Resuming antiviral therapy after withdrawal does not affect HBsAG seroclearance in HBV

Key takeaways:

• Adjusted analysis demonstrated no association between nucleos(t)ide analogue retreatment and HBsAg seroclearance.
• HBsAg level at treatment withdrawal predicted seroclearance, regardless of retreatment.

SAN DIEGO — Retreatment with nucleos(t)ide analogue therapy for relapse after withdrawal did not affect hepatitis B surface antigen seroclearance among patients with chronic HBV infection, according to a researcher at The Liver Meeting.

“Nucleos(t)ide analogue (NA) therapy can effectively inhibit replication of HBV and improve clinical outcomes in individuals with chronic HBV infection, but it does not eradicate the virus,” Yao-Chun “Holden” Hsu, MD, PhD, FAASLD, professor and director of the Graduate Institute of Medicine at I-Shou University in Taiwan, told Healio. “Previous studies have reported that the incidence of HBsAg seroclearance was lower in patients who resumed NA therapy following treatment withdrawal, suggesting a negative impact of retreatment on HBsAg seroclearance.”

He continued, “Accordingly, withholding retreatment during relapses of clinical hepatitis has been recommended in the hope of increasing the chance of functional cure. Nevertheless, clinical relapses can rapidly progress, and timely retreatment is necessary to avert deterioration to liver failure.”

To clarify whether resumption of antiviral therapy could affect HBsAg seroclearance following withdrawal of NA treatment, Hsu and colleagues conducted a retrospective, multicenter study of patients with HBV who received entecavir or tenofovir and subsequently discontinued NA. All patients had negative HBsAg and undetectable HBV DNA at discontinuation.

According to study results, of 841 eligible patients, 320 experienced clinical relapse (median age, 51.6 years; 79.4% men), for a cumulative incidence of 60.6% (95% CI, 43.5-72.5) at 10 years. Of these, 188 patients resumed NA and 132 remained untreated through the study duration.

Fifteen patients achieved HBsAg seroclearance — five who resumed treatment and 10 who did not — with a 10-year cumulative incidence of 12.1% (95% CI, 5.2-18.6).

Of note, when the researchers adjusted for potential confounding by indication, they found “no significant association” between retreatment and HBsAg seroclearance (adjusted HR = 0.41; 95% CI, 0.13-1.29).

According to Hsu, HBsAg level at time of withdrawal predicted seroclearance, regardless of retreatment, with a level higher than 100 IU/mL forecasting low incidence of seroclearance and a high rate of relapse.

“It is not advisable to withhold retreatment during relapses of clinical hepatitis after withdrawal of NA therapy, particularly for those with high HBsAg levels (> 100 IU/mL in Asians),” Hsu told Healio. “Withholding retreatment does not significantly increase the chance of functional cure and may unnecessarily delay timely intervention to prevent disease progression.”

He added, “Our findings highlight the need for further research with larger samples enriched in distinct subgroups — for example, patients with different HBsAg levels at treatment cessation, diverse ethnic backgrounds and various HBV genotypes — to validate our results.”