Combination therapy based on pegylated interferon alfa improves the therapeutic response of patients with chronic hepatitis B who exhibit high levels of hepatitis B e-antigen at 24 weeks

Abstract

Pegylated interferon alpha (PEG-IFN-α) is a first-line treatment for patients with chronic hepatitis B (CHB), but its efficacy varies from individual to individual. Early discrimination between responder and non-responder patients is important for optimal clinical management. In addition, low therapeutic efficacy is still a major issue; thus, treatment timing should be optimized.We reviewed our experience with hepatitis B e-antigen (HBeAg)-positive patients treated with PEG-IFN-α, alone or in combination with nucleoside analogues (NAs), from 2009 through 2014. Collected data included both general characteristics of 113 patients and laboratory data at baseline and at treatment weeks 12, 24, 52, and 76. The endpoint was HBeAg seroconversion at week 76.A total of 113 patients with changed to or start of NAs therapy were included in this study. At the end of treatment, 44 (38.9%) patients exhibited HBeAg seroconversion. Patients with HBeAg seroconversion had lower baseline HBeAg (475.5 vs 751.7; P = .007). The incidence of HBeAg seroconversion was significantly higher among patients with HBeAg ≤ 500 signal-to-cutoff ratio (S/CO) (OR = 2.60, 95% CI: 1.16–5.83, P = .02) at baseline, HBeAg S/CO ≤ 20 (OR = 3.37, 95% CI: 1.47–7.73, P = .003), or a higher than 10-fold HBeAg drop (OR = 3.55, 95% CI: 1.50–8.37, P = .003) at week 12 or HBeAg ≤ 15 S/CO (OR = 10.35, 95% CI: 4.09–26.20, P < .001) at week 24. Subgroup analyses demonstrated that in patients with HBeAg >20 S/CO at 24 weeks, the addition of NAs treatment may increase HBeAg seroconversion (23.3% vs 0%, P = .03).HBeAg levels had an impact on the rate of serological conversion in CHB patients receiving PEG-IFN-based treatment. Combination therapy with NAs should be considered in CHB patients maintaining a high HBeAg level after 24 weeks of PEG-IFN monotherapy.

The Development and Study of the Toxicity of Suppositories With a Modified Substance of Interferon Alfa-2b

“…This leads to the creation of a "water cloud" surrounding the complex of interferon and PEG, resulting in the increase of the solubility rate of the complex (which makes its bioavailability higher) and its protection from destructive external influences (neutralizing agents of the immune system, digestive enzymes). Due to this hydration barrier, the molecule breaks down more slowly and thus the effect of interferon becomes prolonged [11][12][13]. As confirmed by clinical studies, for example, PEGylated interferon alfa-2b was more effective in treating patients with chronic hepatitis C than interferon alfa-2b [14,15].…”

Understanding the antiviral effects of RNAi-based therapy on chronic hepatitis B infection

“…Treatment options for chronic hepatitis B (HBV) infections are limited to two main drug groups: pegylated interferon-α (IFN) and nucleos(t)ide analogues (NAs) [1][2][3].…”