Burden of Hepatitis D Virus Infection in Italy: Interim Results from a Prospective Multicentre Nationwide Study

IntroductionAlthough compulsory hepatitis B virus (HBV) vaccination greatly reduced new hepatitis D virus (HDV) disease in native Italians, migratory flows from HDV endemic areas are increasingly reconstituting the reservoir of this infection in Italy.AimTo report the preliminary results of a survey on the epidemiologic, virologic and clinical features of contemporary HDV cases in Italy.Materials and MethodsConsecutive patients positive for hepatitis B surface antigen (HBsAg) and antibodies to HDV (anti-HD) referred to 27 third-level Italian Centers were prospectively enrolled from August 2022 to October 2023.ResultsA total of 497 patients positive for anti-HD were recruited; median age was 56 (IQR 45–62) years and most patients were male (62.2%). Native Italians were 298 (60.0%). Among patients born abroad, the majority (n=166; 86.5%) were from Eastern Europe, followed by Africa (n=19; 9.9%) and Asia (n=4; 2.1%). Native Italians were older (median age 60, IQR 56–64, years vs. 44, IQR 37–51 years in patients born abroad; p<0.001) and had a more advanced liver disease (cirrhosis: 64.2% vs 51.1%; p=0.005; HCC: 14.5% vs 1.6%; p<0.001; liver stiffness: 12.0, IQR 7.9–18.5 kPa vs 9.2, IQR 6.3–14.4 kPa, p=0.001) compared to patients born abroad. One-hundred-thirty-three patients underwent centralized serum HDV-RNA assessment (RoboGene®v2) and HDV genotyping (direct sequencing). Overall, 103 (77.4%) patients were HDV-RNA-positive (median 5.26, IQR 4.03–6.04 Log IU/mL). The prevalent genotype was HDV-1 (n=100); 3 patients were infected with HDV-5. HDV-RNA correlated with ALT values (rs=0.303, 95%CI 0.105–0.484; p=0.004) and HDV-RNA-positivity was significantly associated with liver cirrhosis (OR=3.03, 95%CI 1.14–8.07; p=0.027).ConclusionsIn Italy, patients born abroad accounted for nearly half of the overall HDV infections collected in the past year. Most patients had advanced liver disease with high levels of serum HDV-RNA. These preliminary findings confirm that HDV infection in migrants represents an increasing medical alert in Italy.This research was supported by Gilead Sciences, Inc (study ID: IN-IT-980-6382).