Clinical trial NCT01361061: AFP - L3% and DCP as Screening Marker for a Hepatocellular Carcinoma in Patients With Cirrhosis of the Liver
Official title: AFP - L3% and DCP as Screening Marker for a Hepatocellular Carcinoma in Patients With Cirrhosis of the Liver- am Multicenter HCC- Surveillance Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Cirrhosis
Keywords: liver cirrhosis
screening
hepatocellular carcinoma
liver cancer markers: AFP, AFP-L3% and DCP
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
Collaborators: name: Wako Diagnostics
name: Johannes Gutenberg University Mainz
name: University Hospital Heidelberg
First posted: 2011-05-26
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients approved cirrhosis of the liver, but without a HCC - suspected lesion, are included in this clinical trial

Brief summary: Hepatocellular carcinoma (HCC) is one of the tumors with a rising incidence worldwide. The aim of this trial is to improve the detection of early HCC nodules in the liver. At the moment screening for HCC in patients with liver cirrhosis is performed by ultrasound and measurement of alpha- fetoprotein (AFP). In this trail the tumor markers AFP- L3 (a subfraction of AFP) and Des-y- carboxyprothromib (DCP) are measured in addition in order to receive information about the course of these markers before the detection of a HCC nodule.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* age between 18 and 80
* cirrhosis of the liver confirmed by ultrasound or other imaging techniques (MRI, CT) or biopsy
* at the time of enrollment: no HCC- suspected lesion detectable in the liver

Exclusion Criteria:

* liver tumors or metastasis or tumor of unknown origin

Primary outcomes:
measure: development of HCC
timeFrame: up to 3 years
Secondary outcomes:
measure: comparison of these liver cancer markers (AFP, AFP-L3% and DCP) between men and women
timeFrame: baseline
measure: comparison of these liver cancer markers (AFP, AFP-L3% and DCP) between different etiologies
timeFrame: baseline
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: University Medical Center Freiburg
state: Baden-Württemberg
city: Mainz
country: Germany
facility: University Medical Center Mainz
state: Rheinland-Pfalz
Study officials:
affiliation: University Medical Center Freiburg
name: Hans Christian Spangenberg, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: