title: Abundance of immunologically active alanine aminotransferase in sera of liver cirrhosis and hepatocellular carcinoma patients.
abstract: BACKGROUND
  Although alanine aminotransferase (ALT) is a widely used indicator of liver function, ALT enzymatic activity may not always reflect the degree of liver damage. Improved methods or approaches would be useful.
  
  
  METHODS
  Monoclonal antibodies (mAbs) to ALT were generated to develop a sandwich enzyme immunoassay system. We used an immunoassay to measure ALT mass concentration and a common biochemical analyzer to assay ALT enzymatic activity in serum samples from patients with liver diseases and healthy individuals. The results from the 2 methods were compared and analyzed by ROC curve analysis.
  
  
  RESULTS
  The ALT sandwich enzyme immunoassay system demonstrated reliable performance in linearity, recovery, and imprecision studies. The ALT activity assay exhibited a higher diagnostic accuracy in acute hepatitis (AH) patients, but the ALT immunoassay exhibited higher sensitivity and specificity in patients with chronic liver diseases. The areas under the ROC curve for ALT mass and enzymatic activity were 0.82 and 0.98, respectively, in AH, 0.99 and 0.52 in hepatocellular carcinoma (HCC), and 0.94 and 0.45 in liver cirrhosis (LC). Serum samples from HCC and LC patients had higher amounts of ALT-immunoglobulin complexes [median A(450), 1.7 (interquartile range, 1.4-1.9)] than the other groups [1.3 (interquartile range, 0.9-1.6)].
  
  
  CONCLUSIONS
  Our analysis of sera from the HCC and LC patient groups revealed considerable amounts of immunologically active but catalytically inactive ALT. The amount of the ALT-immunoglobulin complex increased with the severity of the liver disease. The 2-site immunoassay method may be useful in the differential diagnosis of some causes of liver disease.
authors.affiliation: Department of BioMedical Sciences, Hallym University, ChunCheon, Korea.
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Oh
authors.forename: Dong Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Eui Yul
authors.initials: EY
authors.lastname: Choi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D008103:Liver Cirrhosis / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology*; D012372:ROC Curve
chemical_list: D000911:Antibodies, Monoclonal; D000410:Alanine Transaminase