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Revised ALT parameters in children with HBV refine classifications

Revision of standard upper limits of normal to age-specific and sex-specific alanine aminotransferase parameters in children with chronic hepatitis B highlighted ALT fluctuations during childhood and indeterminate HBV classification, according to recently published data.

“In the present retrospective analysis, in addition to the proposed revision of ULNs for ALT, we assessed the impact on classifying natural course of chronic HBV infection in the children,” Xiao-Ben Pan, PhD, from the Hangzhou Normal University in China, and colleagues wrote. “Our results emphasize a need to rethink the current conceptions of [immune tolerance], classification of natural course and management of chronic HBV infection in children.”

The researchers included 8,149 pediatric patients in the study with a median ALT of 23.5 U/L and 2,054 in their baseline analysis. Median ALT was higher in boys than in girls in the baseline analysis (24 vs. 22 U/L; P < .001).

In children older than 1 year, both mean (15.8 vs. 13.9 U/L) and median ALT levels (14 vs. 13 U/L) were higher in boys than in girls. ALT levels also varied by age, as the researchers found significantly higher levels in children younger than 2 years compared with children aged 3 years to 6 years.

Peak median HBV DNA occurred between age 1 year and 2 year with declining viral loads after 2 years. Most children were positive for HBV e-antibody (78.1%). Of those positive for HBeAb, most had detectable serum HBV DNA (80%).

Based on current ULN parameters for ALT, 72.4% of the pediatric patients had a determinate classification and 40.5% were classified as positive for HBV e-antigen. The proportion of children classified as HBeAg-positive but negative for chronic hepatitis was 19.8%. However, 27.6% of children fell into an “indeterminate gray area” due to high HBV DNA levels with abnormal ALT or midlevel HBV DNA with normal ALT.

After applying a revised ULN, the proportion of children with a HBeAg-positive and chronic HBV-negative increased to 28.8%, the proportion of indeterminate classifications increased to 36.8%, and the proportion of HBeAg-positive infections decreased to 23.8%.

“The age-specific classification showed that children with HBeAg-negative infection increased by age, and the peak proportions of indeterminate data and phase of HBeAg-positive hepatitis were seen in the first year,” the researchers wrote.

The researchers conducted a follow-up of 153 children with a median age of 8 years (range, 0-15 years) over a median of 62 months (range, 36-156 months). Thirty-nine of 125 children who were HBeAg-positive achieved viral clearance and HBeAg seroconversion. HBeAg seroconversion occurred more frequently in those with a higher peak ALT level during follow-up.

Among those who achieved seroconversion, 36 had intermittently elevated ALT levels, which were higher than current ULN parameters. Additionally, three children had persistently “normal” ALT levels, which were intermittently higher than the revised ULN.

“Because ALT may be influenced, not only by immune response against HBV but also by other factors such as fatty liver, alcohol consumption and hepatotoxic medications, a ‘logical’ association of ALT and HBV DNA level is required for assessing the clinical phase in the guidelines,” Pan and colleagues wrote. “However, hepatitis in children caused by the factors above is less likely to happen in the adults, and the immunocompetence inhibiting HBV DNA seems much more compromised in the children. These indicate that HBV DNA limit for the classification could be looser in the children.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.