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
Olympia E Anastasiou 1 , Cihan Yurdaydin 2 , Benjamin Maasoumy 3 , Svenja Hardtke 4 5 , Florin Alexandru Caruntu 6 , Manuela G Curescu 7 , Kendal Yalcin 8 , Ulus S Akarca 9 , Selim Gürel 10 , Stefan Zeuzem 11 , Andreas Erhardt 12 , Stefan Lüth 13 , George V Papatheodoridis 14 , Monica Radu 6 , Stephanie Liebig 3 , Heike Bantel 3 , Birgit Bremer 3 , Michael P Manns 3 5 , Markus Cornberg 3 5 , Heiner Wedemeyer 3 5 15
Affiliations
Affiliations
1
Institute of Virology, Essen University Hospital and Medical Faculty of the University of Duisburg, Essen, Germany.
2
Department of Gastroenterology and Hepatology, Koç University Medical School, Istanbul, TR, Germany.
3
Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
4
University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
5
German Center for Infectious Disease Research (DZIF), HepNet Study-House, Hannover, Germany.
6
National Institute for Infectious Diseases Prof. Dr. Matei Bals, Romania.
7
Spitalul Clinic de Boli Infectioase si, Timisoara, Romania.
8
Dicle University Medical Faculty, Diyarbakir, Turkey.
9
Ege University Medical Faculty, Izmir, Turkey.
10
Uludağ University Medical Faculty, Bursa, Turkey.
11
Johann Wolfgang Goethe University Medical Center, Frankfurt/Main, Germany.
12
Heinrich Heine University, Düsseldorf, Germany.
13
Center of Internal Medicine II, University Hospital Brandenburg, Brandenburg Medical School, Brandenburg, Germany.
14
School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
15
Dept. of Gastroenterology and Hepatology, Essen University Hospital and Medical Faculty of the University of Duisburg, Essen, Germany.
PMID: 33185325 DOI: 10.1111/jvh.13439
Abstract
HBV-DNA levels are low or even undetectable in the majority HDV infected patients. The impact of PEG-IFNα on HBV-DNA kinetics in HDV infected patients has not been studied in detail. We analyzed data of a prospective treatment trial where 120 HDV-RNA positive patients were randomized to receive PEG-IFNα-2a plus tenofovir-disoproxil-fumarate (PEG-IFNα/TDF, n=59) or placebo (PEG-IFNα/PBO; n=61) for 96 weeks. At week 96, HBV-DNA was still quantifiable in 71% of PEG-IFNα/PBO-treated patients but also in 76% of PEG-IFNα/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-IFNα/TDF-treated and 12 PEG-IFNα/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 of HBV-DNA during PEG-IFNα-2a therapy occurred in more than 20% of patients, even in TDF-treated patients. This transient HBV-DNA rise may indicate PEG-IFNα-induced cell death and lead to long-term HDV-RNA suppression and HBsAg loss.