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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, 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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“People with NASH have a much higher risk of liver fibrosis, cirrhosis, and even hepatocellular carcinoma [6,7].”
BackgroundGenetic predisposition similarities between NASH and ASH: Identification of new therapeutic targets
Bianco, C., Casirati, E., Malvestiti, F., & Valenti, L. V. C. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100284 · Cited by 51
Berberine prevents NAFLD and HCC by modulating metabolic disorders
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“However, most studies showed a similar survival despite patients having an older age at presentation (17,28,111) and after matching patients with each tumor stage, a similar prognosis to other HCC etiologies.”
BackgroundResultInfluentialImmunological distinctions between nonalcoholic steatohepatitis and hepatocellular carcinoma
Koo, S.-Y., Park, E.-J., & Lee, C.-W. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0480-3 · Cited by 47
Zeng, R. W., Ong, C. E. Y., Ong, E. Y. H., Chung, C. H., Lim, W. H., Xiao, J., Danpanichkul, P., Law, J. H., Syn, N., Chee, D., et al. (2024) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2024.06.026 · Cited by 47
Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma: Implications for Lycopene Intervention
Ip, B. C., & Wang, X. (2013) · Nutrients · doi:10.3390/nu6010124 · Cited by 47
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
“MAFLD is currently progressively increasing as the main cause of hepatocellular carcinoma (HCC) globally.[34] The available data suggest that Egypt has one of the highest increases in the age‐standardized incidence rate of MAFLD‐related HCC globally, with an increase of 89.”
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
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“Glucosa en ayunas, mg/dl, mediana (RIQ) 130 (100-181) 94 (87-113) < 0.”
de Sousa, J. H. B., Calil, I. L., Tustumi, F., Khalil, D. D. C., Felga, G. E. G., Pécora, R. A. A., & de Almeida, M. D. (2020) · Translational Gastroenterology and Hepatology · doi:10.21037/tgh.2020.01.06 · Cited by 44
“In the US, Europe, and Japan, hepatitis C and alcohol abuse are major risk factors (2-4).”
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Chronic Viral Hepatitis B and C Outweigh MASLD in the Associated Risk of Cirrhosis and HCC
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Case-finding strategies in non-alcoholic fatty liver disease
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Recurrence of hepatocellular carcinoma following liver transplantation
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“83,84 Obesity is also an independent risk factor of HCC. 85,86 Several studies have provided strong evidence that obesity, especially early age onset, impacts HCC development with an associated increase in mortality.”
BackgroundKawaguchi, T., Tokushige, K., Hyogo, H., Aikata, H., Nakajima, T., Ono, M., Kawanaka, M., Sawada, K., Imajo, K., Honda, K., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-28650-0 · Cited by 38
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“Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease and cirrhosis [1–3], a major risk factor for hepatocellular carcinoma [4], the second most common cause of liver transplantation inmajormedical centers [5], themost likely cause of abnormal liver enzymes in Western countries…”
BackgroundTriglycerides Mediate Body Mass Index and Nonalcoholic Fatty Liver Disease: A Population-Based Study
Xing, J., Guan, X., Zhang, Q., Chen, S., Wu, S., & Sun, X. (2021) · Obesity Facts · doi:10.1159/000514848 · Cited by 40
Toxic AGE (TAGE) Theory for the Pathophysiology of the Onset/Progression of NAFLD and ALD
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“NAFLD is the second most common reason for being on a waiting list for a liver transplant in the United States [27] and the most common cause of hepatocellular carcinoma (HCC) in the USA [28] and United Kingdom [29].”
BackgroundNutrition and Hepatocellular Cancer
Schütte, K., Schulz, C., & Malfertheiner, P. (2015) · Gastrointestinal Tumors · doi:10.1159/000441822 · Cited by 39
Synergistic and Detrimental Effects of Alcohol Intake on Progression of Liver Steatosis
Ciaula, A. D., Bonfrate, L., Krawczyk, M. J., Frühbeck, G., & Portincasa, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052636 · Cited by 37
Surveillance for Hepatocellular Carcinoma in Patients with NASH
Kolly, P., & Dufour, J. (2016) · Diagnostics · doi:10.3390/diagnostics6020022 · Cited by 38
“The number of patients affected by HCC is increasing [6], probably for several reasons: Better surveillance of patients at risk, the aging cohort of hepatitis C (HCV)-infected patients, and the increasing importance of non-alcoholic steatohepatitis (NASH) in the landscape of liver diseases [7].”
BackgroundChen, X., Shen, T., Li, Q., Chen, X., Li, Y., Li, D., Chen, G., Ling, W., & Chen, Y. (2017) · Scientific Reports · doi:10.1038/srep45100 · Cited by 39
“NAFLD encompasses simple steatosis and non-alcoholic steatohepatitis (NASH), which can progress to fibrosis and, finally, cirrhosis, even with hepatic cellular cancer (HCC) 3 .”
Ho, C., Lee, C., Lee, M., Zhang, J.-F., Wang, J., Hu, R., & Lee, P. (2018) · BMC Cancer · doi:10.1186/s12885-018-4292-y · Cited by 38
“We could not identify NASH patients accurately by ICD-9 classification, which is also a risk factor for HCC [50].”
BackgroundZhang, X. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i12.3554 · Cited by 38
Diabetes and Hepatocellular Carcinoma: Incidence Trends and Impact of Liver Disease Etiology
Doycheva, I., Zhang, T., Amjad, W., & Thuluvath, P. J. (2019) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2019.11.004 · Cited by 40
“An HCC database study from the United Kingdom suggested that patients without underlying chronic liver disease presented with larger tumors, at more advanced stage, and were less likely to be referred for liver transplantation.(21) Moreover, in their study, only 23% of patients with NAFLD-related HCC were detected by…”
MethodTraussnigg, S., Kienbacher, C., Halilbasic, E., Rechling, C., Kazemi-Shirazi, L., Hofer, H., Munda, P., & Trauner, M. A. (2015) · Digestive Diseases · doi:10.1159/000375353 · Cited by 37
Metadata
- 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
- 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 › 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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