Publication:
A transient early hbv-dna increase during peg-ifnα therapy of hepatitis d indicates loss of infected cells and is associated with hdv-rna and hbsag reduction

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Date

2020-12-12

Authors

Gürel, Selim

Authors

Anastasiou, Olympia E.
Yurdaydin, Cihan
Maasoumy, Benjamin
Hardtke, Svenja
Caruntu, Florin Alexandru
Curescu, Manuela G.
Yalcin, Kendal
Akarca, Ulus S.
Zeuzem, Stefan
Erhardt, Andreas

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Publisher

Wiley

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Abstract

HBV-DNA levels are low or even undetectable in the majority HDV-infected patients. The impact of PEG-IFN alpha on HBV-DNA kinetics in HDV-infected patients has not been studied in detail. We analysed data of a prospective treatment trial where 120 HDV-RNA-positive patients were randomized to receive PEG-IFN alpha-2a plus tenofovir-disoproxil-fumarate (PEG-IFN alpha/TDF, n = 59) or placebo (PEG-IFN alpha/PBO; n = 61) for 96 weeks. At week 96, HBV-DNA was still quantifiable in 71% of PEG-IFN alpha/PBO-treated patients but also in 76% of PEG-IFN alpha/TDF-treated patients, despite low HBV-DNA baseline values. Surprisingly, a transient HBV-DNA increase between weeks 12 and 36 was observed in 12 in PEG-IFN alpha/TDF-treated and 12 PEG-IFN alpha/PBO-treated patients. This increase was positively associated with HBsAg loss [(P = 0.049, odds ratio (OR) 5.1] and HDV-RNA suppression (P = 0.007, OR 4.1) at week 96. Biochemical markers of cell death (M30 and ALT) were higher during the HBV-DNA peak but no distinct systemic immune pattern could be observed by screening 91 soluble inflammatory markers. In conclusion, an early increase in HBV-DNA during PEG-IFN alpha-2a therapy occurred in more than 20% of patients, even in TDF-treated patients. This transient HBV-DNA rise may indicate PEG-IFN alpha-induced cell death and lead to long-term HDV-RNA suppression and HBsAg loss.

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Tenofovir disoproxil fumarate, D virus, Replication, Combination, Induction, Responses, Kinetics, Adefovir, Innate, Drug, Hbv, Hepatitis b, Hepatitis d, Interferon, Viral kinetics, Science & technology, Life sciences & biomedicine, Gastroenterology & hepatology, Infectious diseases, Virology

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