The Medical Impact of Hepatitis D Virus Infection in Natives and Immigrants: The Italian Paradigm

Background and Aim: Ongoing migratory flows are reconstituting the hepatitis D virus (HDV) reservoir in Italy. We aimed to characterise the current clinical and virologic features of HDV infection in both native Italians and migrants. Methods: We enrolled 515 hepatitis B surface antigen (HBsAg)-positive patients with detectable anti-HDV antibodies from 32 Italian centres between August 2022 and July 2024; all patients underwent centralised virologic assessment. Results: Overall, 432 out of 515 (83.9%) patients were HDV-RNA-positive (4.39, 1.30–5.82 Log IU/mL; 99.0% HDV genotype-1). HDV-RNA levels correlated with ALT (rs = 0575, 0.514–0.630) and hepatitis B core-related antigen (rs = 0.521, 0.455–0.581). Native Italians (n = 317; 61.6%) were older than migrants (n = 198; 38.4%) (median age: 60, 55–65 vs. 46, 39–54 years; p < 0.001) and were more frequently male (68.1% vs. 49.5%; p < 0.001), with a higher prevalence of liver cirrhosis (70.3% vs. 50.5%; p < 0.001) and hepatocellular carcinoma (14.8% vs. 0.5%; p < 0.001). Among Italians, 223 (70.3%) had liver cirrhosis, 46 (14.5%) had chronic hepatitis D (CHD) without cirrhosis and 48 (15.1%) exhibited inactive/minimal disease with low viremia (≤ 3 Log IU/mL). Among migrants, 100 (50.5%) had liver cirrhosis, 58 (29.3%) had CHD and 40 (20.2%) showed inactive/minimal disease with low viremia (≤ 3 Log IU/mL). Conclusions: The current clinical landscape of chronic HDV infections in Italy is heterogeneous, changing the perspective of CHD as uniformly severe; although cirrhosis remains common, a substantial proportion of both native Italians and migrants present with milder forms of disease.