RESUMO
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.
Assuntos
Antígenos de Superfície da Hepatite B , Hepatite D , Antivirais/uso terapêutico , DNA Viral , Vírus da Hepatite B/genética , Hepatite D/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , RNA , Resultado do TratamentoRESUMO
Periodontitis, a common infectious disease, is initiated by various gram-negative bacteria and characterized by the destruction of the periodontal tissue. Here, we investigated the role of caspases, intracellular proteases that are the key mediators of apoptosis. We show that activation of caspase-3 and caspase-7 is considerably enhanced in gingival tissue from patients with periodontitis. We also demonstrate in in vitro experiments that various periodontopathic bacteria exert a direct growth-suppressing effect and, moreover, can trigger a host-mediated cytotoxic activity involving the CD95 death receptor. Our data suggest that caspase activation is a prominent feature in periodontitis-associated tissue injury.