Development of Hepatic Steatosis in Chronic Hepatitis D: A 36-Month Prospective Cohort Study

Abstract

Background and aim: Hepatic steatosis is an important metabolic condition that may contribute to disease progression in patients with chronic viral hepatitis, including chronic hepatitis D virus (HDV) infection. However, longitudinal data on the development of hepatic steatosis in patients with chronic HDV infection remain limited. This study aimed to assess the cumulative incidence of hepatic steatosis over 36 months and to evaluate its demographic, occupational, anthropometric, metabolic, and comorbidityrelated associations. Materials and methods: A prospective cohort study was conducted at Ferghana City Infectious Diseases Hospital from January 3, 2023, to January 3, 2026. A total of 221 patients with chronic HDV infection were included, all of whom received antiviral therapy. Hepatic steatosis was assessed by ultrasonography every 6 months during the 36-month follow-up. Time to development of hepatic steatosis was analyzed using the Kaplan–Meier method. Body mass index (BMI), demographic and occupational characteristics, adiponectin levels, liver enzymes, viral load, and comorbidities were compared between patients with and without hepatic steatosis. Correlations between anthropometric and biochemical parameters were assessed using regression analysis. Results: During follow-up, hepatic steatosis developed in 69 patients (31.2%), while 152 (68.8%) remained free of steatosis. Kaplan–Meier analysis demonstrated a progressive increase in the cumulative probability of hepatic steatosis, reaching approximately 33% at 36 months. Mean BMI did not differ significantly between patients with and without steatosis (26.7±0.38 vs. 25.5±0.28 kg/m²; p>0.05); however, obesity was more frequent among patients with steatosis (27.5% vs. 7.2%), with a relative risk of 3.8 (95% CI, 1.9–7.55). ALT and AST levels were significantly higher in patients with steatosis than in those without steatosis (89.3±2.3 vs. 59.2±1.1 U/L and 61.2±1.58 vs. 36.6±1.03 U/L, respectively; p<0.001). Adiponectin levels were significantly lower in patients with steatosis (4.7±0.64 vs. 11.2±1.2; p<0.001). BMI showed an inverse correlation with adiponectin (r=−0.58) and positive correlations with ALT (r=0.24) and AST (r=0.31). A strong inverse correlation was observed between adiponectin and ALT (r=−0.83), while a moderate inverse correlation was found between adiponectin and AST (r=−0.59). Type 2 diabetes, chronic pancreatitis, chronic cholecystitis, and cholelithiasis were more frequent among patients with steatosis. Conclusion: Hepatic steatosis developed progressively in patients with chronic HDV infection during 36 months of follow-up, reaching a cumulative probability of approximately one-third by the end of observation. Steatosis was associated with obesity, lower adiponectin levels, higher aminotransferase activity, and selected metabolic and hepatobiliary comorbidities. These findings support the importance of longitudinal metabolic and hepatic monitoring in patients with chronic HDV infection.