title: Improved Detection of Hepatocellular Carcinoma by Using a Longitudinal Alpha-Fetoprotein Screening Algorithm.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: ntayob@mdanderson.org.
authors.forename: Nabihah
authors.initials: N
authors.lastname: Tayob
authors.affiliation: Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Anna S F
authors.initials: AS
authors.lastname: Lok
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Do
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
mesh_terms: D000465:Algorithms; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D042241:Early Diagnosis; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology*; D008137:Longitudinal Studies; D008403:Mass Screening / Q000379:methods*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D000509:alpha-Fetoproteins
keywords: Cirrhosis; Early Detection; Hepatitis C; Surveillance