Diabetes Impairs the Virological Response in Patients with Chronic Hepatitis B: Glycemic Control as a Key Modifiable Risk Factor

Background/Objectives: Chronic hepatitis B (CHB) and type 2 diabetes mellitus (T2DM) frequently coexist. This study aimed to investigate the impact of T2DM and glycemic control on antiviral efficacy in CHB patients. Methods: This single-center, retrospective cohort study included treatment-naïve CHB patients who initiated nucleos(t)ide analogue (NA) therapy between January 2019 and January 2024. The primary endpoint was a complete virological response (CVR), defined as achieving HBV DNA levels below 20 IU/mL after 48 weeks of treatment. Results: The CHB + T2DM group (n = 81) demonstrated a significantly lower CVR rate than the CHB group (n = 106) (26.0% vs. 41.2%, p = 0.038). Multivariate analysis identified T2DM as an independent negative predictor of a CVR (OR = 0.400, 95% CI: 0.196–0.815, p = 0.012). Within the CHB + T2DM subgroup, adequate glycemic control (HbA1c < 7%) was associated with a higher CVR (38.7% vs. 16.7%, p = 0.034). Patients newly diagnosed with diabetes at enrollment showed a higher rate of HBeAg loss than those with pre-existing diabetes (57.1% vs. 10.0%, p = 0.036). Regarding antiviral regimens, entecavir-treated CHB + T2DM patients had a lower CVR than CHB controls (18.8% vs. 46.2%, p = 0.015). Furthermore, tenofovir-based regimens showed a more favorable antiviral trend than entecavir in CHB patients with T2DM. Conclusions: Comorbid T2DM was an independent risk factor for impaired antiviral efficacy in CHB patients. Optimal glycemic control may improve virological outcomes. These findings suggest that the early diagnosis and management of T2DM could enhance antiviral treatment efficacy in CHB patients.