The Etiology of Hepatocellular Carcinoma and Consequences for Treatment
Open accessAbstract
Most patients with hepatocellular carcinoma (HCC) have liver cirrhosis, which develops following long periods of chronic liver disease. Cirrhosis is characterized by a decrease in hepatocyte proliferation, indicating an exhaustion of the regenerative capacity of the liver, and results in an increase in fibrous tissue and a destruction of liver cells, which may ultimately lead to the development of cancerous nodules. Half of all cases of HCC are associated with hepatitis B virus infection, with a further 25% associated with hepatitis C virus. Other risk factors for developing HCC include alcoholic liver disease, nonalcoholic steatohepatitis, intake of aflatoxin-contaminated food, diabetes, and obesity. There are multiple factors involved in the etiology of HCC, all of which have a direct impact on patient characteristics and disease course, and although a causative agent can often be identified, HCC remains an extremely complex condition associated with a poor prognosis. Additionally, the geographic variation in etiology means that information from different countries is needed in order to optimize surveillance methods and develop effective chemoprevention strategies. Unfortunately, there are still many gaps in our current understanding, and further research efforts are needed to fully elucidate the diverse mechanisms involved in the pathogenesis of HCC and offer optimal prevention strategies for those at risk.
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The underlying liver disease type carries a specific hepatocellular carcinoma risk in cirrhosis, with chronic hepatitis B or C and haemochromatosis at relatively high risk and autoimmune hepatitis or alcoholic liver disease at relatively low risk.
“However, additional factors are involved and each type of underlying liver disease entails a specific risk for the development of HCC in cirrhosis; diseases such as chronic hepatitis B and C or haemochromatosis entail a relatively high risk and diseases such as autoimmune hepatitis or ALD a relatively low risk38–40.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [39]
Alcoholic liver disease may have a lower relative hepatocellular carcinoma risk than other chronic liver diseases, but its absolute hepatocellular carcinoma burden is high because many patients have alcoholic cirrhosis.
“Although ALD might have a lower relative risk of causing HCC than other types of CLD39, the sheer number of patients with alcoholic cirrhosis means that the absolute number of HCCs caused by ALD is high.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [39]
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- Authors
- Sanyal, A. J., Yoon, S. K., & Lencioni, R.
- Affiliations
- Virginia Commonwealth University Medical Center (US)
- Catholic University of Korea (KR)
- University of Pisa (IT)
- Venue
- The Oncologist
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-11-01
- Volume
- 15
- Issue
- S4
- Pages
- 14-22
- ISSN
- 1083-7159 (ISSN-L)
- 1549-490X
- OpenAlex
- W2097494822
- Cited by
- 517
- References
- 80
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 16 · 2023: 21 · 2022: 20 · 2021: 39 · 2020: 56 · 2019: 48 · 2018: 66 · 2017: 62 · 2016: 32 · 2015: 32 · 2014: 38 · 2013: 24 · 2012: 26
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Oncologist (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- Bayer HealthCare Pharmaceuticals
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- hepatocellular carcinoma, etiology, liver cirrhosis, hepatitis B virus, hepatitis C virus, alcoholic liver disease, nonalcoholic steatohepatitis, aflatoxins, diabetes mellitus, obesity, risk factors, chemoprevention, surveillance (medicine), prognosis, pathogenesis
- MeSH terms
- Aflatoxins, Fatty Liver, Hepatitis B, Hepatitis B virus, Hepatitis C, Carcinoma, Hepatocellular, Humans, Liver Cirrhosis, Liver Diseases, Alcoholic, Liver Neoplasms, Risk Factors, Survival Rate, Hepacivirus, Treatment Outcome, Non-alcoholic Fatty Liver Disease
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