Trial Information

AFP - L3% and DCP as Screening Marker for a Hepatocellular Carcinoma in Patients With Cirrhosis of the Liver- am Multicenter HCC- Surveillance Study

The incidence of the hepatocellular carcinoma (HCC) is rising worldwide. Usually it arises
in patients with liver cirrhosis. That's the reason why these patients should be screened
every six months by ultrasound performance and by the measurement of alpha-fetoprotein (AFP)
in order to detect a growing tumor in the cirrhotic liver so that a possible curative
treatment may be possible.

In the last years new tumor markers has been identified such as Des-y- carboxyprothromib
(DCP) and AFP - L3. AFP in total consists of three different glycoforms (AFP - L1, AFP - L2
and AFP - L3) which all have a different binding affinity to the lens culinaris agglutinin
(LCA). Among these glycoproteins AFP - L3 has the highest binding affinity to LCA and
occurs predominantly in patients with a HCC whereas the other subtypes can be found rather
in patients with benign diseases of the liver such as a chronic hepatitis or cirrhosis of
the liver.

Some studies have shown that high serum levels of AFP - L3 can be associated with a reduced
function of the liver, low differentiation and a high malignancy of the HCC. Furthermore HCC
- nodules with a diameter smaller than 2 cm could be detected by rising AFP - L3 serum
levels. Moreover there are significant differences in AFP - L3 serum levels in patients with
cirrhosis of the liver without a HCC and those with such a tumor. In conclusion of that
rising AFP - L3 serum levels could indicate a newly developed tumour.

Des-y- carboxyprothromib (DCP), which was first described in 1984 by Liebmann et al. is
another tumor marker for HCC. In contrast to AFP it is not elevated in patients with a
benign disease of the liver. This could be an interesting fact concerning the screening of
patients with liver cirrhosis.

In this examination the diagnostic value of AFP, AFP - L3% and DCP should be evaluated. An
important aim of this prospective clinical trial is to define the specificity of these serum
markers alone and in combination. If a patient develops a primary liver tumor the course of
the tumor markers before the development of the tumor will be analysed. Furthermore it will
be examined which parameters will lead to false positive DCP values (especially chronic
kidney disease or application of phenprocoumon). During 2 years approximately 150 patients
in each center with approved cirrhosis of the liver will be enrolled. According to the
normal screening procedure serum samples will be collected for the measurement of AFP, AFP-
L3% and DCP. If a suspected tumor nodule is detected, a confirmation of the diagnosis "HCC"
according to the AASLD- criteria is needed. These patients will be excluded from the
examination and will be treated according to the actual guidelines.

The aim is to improve the early diagnosis of a HCC so that curative treatment opportunities
can be done.