title: Application of HBx-induced anti-URGs as early warning biomarker of cirrhosis and HCC.
abstract: BACKGROUND
  Hepatitis B virus (HBV) carriers are at high risk for the development of hepatocellular carcinoma (HCC), but there are no reliable markers that will identify such high-risk patients. HBV up-regulates the expression of selected genes (URGs) in the liver during chronic infection. These aberrantly expressed proteins trigger corresponding antibodies (anti-URGs) that appear prior to the detection of HCC. This study was undertaken to see if the anti-URGs could be used as early warning biomarker of HBV-induced liver cirrhosis and HCC.
  
  
  METHODS
  A cross sectional study using a total of 625 serum samples from HBV infected and uninfected controls were tested for the anti-URGs using specific ELISAs.
  
  
  RESULTS
  The number and specificity of anti-URGs correlated with the severity of liver disease Anti-URGs were predominantly present among patients with HBV-associated HCC (55.2%) and cirrhosis (60.7%), and at a lower frequency among patients with chronic hepatitis (35.8%), and at still lower frequencies in most asymptomatic carriers (12.3%) with normal ALT, among patients with chronic hepatitis C (38.5%) and blood donors (0.9%). These anti-URGs were rarely detected in sera from those with tumors other than HCC, except among HBV infected patients with cholangioicarcinoma and in some patients with drug induced hepatitis. 3 or more anti-URGs could precede the diagnosis of cirrhosis or HCC 11.8 months on average, and HBV hepatitis patients with 3 or more anti-URGs have much higher risk (5/20 vs 0/30) to develop cirrhosis and HCC than those patients with less anti-URGs. As the early warning biomarker, 3 or more anti-URGs were served as the threshold to separate the cirrhosis and HCC from others with a moderate sensitivity (58.3%) and specificity (80.0%), which was better than other biomarkers (AFP, AFP-L3, GPC3 and GP73) and would improve up to 70.3% when combined with another biomarker.
  
  
  CONCLUSIONS
  The results of this clinical validation study suggest that the anti-URGs might have diagnostic/prognostic utility among patients at high risk for the development of cirrhosis and HCC.
authors: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors: Wen
authors: W
authors: Wang
authors: Lan-Juan
authors: LJ
authors: Zhao
authors: Yan
authors: Y
authors: Wang
authors: Qing-Yuan
authors: QY
authors: Tao
authors: Mark A
authors: MA
authors: Feitelson
authors: Ping
authors: P
authors: Zhao
authors: Hao
authors: H
authors: Ren
authors: Zhong-Tian
authors: ZT
authors: Qi
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D015534:Trans-Activators / Q000502:physiology*; D059467:Transcriptome; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D014408:Biomarkers, Tumor; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein