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

Abstract

Background and aims The role of alphafetoprotein (AFP) in the diagnosis and surveillance of hepatocellular carcinoma (HCC) is getting smaller owing to the advances in imaging modalities. The aims of this study were to assess the diagnostic accuracy of tumor markers in small HCC and to find the optimal cutoff value of each tumor marker for efficient surveillance. Methods Studies in all languages were identified by searching MEDLINE from 1982 to 2002. Studies were included when they showed sensitivity and specificity for HCCs 5 cm or smaller and recruited only patients with chronic hepatitis or liver cirrhosis as control. We assessed diagnostic odds ratios (DORs) for the evaluation of diagnostic accuracy of tumor markers and positive likelihood ratios (LRs+) to find the optimal cutoff value. DORs and LRs+ were combined according to the random effect model. The summary receiver operating characteristics (ROC) curve was also assessed. Results Seventeen articles on three tumor markers-AFP, des-gamma-carboxyprothrombin (DCP), and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3)-were enrolled after full-text evaluation. AFP was inferior to DCP and AFP-L3 in both DOR (4.50 vs. 8.16 and 10.50) and area under the ROC curve (0.647 vs. 0.688 and 0.695). Optimal cutoff values that provide the best LR+ were 200 ng/ml for AFP, 40 mAU/ml for DCP, and 15% for AFP-L3. Conclusions Diagnostic accuracy of AFP in small HCC was substantially limited. Surveillance including other tumor markers with optimal cutoff value should be conducted to confirm the efficacy of the policy.

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

“…Therefore, the range of tumor sizes should be considered in the evaluation of studies. A systematic review of studies published between 1982 and 2002 to evaluate the diagnostic accuracy of tumor markers for HCC is already available [159]. For the development of APASL consensus statement for HCC, we performed additional systematic review of studies published from 2003 to August 2008.…”

“…According to this systematic review, the sensitivity, specificity, and LR? of AFP in diagnosing HCC smaller than 5 cm in diameter ranged from 0.49 to 0.71, 0.49 to 0.86, and 1.28 to 4.03, respectively, with a cutoff value of 20 ng/mL and 0.04 to 0.31, 0.76 to 1.0, and 1.13 to 54.25, respectively, with a cutoff value of 200 ng/mL [159]. In a meta-analysis, AFP with a cutoff value of 200 ng/mL showed a better combined LR?…”

Serum levels of β-catenin as a potential marker for genotype 4/hepatitis C-associated hepatocellular carcinoma

“…Currently, HCC diagnosis relies on the radiology imaging systems, and elevated serum α-fetoprotein (AFp). serum AFp is not always elevated to a diagnostic level in all patients in small HCC, thus, considerable numbers of patients with more advanced stages would be missed unless other diagnostic tools are used (7,8). Moreover, the level of AFp may be elevated in non-malignant chronic liver diseases, including chronic hepatitis and cirrhosis (9,10).…”

Current Trends and Recent Advances in Diagnosis, Therapy, and Prevention of Hepatocellular Carcinoma

“…Besides, AFP has a role in the diagnosis of HCC, because a hepatic tumor with AFP greater than a cutoff value of 200 ng/mL in cirrhotic patients has a very high positive predictive value for HCC (Trevisani et al, 2001;Tateishi et al, 2008). In addition, using AFP to detect cancer has assisted to screen for HCC and save medical resources.…”