Diabetes, male sex, low levels of HBsAg, HDV RNA and ALT predict spontaneous HDV suppression in chronic hepatitis D

Background & Aims: Persistent HDV replication is associated with severe liver disease, yet predictors of spontaneous HDV RNA suppression remain poorly defined. We assessed the incidence and predictors of spontaneous HDV suppression in a large cohort of chronic hepatitis D (CHD). Methods: We included 1,610 adult, treatment-naive CHD patients with ≥3 HDV RNA tests, who attended the Liver Center, Mongolia, between 2015-2025. Patients were categorized according to the last HDV RNA result: 1. Suppression (HDV RNA <50 IU/mL or HBsAg loss), 2. Persistent infection (HDV RNA ≥50 IU/mL). The incidence and predictors of HDV suppression during follow-up were analyzed using Kaplan-Meier curves and Cox regression. Results: The median baseline age was 40.5 years, and 44.5% were male. Over a median of 3.9 years (IQR=2.1–5.9), 136 patients (8.4%) achieved spontaneous suppression, yielding cumulative incidences of 7.8% and 23.3% at 5 and 8 years, respectively. Independent predictors of HDV suppression were diabetes (adjusted hazard ratio [aHR] 2.13; 95% CI 1.21–3.74) and male sex (aHR 1.61; 95% CI 1.19–2.40), whereas higher baseline levels of HBsAg (aHR 0.42; 95% CI 0.31–0.55), HDV RNA (aHR 0.74; 95% CI 0.62–0.89), and ALT (aHR=0.35, 95% CI 0.21–0.57) were negatively associated. The risk of liver-related events was significantly lower in in patients with HDV suppression than in those with persistent replication ( p =0.03). Conclusion: Diabetes, male sex, lower baseline HBsAg, HDV RNA and ALT independently predicted HDV spontaneous suppression. These factors may inform treatment decisions in this era of emerging anti-HDV therapies.