Hepatitis B surface antigen (HBsAg) loss after nucleos(t)ide analogue or peginterferon (Peg-IFN)-containing regimens is durable in most patients with chronic hepatitis B virus infection (CHB), according to a retrospective analysis in Hepatology Communications.

Although loss of HBsAg is considered functional cure in patients with CHB, it is uncommon with existing therapies and predictive factors associated with HBsAg seroreversion are unknown. Therefore, researchers conducted an analysis of pooled data from three phase 3 clinical trials of patients with CHB treated with nucleos(t)ide analogue monotherapy or Peg-IFN with or without nucleos(t)ide analogue combination therapy. Researchers sought to characterize patients who achieved sustained HBsAg loss, the predictors of HBsAg seroreversion, and the effect of hepatitis B surface antibody (anti-HBs) seroconversion on durability of HBsAg loss.

Results found that among 1381 adults with CHB who received either nucleos(t)ide analogue monotherapy for ≤10 years or Peg-IFN-containing regimens for ≤1 year, a total of 55 patients had confirmed HBsAg loss. Through a median of 96 weeks of follow-up after HBsAg loss, HBsAg loss was durable in 82% (n=45) of patients, with 10 patients experiencing HBsAg seroreversion. Anti-HBs seroconversion was also observed during follow-up in 78% of patients who lost HBsAg and in 60% of those who subsequently seroreverted.

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Study treatment was a significant predictor of HBsAg seroreversion, but anti-HBs seroconversion and treatment duration after initial HBsAg loss were not. Risk for HBsAg seroreversion was lower if HBsAg loss was sustained through posttreatment week 24.

“Based on the results of our study, we propose that HBsAg loss should be confirmed on repeat tests ≥24 weeks after HBsAg first becomes negative and after completion of treatment,” the study authors concluded. They added, “Additional testing at later time points to confirm long-term durability of HBsAg loss should be performed in posttreatment registry studies.”   

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Disclosure: This clinical trial was supported by Gilead Sciences. Please see the original reference for a full list of authors’ disclosures.


Lok AS, Zoulim F, Dusheiko G, et al. Durability of hepatitis B surface antigen loss with nucleotide analogue and peginterferon therapy in patients with chronic hepatitis B. Hepatol Commun. 2020;4(1):8-20.