Background: Des-gamma-carboxy prothrombin (DCP), also known as protein induced by vitamin K absence or antagonist II absence (PIVKA-1I), has been cited in several studies to be an important prognostic factor in patients with hepatocellular carcinoma (HCC). Hepatocellular carcinoma is one of the world's major malignancies, especially in Asian countries. Most previous studies reported that the median survival was only three to six months after the onset of symptoms, hence periodic screening among high-risk population would benefit in detecting HCC in an early curable stage and yield long-term survival.
Objectives: To evaluate whether DCP is comparable to Alpha feto-protein (AFP) in differentiating HCC from non-malignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC (sHCC) defined as <2cm in two dimensions (Liver cancer study group of Japan, 1990).
Methodology: A literature search was conducted in PubMed, Medline, Alexa, Cochrane database between 1995 and December 2005 for published full studies. Clinical trials comparing DCP and AFP in distinguishing HCC from non-malignant chronic liver disease were included in this meta-analysis. Inclusion criteria, trial quality assessment using a standardized form and data extraction were done in duplicate. Disagreements were resolved by a third party. Two reviewers assessed trial quality and compared outcomes independently. Weighted Mean Difference (WMD) and relative risk ratios were computed using Revman Manager 4.2.8. Heterogeneity was determined using forest plots, chi2 and I2 tests.
Main results: A total of 878 patients, from five out of 13 randomized clinical trials within a 10-year period, who met our inclusion and exclusion criteria were included in the study. Sensitivity (sn) and specificity (sp) in detecting hepatocellular carcinoma of the five studies were analyzed using the Revman manager v4.2.8 (Wang: DCP, sn77 percent sp86.4 percent, sHCC sn56.5 percent AFP, sn59 percent sp77.3 percent, sHCC sn43.5 percent), (Cui: DCP, sn53.3 percent & sp85.6 percent, sHCC 40.6 percent AFP, snS8.3 percent and sp63.3 percent, sHCC sn43.5 percent), (Mita: DCP sn62 percent sp95 percent, sHCC 53 percent AFP sn47 percent sp86 percent, sHCC 41 percent), (Cui R: DCP sn51.7 percent, sp86.7 percent, sHCC 36.8 percent AFP, sn56.7 percent, sp63 percent, sHCC sn4.1 percent), (Suehiro DCP sn35.1 percent, sp 95.3 percent, sHCC sn23.7 percent AFP, sn65.4 percent, sp71.8 percent, sHCC sn28.2 percent). Test for heterogeneity using forest plot, chi2 and P tests were determined. The use of DCP as a diagnostic tool in detecting HCC as compared to AFP showed a significant heterogeneity, hence no summary statistics can be derived but shows a trend favoring DCP.
Reviewer's Conclusion: Our study indicates that DCP is comparable to AFP in differentiating HCC from non-malignant chronic liver disease. DCP seems to have a better correlation with HCC than AFP in detecting the small size of HCC.