Hepatitis B Surface Antigen Seroclearance in HBV Unlikely With Entecavir, Tenofovir

Patients with chronic hepatitis B virus (HBV) infection who are treated with entecavir or tenofovir disoproxil fumarate have been found to have low seroclearance of hepatitis B surface antigen (HBsAg), according to study results published in The Journal of Infectious Diseases. The results of this study also suggested that baseline factors that may predict HBsAg seroclearance include low levels of viremia, a flare in alanine transaminase, serum bilirubin levels, and fatty liver.

Although antiviral treatment with nucleoside/nucleotide analogues has been shown to reduce the risk of clinical complication in patients with chronic HBV infection, continuous treatment to overcome drug resistance is often needed for continued viral remission. For patients treated with nucleoside/nucleotide analogue therapies, HBsAg seroclearance is linked to improved clinical outcomes and off-therapy remission; however, such outcomes are rare with short-term therapy, and the effects that long-term nucleoside/nucleotide analogues have on HBsAg seroclearance are unclear.

A team of investigators conducted an international, multicenter, retrospective cohort study of patients with chronic HBV infection to address these knowledge gaps by determining the incidence of HBsAg seroclearance, how that incidence might change over time, and what baseline factors would affect HBsAg seroclearance in patients on long-term therapy.

A total of 4769 treatment-naive patients (median age, 50 years; 69.05% men; 88.78% Asian) who did not have any malignancies at the start of the study were treated with either entecavir (84.25%) or tenofovir (15.75%). HBsAg seroclearance was recorded until death or loss due to follow-up with a median follow-up of 5.16 years.

Of the cohort, 58 (1.22%) of the patients had HBsAg seroclearance, and 213 patients died prior to HBsAg seroclearance. The 10-year cumulative incidence of HBsAg seroclearance was low (2.11%), and the annual incidence averaged 0.22% per year. There were no significant trends observed for rate changes over time (P =.93).

In the final statistical model generated, baseline factors that affected the likelihood of HBsAg seroclearance included low-level viremia with HBV DNA of less than 2000 IU/mL (adjusted subdistribution hazard ratio [aSHR], 3.14), elevated alanine transaminase of more than 200 U/L (aSHR, 3.68), serum bilirubin (aSHR, 1.11 per mg/dL), and fatty liver (aSHR, 1.84).

“These findings indicate HBsAg seroclearance is a remote or even unrealistic endpoint of the current antiviral strategy, while providing a realistic reference point for future HBV cure clinical trial design,” the study authors concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical and/or device companies. Please see the original article for a full list of authors’ disclosures.

Reference

Hsu Y-C, Yeh M-L, Wong GL-H, et al. Incidences and determinants of functional cure during entecavir or tenofovir disoproxil fumarate for chronic hepatitis B. J Infect Dis. Published online May 17, 2021. doi:10.1093/infdis/jiab241