Better biomarkers needed for liver cancer detection
21 April 2010
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 study published in 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 MD, 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 (AGA) Institute.
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. “This 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
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%. 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.