Hepatitis Delta in Spain: A Nationwide Prospective Characterization of Active Infection and Liver Disease Severity.

OBJECTIVES

Hepatitis delta virus (HDV) infection is associated with rapid progression to cirrhosis and liver-related complications. We aimed to characterize the clinical and virological profile of anti-HDV-positive individuals in Spain and identify factors associated with active infection and advanced fibrosis.

METHODS

This nationwide, multicentre, prospective observational study included adults with positive anti-HDV serology enrolled between April 2024 and March 2026 across 72 hospitals in 15 Spanish Autonomous Communities. Demographic, virological, laboratory and clinical data were collected in a centralized database. Multivariable logistic regression was used to identify factors independently associated with active HDV infection and advanced liver fibrosis.

RESULTS

Among 1,112 anti-HDV-positive individuals, 670/1,112 (60%) were male, median age was 54 years (IQR 43-61), and 457/926 (49%) were born in Spain. HIV co-infection and anti-HCV positivity were present in 189/944 (20%) and 217/1,112 (21%), respectively. HDV-RNA was detectable in 436/1,047 patients (42%), with a median viral load of 4.1 log IU/mL (IQR 2.9-5.1). Genotype 1 accounted for 108/121 (89%) genotyped infections. Advanced fibrosis was present in 222/536 (41%) evaluable patients and was more frequent in those with active infection than in non-viremic individuals (155/261, 59% versus 59/256, 23%; p<0.001). Active HDV infection was independently associated with younger age, hepatitis B virus (HBV) antiviral therapy, lower platelet count and lower albumin levels, whereas African origin was associated with lower odds of detectable HDV-RNA. Advanced fibrosis was independently associated with active HDV infection, HBV antiviral therapy and higher gamma-glutamyltransferase levels, while higher platelet count and haemoglobin levels were associated with lower odds of advanced fibrosis.

CONCLUSIONS

Active HDV infection and advanced liver disease remain common in Spain. These findings support systematic HDV-RNA testing, standardized fibrosis assessment and close clinical follow-up of anti-HDV-positive individuals.