Preventing Hepatitis B, Hepatocellular Cancer: Made in Taiwan

September 1, 1996

In most developed nations, cancer is second only to heart disease as a cause of death; in less developed countries, it is second to infectious disease. It is estimated that if the current trends of rising worldwide incidence continue, cancer will become the leading cause of death in the 21st century. This is particularly troubling since many of the factors contributing to cancer (eg, occupation, diet, lifestyle, and tobacco use) are known.

In most developed nations, cancer is second only to heart diseaseas a cause of death; in less developed countries, it is secondto infectious disease. It is estimated that if the current trendsof rising worldwide incidence continue, cancer will become theleading cause of death in the 21st century. This is particularlytroubling since many of the factors contributing to cancer (eg,occupation, diet, lifestyle, and tobacco use) are known.

The politics of science have had an enormous impact on the developmentof public policy programs for the prevention and treatment ofmany types of cancer. Highly politicized and well-financed interestgroups include environmentalists, tobacco companies, labor unions,physicians, scientists, and patient advocates. They have the capacityto affect which diseases and therapies are and are not researched,evaluated, and treated, and which information is disseminatedand by what means.

Balancing these often conflicting interests affects the successof large-scale initiatives. Despite these obstacles, broad education,prevention, and treatment measures must be considered, to establishcontrol over the incidence and costs of cancer.

Excellent practical examples of highly organized and effectiveinitiatives are the programs developed to eradicate hepatitisB virus infection and hepatocellular carcinoma. These programshave proven so successful that the World Health Organization considershepatitis B vaccination the most important cancer prevention programtoday, with the exception of smoking cessation programs.

More than 75% of the world's chronic hepatitis B carriers livein the Asia-Pacific region. In countries with large economic resourcesand a significant hepatitis B problem, such as Malaysia, Singapore,and Taiwan, national immunization programs have reduced hepatitisB carrier rates from approximately 10% to 1%-2% in 3 to 5 years.[1]In China, the seropositivity rate for HBsAg has been reduced from16.3% to 1.4% since 1986.[2] In Thailand and the Philippines,despite fewer resources, similar improvements have been noted.

However, in countries that are poor and involved in politicalturmoil, such as Myanmar, Indonesia, and Cambodia, programs havenot been initiated because of a lack of political commitment andeconomic resources. Likewise, most African countries are unableto obtain funding for vaccination programs, despite politicalinterest and even though it is estimated that vaccination wouldcontrol more than 75% of hepatitis B cases in Africa.[3]

In areas with a lower incidence, vaccination program developmenthas been variable. New Zealand has been a pioneer in hepatitisB immunization, while Australia has not adopted any program.

In the South Pacific island countries, a UNICEF-sponsored VaccineIndependence Initiative has provided the opportunity to test noveldelivery methods, including disposable injection devices and combinationDTP-HB vaccines.

The Taiwan Example

The central elements of a successful program for large-scale hepatitisB management include political commitment, a reliable source ofrecurrent funding of public sector programs, and delivery mechanismsintegrated with primary maternal and child health care. An exampleof how the integration of these elements has provided an effectivehepatitis B vaccination program is the hepatitis B eradicationprogram in Taiwan.

A nationwide hepatitis B vaccination program was initiated inTaiwan in early 1983 with the goal of decreasing the incidenceand costs of hepatitis B infection, hepatocellular carcinoma,and cirrhosis.[4] A National Hepatitis Advisory Steering Committeewas organized at the cabinet level with representatives from theDepartment of Health, the National Science Council, and GovernmentMinistries and Offices. Each of these committees was assignedspecific hepatitis B virus-related tasks (see table ).

Beginning in July 1984, voluntary screening of expectant mothersfor HBsAg during the last trimester of pregnancy was begun, with78% participation during the first 15 months.[5]

Each identified carrier mother was registered with the appropriateHealth Station. A vaccination booklet and coupons for future vaccinesand hepatitis B immune globulin (HBIG) injections were mailedto each participant.

Infants of HBsAg carrier mothers received a four-dose regimenof hepatitis B vaccine. Those babies born to highly infectiousmothers also received a dose of HBIG within 24 hours after birth.

As follow-up, seroepidemiological studies were conducted usinga random sample of the previously vaccinated infants. Local publichealth nurses visited each selected child and obtained blood samplesat 18, 24, 36, and 48 months; these were analyzed for HBsAg, anti-HBs,and anti-HBc.

Infants of highly infectious mothers had HBsAg positivity ratesof 14.2% (vaccine plus HBIG) and 19.7% (vaccine only) when onschedule, and 17.0% when off schedule.[5] Infants of moderatelyinfectious mothers had HBsAg positivity rates of 3.0% when onschedule and 6.4% when off schedule. These low positivity ratespersisted throughout the 48-month follow-up period. This representsa dramatic improvement over the 40% to 96% vertical transmissionrate seen before program implementation.[6]

The costs of medical care and loss of income related to hepatitisB virus infection in Taiwan have been estimated to be US $318.3million during the period from 1984 to 1994, whereas the costof immunization was US $100 million for this same period, thusdemonstrating the cost effectiveness of this effort.[7]

Cancer-related benefits have also been observed. The annual incidenceof hepatocellular carcinoma for children aged 0 to 14 years declinedfrom 4.48-7.13 cases per 100,000 in 1981/1991 to 1.74-2.39 casesper 100,000 in 1992/1993.[8] These benefits are expected to becomemore dramatic beginning in 2004, when the time period from immunizationcorresponds to the latency period for hepatocellular carcinomaattributed to chronic hepatitis B infection (20 to 40 years).

Worldwide, well-implemented hepatitis B vaccination programs havereported similar success, demonstrating the cost effectivenessof this intervention as a preventive measure for cancer. It isestimated that routine infant hepatitis vaccination programs inthe United States cost $1,852 per year of life saved, while smokingcessation with nicotine gum therapy costs $7,450 per year of lifesaved.[9]

Nationwide policies to effectively combat the rising incidenceand costs of cancer are possible, as demonstrated by programsdeveloped to eradicate hepatitis B and hepatocellular carcinoma.Such programs require a political and financial commitment atthe highest levels of government; centralized implementation andmonitoring; and broad support for a scientifically based consensuson the best educational, prevention, and treatment measures forthe public good.

Tasks for Development of a Hepatitis B Vaccination Program:Taiwan

References:

1. Ruff TA: Control of hepatitis B in Asia and the Pacific Basin.Proceedings of the IX Triennial International Symposium on ViralHepatitis and Liver Disease, Rome, Italy, April 21-25, 1996 (abstract69).

2. Xu ZY, Yan TQ, Zhao SJ, et al: Control of hepatitis B virusin China. Proceedings of the IX Triennial International Symposiumon Viral Hepatitis and Liver Disease, Rome, 1996.

3. Ndumbe P, Maynard J, Goudeau A, et al: Control of hepatitisB in Africa. Proceedings of the IX Triennial International Symposiumon Viral Hepatitis and Liver Disease (abstract 72).

4. Chen DS, Hsu HM, Sung JL, et al: A mass vaccination programin Taiwan against hepatitis B virus infection in infants of hepatitisB surface-antigen carrier mothers. JAMA 257:2597-2603, 1987.

5. Chen DS, Hsu HM, Bennett CL, et al: A program for eradicationof hepatitis B from Taiwan by a 10 year, four dose vaccinationprogram. Cancer Causes & Control 7:1-7, 1996.

6. Stevens CE, Beasley RP, Tsiu J, et al: Vertical transmissionof hepatitis B antigen in Taiwan. N Engl J Med 292:771-774, 1975.

7. Sung JL: Control of hepatitis B in Taiwan, in Sung JL, ChenDS (eds): Viral Hepatitis and Hepatocellular Carcinoma, p 435.Hong Kong, Excerpta Medica, Current Clinical Practices Series57, 1990.

8. Chang M, Chen C, Lai M, et al: Hepatitis B mass vaccinationprogram decreases childhood hepatocellular carcinoma in Taiwan.Proceedings of the IX Triennial International Symposium on ViralHepatitis and Liver Disease. Rome, Italy, April 21-25, 1996 (abstractC243).

9. Holliger FB: Control of HBV transmission in the US. Gut 38(suppl):S24-S30,1996.