Progress in Chronic Disease Prevention Summary of a Workshop on Screening for Hepatocellular Carcinoma

When patients present with hepatocelluar carcinoma (HCC) at the symptomatic stage, the disease is rapidly fatal, with a mean survival time of less than 4 months (1). Because prolonged survival has been reported following resection or other therapies when HCC has been detected at an early stage, screening for early detection of HCC may be useful. On September 11 and 12, 1989, a workshop to review available data on the use of screening for early detection of HCC was held in Anchorage, Alaska. The conference was sponsored by the Alaska Area Native Health Service of the Indian Health Service, the Fox Chase Cancer Center, and CDC's Arctic Investigations Program, Center for Infectious Diseases. Participants included investigators from China, Hong Kong, Japan, South Africa, and the United States who had studied the early detection of HCC.

Workshop participants addressed several questions regarding HCC, including whether HCC can be detected at an early stage using serologic markers or radiologic tests, whether treatment of HCC detected at an early stage can lead to prolonged survival, and whether high-risk groups for HCC in which routine screening should be considered can be identified. Although workshop participants considered a range of available data, their conclusions were not based on formal quantitative measures of cost and effectiveness of screening.

Based on clinical and laboratory data on serologic markers associated with HCC and on radiologic tests for HCC, the workshop participants concluded that serum alpha-fetoprotein (AFP) and ultrasound are the most sensitive markers available at this time for the early detection of HCC. Serum AFP levels have been reported to be elevated in 55%-95% of patients with HCC (2-6). Screening programs in Shanghai and Alaska demonstrated that AFP screening of hepatitis B virus (HBV) carriers, a known high-risk group for HCC, enabled early detection of small encapsulated tumors; resection of these tumors resulted in long tumor-free survival in some patients (5,6). In Japan, similar results were obtained when ultrasound was used as a primary screening tool among persons with cirrhosis (7). High-risk groups for HCC in which screening could be considered include HBV carriers (6,8), patients with cirrhosis of any etiology or hemochromatosis (9,10), and possibly patients with hepatitis C virus infection and other non-A, non-B hepatitis infections (11,12).

Although participants agreed that more studies are needed before firm screening recommendations can be made, the group concluded that periodic AFP testing every 6-12 months of HBV carriers may be useful to detect HCC at an early stage. Subsets of HBV carriers with a family history of HCC or with the presence of cirrhosis may be at higher risk and may benefit from more frequent screening. The participants concluded that other issues requiring further study include 1) the frequency of screening, 2) the effectiveness of using AFP as a primary screening marker for HCC, with ultrasound as an adjunct in patients with elevated AFP values, 3) the use of ultrasound as a primary screening marker for HCC, and 4) the development of more specific screening markers for HCC. Participants encouraged prospective cohort studies of persons with chronic liver diseases in which the use of various screening modalities and regimens could be assessed and suggested that cost-effectiveness studies of AFP screening could be useful in decision-making. Reported by: WT London, Fox Chase Cancer Center, Philadelphia, Pennsylvania. BJ McMahon, Alaska Area Native Health Svc, Indian Health Svc, Anchorage, Alaska. Arctic Investigations Laboratory and Hepatitis Br, Div of Viral and Rickettsial Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: HCC causes an estimated 250,000 deaths worldwide each year and in many parts of the world is the leading cause of cancer mortality. In the United States, HCC is relatively uncommon; in 1986, based on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, the incidence for HCC was 2.4 per 100,000 population, compared with 55.8 per 100,000 for lung cancer and 50.5 per 100,000 for cancer of the colon and rectum (13). Nonetheless, certain groups in the United States (e.g., male Alaskan Native HBV carriers) have annual HCC rates greater than 60 per 100,000 (14).

In the United States, 15%-36% of HCC cases are associated with chronic HBV infection (15,16). Because of the high risk for developing HCC after prolonged HBV infection, HBV carriers represent a likely target group for screening programs for early detection. The workshop participants concluded that more studies are needed to identify other high-risk groups in which screening might be useful.

References

1. Tang ZW. Subclinical hepatocellular carcinoma: historical

aspects and general considerations. In: Tang ZW, ed. Subclinical hepatocellular carcinoma. New York: Springer-Verlag, 1985:1-11.

2. Kingston M, Ashraf M, Lewell D. Hepatic tumors in Saudi Arabia: a practical approach to diagnosis. Cancer 1985;55:1579-85.

3. Ebara M, Ohto M, Shinagawa T, et al. Natural history of minute hepatocellular carcinoma smaller than three centimeters complicating cirrhosis: a study of 22 patients. Gastroenterology 1986;90:789-98.

4. Maringhini A, Cottone M, Sciarrino E, et al. Ultrasound and alpha-fetoprotein in diagnosis of hepatocellular carcinoma in cirrhosis. Dig Dis Sci 1988;33:47-51.

5. Tang ZY, Yu YQ, Zhou XD, et al. Surgery of small hepatocellular carcinoma: analysis of 144 cases. Cancer 1989;64:536-41.

6. McMahon BJ, Lanier AP, Wainwright RB, Kilkenny SJ. Hepatocellular carcinoma in Alaska Eskimos: epidemiology, clinical features and early detection. In: Popper H, Schaffner F, eds. Progress in liver diseases. Vol IX. New York: Harcourt Brace Jovanovich 1990:546-55.

7. Shinagawa T, Ohto M, Kimura F, et al. Diagnosis and clinical features of small hepatocellular carcinoma with emphasis on the utility of real-time ultrasound: a study of 51 patients. Gastroenterology 1984;86:495-502.

8. Beasley RP. Hepatitis B: the major etiology of hepatocellular carcinoma. Cancer 1988;61: 1942-56.

9. Bradbear RA, Halliday JW, Bassett ML, Cooksley WG, Powell LW. Hepatocellular carcinoma in hemochromatosis. In: Okuda K, Ishak KG, eds. Neoplasms of the liver. New York: Springer-Verlag, 1987:189-97. 10. Di Bisceglie AM, Rustgi VK, Hoofnagle JH, Dusheiko GM, Lotze MT. Hepatocellular carcinoma. Ann Intern Med 1988;108:390-401. 11. Bruix J, Berrera JM, Calvet X, et al. Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and cirrhosis. Lancet 1989;2:1004-6. 12. Colombo M, Kuo G, Choo M, et al. Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet 1989;2:1006-8. 13. National Cancer Institute. Cancer statistics review 1973-1986, including a report on the status of cancer control. Bethesda, Maryland: US Department of Health and Human Services, Public Health Service, National Institutes of Health, 1989:III.20; NIH publication no. 89-2789. 14. McMahon BJ, Alberts SR, Wainwright RB, Bulkow L, Lanier AP. Prospective study of hepatitis B-related sequelae in 1400 HBsAg-positive Alaska Native carriers. Arch Intern Med 1990;150:1051-4. 15. Omata M, Achcavai M, Liew C-T, Peters RL. Hepatocellular carcinoma in the U.S.A., etiologic considerations: localization of hepatitis B antigens. Gastroenterology 1979;70:279-87. 16. Yarish RL, Werner BG, Blumberg BS. Association of hepatitis B virus infection with hepatocellular carcinoma in American patients. Int J Cancer 1980;26:711-5.

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