LAUSR

Background and Aims: Type 2 diabetes (T2D) is common among patients with chronic hepatitis B infection (CHB) and has been associated with increased risk of carcinogenesis, including HCC. We investigated factors associated with HCC and fibrosis progression among patients with CHB with T2D (CHB+T2D). Approach and Results: Chinese patients with CHB were prospectively recruited for the incidence of HCC and fibrosis progression defined by transient elastography. Among patients with CHB+T2D, glycemic control was assessed by mean glycated hemoglobin (HbA1c) and HbA1c variability determined using HbA1c measurements in the 5 years preceding recruitment. A total of 2330 patients with CHB were recruited (mean age 54.6 ±11.8 years old, 55.5% male, 57.9% antiviral‐treated), with 671 (28.8%) having CHB+T2D (mean T2D duration 7.2 ± 4.6 years, mean HbA1c 7.2 ± 0.9%). T2D was independently associated with HCC (HR 2.080, 95% CI 1.343–3.222) and fibrosis progression (OR 4.305, 95% CI 3.416–5.424) in the overall cohort. In patients with CHB+T2D, factors reflecting glycemic burden (T2D duration [HR 1.107, 95% CI 1.023–1.198]), mean HbA1c (HR 1.851, 95% CI 1.026–3.339), time reaching target HbA1c (HbA1c‐TRT; HR 0.978, 95% CI 0.957–0.999), liver stiffness (HR 1.041–1.043), and smoking (HR 2.726–3.344) were independently associated with HCC (all p < 0.05), but not HbA1c variability or controlled attenuation parameter. The same glycemic burden–related factors (T2D duration, mean HbA1c, and HbA1c‐TRT), in addition to baseline fasting glucose, baseline HbA1c, AST and antiviral therapy, were independently associated with fibrosis progression at 3 years. Conclusions: High glycemic burden was associated with HCC development and fibrosis progression among patients with CHB+T2D, highlighting the importance of glycemic control in reducing liver‐related complications.