Epidemiology of Hepatocellular Carcinoma

https://doi.org/10.1016/j.soc.2014.09.001Get rights and content

Section snippets

Key points

  • HCC is a common malignancy worldwide with nearly equal numbers of new cases and cancer-related death each year.

  • Most HCCs arise in the background of chronic liver disease caused by hepatitis B virus, hepatitis C virus, and chronic excessive alcohol intake.

  • A detailed understanding of these risk factors and how they lead to cancer development is necessary to improve the screaming, prevention, early identification and management of HCC.

Incidence

The incidence of HCC is not evenly distributed throughout the globe. A great preponderance of cases occur in sub-Saharan Africa and Eastern Asia (>80%), and China is believed to account for approximately 50% of all cases of HCC worldwide. Conversely, North and South America, as well as Europe, have a comparatively low incidence of HCC. These marked differences can be attributed to several specific factors.

Risk factors

HCC is a genetically heterogeneous tumor. Hepatocarcinogenesis is complex, requiring multiple genetic and epigenetic alterations and the involvement of several signal transduction pathways, including p53, Ras, MAPK, JAK/STAT, Wnt/β-catenin, and hedgehog.13, 14 Multiple predisposing causes of HCC have been defined, including HBV, HCV, excessive alcohol consumption, obesity, and aflatoxins, and the prevalence/contribution of these risk factors vary by region (Fig. 2).

Metabolic Syndromes

Although worldwide, most HCC is related to hepatitis viral infection and alcoholic liver disease, many patients (5%–20%) with HCC are negative for both HBV and HCV. Nonalcoholic fatty liver disease (NAFLD) and the more severe form, biopsy proven nonalcoholic steatohepatitis (NASH), are characterized by liver disease in the absence of a history of significant alcohol use, or liver disease of unknown cause, and have become the most common cause of cryptogenic chronic liver disease in the United

Economic/public health aspect

The burden of HCC on the health systems of Western countries will likely increase in the coming years as a result of disease progression of HCV-positive baby boomers, and the 20-year to 40-year lag time between viral infection and development of HCC. Because of HCV, as well as other risk factors discussed earlier, it is projected that both compensated cirrhosis and HCC will increase by more than 80% from 2000 to 2020 in the United States.99 Although the figure is dated, the total cost of

Summary

HCC is a common malignancy worldwide, with nearly equal numbers of new cases and cancer-related death each year. Most HCCs develop in the setting of chronic underlying liver disease, the cause of which can differ widely based on multiple factors. The principal causal factors for carcinogenesis in HCC are HBV, HCV, and alcohol abuse, although there seems to be an increasing incidence of NASH-associated HCC in Western countries. A detailed understanding of these risk factors and how they lead to

First page preview

First page preview
Click to open first page preview

References (100)

  • M. Yuen et al.

    Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B

    J Hepatol

    (2009)
  • A. Sangiovanni et al.

    Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance

    Gastroenterology

    (2004)
  • K. McGlynn et al.

    The global epidemiology of hepatocellular carcinoma: present and future

    Clin Liver Dis

    (2011)
  • A. Freeman et al.

    Estimating progression to cirrhosis in chronic hepatitis C virus infection

    Hepatology

    (2001)
  • T. Poynard et al.

    Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups

    Lancet

    (1997)
  • M. Shindo et al.

    The virological and histological states of anti-hepatitis C virus-positive subjects with normal liver biochemical values

    Hepatology

    (1995)
  • P. Grewal et al.

    Liver cancer and alcohol

    Clin Liver Dis

    (2012)
  • J. Marrero et al.

    Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma

    J Hepatol

    (2005)
  • G. Corrao et al.

    A meta-analysis of alcohol consumption and the risk of 15 diseases

    Prev Med

    (2004)
  • A. Boveris et al.

    Increased chemiluminescence and superoxide production in the liver of chronically ethanol-treated rats

    Arch Biochem Biophys

    (1983)
  • E. Kukiełka et al.

    Increased production of reactive oxygen species by rat liver mitochondria after chronic ethanol treatment

    Arch Biochem Biophys

    (1994)
  • S. Kubo et al.

    High malignancy of hepatocellular carcinoma in alcoholic patients with hepatitis C virus

    Surgery

    (1997)
  • B. Neuschwander-Tetri et al.

    Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference

    Hepatology

    (2003)
  • H. El-Serag et al.

    Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma

    Gastroenterology

    (2004)
  • J. Polesel et al.

    The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma

    Ann Oncol

    (2009)
  • C. Alexia et al.

    An evaluation of the role of insulin-like growth factors (IGF) and of type-I IGF receptor signalling in hepatocarcinogenesis and in the resistance of hepatocarcinoma cells against drug-induced apoptosis

    Biochem Pharmacol

    (2004)
  • M. Elmberg et al.

    Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives

    Gastroenterology

    (2003)
  • Y. Yun et al.

    Cigarette smoking and cancer incidence risk in adult men: National Health Insurance Corporation Study

    Cancer Detect Prev

    (2005)
  • S. Zaman et al.

    Risk factors in development of hepatocellular carcinoma in cirrhosis: prospective study of 613 patients

    Lancet

    (1985)
  • G. Davis et al.

    Projecting future complications of chronic hepatitis C in the United States

    Liver Transpl

    (2003)
  • R. Sandler et al.

    The burden of selected digestive diseases in the United States

    Gastroenterology

    (2002)
  • J. Ferlay et al.

    GLOBOCAN 2008 v2.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 10

    (2010)
  • M. Shariff et al.

    Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics

    Expert Rev Gastroenterol Hepatol

    (2009)
  • B. Custer et al.

    Global epidemiology of hepatitis B virus

    J Clin Gastroenterol

    (2004)
  • M. Chang et al.

    Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study

    J Natl Cancer Inst

    (2009)
  • H. Yoshizawa

    Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future

    Oncology

    (2002)
  • G. Fattovich et al.

    Hepatocellular carcinoma in cirrhosis: incidence and risk factors

    Gastroenterology

    (2004)
  • A. Pellicelli et al.

    HCV genotype 1a shows a better virologic response to antiviral therapy than HCV genotype 1b

    BMC Gastroenterol

    (2012)
  • S. Altekruse et al.

    Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005

    J Clin Oncol

    (2009)
  • S. Mittal et al.

    Epidemiology of hepatocellular carcinoma: consider the population

    J Clin Gastroenterol

    (2013)
  • M. Branda et al.

    Signal transduction cascades and hepatitis B and C related hepatocellular carcinoma

    Hepatology

    (2006)
  • W. Tsai et al.

    Viral hepatocarcinogenesis

    Oncogene

    (2010)
  • B. McMahon

    The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B

    Hepatol Int

    (2009)
  • H. Chan et al.

    Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma

    Gut

    (2004)
  • C. Lee et al.

    Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan

    Scand J Gastroenterol

    (2003)
  • P. Tangkijvanich et al.

    Hepatitis B virus genotypes and hepatocellular carcinoma in Thailand

    World J Gastroenterol

    (2005)
  • M. Ferber et al.

    Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers

    Oncogene

    (2003)
  • H. Yang et al.

    Hepatitis B e antigen and the risk of hepatocellular carcinoma

    N Engl J Med

    (2002)
  • C. Chen et al.

    Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level

    JAMA

    (2006)
  • R. Simonietti et al.

    Hepatocellular carcinoma. A worldwide problem and the major risk factors

    Dig Dis Sci

    (1991)
  • Cited by (0)

    Funding sources: none (Dr T.M. Pawlik, Dr K.J. Lafaro); Speaker’s Bureau – Bayer, Speaker’s Bureau – Aptalis (Dr A.N. Demirjian).

    Conflicts of interest: none.

    View full text