Type 2 diabetes mellitus as an independent predictor of significant fibrosis in treatment-naïve chronic hepatitis B patients with concurrent hepatic steatosis

Background and Aims: Type 2 diabetes mellitus (T2DM), hepatic steatosis (HS), and chronic hepatitis B (CHB) frequently co-exist, but the association of T2DM with liver histology has not been well characterized. The study investigated the impact of T2DM on the presence and severity of liver fibrosis and inflammation in CHB patients with biopsy-proven HS (CHB-HS). Approach and Results: We enrolled CHB-HS patients who underwent liver biopsy from 19 medical centers (5 countries/regions) from 1990 to 2024. Propensity score matching (PSM) on age, sex, HBeAg, and HBV DNA levels was performed to balance background risks between CHB-HS patients with and without T2DM in a 1:3 ratio. The study included 1019 CHB-HS patients (mean age 40.3±10.4 years, 75.4% male, 10.5% T2DM). In the PSM cohort (106 T2DM, 320 non-T2DM), T2DM patients (vs. non-T2DM) had higher proportions with significant (stage ≥2) fibrosis (62.3% vs. 42.2%, p <0.01) but not with significant hepatic inflammation or moderate-to-severe steatosis (grade ≥2 for both). On multivariable logistic regression analyses, T2DM was an independent factor associated with significant fibrosis (aOR 1.86, 95% CI: 1.15–3.01, p =0.01), but not other components of metabolic syndrome. Meanwhile, HBeAg + and body mass index (BMI) rather than T2DM were associated with significant hepatic inflammation and moderate-to-severe steatosis, respectively, with similar findings in the total pre-PSM cohort. Conclusions: In CHB patients with concurrent HS, T2DM was an independent factor associated with significant fibrosis, HBeAg+ with hepatic inflammation, and BMI with moderate-to-severe steatosis, suggesting that both viral and metabolic control are crucial in the management of CHB patients with HS.