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Effects of on-treatment ALT flares on serum HBsAg and HBV RNA in patients with chronic HBV infection

Authors :
Willem P. Brouwer
Robert A. de Man
Harry L.A. Janssen
Sylvia M. Brakenhoff
Hannah S.J. Choi
Adam J. Gehring
Grishma Hirode
Milan J Sonneveld
Bettina E. Hansen
Mina S. Farag
Gastroenterology & Hepatology
Source :
Journal of Viral Hepatitis, 28(12), 1729-1737. Wiley-Blackwell Publishing Ltd
Publication Year :
2021

Abstract

As pegylated interferon alpha (PEG-IFN-α) is increasingly used in combination regimens of novel drugs, we aimed to characterize ALT flares and their relationship with serum HBsAg and HBV RNA kinetics in a large combined cohort of chronic hepatitis B (CHB) patients on PEG-IFN-α-based therapy. In this post hoc analysis of four international randomized trials, 269/130/124/128 patients on PEG-IFN-α monotherapy, PEG-IFN-α plus nucleos(t)ide analogue (NA) de novo combination, PEG-IFN-α add-on to NA or NA monotherapy were included, respectively. A flare was defined as an episode of ALT ≥5 × ULN. The association between flares and HBsAg and HBV RNA changes were examined. On-treatment flares occurred in 83/651 (13%) patients (median timing/magnitude: week 8 [IQR 4–12], 7.6 × ULN [IQR 6.2–10.5]). Flare patients were more often Caucasians with genotype A/D and had higher baseline ALT, HBV DNA, HBV RNA and HBsAg levels than the no-flare group. More flares were observed on PEG-IFN-α monotherapy (18%) and PEG-IFN+NA de novo combination (24%) vs. PEG-IFN-α add-on (2%) or NA monotherapy (1%) (p 10 at the final visit declines started shortly before the flare, progressing towards 24 weeks thereafter. On-treatment flares were seen in 16/22 (73%) patients who achieved HBsAg loss. In conclusion, ALT flares during PEG-IFN-α treatment are associated with subsequent HBsAg and HBV RNA decline and predict subsequent HBsAg loss. Flares rarely occurred during PEG-IFN-α add-on therapy and associated with low HBsAg loss rates. Combination regimens targeting the window of heightened response could be promising.

Details

Language :
English
ISSN :
13520504
Volume :
28
Issue :
12
Database :
OpenAIRE
Journal :
Journal of Viral Hepatitis
Accession number :
edsair.doi.dedup.....dfa9ffe8998a490aa2bde5597529120e