Des-γ-Carboxy (Abnormal) Prothrombin as a Serum Marker of Primary Hepatocellular Carcinoma

Abstract

We detected des-gamma-carboxy prothrombin, an abnormal prothrombin, in the serum of 69 of 76 patients (91 per cent) with biopsy-confirmed hepatocellular carcinoma (the mean level of the abnormal prothrombin was 900 ng per milliliter). In contrast, levels of the abnormal prothrombin were low in patients with chronic active hepatitis (mean, 10 ng per milliliter) or metastatic carcinoma involving the liver (mean, 42 ng per milliliter), and undetectable in normal subjects. In five patients treated with vitamin K there was no reduction in abnormal prothrombin, indicating that its presence was not due to vitamin K deficiency. Surgical resection of tumors in two patients and chemotherapy in one patient markedly reduced abnormal-prothrombin concentrations, which later increased with recurrence of disease. Serum alpha-fetoprotein levels correlated poorly with abnormal-prothrombin levels. Together, the assay for abnormal prothrombin and the alpha-fetoprotein assay identified 64 of 76 patients with hepatoma (84 per cent). Abnormal prothrombin may be useful in the laboratory diagnosis of primary hepatocellular carcinoma.

Diagnostic accuracy of tumor markers for hepatocellular carcinoma: a systematic review

“…DCP, also known as prothrombin induced by vitamin K absence-II (PIVKA-II), is an abnormal prothrombin protein that is present at higher levels in the serum of HCC patients. Since the report by Liebman et al [18], DCP has been recognized as not only a highly specific marker for HCC but also a predictor of prognosis of HCC patients [86,87]. AFP-L3 is a fucosylated variant of AFP that reacts with Lens culinaris agglutinin A and can differentiate an increase of AFP due to HCC from that due to benign liver disease [20,21,82].…”

“…To date, many tumor markers have been proposed as a complement or substitute for AFP in the diagnosis of HCC, such as des-gamma-carboxyprothrombin (DCP) [18,19], Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) [20,21], and various cytokines [22][23][24]. The aim of this study is to compare the diagnostic accuracy of AFP in small HCC with other biomarkers and to find the optimal cutoff value of each tumor marker for efficient surveillance.…”

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…Since the report by Liebman et al [171], DCP has been recognized as not only a highly specific marker for HCC but also a predictor of prognosis of HCC patients [172,173]. According to the systematic review, the sensitivity, specificity, and LR?…”

Growth inhibitory actions of prothrombin on normal hepatocytes: Influence of matrix

“…The best known is alpha-fetoprotein, which we have found to be elevated in about 50% of our HCC patients (Virji et al, 1992). By contrast, the more recently recognized marker DCP (des-γ carboxy prothrombin) has been found to be increased in over 70% of patients with HCC, although it is less specific than AFP, since it is also increased in biliary diseases and by the anticoagulant action of warfarin (Weitz et al, 1993;Huisse et al, 1994;Liebman et al, 1984;Nakao et al, 1991;Liebman et al, 1989;Li et al, 2002,Lefrere et al, 1987,Shah et al, 1987Tsai et al, 1990). The action of warfarin has been identified to be on the vitamin K cycle, in which oxidized vitamin K cannot be cycled back to the reduced and physiologically active form (Fasco et al, 1982), when warfarin was present.…”

“…As a result, the underlying normal liver produces mature prothrombin, but HCCs within that liver produce under-carboxylated or immature prothrombin, DCP, one of the more useful HCC serum markers (Weitz et al, 1993;Huisse et al, 1994;Liebman et al, 1984;Nakao et al, 1991;Liebman et al, 1989;Li et al, 2002). The biological significance of this has never been clear, but it has recently been suggested that immature prothrombin or DCP has HCC growth promoting properties (Suzuki et al, 2005).…”