title: Development and Internal Validation of a Model for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis.
abstract: BACKGROUND
  Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis; however, early detection efforts are limited by suboptimal effectiveness.
  
  
  OBJECTIVE
  To derive and validate a model to accurately distinguish cirrhotic patients with and without HCC and compare the accuracy of the model to that of α-fetoprotein (AFP) alone.
  
  
  METHODS
  We conducted a case-control study of cirrhotic patients with and without HCC seen at a large urban hospital system between January 2005 and June 2012. We derived multivariate logistic regression models for the presence of HCC and early-stage HCC. Discriminatory power was evaluated using receiver operating characteristic curve analysis in derivation and validation cohorts using a 10-fold cross-validation approach.
  
  
  RESULTS
  We identified 1356 patients with cirrhosis, with (n=455, 147 early stage) and without (n=901) HCC. We found that AFP>20 ng/mL and FIB-4, a noninvasive marker of fibrosis, were significantly associated with the presence of HCC (OR=10.5; 95% CI, 7.9-13.9 and OR=1.05; 95% CI, 1.03-1.07, respectively) and early-stage HCC (OR=4.4; 95% CI, 2.9-6.5 and OR=1.06; 95% CI, 1.03-1.09, respectively). Models incorporating AFP and FIB-4 had good discriminatory power, with c-statistics of approximately 0.80, in both derivation and validation cohorts. The model for early-stage HCC had higher discriminatory power than AFP alone (c-statistic 0.73; 95% CI, 0.69-0.78) in derivation and validation cohorts (P=0.02 and 0.15, respectively).
  
  
  CONCLUSIONS
  Models including AFP and FIB-4 can accurately discriminate cirrhotic patients with early-stage HCC from those without HCC.
authors.affiliation: *Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health Hospital System †Department of Surgery ‡Harold C. Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX §VA Center for Clinical Management Research ∥Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI.
authors.forename: Jaimin
authors.initials: J
authors.lastname: Patel
authors.forename: Adam
authors.initials: A
authors.lastname: Yopp
authors.forename: Akbar K
authors.initials: AK
authors.lastname: Waljee
authors.forename: Amit G
authors.initials: AG
authors.lastname: Singal
mesh_terms: D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D003661:Decision Support Techniques; D016002:Discriminant Analysis; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000175:diagnosis; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016017:Odds Ratio; D010976:Platelet Count; D011237:Predictive Value of Tests; D012372:ROC Curve; D018000:Receptors, Peptide / Q000032:analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D018000:Receptors, Peptide; C042144:alpha-fetoprotein receptor, human; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase