Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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
Συγγραφείς:
Anastasiou, O.E.
Yurdaydin, C.
Maasoumy, B.
Hardtke, S.
Caruntu, F.A.
Curescu, M.G.
Yalcin, K.
Akarca, U.S.
Gürel, S.
Zeuzem, S.
Erhardt, A.
Lüth, S.
Papatheodoridis, G.V.
Radu, M.
Liebig, S.
Bantel, H.
Bremer, B.
Manns, M.P.
Cornberg, M.
Wedemeyer, H.
Περιοδικό:
Journal of Viral Hepatitis
Εκδότης:
Wiley-Blackwell Publishing Ltd
Λέξεις-κλειδιά:
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