Health Library Hepatocellular Cancer: Prevention - Health Professional Information [NCI PDQ]From Healthwise

This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER

Liver (Hepatocellular) Cancer Prevention (PDQ®)

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about hepatocellular cancer prevention. This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board.

Information about the following is included in this summary:

• Hepatocellular cancer incidence and mortality statistics and information about hepatocellular cancer risk factors.
• Interventions for hepatocellular cancer prevention.
• Benefits and harms of interventions to prevent hepatocellular cancer.

This summary is intended as a resource to inform clinicians and other health professionals about the currently available information on hepatocellular cancer prevention. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in reporting the evidence of benefit and potential harms associated with specific interventions. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version, which is written in less technical language.

Note: Separate PDQ summaries on Liver (Hepatocellular) Cancer Screening; Adult Primary Liver Cancer Treatment; Childhood Liver Cancer Treatment; and Levels of Evidence for Cancer Screening and Prevention Studies are also available.

Hepatitis B Vaccine to Prevent Hepatocellular Cancer

Based on solid evidence, immunizing individuals against hepatitis B would lead to a decrease in the incidence of hepatocellular cancer (HCC).

Description of the Evidence

• STUDY DESIGN: Evidence obtained from cohort or case-control study.
• INTERNAL VALIDITY: Fair (ecologic control; no direct comparison group).
• CONSISTENCY: Limited number of studies.
• MAGNITUDE OF EFFECTS ON HEALTH OUTCOMES: Reduction of risk occurs with prevention of hepatitis B infection in one intervention study. A study of vaccination in Taiwan shows that vaccination of newborns (the vaccination program includes administration of hepatitis B immunoglobulin at birth, followed by a course of hepatitis B vaccine) of mothers infected with hepatitis B virus was associated with a reduction in the average annual incidence of HCC from 0.70 per 100,000 children between 1981 and 1986 to 0.57 and 0.36 for the time periods of 1986 to 1990 and 1990 to 1994, respectively (P < .01).[1] Although there was no direct control group, the decline in incidence of HCC over time would unlikely be explained by other causes. Failures in a vaccination program may be related to either failure to receive hepatitis B immunoglobulin or failure of the hepatitis B vaccine itself.[ 2]
• EXTERNAL VALIDITY: Good.

References:

1. Chang MH, Chen CJ, Lai MS, et al.: Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med 336 (26): 1855-9, 1997.
2. Chang MH, Chen TH, Hsu HM, et al.: Prevention of hepatocellular carcinoma by universal vaccination against hepatitis B virus: the effect and problems. Clin Cancer Res 11 (21): 7953-7, 2005.

Incidence and Mortality

Hepatocellular cancer (HCC) is the fourth most common cancer in the world.[1] Age-standardized incidence rates vary from 2.1 per 100,000 population in North America [ 2] to 80 per 100,000 population in China.[ 1] In the United States, it is estimated that there will be 21,370 new cases diagnosed and 18,410 deaths due to this disease in 2008.[ 3] There is a distinct male preponderance among all ethnic groups in the United States, although this trend is most marked among Chinese Americans, in whom the annualized rate of HCC among men is 20.9 per 100,000 and among women 8.0 per 100,000 population.[ 4] The table below summarizes the incidence of hepatocellular carcinoma by geographic region.[ 5]

Table 1. Incidence of Hepatocellular Carcinoma by Geographic Regiona

HCC is very rare in persons younger than 40 years in the United States, and a much higher risk of HCC is associated with a long duration of infection with hepatitis C (e.g., greater risk after 30 years of infection). About 80% of persons with HCC have cirrhosis.[6]

Risk Factors

Hepatitis B and C

Chronic hepatitis B and C are recognized as the major factors worldwide that increase the risk of HCC, with risk being greater in the presence of coinfection with hepatitis B virus and hepatitis C virus.[7, 8, 9, 10, 11, 12] The incidence of HCC in individuals with chronic hepatitis is as high as 0.46% per year. In the United States, chronic hepatitis B and C account for about 30% to 40% of HCC. Chronic hepatitis G infection is not associated with HCC in either hepatitis B surface antigen–positive carriers or noncarriers.[ 13]

Cirrhosis and other factors

Cirrhosis is a risk factor for HCC, irrespective of the etiology of the cirrhosis.[7, 8] The annual risk of developing HCC among persons with cirrhosis is between 1% and 6%.[ 9] Other risk factors include hemochromatosis, alpha-1-antitrypsin deficiency, glycogen storage disease, porphyria cutanea tarda, tyrosinemia, and Wilson disease,[ 2] but rarely biliary cirrhosis.[ 14] Aflatoxins, which are mycotoxins formed by certain Aspergillus species, are a frequent contaminant of improperly stored grains and nuts. In parts of Africa, the high incidence of HCC in humans may be related to ingestion of foods contaminated with aflatoxins. This association, however, is blurred by the frequent coexistence of hepatitis B infection in those population groups. Heavy aflatoxin exposure is associated with inactivation of the p53 tumor suppressor gene, but epidemiological evidence of a causal association is limited.[ 15] The likely etiology of HCC is summarized in Table 2.[ 16]

Table 2. Likely Etiology of HCC

References:

1. Parkin DM, Whelan SL, Ferlay J, et al., eds.: Cancer Incidence in Five Continents. Volume VII. Lyon, France: International Agency for Research on Cancer, 1997.
2. Di Bisceglie AM, Carithers RL Jr, Gores GJ: Hepatocellular carcinoma. Hepatology 28 (4): 1161-5, 1998.
3. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed July 24, 2008.
4. Ries LAG, Harkins D, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2003. Bethesda, Md: National Cancer Institute, 2006. Also available online. Last accessed July 31, 2008.
5. Russo MW, Jacobson IM: Hepatocellular cancer: screening, surveillance, and prevention. In: Kelsen DP, Daly JM, Kern SE, et al., eds.: Gastrointestinal Oncology: Principles and Practices. Philadelphia, Pa: Lippincott, Williams and Wilkins, 2002, pp 559-568.
6. Okuda K, Nakashima T, Kojiro M, et al.: Hepatocellular carcinoma without cirrhosis in Japanese patients. Gastroenterology 97 (1): 140-6, 1989.
7. Benvegnù L, Fattovich G, Noventa F, et al.: Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. A prospective study. Cancer 74 (9): 2442-8, 1994.
8. Chiaramonte M, Stroffolini T, Vian A, et al.: Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 85 (10): 2132-7, 1999.
9. Ikeda K, Saitoh S, Koida I, et al.: A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 18 (1): 47-53, 1993.
10. Beasley RP: Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61 (10): 1942-56, 1988.
11. Bruix J, Barrera JM, Calvet X, et al.: Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and hepatic cirrhosis. Lancet 2 (8670): 1004-6, 1989.
12. Tsukuma H, Hiyama T, Tanaka S, et al.: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328 (25): 1797-801, 1993.
13. Yuan JM, Govindarajan S, Gao YT, et al.: Prospective evaluation of infection with hepatitis G virus in relation to hepatocellular carcinoma in Shanghai, China. J Infect Dis 182 (5): 1300-3, 2000.
14. Farinati F, Floreani A, De Maria N, et al.: Hepatocellular carcinoma in primary biliary cirrhosis. J Hepatol 21 (3): 315-6, 1994.
15. Ross RK, Yuan JM, Yu MC, et al.: Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 339 (8799): 943-6, 1992.
16. Shiratori Y, Yoshida H, Omata M: Management of hepatocellular carcinoma: advances in diagnosis, treatment and prevention. Expert Rev Anticancer Ther 1 (2): 277-90, 2001.

Prevention of Hepatitis B

Strong evidence that hepatocellular cancer (HCC) can be prevented is provided by a study of immunization to prevent transmission of hepatitis B from infected mothers to their children, suggesting that if hepatitis can be prevented, then much HCC can be prevented. Of course, immunization programs are justified for preventing important short-term consequences of hepatitis B infection, such as acute hepatitis, chronic hepatitis, and cirrhosis.[1]

References:

1. Chang MH, Chen CJ, Lai MS, et al.: Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med 336 (26): 1855-9, 1997.

CALL 1-800-4-CANCER

For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.

CHAT ONLINE

The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

WRITE TO US

For more information from the NCI, please write to this address:

SEARCH THE NCI WEB SITE

The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use our “Best Bets” search box in the upper right hand corner of each Web page. The results that are most closely related to your search term will be listed as Best Bets at the top of the list of search results.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

FIND PUBLICATIONS

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615.

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

SIGNIFICANCE

Updated incidence and mortality estimates for 2008 (cited American Cancer Society as reference 3).

If you have questions or comments about this summary, please send them to Cancer.gov through the Web site’s Contact Form. We can respond only to email messages written in English.

ABOUT PDQ

• PDQ® - NCI's Comprehensive Cancer Database.

  Full description of the NCI PDQ database.

ADDITIONAL PDQ SUMMARIES

• PDQ® Cancer Information Summaries: Adult Treatment

  Treatment options for adult cancers.

• PDQ® Cancer Information Summaries: Pediatric Treatment

  Treatment options for childhood cancers.

• PDQ® Cancer Information Summaries: Supportive and Palliative Care

  Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.

• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)

  Tests or procedures that detect specific types of cancer.

• PDQ® Cancer Information Summaries: Prevention

  Risk factors and methods to increase chances of preventing specific types of cancer.

• PDQ® Cancer Information Summaries: Genetics

  Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.

• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine

  Information about complementary and alternative forms of treatment for patients with cancer.

IMPORTANT:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Date Last Modified: 2008-04-03

This information does not replace the advice of a doctor. Healthwise disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use. How this information was developed to help you make better health decisions.