ARBOR, Mich., Feb.
-- Widely used biomarkers are not optimal in
early detection of liver cancer, the third
most common cause of cancer-related death
worldwide, according to a new study
published in this month's Gastroenterology.
Two biomarkers used to complement ultrasound
in the early detection of hepatocellular
carcinoma, or liver cancer, are not ideal,
according to Anna
S. Lok, M.D., professor of internal
medicine at the University
of Michigan Medical
School and lead author of the study
published in the official journal of the
American Gastroenterological Association
The study analyzed the use of des-gamma-carboxy
prothrombin (DCP) and the most widely used
biomarker, alpha fetoprotein (AFP).
Biomarkers are found in patient's blood and
are used to indicate whether a disease or
condition is present.
Liver cancer is the sixth most common
malignancy, with 22,620 Americans expected
to be diagnosed this year. The incidence of
HCC in the
United States is
increasing and is largely attributed to
"Most surprising was the finding that
patient demographics influenced both
des-gamma-carboxy prothrombin and alpha
fetoprotein values, but in opposite
directions," said Lok, who also is the University
of Michigan's Alice Lohrman Andrews
Research Professor in Hepatology.
observation merits further investigation, as
it might impact the accuracy of these
biomarkers in the detection of liver cancer
in men versus women and in patients of
various races and ethnicity."
The survival of patients with most
malignancies has improved over the last
decade, but five-year survival of patients
with hepatocellular carcinoma (HCC) has
remained less than 10 percent. The poor
outcome of patients with HCC is related to
late detection with more than two-thirds of
patients diagnosed at advanced stages of
disease. A major problem with HCC
surveillance is the lack of reliable
biomarkers. While AFP is the most widely
used biomarker for HCC surveillance,
experience with DCP is limited.
The study was conducted in 10 centers in the
United States and
funded by the National Institute of Diabetes
and Digestive and Kidney Diseases, National
Institutes of Health.
Among 1,031 patients randomized in the
Hepatitis C Antiviral Long-Term Treatment
Against Cirrhosis Trial, a nested
case-control study of 39 HCC cases (24 early
stage) and 77 matched controls was conducted
to compare the performance of AFP and DCP.
Testing was performed on serial serum
samples collected during a 12 month period
prior to the time of HCC diagnosis.
DCP was not superior to AFP in the early
detection of HCC in patients with advanced
hepatitis C and neither AFP alone, DCP
alone, nor the combination of AFP and DCP
was sufficiently accurate to be used for HCC
surveillance. The combination of both
markers enhanced the sensitivity, indicating
that these two markers are complementary.
Therefore, prospective studies should be
conducted to determine if combining both
markers will improve the detection of early
HCC and to establish the optimal cutoff
values that should be used for patient
recall and further testing.
"Until better serum markers are available,
ultrasonography remains the preferred tool
for HCC surveillance. However, reliable
biomarkers to complement ultrasound may
improve the detection of early HCC in
clinical practice where interpretation of
ultrasound is variable," says Lok. In this
study, diagnosis of early HCC was triggered
by surveillance ultrasound in only 58
percent of patients.