Cited by 609Hepatocellular Carcinoma Treatment and PrognosisLiver Disease Diagnosis and TreatmentHead and Neck Cancer Studies

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Hepatocellular cancer: The impact of obesity, type 2 diabetes and a multidisciplinary team

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Dyson, Jessica, Jaques, Bryan, Chattopadyhay, Dipankar, Lochan, Rajiv, Graham, Janine, Das, Debasish, Aslam, Tahira, Patanwala, Imran, Gaggar, Sameer, Cole, Michael, Sumpter, Kate, Stewart, Stephen, Rose, John, Hudson, Mark, Manas, Derek, Reeves, Helen L.·2014·Journal of Hepatology

DOI 10.1016/j.jhep.2013.08.011

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Abstract

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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Influential
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Júnior, A. D. D. C., Carrilho, L. A. O., Filho, P. N., Cantini, L., Vidal, L., Mendes, M. C. S., Carvalheira, J. B. C., & Saini, K. S. (2025) · Onco · doi:10.3390/onco5040047 · Cited by 18
Molecular Genealogy of Metabolic-associated Hepatocellular Carcinoma
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“14 15 – 17 Importantly, a substantial proportion of MASLD-related HCC patients develop a noncirrhotic liver background.”
Cost-Effectiveness of Hepatocellular Carcinoma Surveillance Strategies in Patients With Compensated Liver Cirrhosis in the United Kingdom
Garay, O. U., Ambühl, L., Bird, T. G., Barnes, E. J., Irving, W. L., Walkley, R., & Rowe, I. A. C. (2024) · Value in Health · doi:10.1016/j.jval.2024.07.015 · Cited by 11
Non‐alcoholic steatohepatitis, but not simple steatosis, disturbs the functional homogeneity of the liver – a human galactose positron emission tomography study
Eriksen, P. L., Thomsen, K. L., Larsen, L. P., Grønbæk, H., Vilstrup, H., & Sørensen, M. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15293 · Cited by 11
Development of a prognostic scoring model for predicting the survival of elderly patients with hepatocellular carcinoma
Wan, S., Nie, Y., & Zhu, X. (2020) · PeerJ · doi:10.7717/peerj.8497 · Cited by 11
Early diagnosis of hepatic inflammation in Japanese nonalcoholic fatty liver disease patients using 3D MR elastography
Komiyama, Y., Motosugi, U., Maekawa, S., Osawa, L., Nakakuki, N., Takada, H., Muraoka, M., Suzuki, Y., Sato, M., Takano, S., et al. (2022) · Hepatology Research · doi:10.1111/hepr.13858 · Cited by 11
Clinical features and management issues of NAFLD-related HCC: what we know so far
Pugliese, N., Alfarone, L., Arcari, I., Giugliano, S., Parigi, T. L., Rescigno, M., Lleò, A., & Aghemo, A. (2022) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2023.2162503 · Cited by 11
“Recently, the appropriateness of the BCLC system for NAFLD-HCC patients has been debated [13,22].”
BackgroundInfluential
Epidemiological Trends of Hepatocellular Carcinoma in Austria
Pinter, M., Hucke, F., Zielonke, N., Trauner, M. A., Sieghart, W., & Peck‐Radosavljevic, M. (2014) · Digestive Diseases · doi:10.1159/000367983 · Cited by 11
Essential phospholipids for people with non-alcoholic fatty liver disease
Varganova, D. L., Pavlov, C. S., Casazza, G., Nikolova, D., & Gluud, C. N. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013301 · Cited by 11
Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH
Forner, A., Reig, M., Varela, M., Burrel, M., Feliú, J., Briceño, J., Sastre, J., Martí‐Bonmatí, L., Llovet, J. M., Bilbao, J. I., et al. (2016) · Medicina Clínica (English Edition) · doi:10.1016/j.medcle.2016.07.013 · Cited by 13
Recent Advancements in Known and Emerging Risk Factors of Hepatocellular Carcinoma
Hussain, M. M., Bi, F., Wang, J., Zhai, A., Li, F., & Hu, H. (2025) · Cancer Medicine · doi:10.1002/cam4.71330 · Cited by 11
“Likewise, a 4.9-year follow-up study of 58,927 Korean patients with MASLD found that deteriorating fibrosis scores were likewise linked to light and moderate drinkers [199].”
Influential
General Overview About the Current Management of Nonalcoholic Fatty Liver Disease
Ampuero, J. (2022) · Clinical Drug Investigation · doi:10.1007/s40261-022-01142-w · Cited by 10
“5%; in 2010, NAFLD-associated hepatocellular carcinoma accounted for 35% of all cases [7].”
Background
Common Denominator of MASLD and Some Non-Communicable Diseases
Ferenc, K., Jarmakiewicz-Czaja, S., Sokal-Dembowska, A., Stasik, K., & Filip, R. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46070399 · Cited by 9
“Dyson et al. showed that older people with established diabetes or metabolic syndrome had the highest mortality associated with HCC [118].”
Background
The painful reality of end-stage liver disease in NASH
Ratziu, V. (2017) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(17)30365-5 · Cited by 10
Hepatocellular carcinoma in the context of non-alcoholic steatohepatitis (NASH): recent advances in the pathogenic mechanisms
Lequoy, M., Gigante, E., Couty, J., & Desbois‐Mouthon, C. (2020) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2019-0044 · Cited by 12
Fat and hepatocellular carcinoma
Balsano, C., Porcu, C., Sideri, S., & Tavolaro, S. (2018) · Hepatoma Research · doi:10.20517/2394-5079.2018.51 · Cited by 10
The absence of lactation after pregnancy induces long-term lipid accumulation in maternal liver of mice
Vicente, J. M., Teixeira, C. J., Santos-Silva, J. C., de Souza, D. N., Tobar, N., Furtuoso, F. S., Adabo, I. G., Sodré, F. S., Murata, G. M., Bordin, S. A., et al. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.12.026 · Cited by 10
Epidemiology of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a western perspective
Farrell, A., Ryan, M. C., & Howell, J. A. (2020) · Hepatoma Research · doi:10.20517/2394-5079.2019.019 · Cited by 9
“8% of all HCC cases in 2010 in one cohort of 633 patients([34]).”
BackgroundInfluential
Shifting perspectives – interplay between non-alcoholic fatty liver disease and insulin resistance in lean individuals
Bilić-Ćurčić, I., Berković, M. C., Virovic-Jukic, L., & Mrzljak, A. (2021) · World Journal of Hepatology · doi:10.4254/wjh.v13.i1.80 · Cited by 6
Input of serum haptoglobin fucosylation profile in the diagnosis of hepatocellular carcinoma in patients with non-cirrhotic liver disease
Peta, V., Zhu, J., Lubman, D. M., Huguet, S., Imbert‐Bismut, F., Bolbach, G., Clodic, G., Mathéron, L., Ngo, Y., Pais, R., et al. (2020) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2019.12.010 · Cited by 10
The Hidden Epidemic: The Prevalence and Impact of Concurrent Liver Diseases in Patients Undergoing Liver Transplantation in Australia and New Zealand
Howell, J. A., Majumdar, A., Fink, M. A., Byrne, M., McCaughan, G. W., Strasser, S. I., Crawford, M. W., Hodgkinson, P., Stuart, K. A., Tallis, C. J., et al. (2022) · Transplantation Direct · doi:10.1097/txd.0000000000001345 · Cited by 9
Evolving epidemiology of HCC in Spain
Sala, M., Pascual, S., Roca, M. R. R., Matilla, A. M., Campos, M., Delgado, M. B., Ferrer, M. T., Montero, J. L., Santiago, J. M. G., Guerrero, A. F., et al. (2025) · JHEP Reports · doi:10.1016/j.jhepr.2025.101336 · Cited by 10
“Dyson et al. 38 have assessed the impact of obesity and T2DM in a cohort of patients with HCC managed in Newcastle from 2000 to 2010.”
The Emerging Challenge of Non-Cirrhotic MASLD-Related Hepatocellular Carcinoma: Etiology, Immunopathology, and Precision Oncology
Liu, Y. (2025) · Liver Cancer · doi:10.1159/000550163 · Cited by 12
“Obesity and MASLD act as co-factors as well as primary drivers and are expected to change the global landscape of HCC [38–40].”
Roux-en-Y gastric bypass, but not sleeve gastrectomy, decreases plasma PCSK9 levels in morbidly obese patients
Blanchard, C. L., Ledoux, S., Verhaegen, A. A., Wargny, M., Letessier, E., Stépanian, A., Huten, N., Jacobi, D., Krempf, M., Bras, M. L., et al. (2020) · Diabetes & Metabolism · doi:10.1016/j.diabet.2020.01.003 · Cited by 9
What Not to Overlook in the Management of Patients with Type 2 Diabetes Mellitus: The Nephrological and Hepatological Perspectives
Alfieri, C., Molinari, P., Cinque, F., Vettoretti, S., Cespiati, A., Bignamini, D., Nardelli, L., Fracanzani, A. L., Castellano, G., & Lombardi, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147728 · Cited by 10
“Fibrosis, either assessed by histology or Fibroscan, is a risk factor for HCC but also metabolic comorbidities, especially T2DM and obesity [95,96].”
Background
Liver transplantation for non-alcoholic fatty liver disease—a review
Jayakumar, S. (2018) · AME Medical Journal · doi:10.21037/amj.2018.01.16 · Cited by 9
“Rates of HCC in NASH have increased significantly over the past two decades; it has increased by 9% between 2004 and 2009 in the US (4,18), while in Europe, 35% of all HCC cases were seen in patients with NASH (19).”
Background
Simple blood fibrosis tests reduce unnecessary referrals for specialized evaluations of liver fibrosis in NAFLD and ALD patients
Broussier, T., Lannes, A., Zuberbuhler, F., Oberti, F., Fouchard, I., Hunault, G., Calès, P., & Boursier, J. (2019) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2019.07.010 · Cited by 9
Hepatocellular carcinoma in patients with metabolic dysfunction-associated fatty liver disease: Can we stratify at-risk populations?
Fassio, E., Barreyro, F., Perez, M. S., Dávila, D., Landeira, G., Gualano, G., & Ruffillo, G. (2022) · World Journal of Hepatology · doi:10.4254/wjh.v14.i2.354 · Cited by 13
From NAFLD to cardiovascular disease. Is it (still) the metabolic syndrome?
Munteanu, M. A., & Mircea, P. A. (2014) · Medicine and Pharmacy Reports · doi:10.15386/cjmed-277 · Cited by 9
“showed that at the end of 2010, of all patients with HCC, 35% had NAFLD, representing the most common etiology and constantly growing [23].”
Background
Role of MicroRNAs in the Development of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease
Zhang, C., Wang, P., Li, Y., Huang, C., Wei Min, N. I., Chen, Y., Shi, J., Chen, G., Hu, X., Ye, M., et al. (2018) · The Anatomical Record · doi:10.1002/ar.23954 · Cited by 9
“However, the quantitative proportion of HCC associated with nonalcoholic fatty liver disease (NAFLD) is rapidly increasing in the Western countries (Dyson et al., 2014), and socioeconomic transformations toward Westernized diet also render Asian populations highly susceptible to these rising…”
Background
Porphyromonas gingivalis-odontogenic infection is the potential risk for progression of nonalcoholic steatohepatitis-related neoplastic nodule formation
Sakamoto, S., Nagasaki, A., Shrestha, M., Shintani, T., Watanabe, A., Furusho, H., Chayama, K., Takata, T., & Miyauchi, M. (2023) · Scientific Reports · doi:10.1038/s41598-023-36553-y · Cited by 9
Metabolic dysfunction-associated steatotic liver disease and its associated health risks
Liu, X.-R., Yin, S., Chen, Y.-T., & Lee, M. (2025) · Journal of the Chinese Medical Association · doi:10.1097/jcma.0000000000001230 · Cited by 8
“22 MASLD significantly increases the risks of advanced liver diseases, including cirrhosis and HCC. Table 1 HCC among individuals with NAFLD.”
Mediterranean Diet Adherence Is Associated With Reduced Liver Fibrosis Risk in Metabolic Dysfunction–Associated Steatotic Liver Disease
Hsieh, M.-L., Su, T., Lin, Y., Chen, Y., Tung, C.-F., Huang, L., Wu, C.-H., Peng, Y., & Hsieh, V. C. (2026) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.70259 · Cited by 8
Association between PNPLA3 rs738409 polymorphisms and risk of hepatocellular carcinoma and its development in patients with cirrhosis: a meta-analysis.
Zhang, S., Wu, H., Wu, X., Lian, W., Wang, Y., Zhang, X., & Peng, X. (2015) · Europe PMC (PubMed Central) · Cited by 8
Patterns and co-occurrence of risk factors for hepatocellular carcinoma in four Asian American communities: a cross-sectional study
STEWART, S. L., Dang, J. H. T., Torok, N. J., & Chen, M. S. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-026409 · Cited by 8
“Family history of liver cancer 4 (4) 1 (1) 7 (8) 6 (7) 18 (5)”
Background
Peculiarities of Cirrhosis due to Nonalcoholic Steatohepatitis (NASH)
El‐Sherif, O., & Armstrong, M. J. (2019) · Seminars in Liver Disease · doi:10.1055/s-0039-1697616 · Cited by 8
“42 The increasing prevalence of obesity and T2D have contributed to this rise in patients without NAFLD, 43 but there is growing evidence of the risk of HCC in NASH cirrhosis.”
Animal models for hepatocellular carcinoma arising from alcoholic and metabolic liver diseases
Liu, K., Chen, J., & McCaughan, G. W. (2020) · Hepatoma Research · doi:10.20517/2394-5079.2019.39 · Cited by 8
“Indeed, NAFLD has either already become or is on the verge of becoming the leading cause of HCC in most Western countries([5-8]).”
Background
A systematic assessment of the epidemiologic literature regarding an association between acetaminophen exposure and cancer
Weinstein, R. B., Parikh-Das, A. M., Salonga, R., Schuemie, M. J., Ryan, P. B., Atillasoy, E. O., Hermanowski‐Vosatka, A., Eichenbaum, G. M., & Berlin, J. A. (2021) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2021.105043 · Cited by 8
Liraglutide + PYY3-36 Combination Therapy Mimics Effects of Roux-en-Y Bypass on Early NAFLD Whilst Lacking-Behind in Metabolic Improvements
Metzner, V., Herzog, G., Heckel, T., Bischler, T., Hasinger, J., Otto, C., Faßnacht, M., Geier, A., Seyfried, F., & Dischinger, U. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11030753 · Cited by 8
Reptin regulates insulin‐stimulated Akt phosphorylation in hepatocellular carcinoma via the regulation of SHP‐1/PTPN6
Raymond, A., Javary, J., Breig, O., Neaud, V., & Rosenbaum, J. (2017) · Cell Biochemistry and Function · doi:10.1002/cbf.3274 · Cited by 8
“The predominant causes of cirrhosis and thus HCC are chronic hepatitis viral B or C, alcoholic liver disease, and the metabolic syndrome emerging as a new major aetiology.(1,2) Hepatocarcinogenesis is a multi‐step process that is now better understood thanks in part to large‐scale genomic analyses that have evidenced…”
Background

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: Dyson, Jessica
Das, Debasish
Patanwala, Imran
Cole, Michael
Stewart, Stephen
Hudson, Mark
Manas, Derek
Reeves, Helen L.
Venue: Journal of Hepatology
Publisher: Elsevier BV
Published: 2014-01
Volume: 60
Issue: 1
Pages: 110-117
ISSN: 0168-8278 (ISSN-L)
DOI: 10.1016/j.jhep.2013.08.011
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
FWCI: 19.26
Type: journal article
Language: en
Open access: green
zenodo.org
Licence: other-oa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 › Hepatology › 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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Hepatocellular cancer: The impact of obesity, type 2 diabetes and a multidisciplinary team

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