Effectiveness of Different Antiviral Treatments and Timing of the Treatment Initiation in Hepatitis B Virus (HBV)-Infected Newborn Mice after Failure of Blocking Mother-to-Offspring Transmission

Abstract

Background: The aim of this study was to investigate the effectiveness of different antiviral treatments and the timing of the initiation of treatment in hepatitis B virus (HBV)-infected newborn mice. Methods: Newborn mice, infected with HBV after the failure of blocking maternal-fetal transmission, received an 8-week treatment with the following antiviral agents, either alone or in combination: Entecavir (ETV), ETV + pegylated interferon a-2b (PEG IFN-a2b), tenofovir disoproxil fumarate (TDF), TDF + PEG IFN-a2b, PEG IFN-a2b, or normal saline at 4, 8, or 12 weeks after birth. HBV DNA, HBV RNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) were examined before or after treatment. Results: The greatest rate of HBV DNA inhibition was achieved after an 8-week treatment with ETV + PEG IFN-a2b in the newborn mice with antiviral therapy initiated at 4 weeks of age (p < 0.05). Moreover, ETV, ETV + PEG IFN-a2b, TDF, or TDF + PEG IFN-a2b elicited a significantly greater inhibition of HBV DNA than PEG IFN-a2b at all treatment initiation timings (p < 0.05). There was no significant difference in the effects of HBV RNA and HBV DNA. Furthermore, antiviral therapy initiation at 4 weeks of age had significantly greater effects on HBsAg and HBeAg than when the therapy was initiated at 8 weeks of age for ETV + PEG IFN-a2b (p < 0.05). Alanine transaminase was significantly elevated after 8-week treatment with ETV + PEG IFN-a2b or TDF + PEG IFN-a2b in the newborn mice with treatment initiation at 12 weeks after birth, whereas the creatinine and phosphorus levels remained within the normal ranges at all treatment initiation timings (p < 0.05). Conclusions: ETV or TDF in combination with PEG IFN-a2b was significantly more effective than either drug alone in the treatment of HBV-infected newborn mice. Furthermore, 4 weeks of age was found to be the optimal timing to initiate antiviral therapy. Therefore, these findings may help to develop an optimal treatment to improve the care of patients infected with HBV as a consequence of the failure of blocking mother-to-baby/neonata transmission.