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 studies.
• 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 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. [PubMed: 9197213]
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. [PubMed: 16278421]

Incidence and Mortality

Hepatocellular cancer (HCC) is the fifth most common cancer in the world in men and the second leading cause of cancer mortality worldwide. In women, hepatocellular cancer is the seventh most common cancer and the sixth leading cause of cancer mortality worldwide.[1] Age-standardized incidence rates are 2.1 per 100,000 population in North America.[2] In the United States, HCC incidence and mortality rates continue to increase, particularly among middle-aged black, Hispanic, and white men.[3]

It is estimated that there will be 39,230 new cases diagnosed and 27,170 deaths due to this disease in the United States in 2016.[4] 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 is 19.9 per 100,000 population among men and 8.4 per 100,000 population among women.[5] Table 1 summarizes the incidence of HCC by geographic region.[6]

In the United States, chronic hepatitis B is the underlying cause of an estimated 2,000 to 4,000 deaths each year from cirrhosis and liver cancer; it is estimated that more than one million Americans have a chronic hepatitis B infection, many of whom do not know they are infected. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most frequent viral infections in humans and represent a major global public health problem. HBV- and HCV-related chronic hepatitis are the main causes of cirrhosis and HCC, which are responsible for a high rate of morbidity and mortality. In the last few years, knowledge of the epidemiology and the natural history of HBV and HCV infections has markedly improved, and considerable progress has been made in the efficacy of therapy.

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.[7]

Viruses Associated With Hepatitis and/or Hepatocellular Cancer

There are several types of viruses associated with hepatitis and/or HCC. Hepatitis is also the name of a family of viral infections that affect the liver; the most common types are hepatitis A, hepatitis B, and hepatitis C.[8]

Hepatitis A, hepatitis B, and hepatitis C are diseases caused by three different viruses. Although each disease can cause similar symptoms, the diseases have different modes of transmission and can affect the liver differently.

Hepatitis A appears only as an acute or newly occurring infection and does not become chronic. People with hepatitis A usually improve without treatment.[9]

Hepatitis B and hepatitis C can also begin as acute infections, but in some people, the virus remains in the body, resulting in chronic disease and long-term liver problems. There are vaccines to prevent hepatitis A and B; however, there is not a vaccine for hepatitis C. If a person has had one type of viral hepatitis in the past, it is still possible to get the other types.[8]

After the hepatitis A and hepatitis B viruses were discovered, neither agent was found responsible for many cases of transfusion-related hepatitis—hence the designation non-A, non-B (NANB) hepatitis. Initial follow-up of these cases showed that approximately 50% of patients developed chronic hepatitis, based on persistence of serum enzymes for at least 6 months. Approximately 15 years later, after HCV had been identified as the cause of NANB hepatitis, chronic hepatitis was found to develop more frequently as indicated by persistent viral infection in more than 80% of infected adults but in only about 50% of infected children or young women.[10]

Risk Factors

References

1. American Cancer Society: Global Cancer Facts and Figures. 2nd ed. Atlanta, Ga: American Cancer Society, 2011. Available online. Last accessed February 8, 2016.
2. Di Bisceglie AM, Carithers RL Jr, Gores GJ: Hepatocellular carcinoma. Hepatology 28 (4): 1161-5, 1998. [PubMed: 9755258]
3. Altekruse SF, McGlynn KA, Reichman ME: Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 27 (9): 1485-91, 2009. [PMC free article: PMC2668555] [PubMed: 19224838]
4. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed May 19, 2016.
5. Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2012. Bethesda, Md: National Cancer Institute, 2015. Also available online. Last accessed February 8, 2016.
6. 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.
7. Okuda K, Nakashima T, Kojiro M, et al.: Hepatocellular carcinoma without cirrhosis in Japanese patients. Gastroenterology 97 (1): 140-6, 1989. [PubMed: 2542116]
8. Centers for Disease Control and Prevention: Viral Hepatitis FAQs for the Public. Atlanta, Ga: Centers for Disease Control and Prevention, Division of Viral Hepatitis, 2008. Available Online. Last accessed February 6, 2015.
9. Fiore AE, Wasley A, Bell BP, et al.: Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 55 (RR-7): 1-23, 2006. [PubMed: 16708058]
10. Seeff LB: The history of the "natural history" of hepatitis C (1968-2009). Liver Int 29 (Suppl 1): 89-99, 2009. [PMC free article: PMC4373556] [PubMed: 19207971]
11. Liu CJ, Jeng YM, Chen CL, et al.: Hepatitis B virus basal core promoter mutation and DNA load correlate with expression of hepatitis B core antigen in patients with chronic hepatitis B. J Infect Dis 199 (5): 742-9, 2009. [PubMed: 19199543]
12. Marcellin P: Hepatitis B and hepatitis C in 2009. Liver Int 29 (Suppl 1): 1-8, 2009. [PubMed: 19207959]
13. Lavanchy D: The global burden of hepatitis C. Liver Int 29 (Suppl 1): 74-81, 2009. [PubMed: 19207969]
14. Bruno S, Crosignani A, Maisonneuve P, et al.: Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study. Hepatology 46 (5): 1350-6, 2007. [PubMed: 17680653]
15. Persico M, Persico E, Suozzo R, et al.: Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels. Gastroenterology 118 (4): 760-4, 2000. [PubMed: 10734027]
16. Rizzetto M: Hepatitis D: thirty years after. J Hepatol 50 (5): 1043-50, 2009. [PubMed: 19285743]
17. Rizzetto M: Hepatitis D: the comeback? Liver Int 29 (Suppl 1): 140-2, 2009. [PubMed: 19207978]
18. Abro AH, Abdou AM, Saleh AA, et al.: Hepatitis E: a common cause of acute viral hepatitis. J Pak Med Assoc 59 (2): 92-4, 2009. [PubMed: 19260572]
19. 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. [PubMed: 11023453]
20. Schröter M, Polywka S, Zöllner B, et al.: Detection of TT virus DNA and GB virus type C/Hepatitis G virus RNA in serum and breast milk: determination of mother-to-child transmission. J Clin Microbiol 38 (2): 745-7, 2000. [PMC free article: PMC86193] [PubMed: 10655378]
21. 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. [PubMed: 7922998]
22. 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. [PubMed: 10326690]
23. 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. [PubMed: 7686879]
24. Beasley RP: Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61 (10): 1942-56, 1988. [PubMed: 2834034]
25. 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. [PubMed: 2572739]
26. 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. [PubMed: 7684822]
27. Kato J, Miyanishi K, Kobune M, et al.: Long-term phlebotomy with low-iron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C. J Gastroenterol 42 (10): 830-6, 2007. [PubMed: 17940836]
28. Farinati F, Floreani A, De Maria N, et al.: Hepatocellular carcinoma in primary biliary cirrhosis. J Hepatol 21 (3): 315-6, 1994. [PubMed: 7530737]
29. Ross RK, Yuan JM, Yu MC, et al.: Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 339 (8799): 943-6, 1992. [PubMed: 1348796]
30. 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. [PubMed: 12113033]

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. 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. [PubMed: 9197213]

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about liver (hepatocellular) cancer prevention. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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PDQ® Screening and Prevention Editorial Board. PDQ Liver (Hepatocellular) Cancer Prevention. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: http://www.cancer.gov/types/liver/hp/liver-prevention-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389403]

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