Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta.
Adult
Carcinoma, Hepatocellular
/ ethnology
Female
France
/ epidemiology
Hepatitis D, Chronic
/ complications
Hepatitis Delta Virus
/ genetics
Humans
Interferons
/ therapeutic use
Liver Cirrhosis
/ diagnosis
Liver Neoplasms
/ ethnology
Male
Residence Characteristics
/ statistics & numerical data
Retrospective Studies
Severity of Illness Index
Viral Load
/ methods
Viremia
/ diagnosis
African origin
Deltavir study
HDV genotype
HDV persistent viremia
Liver outcome
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
29
08
2019
revised:
04
06
2020
accepted:
23
06
2020
pubmed:
8
7
2020
medline:
16
11
2021
entrez:
8
7
2020
Statut:
ppublish
Résumé
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. 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. 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. Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients. 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.
Sections du résumé
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.
Identifiants
pubmed: 32634548
pii: S0168-8278(20)30441-4
doi: 10.1016/j.jhep.2020.06.038
pii:
doi:
Substances chimiques
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1046-1062Investigateurs
Jean-Didier Grangé
(JD)
Roland Landman
(R)
Christophe Hezode
(C)
Ghassan Riachi
(G)
Caroline Lascoux-Combe
(C)
Véronique Loustaud-Ratti
(V)
Isabelle Rosa
(I)
Philippe Mathurin
(P)
Eric Nguyen-Khac
(E)
Xavier Causse
(X)
Sylvie Naveau
(S)
François Habersetzer
(F)
Sophie Metivier
(S)
Hélène Labadie
(H)
Pierre Sellier
(P)
Julie Bottero
(J)
Victor de Ledinghen
(V)
Laurent Alric
(L)
Paul Calès
(P)
Cecile Goujard
(C)
Jean-François Cadranel
(JF)
Dominique Salmon
(D)
Sophie Hillaire
(S)
Informations de copyright
Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest Dr. Nahon received honoraria from Astra-Zeneca, Abbvie, Bayer, Bristol-Myers Squibb, Gilead and Ipsen. He consults for Abbvie and Bristol-Myers Squibb. Dr Roudot-Thoraval received honoraria from Gilead and AbbVie. Dr Roulot received honoraria from Gilead. All other authors report no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details.