title: Improving screening for hepatocellular carcinoma by incorporating data on levels of α-fetoprotein, over time.
abstract: OBJECTIVE
  Current screening algorithms for hepatocellular carcinoma (HCC) view each testing interval independently, without considering prior test results. We investigated whether measurements of α-fetoprotein (AFP), over time, can be used to identify patients most likely to develop HCC.
  
  
  METHODS
  We performed a nested case-control study using data from subjects in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial; 82 patients with HCC were matched 1:3 to individuals without HCC (controls), using bootstrap methods to ensure similar follow-up times between groups. We assessed the independent association between development of HCC and the following: (1) most recent level of AFP, (2) standard deviation in level of AFP, and (3) rate of increase in AFP using a multiple logistic regression that included patient-specific risk factors such as age, platelet count, and smoking status.
  
  
  RESULTS
  In bivariable analysis, all 3 AFP metrics were associated with HCC development; the most strongly associated was the standard deviation of AFP (odds ratio, 1.03 per unit increase in standard deviation; P < .001). Incorporating the standard deviation of AFP and rate of AFP increase, along with patient-specific risk factors, improved the prognostic accuracy to an area under the receiver-operating characteristic curve of 0.81, compared with 0.76 when only the most recent AFP level was used.
  
  
  CONCLUSIONS
  Patterns of AFP test results can more accurately identify patients with hepatitis C and advanced fibrosis or cirrhosis most likely to develop HCC, compared with most recent AFP test results.
authors.affiliation: Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, Michigan 48105, USA. elliotdl@umich.edu
authors.forename: Elliot
authors.initials: E
authors.lastname: Lee
authors.forename: Selwan
authors.initials: S
authors.lastname: Edward
authors.forename: Amit G
authors.initials: AG
authors.lastname: Singal
authors.forename: Mariel S
authors.initials: MS
authors.lastname: Lavieri
authors.forename: Michael
authors.initials: M
authors.lastname: Volk
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D015415:Biomarkers; D000509:alpha-Fetoproteins