Comparative efficacy and safety of pegylated interferon-alpha monotherapy vs combination therapies with entecavir or tenofovir in chronic hepatitis B patients.

Abstract

Current treatments for chronic hepatitis B (CHB) virus involve nucleos(t)ide analogs and pegylated interferon-alpha (PEG-IFNα). This study compares the efficacy and safety of PEG-IFNα monotherapy with its combinations with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in managing CHB. We included 147 treatment-naïve patients divided into three groups: Group A (PEG-IFNα-2b with ETV), Group B (PEG-IFNα-2b with TDF), and Group C (PEG-IFNα-2b monotherapy). Evaluations occurred every 12 weeks up to 48 weeks. The Kaplan-Meier method showed no significant differences in cumulative HBsAg loss, but HBV DNA clearance rates were higher in the TDF group than in the ETV group (P = 0.01). Higher incidences of elevated alanine aminotransferase (ALT), aspartate aminotransferase, and thrombocytopenia were observed in the TDF group compared to other groups. After propensity score matching, the TDF group had a higher undetectable HBV DNA rate than the IFN group, but no significant differences in HBsAg clearance rates. Both TDF and ETV groups achieved more significant HBsAg reductions from baseline to week 48 than the IFN group (P < 0.05). ETV showed a lower HBeAg clearance rate (30.00% vs 87.50%, P < 0.05) but higher ALT normalization (76.92% vs 45.45%, P < 0.05). In the TDF group, patients with lower baseline HBsAg levels, high ALT levels, and lower aspartate aminotransferase-to-platelet ratio index (APRI) scores were more likely to achieve HBsAg loss. These findings suggest that TDF and ETV are effective for viral suppression, with TDF showing superior HBV DNA clearance but more adverse events.

Importance: This study investigates how different treatments for chronic hepatitis B (CHB), a widespread liver infection, compare in effectiveness and safety. By evaluating the use of pegylated interferon-alpha alone and in combination with two other drugs, entecavir and tenofovir disoproxil fumarate (TDF), researchers found that TDF offers better viral suppression but also comes with more side effects. For patients receiving TDF combined with PEG-IFN therapy, low HBsAg levels, elevated alanine aminotransferase levels, and lower APRI scores were associated with a higher likelihood of achieving HBsAg loss. Consistent with previous findings, this study confirms the benefits of nucleos(t)ide analog plus PEG-IFN therapy for CHB treatment and further explores which patients are more likely to benefit from combination therapy. Furthermore, this study underscores the importance of further monitoring adverse events in patients receiving combination therapy.