Improved Detection of Hepatocellular Carcinoma by Using a Longitudinal Alpha-Fetoprotein Screening Algorithm

Background & AimsHepatocellular carcinoma (HCC) has limited treatment options when diagnosed at advanced stages; therefore, early detection is critical to reduce mortality. There is disagreement about the value of α-fetoprotein (AFP) in HCC surveillance. We aim to improve the sensitivity of AFP in HCC surveillance by using an algorithm that incorporates screening history to define patient-specific thresholds for positive a screen.MethodsDe-identified data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial, which enrolled 1050 patients with hepatitis C and advanced fibrosis or cirrhosis who were prospectively followed every 3–6 months, were analyzed. AFP was assayed at each visit, and ultrasonography was performed every 6–12 months. A panel adjudicated the diagnosis of HCC. A parametric empirical Bayes (PEB) screening algorithm, which incorporates screening history, was compared with a single threshold approach for interpreting AFP results.ResultsDuring a median follow-up of 80 months, 88 patients (48 of 427 with cirrhosis and 40 of 621 with advanced fibrosis) were diagnosed with HCC. PEB improved the sensitivity of AFP for detecting all HCC from 60.4% to 77.1% (P < .0005) in patients with cirrhosis and from 72.5% to 87.5% (P = .0015) in patients with advanced fibrosis, when the false-positive rate among all screenings was set at 10%. PEB algorithm detected HCC 1.7–1.9 years earlier in the cirrhosis group and 1.4–1.7 years earlier in the advanced fibrosis group, compared with single threshold approach.ConclusionsPEB increases the sensitivity of AFP testing and detects HCC earlier among hepatitis C patients with advanced fibrosis or cirrhosis. These data should prompt a reevaluation of how AFP is used in combination with ultrasound in HCC surveillance. Hepatocellular carcinoma (HCC) has limited treatment options when diagnosed at advanced stages; therefore, early detection is critical to reduce mortality. There is disagreement about the value of α-fetoprotein (AFP) in HCC surveillance. We aim to improve the sensitivity of AFP in HCC surveillance by using an algorithm that incorporates screening history to define patient-specific thresholds for positive a screen. De-identified data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial, which enrolled 1050 patients with hepatitis C and advanced fibrosis or cirrhosis who were prospectively followed every 3–6 months, were analyzed. AFP was assayed at each visit, and ultrasonography was performed every 6–12 months. A panel adjudicated the diagnosis of HCC. A parametric empirical Bayes (PEB) screening algorithm, which incorporates screening history, was compared with a single threshold approach for interpreting AFP results. During a median follow-up of 80 months, 88 patients (48 of 427 with cirrhosis and 40 of 621 with advanced fibrosis) were diagnosed with HCC. PEB improved the sensitivity of AFP for detecting all HCC from 60.4% to 77.1% (P < .0005) in patients with cirrhosis and from 72.5% to 87.5% (P = .0015) in patients with advanced fibrosis, when the false-positive rate among all screenings was set at 10%. PEB algorithm detected HCC 1.7–1.9 years earlier in the cirrhosis group and 1.4–1.7 years earlier in the advanced fibrosis group, compared with single threshold approach. PEB increases the sensitivity of AFP testing and detects HCC earlier among hepatitis C patients with advanced fibrosis or cirrhosis. These data should prompt a reevaluation of how AFP is used in combination with ultrasound in HCC surveillance.