Application of HBx-induced anti-URGs as early warning biomarker of cirrhosis and HCC

摘要

Background: Hepatitis B virus (HBV) carriers are at high risk for the development of hepatocellular carcinoma (HCC),nbut there are no reliable markers that will identify such high-risk patients. HBV up-regulates the expression of selected genesn(URGs) in the liver during chronic infection. These aberrantly expressed proteins trigger corresponding antibodies (anti-URGs)nthat appear prior to the detection of HCC. This study was undertaken to see if the anti-URGs could be used as early warningnbiomarker of HBV-induced liver cirrhosis and HCC.nMethods: A cross sectional study using a total of 625 serum samples from HBV infected and uninfected controls were tested fornthe anti-URGs using specific ELISAs.nResults: The number and specificity of anti-URGs correlated with the severity of liver disease Anti-URGs were predominantlynpresent among patients with HBV-associated HCC (55.2%) and cirrhosis (60.7%), and at a lower frequency among patients withnchronic hepatitis (35.8%), and at still lower frequencies in most asymptomatic carriers (12.3%) with normal ALT, among patientsnwith chronic hepatitis C (38.5%) and blood donors (0.9%). These anti-URGs were rarely detected in sera from those with tumorsnother than HCC, except among HBV infected patients with cholangioicarcinoma and in some patients with drug induced hepatitis.n3 or more anti-URGs could precede the diagnosis of cirrhosis or HCC 11.8 months on average, and HBV hepatitis patients with 3nor more anti-URGs have much higher risk (5/20 vs 0/30) to develop cirrhosis and HCC than those patients with less anti-URGs.nAs the early warning biomarker, 3 or more anti-URGs were served as the threshold to separate the cirrhosis and HCC from othersnwith a moderate sensitivity (58.3%) and specificity (80.0%), which was better than other biomarkers (AFP, AFP-L3, GPC3 andnGP73) and would improve up to 70.3% when combined with another biomarker.nConclusions: The results of this clinical validation study suggest that the anti-URGs might have diagnostic/prognostic utilitynamong patients at high risk for the development of cirrhosis and HCC.