Very low HBsAg levels predict HBsAg loss, disease remission after therapy cessation

Following discontinuation of nucleot(s)ide analogue (NA) therapy, only about one-third of patients with HBeAg-negative chronic hepatitis B (CHB) achieve disease remission, with rare HBsAg loss, as reported in a study. The likelihood of HBsAg loss and disease remission is high in the presence of very low HBsAg levels at baseline.

The study included a prospective multicentre cohort study of 110 HBeAg-negative CHB patients who discontinued NA therapy. None of the patients had cirrhosis, and the HBVDNA was <lower limit of quantification for ≥18 months.

Researchers evaluated virological and biochemical outcomes, including HBsAg loss, as well as NA restart rates, over 96 weeks.

Of the patients, 62 percent had been on entecavir (ETV), 28 percent on tenofovir (TDF), and 10 percent on other medications. The median age of the population was 56 years, and 57 percent were men and 85 percent were Asian. The median HBsAg level at baseline was 705 IU/ml.

Virological reactivation occurred in 109 patients, with median time to detection of 8 weeks. Reactivation occurred earlier after stopping TDF vs ETV (median, 4 vs 12 weeks; p<0.001).

At week 96, 77 (70 percent) patients remained off-treatment, 65 (59 percent) had ALT <2× ULN, 31 (28 percent) were in disease remission with HBVDNA <2,000 IU/ml plus ALT <2× ULN, and seven (6 percent) achieved HBsAg loss.

Baseline HBsAg ≤10 IU/ml was associated with HBsAg loss (p<0.001). Of note, 35 (32 percent) patients showed ALT >5× ULN, but ALT flares were not associated with HBsAg loss.

There were no unexpected safety issues.