Background: Steatotic liver disease (SLD) can worsen the prognosis of other chronic liver diseases, including viral hepatitis.

Objective: To compare SLD and non-SLD patients with chronic hepatitis B virus (HBV) infection.

Methods: The study included consecutive Caucasian patients with chronic hepatitis B treated with nucleos(t)ide analogs (NA), entecavir or tenofovir, for a median (quartile 1-3) of 6 (2-11) years and evaluated between January 2023 and June 2024.

Results: Of the 273 patients included in the analysis, 86 were diagnosed with SLD. Men dominated the overall population, but their percentage was higher in the SLD group (77.9% vs. 63.6%, P = 0.02). The burden of comorbidities was higher in the SLD population compared to non-SLD (P <0.001), including obesity (P <0.001), diabetes (P = 0.004), and gout (P = 0.03). Cirrhosis was diagnosed in 16.3% of SLD and 11.8% of non-SLD patients (P = 0.31). Aminotransferases activity was higher in the SLD group (P <0.001), while positive HBe antigen was significantly less frequent in this population, and HBV DNA viral load was comparable in both groups. More than 97% of patients in both groups achieved HBV DNA clearance during therapy, with a negative rate of 69.5% in the SLD and 66.7% in the non-SLD group after 1 year of treatment.

Conclusions: Liver steatosis was diagnosed in nearly one-third of HBV-infected patients treated with NA. They were significantly more likely to have obesity, diabetes, and gout compared to the non-SLD population. Despite higher baseline aminotransferases activity in the SLD group, the virological HBV activity and response to therapy were comparable.