Metabolic and Thyroid Alterations in HBV Monoinfection and HBV–HDV Coinfection: Insights from a Liver Transplant Cohort

Background: Metabolic alterations associated with hepatitis B virus (HBV)–hepatitis D virus (HDV) coinfection remain poorly characterized. We investigated metabolic and endocrine profiles in HBV monoinfection and HBV–HDV coinfection, with emphasis on quantitative HDV activity. Methods: This retrospective observational study included HBsAg-positive adult liver transplant candidates. Pre-transplant metabolic, biochemical, thyroid, and virological parameters were evaluated. Associations between quantitative HDV RNA and metabolic parameters were assessed using Spearman correlation and multivariable regression. Results: Conventional circulating metabolic parameters were broadly comparable between groups. HBV–HDV coinfection was associated with higher adjusted odds of diabetes mellitus, although this association was attenuated after accounting for liver disease severity. TSH was independently lower in HBV–HDV coinfection, whereas FT3 and FT4 did not differ independently. Among patients with HBV–HDV coinfection, HDV RNA correlated positively with triglycerides (ρ = 0.437, p = 0.009). Each 1-log10 increase in HDV RNA was associated with a 5.42 mg/dL increase in triglycerides after adjustment for HBV DNA, age, sex, and MELD score (95% CI 1.84–9.00; p = 0.003), with consistent associations in BMI- and diabetes-adjusted sensitivity models. Conclusions: Higher quantitative HDV RNA was independently associated with higher triglyceride concentrations, identifying a potential viral–metabolic interaction that warrants prospective validation.