Improving screening for hepatocellular carcinoma by incorporating data on levels of α-fetoprotein, over time

Clin Gastroenterol Hepatol. 2013 Apr;11(4):437-40. doi: 10.1016/j.cgh.2012.11.029. Epub 2012 Dec 12.


Background & aims: 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / pathology
  • Case-Control Studies
  • Early Detection of Cancer / methods*
  • Female
  • Hepatitis C, Chronic / complications*
  • Humans
  • Liver Cirrhosis / complications*
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / pathology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Time Factors
  • alpha-Fetoproteins / analysis*


  • Biomarkers
  • alpha-Fetoproteins