Dominique Roulot1, Ségolène Brichler2, Richard Layese3, Zahia BenAbdesselam4, Fabien Zoulim5, Vincent Thibault6, Caroline Scholtes7, Bruno Roche8, Corinne Castelnau9, Thierry Poynard10, Olivier Chazouillères11, Nathalie Ganne12, Hélène Fontaine13, Jerome Gournay14, Dominique Guyader15, Frédéric Le Gal2, Pierre Nahon12, Françoise Roudot-Thoraval16, Emmanuel Gordien2. 1. AP-HP, Hôpital Avicenne, Unité d'hépatologie, Université Paris 13, Bobigny; Inserm U955, équipe 18, Université Paris-Est, Créteil. Electronic address: dominique.roulot@aphp.fr. 2. AP-HP, Hôpital Avicenne, Laboratoire de microbiologie clinique, Université Paris 13, Centre national de référence des hépatites B, C et Delta, Bobigny, Inserm U955, équipe 18, Université Paris-Est, Créteil. 3. AP-HP, Hôpital Henri-Mondor, Unité de Recherche Clinique, Université Paris-Est, DHU A-TVB, IMRB- EA 7376 CEpiA (Clinical Epidemiology and Ageing Unit), Créteil. 4. AP-HP, Hôpital Avicenne, Unité d'hépatologie et Centre de Recherche Clinique, Bobigny. 5. Hospices civils de Lyon, Hôpital Croix Rousse, Service d'hépatologie; Inserm U1052; Université de Lyon. 6. CHU de Rennes, Inserm, EHESP, Irset-UMR S1085, Rennes. 7. Hospices civils de Lyon, Hôpital Croix Rousse, Département de virologie, Université de Lyon. 8. AP-HP, Hopital Paul Brousse, Service d'hépatologie, Villejuif. 9. AP-HP, Hopital Beaujon, Service d'hépatologie, Clichy. 10. AP-HP, Groupe hospitalier Pitié-Salpêtriere, Service d'hépatologie, Sorbonne Université, Paris. 11. AP-HP, Hopital Saint-Antoine, Service d'hépatologie et Centre de Recherche, Inserm, Sorbonne Université, Paris. 12. AP-HP, Hôpital Jean-Verdier, Service d'hépatologie, Bondy, Université Paris 13, Bobigny; Inserm U1162, Université Paris 5, Paris. 13. AP-HP, Hôpital Cochin, Service d'hépatologie, Paris. 14. CHU de Nantes, Hopital Hôtel Dieu, Département d'hépatogastroentérologie, Nantes. 15. CHU de Rennes, Service d'hépatologie, Rennes. 16. AP-HP, Hôpital Henri-Mondor, Unité de Recherche Clinique, Université Paris-Est, DHU A-TVB, IMRB- EA 7376 CEpiA (Clinical Epidemiology and Ageing Unit), Créteil; AP-HP, Hôpital Henri-Mondor, Service d'hépatologie, Créteil.
Abstract
BACKGROUND & AIMS: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection. METHODS: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up. RESULTS: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known 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 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma 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. CONCLUSION: Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients. LAY SUMMARY: Chronic liver infection by hepatitis delta virus (HDV) is the most severe form of chronic viral hepatitis. Despite the fact that at least 15-20 million people are chronically infected by HDV worldwide, factors determining the severity of liver involvement are largely unknown. By investigating a large cohort of 1,112 HDV-infected patients followed-up in France, but coming from different areas of the world, we were able to determine that HDV genotype, place of birth (reflecting both viral and host-related factors) and persistent viremia constitute the main determinants of liver involvement and response to treatment.
BACKGROUND & AIMS:HDVinfection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDVinfection. METHODS: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infectedpatients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up. RESULTS: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known 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 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDVinfection was associated with decompensation, hepatocellular carcinoma 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. CONCLUSION: Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infectedpatients. LAY SUMMARY: Chronic liver infection by hepatitis delta virus (HDV) is the most severe form of chronic viral hepatitis. Despite the fact that at least 15-20 million people are chronically infected by HDV worldwide, factors determining the severity of liver involvement are largely unknown. By investigating a large cohort of 1,112 HDV-infectedpatients followed-up in France, but coming from different areas of the world, we were able to determine that HDV genotype, place of birth (reflecting both viral and host-related factors) and persistent viremia constitute the main determinants of liver involvement and response to treatment.
Authors: Mathias Jachs; Teresa Binter; Caroline Schmidbauer; Lukas Hartl; Michael Strasser; Hermann Laferl; Stephanie Hametner-Schreil; Alexander Lindorfer; Kristina Dax; Rudolf E Stauber; Harald H Kessler; Sebastian Bernhofer; Andreas Maieron; Lorin Loacker; Simona Bota; Isabel Santonja; Petra Munda; Mattias Mandorfer; Markus Peck-Radosavljevic; Heidemarie Holzmann; Michael Gschwantler; Heinz Zoller; Peter Ferenci; Thomas Reiberger Journal: United European Gastroenterol J Date: 2021-12-07 Impact factor: 4.623