title: Improved Performance of Serum Alpha-Fetoprotein for Hepatocellular Carcinoma Diagnosis in HCV Cirrhosis with Normal Alanine Transaminase.
abstract: Background:The utility of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is controversial. We aimed to identify factors associated with elevated AFP and define the patients for whom AFP is effective for surveillance.Methods:Data from the NCI Early Detection Research Network phase II HCC biomarker study (233 early-stage HCC and 412 cirrhotic patients) were analyzed. We analyzed 110 early-stage HCC and 362 cirrhotic hepatitis C virus (HCV) patients for external validation. Sensitivity, specificity, and area under the ROC curve (AUC) for HCC were calculated.Results:HCV etiology, non-White race, and serum alanine transaminase (ALT) predicted elevated AFP in cirrhotics. Non-White race and ALT predicted elevated AFP in HCC patients. Higher AUC of AFP for HCC was noted in patients with HBV (0.85) and alcohol (0.84), whereas it was lower in patients with hepatitis C virus (HCV; 0.80) and nonviral/alcohol etiology (0.76). The AUC was higher in HCV patients with serum ALT ≤40 U/L than patients with serum ALT >40 U/L (0.91 vs. 0.75,P< 0.01). At 90% specificity, the sensitivity of AFP increased from 44% to 74% in Whites with HCV and from 50% to 85% in non-Whites with HCV. There was a trend toward higher AUC in HCV patients with serum ALT ≤40 U/L than those with serum ALT >40 U/L (0.79 vs. 0.69,P= 0.10) in the validation cohort.Conclusions:The satisfactory performance of AFP in HCV patients with normal ALT should be further validated.Impact:The AFP may serve as a valuable surveillance test in HCV patients with normal ALT.Cancer Epidemiol Biomarkers Prev; 26(7); 1085-92. ©2017 AACR.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
authors.forename: Ju Dong
authors.initials: JD
authors.lastname: Yang
authors.affiliation: Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Dai
authors.affiliation: Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Amit G
authors.initials: AG
authors.lastname: Singal
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Purva
authors.initials: P
authors.lastname: Gopal
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
authors.forename: Benyam D
authors.initials: BD
authors.lastname: Addissie
authors.affiliation: Division of Gastroenterology, Stanford University Medical Center, Palo Alto, California.
authors.forename: Mindie H
authors.initials: MH
authors.lastname: Nguyen
authors.affiliation: Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, Missouri.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Befeler
authors.affiliation: Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.affiliation: Department of General Surgery, The Mount Sinai Medical Center, New York, New York.
authors.forename: Myron
authors.initials: M
authors.lastname: Schwartz
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Jacksonville, Florida.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Harnois
authors.affiliation: Wako Diagnostics, Mountain View, California.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gores
authors.affiliation: Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Marrero
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. roberts.lewis@mayo.edu.
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D000437:Alcoholism / Q000150:complications; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000302:isolation & purification; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000209:etiology; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012372:ROC Curve; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D000509:alpha-Fetoproteins; D000410:Alanine Transaminase