title: Sequential fluctuation pattern of serum des-gamma-carboxy prothrombin levels detected by high-sensitive electrochemiluminescence system as an early predictive marker for hepatocellular carcinoma in patients with cirrhosis.
abstract: Serum concentration levels of des-gamma-carboxy prothrombin (DCP), alpha-fetoprotein (AFP) and Lens culinaris agglutinin-reactive fraction (AFP-L3) are useful tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Recently, a novel immunoassay using the electrochemiluminescence (ECLIA) was developed to enable measurement of low-concentration of DCP. This study investigated the usefulness of high-sensitive DCP for the early diagnosis of HCC. The subjects consisted of 90 patients with viral cirrhosis who could be followed for at least 24 months from 1992 to 1997. Fifty-six of these patients developed HCC and 34 patients had not by 1998. We measured the serum levels of high-sensitive DCP, AFP and %AFP-L3 every 3 months during 2 years before the detection of tumor in patients with HCC and during 2 years from 1995 to 97 in patients without HCC. Youden's index was calculated for evaluation of the ideal cut-off levels. The patterns of serial changes during 2 years were divided into two types: fluctuating type and non-fluctuating type. Cut-off levels of 40 mAU/ml for high-sensitive DCP (Youden's index = 0.435), 20 ng/ml for AFP (Youden's index = 0.442) and 10% for %AFP-L3 (Youden's index = 0.364) gave the highest index for each marker. When these markers were combined, the combination of high-sensitive DCP, AFP and %AFP-L3 gave the highest accuracy (sensitivity = 82.1%, specificity = 82.4%, accuracy = 82.2%). Fluctuating type of high-sensitive DCP, AFP and %AFP-L3 levels were found in 15 (17%), 29 (32%) and 11 (12%) patients, respectively. The rate of complication with HCC in the patients who showed the fluctuating type of high-sensitive DCP levels was significantly greater than that in the patients who showed non-fluctuating type (P<0.01). These results suggest that periodic measurement of serum DCP levels using ECLIA method is very useful for HCC screening and predicting the development of HCC.
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8597, Japan.
authors.forename: Atsuya
authors.initials: A
authors.lastname: Shimizu
authors.forename: Katsuya
authors.initials: K
authors.lastname: Shiraki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ito
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Takahisa
authors.initials: T
authors.lastname: Sakai
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohmori
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Murata
authors.forename: Koujirou
authors.initials: K
authors.lastname: Takase
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Tameda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D004563:Electrochemistry; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood* / Q000737:chemistry; D011516:Prothrombin / Q000737:chemistry; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin