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.

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 analyzed 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 of 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.