title: Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Early detection of hepatocellular carcinoma (HCC) is essential for improved prognosis and long-term survival. To date, screening for HCC depends on serological testing (alpha-fetoprotein, AFP) and imaging (ultrasonography), both of which are not highly sensitive. A meta-analysis was performed to discuss recent developments in biomarkers that may be effective in screening for HCC.
  
  
  METHODS
  A systematic search of PubMed, Embase, and Web of Science was performed for articles published between January 2005 and October 2010, and focusing on biomarkers for HCC in urine, serum, or saliva. Data on sensitivity and specificity of tests were extracted from each included article and displayed with a summary ROC. A meta-analysis was carried out in which the area under the curve for each biomarker was used to compare the accuracy of different tests.
  
  
  RESULTS
  In seven well-defined studies, three biomarkers were identified for potential use, namely, Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA). Comparison with AFP showed that GP73 was superior (p = 0.006; 95 % CL -0.23, -0.12), IL-6 was similar (p = 0.66; 95 % CL -0.31, 0.25), and SCCA was inferior to AFP (p = 0.001; 95 % CL 0.12, 0.23).
  
  
  CONCLUSIONS
  GP73 is a valuable serum marker that seems to be superior to AFP and can be useful in the diagnosis and screening of HCC. Although GP73 may improve the detection and treatment of one of the most common malignancies worldwide, additional research is required.
authors.affiliation: Department of Hepatobiliary and Transplantation Surgery, Erasmus University Medical Centre, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Caroline D M
authors.initials: CD
authors.lastname: Witjes
authors.forename: Susanna M
authors.initials: SM
authors.lastname: van Aalten
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Gerard J J M
authors.initials: GJ
authors.lastname: Borsboom
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.forename: Jan N M
authors.initials: JN
authors.lastname: Ijzermans
keywords: Biomarkers; Hepatocellular carcinoma; Screening