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Clinical Trial
. 2025 Apr;32(4):e70022.
doi: 10.1111/jvh.70022.

Frequency, Severity and Impact of Pegylated Interferon Alpha-Associated Flares in Hepatitis D Infection

Svenja Hardtke  1   2   3 , Cihan Yurdaydin  4   5 , Florin A Caruntu  6   7 , Manuela G Curescu  8 , Kendal Yalcin  9 , Ulus S Akarca  10 , Selim Gürel  11 , Stefan Zeuzem  12 , Andreas Erhardt  13   14 , Stefan Lüth  15   16 , George V Papatheodoridis  17 , Kerstin Port  1 , Michael P Manns  1 , Markus Cornberg  1   2   7   18   19 , Julia Kahlhöfer  1   2   7 , Heiner Wedemeyer  1   2   7   18   19
Affiliations
Clinical Trial

Frequency, Severity and Impact of Pegylated Interferon Alpha-Associated Flares in Hepatitis D Infection

Svenja Hardtke et al. J Viral Hepat. 2025 Apr.

Abstract

We analysed the frequency, severity and impact of hepatitis flares in a large Phase 2 study investigating pegylated interferon-alfa-2a (PEG-IFNa) for the treatment of hepatitis D. In the HIDIT-II study, 120 patients were treated for 96 weeks with PEG-IFNa (180 μg weekly) in combination with tenofovir disoproxil fumarate (TDF, 300 mg once daily) or placebo. Hepatitis flares were defined as ALT increases above 10 times the upper limit of normal or increases of more than 2.5-fold above baseline or nadir values. ALT flares occurred in 28 patients (23%) during treatment (< 96) and in 14 patients post-treatment until follow-up Week 24. There were no differences in the flare frequency between the two treatment arms (12 PEG-IFNa + placebo vs. 16 PEG-IFNa + TDF). The frequency of ALT increases did not differ between cirrhotic and noncirrhotic patients. None of the patients with cirrhosis experienced liver decompensation during or after a flare. Fifty-four per cent of the patients with ALT flare experienced a decrease in HDV RNA (> 1 log10 cop/ml) during subsequent study visits. Mean ALT levels early during treatment were higher in patients with HBsAg loss at follow-up Week 24. More than a third of hepatitis D patients undergoing PEG-IFNa therapy may experience ALT flares during or after treatment. ALT flares in this study posed no obvious safety risk to patients and should not lead to premature withdrawal from treatment. If ALT flares may be beneficial in single patients requires further investigation. Clinical Trial Registration: NCT00932971, EudraCT 2008-005560-13.

Keywords: HDV; HIDIT‐II; alanine aminotransferase; beneficial flares; combination therapy; delta; hepatitis flares; interferon; randomised trial; virological outcome.

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Conflict of interest statement

S.H. declares that she has no Conflicts of Interest. C.Y. reports personal fees from AbbVie, Gilead, Eiger and Roche. Florin A. Caruntu declares a grant/research support from HORIZON‐HLTH‐2021‐Disease‐04‐07. M.G.C. declares that she has no conflict of interest. K.Y. declares that he has no conflict of interest. U.S.A. declares that he has no conflict of interest. S.G. declares that he has no conflict of interest. S.Z. declares function as consultancy and/or speaker's bureau: Abbvie, BioMarin, Boehringer Ingelheim, Gilead, GSK, Ipsen, Madrigal, Merck/NSD, Novo Nordisk and SoBi. A.E. declares that he has no conflicts of interest. S.L. declares that he has no conflict of interest. G.V.P. declares that he has served as advisor and/or lecturer for Abbvie, Albireo, Amgen, AstraZeneca, Genesis, Gilead, GlaxoSmithKline, Ipsen, Janssen, Novo Nordisk, Roche and Takeda and has received research grants from Abbvie, Gilead and Takeda. K.P. declares that she has no conflicts of interest. M.P.M. reports a research grant from Merck, personal fees from Abbvie, Assembly Bio, BMS, Gilead, GSK, Merck and Precision Biosciences, and is the principal investigator in clinical trials for Merck. M.C. reports personal fees from AbbVie, AiCuris, Gilead, GlaxoSmithKline (GSK), Janssen, Merck/MSD, Novartis, Roche and Swedish Orphan Biovitrum (SOBI) Falk. J.K. declares that she has no conflicts of interest. H.W. reports research grants from Abbvie, Biotest, Gilead and HORIZON, personal fees from AbbVie, Aligos, Altimmune, Biotest, BMS, BTG, Dicerna, Enanta, Gilead, Janssen, Merck/MSD, MYR GmbH, Roche, Vir Biotechnology, Intercept, Falk, Norgine and Pfizer, serves as principal investigator in clinical trials for Abbvie, Altimmune, Bristol‐Myers Squibb, Gilead, Janssen, MYR GmbH, Novartis and Vir Biotechnology and holds a role in the DGVS executive board.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study.
FIGURE 2
FIGURE 2
Individual courses of ALT, HDV RNA and HBsAg for the patients with ALT flares under treatment.
FIGURE 3
FIGURE 3
Virological outcome for patients with ALT flares during treatment (n = 26).
FIGURE 4
FIGURE 4
ALT course stratified for patients according to virological outcome.
See this image and copyright information in PMC

References

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