title: Incorporating Serum Level of Hepatitis B Surface Antigen or Omitting Level of Hepatitis B Virus DNA Does not Affect Calculation of Risk for Hepatocellular Carcinoma in Patients Without Cirrhosis.
abstract: OBJECTIVE
  Tests for hepatitis B virus (HBV) DNA are expensive, and levels of hepatitis B surface antigen (HBsAg) can help determine the risk for hepatocellular carcinoma (HCC) in patients with chronic HBV infection. We investigated how adding data to knowing the level of HBsAg or excluding measurement of HBV DNA affected the accuracy of the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) scoring system in determining the risk for HCC.
  
  
  METHODS
  We collected data from 3584 patients with chronic HBV infection who were positive for HBsAg, free of cirrhosis, and participated in the community-based Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL)-HBV cohort (208 cases of HCC) from 1991 through 1992; they were followed up until December 31, 2008. Data from this cohort were used to derive our scoring system. We validated our system using data from 2688 HBsAg-seropositive patients (191 cases of HCC) who participated in the hospital-based Elucidation of Risk Factors for Disease Control or Advancement in Taiwanese Hepatitis B Carriers (ERADICATE-B) study at the National Taiwan University Hospital from 1985 through 2000; they were followed up until December 31, 2010. We also validated the system using data from 426 patients with chronic HBV infection who participated in the Chinese University of Hong Kong (CUHK) study (46 cases of HCC) from 1997 through 2000; patients were followed up for a median of 225 weeks. Discrimination and calibration were evaluated using area under the receiver operating characteristic (AUROC) curves and calibration charts.
  
  
  RESULTS
  When data on HBsAg were added to the REACH-B scoring system, it identified patients in the ERADICATE-B study who developed HCC within 3, 5, and 10 years, with AUROC curve values of 0.92 (95% confidence interval [CI], 0.82-1.02), 0.78 (95% CI, 0.70-0.86), and 0.80 (95% CI, 0.76-0.84), respectively. It identified patients in the CUHK study who developed HCC in 3, 5, and 10 years, with AUROC curve values of 0.85 (95% CI, 0.75-0.95), 0.82 (95% CI, 0.70-0.93), and 0.78 (95% CI, 0.70-0.870), respectively. When data on HBV DNA were removed from the REACH-B scoring system, it identified patients in the ERADICATE-B cohort who developed HCC in 3, 5, and 10 years, with AUROC curve values of 0.90 (95% CI, 0.81-1.0), 0.76 (95% CI, 0.68-0.85), and 0.78 (95% CI, 0.73-0.82), respectively. It identified patents in the CUHK cohort who developed HCC in 3, 5, and 10 years, with AUROC curve values of 0.84 (95% CI, 0.79-0.92), 0.81 (95% CI, 0.71-0.91), and 0.79 (95% CI, 0.72-0.87). These modified systems identified patients who developed HCC with similar levels of accuracy as the original REACH-B score (P > .05 in tests of noninferiority).
  
  
  CONCLUSIONS
  Including data on serum level of HBsAg or removing data on level of HBV DNA do not alter the accuracy of the REACH-B scoring system in determining HCC risk in patients with chronic HBV infection without cirrhosis. It might be cost effective to replace the test for HBV DNA with assays to measure HBsAg in determining HCC risk. These modified scoring systems might replace the REACH-B system in specific situations.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Tseng
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Jessica
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, and Hepatitis Research Center, National Taiwan University, Taipei, Taiwan.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, and Hepatitis Research Center, National Taiwan University, Taipei, Taiwan.
authors.forename: Tung-Hung
authors.initials: TH
authors.lastname: Su
authors.affiliation: Roche Diagnostics Ltd, Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Batrla-Utermann
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong. Electronic address: hlychan@cuhk.edu.hk.
authors.forename: Henry Lik-Yuen
authors.initials: HL
authors.lastname: Chan
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, and Hepatitis Research Center, National Taiwan University, Taipei, Taiwan; Department of Medical Research, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: kaojh@ntu.edu.tw.
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan; Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: chencj@gate.sinica.edu.tw.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000473:pathology*; D006723:Hong Kong; D006785:Hospitals, University; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D044967:Serum / Q000737:chemistry*; D013624:Taiwan
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: Liver Cancer; Prediction; Prognostic Tool; Risk Factor