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Medical Science Monitor Basic Research


eISSN: 1643-3750

Frequency of elevated biomarkers in patients with cryptogenic hepatocellular carcinoma

Naota Taura, Tatsuki Ichikawa, Hisamitsu Miyaaki, Eisuke Ozawa, Takuya Tsutsumi, Shotaro Tsuruta, Yuji Kato, Takashi Goto, Noboru Kinoshita, Masanori Fukushima, Hiroyuki Kato, Kazuyuki Ohata, Kazuo Ohba, Junichi Masuda, Keisuke Hamasaki, Hiroshi Yatsuhashi, Kazuhiko Nakao

Nagasaki, Japan

Med Sci Monit 2013; 19:742-750

DOI: 10.12659/MSM.889361

Available online:

Published: 2013-09-06


Background: The incidence of hepatocellular carcinoma (HCC) continues to increase in Japan, but the clinical characteristics of Japanese patients with HCC have not been well described. The aim of this study was to determine the frequencies and utilities of elevated a-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels as biomarkers in cryptogenic HCC.
Material and Methods: A total of 2638 patients with HCC diagnosed between 1999 and 2010 in the Nagasaki Association Study of Liver (NASLD) were recruited for this study. The cause of HCC was categorized into 4 groups; HCC-B, HCC-C, HCC-BC, and HCC-nonBC. The significance of factors was examined for HCC-nonBC using logistic regression analysis in all patients.
Results: Multivariate analysis identified age, sex, BMI, alcohol consumption, platelet count, AST, ALT, AFP, DCP, and TNM stage as independent and significant risk factors for HCC-nonBC. According to TNM stage, the median AFP levels in HCC-nonBC with TNM stages I, II, and III were significantly lower than in either HCC-B or HCC-C. In TNM stage IV, the median AFP level in HCC-nonBC was significantly lower than in either HCC-B or HCC-BC. The median DCP levels in HCC-nonBC with TNM stages I and II were significantly higher than those in either HCC-B or HCC-C. In TNM stage III, the median DCP level in HCC-nonBC was significantly higher than that in HCC-C.
Conclusions: DCP was more sensitive than AFP for the diagnosis of early stage cryptogenic HCC. DCP should be used as the main serum test for cryptogenic HCC detection.

Keywords: Age Factors, Alcohol Drinking, Biological Markers - blood, Blood Chemical Analysis, Body Mass Index, Carcinoma, Hepatocellular - etiology, Enzyme-Linked Immunosorbent Assay, Incidence, Japan - epidemiology, Kaplan-Meier Estimate, Liver Neoplasms - etiology, Logistic Models, Protein Precursors - blood, Prothrombin, Sex Factors, Tumor Markers, Biological - blood, alpha-Fetoproteins - analysis