Ratio of Creatine Kinase to Alanine Aminotransferase as a Biomarker of Acute Liver Injury in Dystrophinopathy

Abstract

Objective. To investigate the ratios of creatine kinase (CK) to aminotransferases as biomarkers of acute liver injury in dystrophinopathy. Methods. C57 and mdx (dystrophic) mice were treated with a hepatotoxic reagent D-galactosamine (D-GalN). The degrees of liver and muscle injury were assessed using histological examinations. To examine whether serum CK-adjusted aminotransferase levels could indicate liver status in dystrophic mice, the CK/alanine aminotransferase (ALT) and CK/aspartate aminotransferase (AST) ratios were analyzed. Furthermore, we enrolled 658 male patients with dystrophinopathy and 378 male patients without muscle and liver injury as control, whose serum ALT, AST, and CK levels were examined. Results. Animal experiments indicated that D-GalN treatment could induce acute liver injury but not muscle injury. Additionally, D-GalN decreased the CK/ALT and CK/AST ratios in both C57 mice and mdx mice (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.001</mml:mn></mml:math>). However, there was an overlap of the CK/AST ratio between dystrophic mice with and without acute liver injury. In patients with dystrophinopathy, CK-adjusted ALT diminished the variability associated with age, genotype, clinical phenotype, and motor function (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>P</mml:mi><mml:mo>&gt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>). Conclusions. CK/ALT is a potential biomarker for the differential evaluation of acute liver injury in dystrophic mice, which highlights the value to further evaluate the practice of CK/ALT in dystrophinopathy patients.