Misclassification of chronic hepatitis B natural history phase: Insight from new ALT, AST, AKP, and GGT reference intervals in Chinese children

Background: The age- and sex-specific reference intervals (RIs) for liver chemistry in children are not available in China. Our study aimed to establish age and gender related RIs for ALT, AST, AKP, and GGT in China, and apply the new RI for ALT in children with chronic hepatitis B to use as a biochemical marker for disease progression. Methods: Data were collected from the Children's Healthcare Center. The measurements of ALT, AST, AKP and GGT were performed on a Hitachi 7600 Chemistry Analyzer. Age- and sex-specific RIs were determined using a percentile (3rd-97th) method. The sensitivity and specificity were determined to test the ability of the newly proposed ALT thresholds to classify children with chronic HBV infection. Results: The age- and sex-specific RN of ALT, AST, AKP and GGT were established based on 4232 Chinese healthy children. Using the new median ALT threshold, the sensitivity was higher. The detection of chronic HBV infection was 31.2% in boys and 35.5% in girls, while a very slight decrease in specificity was found. Based on the newly proposed His of ALT, approximately 16.1% boys and 19.0% girls would be classified in the HBeAgpositive chronic hepatitis phase, but using the current ALT threshold of children's hospitals they were in HBeAg-positive chronic infection phase. Conclusions: Based on a large healthy population, we established the sex- and age-specific RIs of ALT, AST, AKP and GGT serum activities for Chinese children. Meanwhile, newly proposed liver chemistry RIs will benefit the understanding of liver function and the natural history of chronic HBV infection in children.