Abundance of immunologically active alanine aminotransferase in sera of liver cirrhosis and hepatocellular carcinoma patients.
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.
Kim
Hyun Jeong
HJ
Department of BioMedical Sciences, Hallym University, ChunCheon, Korea.
Oh
Sang Wook
SW
Kim
Dong Joon
DJ
Choi
Eui Yul
EY
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
D000911:Antibodies, Monoclonal; D000410:Alanine Transaminase