Hepatitis delta virus (HDV) infection causes severe chronic liver disease in Hepatitis B virus (HBV) infected individuals. Factors associated with poor prognosis are largely unknown.The French National Reference Centre for HDV performed a nationwide retrospective study on 1112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up.68.6% of patients were male with a median age of 36.5 [29.9-43.2] years. Most patients with known birth place were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were french native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%) followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least one episode of hepatic decompensation (HD). Cirrhosis was significantly less frequent in African than in European patients regardless HDVgenotype. At the end of follow-up (median 3.0 [0.8-7.2]), 48.8% of the patients had developed cirrhosis, 24.2% had one or more episodes of HD and 9.2% had hepatocellular carcinoma (HCC). European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, HCC occurrence and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs 29.1%, p<0.001). HDV viral load at baseline was significantly lower in responders than in non-responders.Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients.