TY - JOUR
TI - 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
AU - Anastasiou, O.E.
AU - Yurdaydin, C.
AU - Maasoumy, B.
AU - Hardtke, S.
AU - Caruntu, F.A.
AU - Curescu, M.G.
AU - Yalcin, K.
AU - Akarca, U.S.
AU - Gürel, S.
AU - Zeuzem, S.
AU - Erhardt, A.
AU - Lüth, S.
AU - Papatheodoridis, G.V.
AU - Radu, M.
AU - Liebig, S.
AU - Bantel, H.
AU - Bremer, B.
AU - Manns, M.P.
AU - Cornberg, M.
AU - Wedemeyer, H.
JO - Journal of Viral Hepatitis
PY - 2021
VL - 28
TODO - 2
SP - 410-419
PB - Wiley-Blackwell Publishing Ltd
SN - 1352-0504, 1365-2893
TODO - 10.1111/jvh.13439
TODO - alanine aminotransferase;  caspase;  hepatitis B surface antigen;  M30 protein;  peginterferon alpha2a;  placebo;  tenofovir disoproxil;  unclassified drug;  virus DNA;  virus RNA;  alpha interferon;  antivirus agent;  hepatitis B surface antigen;  macrogol;  RNA;  virus DNA, adult;  Article;  cell death;  delta agent hepatitis;  female;  Hepatitis B virus;  human;  immune response;  inflammation;  major clinical study;  male;  priority journal;  treatment outcome;  controlled study;  genetics;  Hepatitis B virus;  hepatitis D;  prospective study;  randomized controlled trial, Antiviral Agents;  DNA, Viral;  Hepatitis B Surface Antigens;  Hepatitis B virus;  Hepatitis D;  Humans;  Interferon-alpha;  Polyethylene Glycols;  Prospective Studies;  RNA;  Treatment Outcome
TODO - 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 analysed 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 in 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. © 2020 John Wiley & Sons Ltd
ER -