Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA.

Background Serum hepatitis B surface antigen (HBsAg) level<100 IU/ml and undetectable hepatitis B virus (HBV) DNA has been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Methods Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into low HBsAg group (<100 IU/ml) and high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). Results A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P<0.001) than those in high HBsAg group, while the NITs parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P<0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P=0.049) compared to patients with high HBsAg. No patient developed HCC in both groups. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P<0.001) and patients with HBsAg<100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P=0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Conclusions Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favorable outcomes with a high rate of HBsAg clearance and low risk of fibrosis progression.