In a cohort study of 1,610 treatment-naive adults with chronic hepatitis D in Mongolia, 8.4% achieved spontaneous HDV RNA suppression over a median 3.9 years, with cumulative incidences of 7.8% at 5 years and 23.3% at 8 years. The study found that diabetes, male sex, and lower baseline HBsAg, HDV RNA, and ALT predicted spontaneous suppression, and patients with suppression had fewer liver-related events.

Why It Matters To Your Practice

• Chronic hepatitis D can progress to severe liver disease, but a subset of patients may suppress HDV without treatment.

• Baseline clinical and lab features may help clinicians identify which patients are more likely to experience spontaneous viral suppression.

• These findings may support risk stratification as anti-HDV therapies become more available.

Clinical Benefits

• Lower baseline HBsAg, HDV RNA, and ALT were independently associated with a higher likelihood of spontaneous HDV suppression.

• Diabetes mellitus (DM) was linked to greater odds of suppression (aHR 2.13; 95% CI 1.21-3.74), and male sex was also predictive (aHR 1.61; 95% CI 1.19-2.40).

• Patients who achieved suppression had a significantly lower risk of liver-related events than those with persistent HDV replication.

Managing Risks

• Higher baseline HBsAg, HDV RNA, and ALT were negatively associated with spontaneous suppression, suggesting a need for closer monitoring in these patients.

• Do not assume spontaneous suppression is common: only 8.4% suppressed over follow-up.

• Patients with ongoing replication may remain at higher risk for liver-related complications and may warrant earlier treatment consideration.

The Bottom Line

• In chronic hepatitis D, spontaneous HDV suppression was uncommon but clinically meaningful.

• Diabetes, male sex, and lower baseline HBsAg, HDV RNA, and ALT can help identify patients more likely to suppress virus spontaneously.

• Use these predictors to inform follow-up intensity and treatment timing as newer HDV therapies enter practice.