A transient early HBV-DNA increase during PEG-IFN alpha therapy of hepatitis D indicates loss of infected cells and is associated with HDV-RNA and HBsAg reduction

Anastasiou O. E., Yurdaydin C., Maasoumy B., Hardtke S., Caruntu F. A., Curescu M. G., ...More

JOURNAL OF VIRAL HEPATITIS, vol.28, no.2, pp.410-419, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 28 Issue: 2
  • Publication Date: 2021
  • Doi Number: 10.1111/jvh.13439
  • Journal Name: JOURNAL OF VIRAL HEPATITIS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.410-419
  • Keywords: HBV, HDV, hepatitis B, hepatitis D, interferon, viral kinetics, TENOFOVIR DISOPROXIL FUMARATE, D VIRUS, REPLICATION, COMBINATION, INDUCTION, RESPONSES, KINETICS, ADEFOVIR, INNATE, DRUG
  • Bursa Uludag University Affiliated: Yes

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.