Abstract / Summary
Abstract Background and Aims: Persistent HDV RNA replication predicts worse outcomes in chronic hepatitis D (CHD), but the clinical significance of HDV RNA’s levels, relative to other predictors of liver-related events (LREs), remains unclear. Methods: Adults with CHD attending a Mongol liver center, 2015–2025, without prior LREs or anti-CHD therapy, were eligible. HDV RNA levels were quantified using Bio-Rad kit (lower limit of quantification of 50 IU/mL). Associations of baseline and longitudinal HDV RNA levels with cirrhosis progression, and LREs were assessed using Cox regression models. Results: Overall 2,447 patients were included with: median age 40.3 years, 56.1% females, median HDV RNA 5.3 log 10 IU/mL, 37.4% HBeAg+, 76.5% with elevated ALT, and 23.6% with cirrhosis at baseline. During a median follow-up of 7.3 years (range 0.6–12.7), 247 of 1,870 patients (13.2%) progressed to cirrhosis, and 287 of 2,447 patients (11.7%) experienced any LREs, with cumulative risks of 6.9%, and 18.0% at 5 and 10 years, respectively. The risk of HCC, and LREs increased from HDV RNA level above 3 log 10 IU/mL, without further increase at higher levels (threshold pattern), while cirrhosis risk rose more gradually to 5 log 10 IU/mL. HDV RNA level alone showed limited prognostic discrimination (AUROC <0.70), while age, ALT, GGT, platelet count, liver stiffness, and cirrhosis provided additional prognostic information (AUROC ≥0.83). Conclusion: HDV RNA levels showed a threshold, not a dose-response, association with HCC and liver-related events, with limited prognostic accuracy alone. Adding other liver-related parameters improved risk stratification, potentially guiding monitoring, and treatment decisions.