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Hepatitis Delta in Spain: A Nationwide Prospective Characterization of Active Infection and Liver Disease Severity
Ana Alberola1, Adolfo de Salazar1, Ana Fuentes1
1Hospital Universitario Clínico San Cecilio, Granada, Spain; Instituto de Investigación Biosanitaria ibs.Granada, Granada, Spain; Centro de Investigación Biomédica en Red Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
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.