title: Comprehensive analysis of common serum liver enzymes as prospective predictors of hepatocellular carcinoma in HBV patients.
abstract: BACKGROUND
  Serum liver enzymes are frequently tested in clinics to aid disease diagnosis. Large observational studies indicated that these enzymes might predict cancer risk and mortality. However, no prospective study has reported on their relationships with the risk of HBV-related hepatocellular carcinoma (HCC).
  
  
  RESULTS
  We evaluated the predictive values of four routinely tested liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT]) in HCC risk in a prospectively enrolled clinical cohort of 588 Korean American HBV patients. For all four enzymes, the baseline level as well as the average and maximum levels during the first 1 or 2 years of follow-up were analyzed using multivariate Cox proportional hazards model. Patients were categorized into a normal or an elevated group based on the clinical cut-off of each enzyme. During a median follow-up of 7.5 years, 52 patients (incidence rate, 8.8%) developed HCC. The incidence rates were higher in the elevated groups for all four enzymes. The most significant finding was for GGT, with the highest incidence rate of 16.4% in the elevated group compared to 4.6% in the normal group (P<0.001). Compared to patients with normal baseline GGT, those with elevated GGT exhibited a significantly increased HCC risk with a hazards ratio (HR) of 2.60 (95% confidence interval [CI], 1.41-4.77, P = 0.002). Further analyses revealed a cumulative effect between baseline GGT and ALP (HR = 3.41, 95% CI 1.54-7.56, P = 0.003).
  
  
  CONCLUSIONS
  Serum GGT might predict HCC risk in HBV patients individually or jointly with other enzymes.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Liver Disease Prevention Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hie-Won
authors.initials: HW
authors.lastname: Hann
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wan
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Myers
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hann
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.forename: Bicui
authors.initials: B
authors.lastname: Chen
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000469:Alkaline Phosphatase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000201:enzymology / Q000453:epidemiology / Q000821:virology; D005260:Female; D006509:Hepatitis B / Q000150:complications; D006515:Hepatitis B virus / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000097:blood* / Q000201:enzymology / Q000453:epidemiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase