Abstract
There are two main types of drugs that are used to treat chronic hepatitis B (CHB), including interferon (IFN) and nucleotide analogues. IFN inhibits the virus through direct antiviral activity and via immune regulation, and it has been widely applied for the treatment of CHB and other infections. However, the efficiency of IFN therapy is not entirely satisfactory. The aim of the present study was to investigate the factors affecting IFN therapy. The plasma of patients with CHB treated with IFN was collected and divided into the virological response group and non-virological response group according to their virological response. Serum proteins of virologically responsive patients were compared before and after IFN therapy using isobaric tags for relative and absolute quantitation technology. ELISA was used to validate these results in the same sample. In in vitro cell experiments, HepG2.2.15 cells were transfected with haptoglobin (Hp)-targeting small interfering RNA to inhibit expression of the Hp protein, and reverse transcription-quantitative polymerase chain reaction and western blotting were utilized to detect hepatitis B virus (HBV)-DNA, IFN and downstream molecular changes in the cell supernatants. The Hp protein levels were demonstrated to be significantly lower following 48 weeks of IFN therapy, and the levels of Hp in patients in the virological response group were significantly lower than those in the non-virological response group. In in vitro cell experiments, following inhibition of Hp protein expression, significantly decreased levels of HBV-DNA, and elevated levels of IFN and its downstream molecules were observed. These findings suggest that Hp may be able to predict the efficacy of IFN therapy, and it may inhibit HBV clearance. There is an association between Hp and IFN, which requires further clinical and laboratory studies to explore.