A high prevalence of hepatitis delta virus (HDV) infection, the most severe form of viral hepatitis, has been reported among persons with HIV (PWH) and hepatitis B virus (HBV) infection in European cohorts. We analyzed data from two large HIV cohorts to characterize the current epidemiological trends in HDV infections across Europe.
All PWH with a positive hepatitis B surface antigen (HBsAg) test in the Swiss HIV cohort Study and EuroSIDA were considered and tested for anti-HDV antibodies. HDV RNA amplification was performed in anti-HDV-positive patients. Demographic and clinical characteristics at initiation of antiretroviral therapy were compared between HDV-positive and HDV-negative individuals using descriptive statistics. The associations between HDV infection and overall mortality, liver-related mortality as well as hepatocellular carcinoma (HCC) were assessed using Kaplan-Meier and multivariable Cox regression adjusted for age, gender, HIV transmission group, baseline CD4 and cohort.
Of 2793 HBsAg-positive patients, 1556 (56%) had stored serum available and were included. The prevalence of HDV co-infection was 15.2% (237/1556, 95% CI: 13.5%-17.1%), of whom 66% (132/200) had active HDV replication. Anti-HDV antibody positive prevalence ranged from 32.8% (95% CI: 24.7%-41.7%) in Eastern Europe, to 29.7% (95% CI: 21.4%-39.1%) in the South and 14.9% (95% CI: 12.7%-17.4%) in Northwestern Europe. HDV-positive persons were more likely to be persons who inject drugs (PWID) (76.8% vs 14.3%, p<0.001) and to have positive hepatitis C serology (75.5% vs. 24.3%, p<0.001), compared to those without HDV-infection. Among PWID, the prevalence of HDV co-infection was 49.2%, with similar estimates across the three regions. During a median follow-up time of 9.8 years [IQR 4-4-16.6], seventy-five (31.6%) HDV-positive patients and 261 (19.8%) HDV-negative individuals died. 43% (32/75) of the deaths were liver related in HDV-positive patients compared to 18% (46/261) in HDV-negative individuals. HDV infection was associated with overall mortality (adjusted hazard ratio 1.4; 95% CI 1.1-1.95, p=0.03), liver-related death (2.9, 1.6-5.1, p<0.001) and hepatocellular carcinoma (6.5, 2.6-16.6, p<0.001).
Hepatitis delta prevalence among PWH in Europe varies strongly across regions and is particularly high in PWIDs. This could reflect different availability of harm reduction programs. HDV coinfection is associated with increased mortality and liver related events including HCC.