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

Liver Int. 2025 Sep;45(9):e70242. doi: 10.1111/liv.70242.

Abstract

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.

Keywords: HDV; HDV‐RNA; chronic hepatitis D; cirrhosis; epidemiology.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / virology
  • Emigrants and Immigrants* / statistics & numerical data
  • Female
  • Hepatitis Antibodies / blood
  • Hepatitis B Surface Antigens / blood
  • Hepatitis D* / epidemiology
  • Hepatitis D, Chronic* / epidemiology
  • Hepatitis Delta Virus* / genetics
  • Hepatitis Delta Virus* / isolation & purification
  • Humans
  • Italy / epidemiology
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / virology
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • RNA, Viral / blood

Substances

  • Hepatitis B Surface Antigens
  • RNA, Viral
  • Hepatitis Antibodies