Department of Industrial and Operations Engineering, University of Michigan.
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.
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 individual without HCC (controls), using bootstrap methods to ensure similar follow-up times between groups. We assessed the independent association between development of HCC and a) most recent level of AFP, b) standard deviation in level of AFP, and c) rate of increase in AFP using a multiple logistic regression that included patient-specific risk factors such as age, platelet count, and smoking status.
In bi-variable 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 to 0.76 when the only the most recent AFP level was used.
Patterns of AFP test results can more accurately identify the patients with hepatitis C and advanced fibrosis or cirrhosis most likely to develop HCC, compared with most recent AFP test results.