Effect of switching from nucleos(t)ide maintenance therapy to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomized trial

Hyun Young Woo, Jeong Heo, Won Young Tak, Heon Ju Lee, Woo Jin Chung, Jung Gil Park, Soo Young Park, Young Joo Park, Yu Rim Lee, Jae Seok Hwang, Young Oh Kweon, Hyun Young Woo, Jeong Heo, Won Young Tak, Heon Ju Lee, Woo Jin Chung, Jung Gil Park, Soo Young Park, Young Joo Park, Yu Rim Lee, Jae Seok Hwang, Young Oh Kweon

Abstract

Aims: Induction of a durable viral response is difficult to achieve in patients with chronic hepatitis B (CHB), even from long-term use of a nucleos(t)ide analogue (NA). This study investigated whether switching to peginterferon (PegIFN) alfa-2a after long-term NA therapy induced a durable viral response.

Methods: Patients with hepatitis B e antigen (HBeAg)-positive CHB who received any NA for at least 72 weeks and had a low level of HBV DNA (≤100 IU/mL) were randomized (1:1) to receive PegIFN alfa-2a (180 μg/week) or NA for 48 weeks. The primary endpoint was change in the hepatitis B surface antigen (HBsAg) titer during antiviral therapy.

Results: We randomized 149 CHB patients to the two groups. Compared to baseline, the HBsAg levels in both groups were not lower at week 12, but were lower after 24, 36, and 48 weeks (all p<0.001). The maximal HBsAg decline in the PegIFN alfa-2a group was at week 36 (0.50±0.88 log10 IU/mL), and this decline was smaller in the NA group (0.08±0.46 log10 IU/mL). The percentage of patients with HBeAg seroconversion at week 48 was also greater in the PegIFN alfa-2a group (15/75 [20.0%] vs. 5/74 [6.8%], p = 0.018). Multivariable analysis indicated the PegIFN alfa-2a group had a greater change in HBeAg seroconversion at week 48 (p = 0.027). Patients had relatively good tolerance to PegIFN alfa-2a therapy.

Conclusions: CHB patients who switched to PegIFN alfa-2a for 48 weeks had a significantly lower HBsAg titer and increased HBeAg seroconversion relative to those who remained on NA therapy.

Trial registration: (ClinicalTrials.gov; NCT01769833).

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: [JH received a grant from Roche Korea, HYW, WYT, HJL, WJC, JGP, YJP, YRL, SYP, YOK and JSH report no conflicts of interest.]. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. CONSORT flow diagram.
Fig 1. CONSORT flow diagram.
PegIFN alfa-2a, peginterferon alfa-2a.
Fig 2
Fig 2
Changes of HBsAg level (A), HBsAg reduction (B), HBeAg seroconversion (C) and HBeAg loss (D) during treatment between groups. HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e Antigen; PegIFN alfa-2a, peginterferon alfa-2a. * p

Fig 3. Changes in serum HBV DNA…

Fig 3. Changes in serum HBV DNA levels in the two groups.

PegIFN alfa-2a, peginterferon…

Fig 3. Changes in serum HBV DNA levels in the two groups.
PegIFN alfa-2a, peginterferon alfa-2a. ** p
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JH was supported by an unrestricted grant from Roche Korea and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1F1A1052110). Roche Korea had no role in the study design data collection and analysis, decision to publish, or preparation of the manuscript and the authors retain full responsibility for the collection and interpretation of data, decision to publish, and preparation of the manuscript. https://www.roche.co.kr/https://www.nrf.re.kr/eng/main/.
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Fig 3. Changes in serum HBV DNA…
Fig 3. Changes in serum HBV DNA levels in the two groups.
PegIFN alfa-2a, peginterferon alfa-2a. ** p

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