of NAFLD over 5 years; (2) in those in whom there was a development of new NAFLD between baseline and the follow-up examinations; and (3) in subjects in w…”
BackgroundNon-alcoholic fatty liver disease: A sign of systemic disease
Reccia, I., Jayant, K., Akladios, C. Y., Virdis, F., Pai, M., Habib, N. A., & Spalding, D. R. C. (2017) · Metabolism · doi:10.1016/j.metabol.2017.04.011 · Cited by 170 · see citing works
Non-alcoholic Fatty Liver Disease: Growing Burden, Adverse Outcomes and Associations
Kumar, R. K., Priyadarshi, R. N., & Anand, U. (2019) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2019.00051 · Cited by 167 · see citing works
“A recent large population - based Surveillance, Epidemiology and End Results (known as the SEER) study has demonstrated a 9% annual increase in NAFLD-related HCC between 2004 and 2009.45 Dyson et al.46 noted a nearly 10 - fold increase in NAFLD - related HCC cases in the UK from 2000 to 2010.”
BackgroundInfluentialThe Function of the HGF/c-Met Axis in Hepatocellular Carcinoma
Wang, H., Rao, B., Lou, J., Li, J., Liu, Z., Li, A., Cui, G., Ren, Z., & Yu, Z. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00055 · Cited by 164 · see citing works
Burra, P., Bizzaro, D., Gonta, A., Shalaby, S., Gambato, M., Morelli, M. C., Trapani, S., Floreani, A., Marra, F., Brunetto, M. R., et al. (2021) · Liver International · doi:10.1111/liv.14943 · Cited by 159 · see citing works
The Genetics of Nonalcoholic Fatty Liver Disease: Spotlight on PNPLA3 and TM6SF2
Day, C. P., & Anstee, Q. M. (2015) · Seminars in Liver Disease · doi:10.1055/s-0035-1562947 · Cited by 162 · see citing works
“71,72 The rise in the burden of NAFLD coincides with a marked increase in the incidence of HCC in many countries, 73 – 76 and so it is timely to also consider whether genetic modi fi ers such as PNPLA3 may also increase the risk of NAFLD-associated HCC. 82 – 84 This association is supported by a…”
Global Epidemiology of Hepatocellular Carcinoma
Singh, S. P., Madke, T., & Chand, P. (2024) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2024.102446 · Cited by 178 · see citing works
Petta, S., Wong, V. W., Cammà, C., Hiriart, J., Wong, G. L., Vergniol, J., Chan, A. W. H., Marco, V. D., Merrouche, W., Chan, H. L., et al. (2017) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14219 · Cited by 159 · see citing works
Ipragliflozin improves the hepatic outcomes of patients with diabetes with NAFLD
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Distinctive features of hepatocellular carcinoma in non-alcoholic fatty liver disease
Degasperi, E., & Colombo, M. (2016) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(16)30018-8 · Cited by 155 · see citing works
Grimaudo, S., Pipitone, R. M., Pennisi, G., Celsa, C., Cammà, C., Marco, V. D., Barcellona, M. R., Boemi, R., Enea, M., Giannetti, A., et al. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2019.08.011 · Cited by 152 · see citing works
Hepatocellular carcinoma in nonalcoholic fatty liver: role of environmental and genetic factors
Dongiovanni, P. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i36.12945 · Cited by 145 · see citing works
Hepatocellular Carcinoma in Obesity, Type 2 Diabetes, and NAFLD
Reeves, H. L., Zaki, M. Y. W., & Day, C. P. (2016) · Digestive Diseases and Sciences · doi:10.1007/s10620-016-4085-6 · Cited by 147 · see citing works
Mechanisms Linking Excess Adiposity and Carcinogenesis Promotion
Pérez-Hernández, A. I., Catalán, V., Gómez‐Ambrosi, J., RodrÃguez, A., & Frühbeck, G. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00065 · Cited by 142 · see citing works
Petta, S., Sebastiani, G., Bugianesi, E., Viganò, M., Wong, V. W.-S., Berzigotti, A., Fracanzani, A. L., Anstee, Q. M., Marra, F., Barbara, M., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.05.019 · Cited by 140 · see citing works
“chronic liver disease and cirrhosis [1], an increasing risk factor for hepatocellular carcinoma [2], and the emerging indication for liver transplantation [3].”
Non-alcoholic fatty liver disease and risk of type 2 diabetes
Lallukka, S., & Yki‐Järvinen, H. (2016) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2016.06.006 · Cited by 138 · see citing works
Progression and Natural History of Nonalcoholic Fatty Liver Disease in Adults
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Pais, R., Fartoux, L., Goumard, C., Scatton, O., Wendum, D., Rosmorduc, O., & Ratziu, V. (2017) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14261 · Cited by 129 · 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%…”
BackgroundOgle, L. F., Orr, J. G., Willoughby, C. E., Hutton, C., McPherson, S., Plummer, R., Boddy, A. V., Curtin, N. J., Jamieson, D., & Reeves, H. L. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.04.014 · Cited by 130 · see citing works
Gawrieh, S., Dakhoul, L., Miller, E., Scanga, A. E., deLemos, A. S., Kettler, C. D., Burney, H. N., Liu, H., Abu‐Sbeih, H., Chalasani, N., et al. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15464 · Cited by 130 · see citing works
Nonalcoholic fatty liver disease burden: Australia, 2019–2030
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Gut roundtable meeting paper: selected recent advances in hepatocellular carcinoma
Gerbes, A. L., Zoulim, F., Tilg, H., Dufour, J., Bruix, J., Paradis, V., Salem, R., Peck‐Radosavljevic, M., Galle, P. R., Greten, T. F., et al. (2017) · Gut · doi:10.1136/gutjnl-2017-315068 · Cited by 127 · see citing works
Experience with regorafenib in the treatment of hepatocellular carcinoma
Granito, A., Forgione, A., Marinelli, S., Renzulli, M., Ielasi, L., Sansone, V., Benevento, F., Piscaglia, F., & Tovoli, F. (2021) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848211016959 · Cited by 126 · see citing works
MASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges
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“In cases of non-cirrhotic HCC, as individuals are generally not in a surveillance programme, lesions are more likely to be picked up incidentally or symptomatically (the latter in particular making curative treatment very unlikely) [58].”
BackgroundRare pathogenic variants predispose to hepatocellular carcinoma in nonalcoholic fatty liver disease
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Self-citationGeographical similarity and differences in the burden and genetic predisposition of NAFLD
Yip, T. C., Gómez, E. V., Petta, S., Yilmaz, Y. N., Wong, G. L., Adams, L. A., de Lédinghen, V., Sookoian, S. C., & Wong, V. W. (2022) · Hepatology · doi:10.1002/hep.32774 · Cited by 123 · see citing works
“8% of them with cirrhosis).[72] Notably, although NAFLD overall accounted for 21.”
BackgroundThe changing scenario of hepatocellular carcinoma in Italy: an update
Garuti, F., Neri, A., Avanzato, F., Gramenzi, A., Rampoldi, D., Rucci, P., Farinati, F., Giannini, E. G., Piscaglia, F., Rapaccini, G. L., et al. (2020) · Liver International · doi:10.1111/liv.14735 · Cited by 122 · see citing works
Human biomimetic liver microphysiology systems in drug development and precision medicine
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Metabolic dysfunction-associated steatotic liver disease and the heart
Driessen, S., Francque, S., Anker, S. D., Cabezas, M. C., Grobbee, D. E., Tushuizen, M. E., & Holleboom, A. G. (2023) · Hepatology · doi:10.1097/hep.0000000000000735 · Cited by 125 · see citing works
“…MASH, in turn, relates to liver-related mortality and all-cause mortality, and it may lead to cirrhosis and HCC. [1,9] The burgeoning problem of MASLD is a major health issue for the forthcoming decades, driving the incidence of HCC [10] and becoming a major indication for liver transplantation.”
Rustgi, 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 · see citing works
NAFLD and MAFLD as emerging causes of HCC: A populational study
Myers, S., Neyroud‐Caspar, I., Spahr, L., Gkouvatsos, K., Fournier, E., Giostra, E., Magini, G. M., Frossard, J., Bascaron, M.-E., Vernaz, N., et al. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100231 · Cited by 116 · see citing works
“8-fold increase in HCC mortality between 2000 and 2010 and a high prevalence of metabolic risk factors but this study was also limited by potential referral bias.(20) A Japanese multicentric study also found that the proportion of patients with non-viral HCC increased from 10% in 1991 to 24% in 2010.”
BackgroundDash, S., Aydın, Y., Widmer, K., & Nayak, L. (2020) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s221187 · Cited by 127 · see citing works
- Authors
- Dyson, J., Jaques, B., Chattopadyhay, D., Lochan, R., Graham, J., Das, D., Aslam, T., Patanwala, I., Gaggar, S., Cole, M., Sumpter, K., Stewart, S., Rose, J., Hudson, M., Manas, D., & Reeves, H. L.
- Affiliations
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Newcastle University (GB)
- Corresponding author
- Reeves, Helen L.
- ORCID
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 60
- Issue
- 1
- Pages
- 110-117
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2076341209
- Cited by
- 603
- References
- 25
- Citations by year
- 2026: 23 · 2025: 32 · 2024: 45 · 2023: 43 · 2022: 72 · 2021: 65 · 2020: 63 · 2019: 60 · 2018: 57 · 2017: 48 · 2016: 38 · 2015: 33 · 2014: 18 · 2013: 4
- FWCI
- 19.26
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity)
- 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
- hepatocellular carcinoma, obesity, type 2 diabetes, non-alcoholic fatty liver disease, HCC mortality, chronic liver disease, hepatitis C, alcoholic liver disease, metabolic risk factors, multidisciplinary cancer care, cancer surveillance, liver cirrhosis, overall survival, cancer incidence trends
- MeSH terms
- Age Factors, Aged, Diabetes Mellitus, Type 2, Fatty Liver, Humans, Liver Neoplasms, Middle Aged, Obesity, Risk Factors, Non-alcoholic Fatty Liver Disease
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