November 05, 2025

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Peginterferon Alfa And TDF Combo Tied To Earlier Clearance Of HBsAg

Protocolized peginterferon (PegIFN) with tenofovir disoproxil fumarate (TDF) followed by TDF withdrawal resulted in early HBsAg clearance, says a study published in the American Journal of Gastroenterology.

HBsAg loss is associated with improved long-term outcomes in patients with chronic hepatitis B, but it is infrequently achieved with current monotherapies. This randomized trial by Terrault, Norah and peers was aimed to assess whether combination strategies that included treatment withdrawal enhanced HBsAg loss in patients with chronic hepatitis B.

The study enrolled 201 participants and randomized them into two groups, one group received TDF alone, the other group received TDF plus PegIFN alfa-2a for the first 24 weeks, followed by withdrawal of TDF at week 192 with 48 weeks of off-treatment follow-up to week 240. The primary endpoint of the study was HBsAg loss at week 240.
The findings of the study were:
Of the 201 participants, 6 participants had lost HBsAg at the end of the treatment phase (week 192), 5 (5.3%) in the combination group, and 1 (1.0%) in the TDF alone group. By week 240, 9 participants had cleared HBsAg, 5.3% in the combination group, and 4.1% in the monotherapy group.
The study also found that HBsAg decline and loss occurred earlier with TDF + PegIFN than TDF alone, with a ≥1-logIU/mL qHBsAg decline by week 24 in 28% in TDF + PegIFN compared with 6% in TDF alone (P = 0.04).
The study also found that HBsAg loss was more frequent in patients with subgenotype A2 (58%) compared to the other genotypes (1%). And it also found that HBeAg positivity was a strong predictor for HBsAg clearance (8.6% vs 1.1%)
Source:
Terrault, N. A., Lok, A. S., Wahed, A. S., Ghany, M. G., Perrillo, R. P., Fried, M. W., Wong, D. K., Khalili, M., Lau, D. T. Y., Sterling, R. K., Di Bisceglie, A. M., Cooper, S. L., Chung, R. T., & Janssen, H. L. A. (2023). Randomized Trial of Tenofovir With or Without Peginterferon Alfa Followed by Protocolized Treatment Withdrawal in Adults With Chronic Hepatitis B. In American Journal of Gastroenterology: Vol. Publish Ahead of Print. Ovid Technologies. https://doi.org/10.14309/ajg.0000000000002125

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