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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
Heyward WL, Lanier AP, Bender TR, et al. Primary
hepatocellular
carcinoma in Alaskan Natives, 1969-1979. Int J Cancer
1981;28:47-50.
Schreeder MT, Bender TR, McMahon BJ, et al. Prevalence of
hepatitis B in selected Alaskan Eskimo villages. Am J
Epidemiol
1983;118:543-9.
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.
Report of a WHO meeting. Prevention of liver cancer. In: WHO
Technical Report Series No. 691, 1983.
Moertel CG. The liver. In: Holland JF, Frei E III, eds.
Cancer
medicine. 2nd edition. Philadelphia: Lea & Febiger,
1982:1774-81.
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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