Hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum alanine aminotransferase levels

Chronic hepatitis B patients with high-normal serum ALT (levels of 0.5-1 x upper limit of normal) are still at risk of liver disease progression. We thus investigated the correlation between serum ALT level and hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum ALT level (PNALT). Baseline clinical and virological features of 414 HBeAg-negative carriers, including 176 (42.5%) with low-normal ALT (levels of less than 0.5 x upper limit of normal) and 238 (57.5%) with high-normal ALT, were compared. Compared with HBV carriers with low-normal ALT, those with high-normal ALT were older (41 vs. 37 years, P < 0.001) and had a greater frequency of serum HBV DNA level > 10(4) copies/ml (63.4% vs. 47.5 %, P < 0.001) as well as a higher prevalence of basal core promoter T1762/A1764 mutant (36.5% vs. 24.2%, P = 0.01). Multivariate analysis showed that factors associated with a high-normal serum ALT level included male sex [odds ratio (OR), 1.82; 95% confidence interval (CI), 1.10-3.01, P = 0.019], increasing age (OR, < 30 years: 1, reference; 30-39 years: 2.43, 95% CI, 1.18-5.03, P = 0.016; 40-49 years: 4.22, 95% CI, 1.99-8.93, P < 0.001; >= 50 years: 4.06, 95% CI, 1.69-9.78, P = 0.002) and serum HBV DNA level > 10(4) copies/ml (OR, 1.83; 95% CI, 1.07-3-13, P = 0.027). Conclusion: HBeAg-negative patients with persistently normal ALT are not a homogenous group, and those with high-normal ALT share some of the characteristics that have been associated with adverse long-term outcomes.