Monitoring serum levels of hepatitis B surface antigen (HBsAg), interferon inducible protein-10 (IP10), and hepatitis B core-related antigen (HBcrAg) may be useful for the management of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who discontinue long-term nucleos(t)ide analogue (NA) therapy, according to a study published in the Journal of Viral Hepatitis.

HBsAg loss is the therapeutic goal for patients with CHB, but it rarely occurs during treatment. Thus, discontinuation of NAs before HBsAg loss may be considered in patients who have achieved virological remission. Unfortunately, reliable predictors of outcomes after treatment discontinuation in patients whose serum levels are HBeAg-negative CHB have not been established; therefore, researchers investigated the role of HBsAg, IP10, and HBcrAg serum levels as predictors of HBsAg loss, relapse, and retreatment in those who discontinue long-term antiviral therapy.

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Fifty-seven patients who had HBsAg-positive serum levels were followed monthly for 3 months, every 2/3 months until month 12, and every 3/6 months thereafter. The researchers found that noncirrhotic patients with HBeAg-negative CHB remaining in long-term on-therapy virological remission who achieve an HBsAg<100 IU/mL have a high probability of HBsAg loss and sustained post-NA remission, and can safely stop treatment. However, patients with an HBsAg>1000 IU/mL have less favorable outcomes after NA discontinuation, and therefore such a decision may not be justified. In patients with intermediate HBsAg levels of 100 to 1000 IU/mL, decisions may need to be individualized, depending on the desirable outcome, but IP10 levels at 1 month after discontinuation could be a useful predictor of subsequent HBsAg loss. In addition, HBcrAg at NA discontinuation may be useful in predicting post-NA outcome.

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The authors concluded that, “Larger studies are needed to further evaluate and confirm these findings which may guide the management of HBeAg-negative CHB patients who discontinue NA therapy.”

Disclosure: This clinical trial was supported by Gilead Sciences. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Papatheodoridi M, Hadziyannis E, Berby F, et al. Predictors of HBsAg loss, relapse and retreatment after discontinuation of effective oral antiviral therapy in non-cirrhotic HBeAg-negative chronic hepatitis B [published online September 28, 2019]. J Viral Hepat. doi:10.1111/jvh.13211