Are Biomarkers Still Helpful in Hepatocellular Carcinoma?

surement and, in the case of detection of a suspicious focus of a certain size, additional radiological investigation by CT or MRI and, if HCC was confirmed by imaging or biopsy, a decision to treat. This surveillance-step combination was still maintained at the Asian Oncology Summit 2009 [3] , by the WGO guideline from 2010 [4] and was even extended by the Japanese Society of Hepatology, which, for surveillance other than ultrasound, recommended three biomarkers (AFP, AFP-L3 and DCP) every 3–4 months [for hepatitis B virus (HBV)-related or HCVrelated cirrhosis] or every 6 months (for chronic hepatitis B/C or cirrhosis of other etiology) [5, 6] . In the last practice guideline of the American Association for the Study of Liver Diseases (AASLD) from 2010 [7, 8] , surveillance of patients at risk for HCC was recommended only 6-monthly by ultrasound, omitting AFP and the algorithm for small nodules changed by 1 cm (4-phase multidetectorrow CT, dynamic contrast-enhanced MRI or, in the case of an untypical result for HCC, a biopsy). A similar clinical practice HCC guideline was published this year by the European Association for the Study of the Liver, European Organization for Research and Treatment of Cancer (EASL-EORTC) [9] . It is of note that one of the biggest American working groups for medical practice guidelines, the National Comprehensive Cancer Network (NCCN), evaluating most of their recommendations as evidence category 2A plus strength of consensus, has Since the first description of α-fetoprotein (AFP) as the main serum and tissue tumor marker for hepatocellular carcinoma (HCC) in the 1960s and its detection in germ cell tumors, a tremendous number of clinical studies have investigated this biomarker – particularly in patients with benign chronic liver diseases – up to the development of HCC. The limitations that emerged inspired the search for additional markers intended as adjuncts for a combination with AFP in order to improve the utility in the clinical setting. According to an updated broad review from the National Academy of Clinical Biochemistry (NACB) laboratory medicine practice guidelines for the use of tumor markers in different tumor entities including liver cancer [1] , only AFP was recommended as the best investigated biomarker in the screening and early detection of patients at a high risk of HCC, for determining prognosis and for the monitoring of treatment. Among numerous other biomarkers, the fucosylated fraction of AFP (AFP-L3), des-gamma-carboxyprothrombin (DCP) or PIVKA II (prothrombin produced by vitamin K absence or antagonism II, comprehensive review in [2] ) and glypican 3 (GPC-3), especially, were judged as upcoming markers needing further investigation. The most critical application in HCC was, and still is, the surveillance of patients at a high risk of HCC and a reaction upon increased suspicion. Former recommendations in the USA and Europe included surveillance by ultrasound in combination with AFP meaPublished online: February 8, 2013