Epidemiologic Notes and Reports Early Detection of Primary Hepatocellular Carcinoma -- Alaska

High rates of primary hepatocellular carcinoma (PHC) and hepatitis B virus (HBV) infection have been found in the Alaskan Eskimo population (1,2). Chronic HBV infection is believed to have an etiologic role in the development of PHC. Alpha-fetoprotein (AFP) is frequently elevated in clinically evident PHC, but its use in the preclinical detection of PHC in persons serologically positive for hepatitis B surface antigen (HBsAg) has not been extensively evaluated. In 1980, a pilot AFP screening program was begun among 20 HBsAg-positive Alaskan Natives from three families at high risk for PHC. Each family had a high rate of HBV infection and had two family members die of PHC. In 1982, semiannual AFP screening resulted in the early detection and surgical resection of a 2-cm PHC in an asymptomatic, 19-year-old Eskimo man who has since done well (3). After this success, the AFP screening program was expanded to include all HBsAg-positive Alaskan Natives.

Between November 1, 1982, and December 31, 1983, 925 Alaskan Natives with sera positive for HBsAg were tested for AFP. As a result, four asymptomatic persons with proven or suspected PHC were identified. The following is a report of the most recent case and a description of the AFP screening program.

On November 27, 1983, an 11-year-old Eskimo boy was found to have an AFP level of 1,342 ng/ml (normal 25 ng/ml or less, ELISA). He was HBsAg-positive when first tested in 1975 and had a previously normal AFP level in November 1982. While the boy had no previous family history of PHC, three other persons from the same village (population 331) developed PHC since 1980. On evaluation at the Alaska Native Medical Center in Anchorage, the boy was asymptomatic and normal on physical examination, although his alkaline phosphatase and serum glutamic-oxaloacetic transaminase (SGOT) levels were mildly elevated. Ultrasonography, CAT scan, and hepatic angiography showed a 3-cm tumor in the medial portion of the left lobe of the liver. On December 5, the boy underwent successful surgical resection of a 3-cm, encapsulated PHC. He did well post-operatively and returned to his village on December 23. Following surgery, the AFP level rapidly declined and was 7.6 ng/ml on January 8, 1984.

The expanded AFP screening program, begun in November 1982, consists of semiannual AFP testing of all HBsAg-positive Alaskan Natives who are tracked by a computerized register. In the program's first 14 months, 14 persons, including four with liver tumors, have been identified as having elevated AFP not related to pregnancy. Three of the tumors were biopsied and proved to be PHC: one in a 10-year-old boy who is doing well 5 months after a successful resection; one in a 66-year-old man who died 1 year after an unresectable tumor was discovered; and one in the 11-year-old boy reported above. The fourth liver tumor, documented by ultrasonography and CAT scan, was in an elderly man who declined biopsy and surgery. All patients with tumors were asymptomatic at the time of detection, and all had rising AFP levels or a single level above 1,000 ng/ml. Of the 10 remaining people with elevated AFP, one has had low-level elevations (50-90 ng/ml) and is being evaluated, and nine had transient elevations associated with acute HBV infection. These preliminary results suggest that AFP screening of HBsAg-positive persons can, at least sometimes, detect PHC at a stage when surgical resection may be curative. Reported by L Ingle, MD, S Kilkenny, MD, K Kline, MD, B McMahon, MD, T Paprocki, MD, K Petersen, MD, Alaska Native Medical Center, Alaska Area Native Health Svc, Indian Health Svc, Anchorage, Alaska; Arctic Investigations Laboratory, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: PHC is a leading cause of cancer deaths in much of Asia and Africa. Worldwide, it is estimated that over 150 million chronic carriers of HBV infection--900,000 of whom live in the United States--are at risk for developing PHC (4).

In the past, a PHC diagnosis usually followed the onset of symptoms, and the 5-year survival rate approached zero (5). Of the various treatments for PHC, only surgical resection has resulted in long-term survival. A recent study from the People's Republic of China demonstrated that surgery in asymptomatic patients with tumors less than 5 cm in diameter can result in improved survival (6).

Well-designed prospective studies are needed to evaluate the use of AFP screening in the early detection of PHC. These studies should include measures of sensitivity, specificity, and positive predictive value, as well as an analysis of cost-effectiveness. The preliminary Alaskan experience is promising and will hopefully result in recommendations concerning the use of prospective AFP testing among HBsAg carriers.

While early detection of PHC may improve survival rates, detection is only part of the health-care strategy directed against PHC. Because of the presumed etiologic link between chronic HBV infection and PHC, preventing PHC may be possible by preventing HBV infection. The success of future HBV vaccination programs may well determine the future incidence of PHC.

References

1. Heyward WL, Lanier AP, Bender TR, et al. Primary hepatocellular carcinoma in Alaskan Natives, 1969-1979. Int J Cancer 1981;28:47-50.

2. Schreeder MT, Bender TR, McMahon BJ, et al. Prevalence of hepatitis B in selected Alaskan Eskimo villages. Am J Epidemiol 1983;118:543-9.

3. Heyward WL, Lanier AP, Bender TR, et al. Early detection of primary hepatocellular carcinoma by screening for alpha-fetoprotein in high risk families: a case-report. Lancet 1983;II:1161-2.

4. Report of a WHO meeting. Prevention of liver cancer. In: WHO Technical Report Series No. 691, 1983.

5. Moertel CG. The liver. In: Holland JF, Frei E III, eds. Cancer medicine. 2nd edition. Philadelphia: Lea & Febiger, 1982:1774-81.

6. Tang Z-y, Yu Y-q, Lin Z-y, Yang B-h, Zhou X-d, Cao Y-z. Clinical research of primary liver cancer: a 10 year (1970-1979) survey. Chin Med J 1983;96:247-50.

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