Long-term outcome of hepatitis delta in different regions world-wide: Results of the Hepatitis Delta International Network.

cirrhosis clinical long‐term outcome epidemiology ethnicity hepatitis delta prognostic factors

Journal

Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857

Informations de publication

Date de publication:
18 Jun 2024
Historique:
revised: 23 04 2024
received: 13 02 2024
accepted: 23 05 2024
medline: 18 6 2024
pubmed: 18 6 2024
entrez: 18 6 2024
Statut: aheadofprint

Résumé

Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources. The Hepatitis Delta International Network (HDIN) registry involves researchers from all continents (Wranke, Liver International 2018). We here report long-term follow-up data of 648 hepatitis D patients recruited by 14 centres in 11 countries. Liver-related clinical endpoints were defined as hepatic decompensation (ascites, encephalopathy and variceal bleeding), liver transplantation, hepatocellular carcinoma or liver-related death. Patient data were available from all continents but Africa: 22% from Eastern Mediterranean, 32% from Eastern Europe and Central Asia, 13% from Central and Southern Europe, 14% from South Asia (mainly Pakistan) and 19% from South America (mainly Brazil). The mean follow-up was 6.4 (.6-28) years. During follow-up, 195 patients (32%) developed a liver-related clinical event after 3.5 (±3.3) years. Liver cirrhosis at baseline and a detectable HDV RNA test during follow-up were associated with a worse clinical outcome in multivariate regression analysis while patients receiving interferon alfa-based therapies developed clinical endpoints less frequently. Patients from South Asia developed endpoints earlier and had the highest mortality. The HDIN registry confirms the severity of hepatitis D and provides further evidence for HDV viraemia as a main risk factor for disease progression. Hepatitis D seems to take a particularly severe course in patients born in Pakistan. There is an urgent need to extend access to antiviral therapies and to provide appropriate education about HDV infection.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources.
METHODS METHODS
The Hepatitis Delta International Network (HDIN) registry involves researchers from all continents (Wranke, Liver International 2018). We here report long-term follow-up data of 648 hepatitis D patients recruited by 14 centres in 11 countries. Liver-related clinical endpoints were defined as hepatic decompensation (ascites, encephalopathy and variceal bleeding), liver transplantation, hepatocellular carcinoma or liver-related death.
RESULTS RESULTS
Patient data were available from all continents but Africa: 22% from Eastern Mediterranean, 32% from Eastern Europe and Central Asia, 13% from Central and Southern Europe, 14% from South Asia (mainly Pakistan) and 19% from South America (mainly Brazil). The mean follow-up was 6.4 (.6-28) years. During follow-up, 195 patients (32%) developed a liver-related clinical event after 3.5 (±3.3) years. Liver cirrhosis at baseline and a detectable HDV RNA test during follow-up were associated with a worse clinical outcome in multivariate regression analysis while patients receiving interferon alfa-based therapies developed clinical endpoints less frequently. Patients from South Asia developed endpoints earlier and had the highest mortality.
CONCLUSIONS CONCLUSIONS
The HDIN registry confirms the severity of hepatitis D and provides further evidence for HDV viraemia as a main risk factor for disease progression. Hepatitis D seems to take a particularly severe course in patients born in Pakistan. There is an urgent need to extend access to antiviral therapies and to provide appropriate education about HDV infection.

Identifiants

pubmed: 38888267
doi: 10.1111/liv.16006
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Deutsches Zentrum für Infektionsforschung
Organisme : Gilead Sciences
Organisme : Integrated Research and Treatment Centre Transplantation (IFB-Tx)
Organisme : Flanders

Informations de copyright

© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.

Références

Rizzetto M, Purcell RH, Gerin JL. Epidemiology of HBV‐associated delta agent: geographical distribution of anti‐delta and prevalence in polytransfused HBsAg carriers. Lancet. 1980;1:1215‐1218.
Rizzetto M, Hamid S, Negro F. The changing context of hepatitis D. J Hepatol. 2021;74:1200‐1211.
Urban S, Neumann‐Haefelin C, Lampertico P. Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult‐to‐treat disease. Gut. 2021;70:1782‐1794.
Polaris Observatory Collaborators. Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study. Lancet Gastroenterol Hepatol. 2023;8:879‐907.
Stockdale AJ, Kreuels B, Henrion MYR, et al. The global prevalence of hepatitis D virus infection: systematic review and meta‐analysis. J Hepatol. 2020;73:523‐532.
Razavi HA, Buti M, Terrault NA, et al. Hepatitis D double reflex testing of all hepatitis B carriers in low‐HBV‐ and high‐HBV/HDV‐prevalence countries. J Hepatol. 2023;79:576‐580.
Wedemeyer H, Manns MP. Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol. 2010;7:31‐40.
Negro F, Lok AS. Hepatitis D: a review. JAMA. 2023;330:2376‐2387.
Buti M, Homs M, Rodriguez‐Frias F, et al. Clinical outcome of acute and chronic hepatitis delta over time: a long‐term follow‐up study. J Viral Hepat. 2011;18:434‐442.
Niro GA, Smedile A, Ippolito AM, et al. Outcome of chronic delta hepatitis in Italy: a long‐term cohort study. J Hepatol. 2010;53:834‐840.
Kamal H, Westman G, Falconer K, et al. Long‐term study of Hepatitis Delta virus infection at secondary care centers: the impact of viremia on liver‐related outcomes. Hepatology. 2020;72:1177‐1190.
Fattovich G, Boscaro S, Noventa F, et al. Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B. J Infect Dis. 1987;155:931‐935.
Wranke A, Heidrich B, Deterding K, et al. Clinical long‐term outcome of hepatitis D compared to hepatitis B monoinfection. Hepatol Int. 2023;17:1359‐1367.
Roulot D, Brichler S, Layese R, et al. Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta. J Hepatol. 2020;73:1046‐1062.
Soriano V, Grint D, d'Arminio Monforte A, et al. Hepatitis delta in HIV‐infected individuals in Europe. AIDS. 2011;25:1987‐1992.
Kamal H, Aleman S, D‐SOLVE Consortium. Natural history of untreated HDV patients: always a progressive disease? Liver Int. 2023;43(Suppl 1):5‐21.
Le Gal F, Brichler S, Drugan T, et al. Genetic diversity and worldwide distribution of the deltavirus genus: a study of 2,152 clinical strains. Hepatology. 2017;66:1826‐1841.
Hughes SA, Wedemeyer H, Harrison PM. Hepatitis delta virus. Lancet. 2011;378:73‐85.
Wranke A, Pinheiro Borzacov LM, Parana R, et al. Clinical and virological heterogeneity of hepatitis delta in different regions world‐wide: the Hepatitis Delta international network (HDIN). Liver Int. 2018;38:842‐850.
Duberg A, Lybeck C, Fält A, Montgomery S, Aleman S. Chronic hepatitis B virus infection and the risk of hepatocellular carcinoma by age and country of origin in people living in Sweden: a national register study. Hepatol Commun. 2022;6:2418‐2430.
Wranke A, Serrano BC, Heidrich B, et al. Antiviral treatment and liver‐related complications in hepatitis delta. Hepatology. 2017;65:414‐425.
Manesis EK, Vourli G, Dalekos G, et al. Prevalence and clinical course of hepatitis delta infection in Greece: a 13‐year prospective study. J Hepatol. 2013;59:949‐956.
Romeo R, Foglieni B, Casazza G, Spreafico M, Colombo M, Prati D. High serum levels of HDV RNA are predictors of cirrhosis and liver cancer in patients with chronic hepatitis delta. PLoS One. 2014;9:e92062.
Wranke A, Hardtke S, Heidrich B, et al. Ten‐year follow‐up of a randomized controlled clinical trial in chronic hepatitis delta. J Viral Hepat. 2020;27:1359‐1368.
Coghill S, McNamara J, Woods M, Hajkowicz K. Epidemiology and clinical outcomes of hepatitis delta (D) virus infection in Queensland. Australia Int J Infect Dis. 2018;74:123‐127.
Vieira Barbosa J, Sahli R, Aubert V, Chaouch A, Moradpour D, Fraga M. Demographics and outcomes of hepatitis B and D: a 10‐year retrospective analysis in a Swiss tertiary referral center. PLoS One. 2021;16:e0250347.
An P, Xu J, Yu Y, Winkler CA. Host and viral genetic variation in HBV‐related hepatocellular carcinoma. Front Genet. 2018;9:261.
Casey JL, Niro GA, Engle RE, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis. 1996;174:920‐926.
Melo Da Silva E, Kay A, Lobato C, et al. Non‐F HBV/HDV‐3 coinfection is associated with severe liver disease in Western Brazilian Amazon. J Med Virol. 2019;91:1081‐1086.
Borzacov LM, de Figueiredo Nicolete LD, da Silva LF, Dos Santos AO, Vieira DS, Salcedo JM. Treatment of hepatitis delta virus genotype 3 infection with peg‐interferon and entecavir. Int J Infect Dis. 2016;46:82‐88.
Calle Serrano B, Grosshennig A, Homs M, et al. Development and evaluation of a baseline‐event‐anticipation score for hepatitis delta. J Viral Hepat. 2014;21:154.
Abbas Z, Qadeer MA, Mandviwalla HA, Abbas M. The severity of hepatitis D in young adults of age 18‐25 years. Cureus. 2020;12:e10855.
Moatter T, Abbas Z, Shabir S, Jafri W. Clinical presentation and genotype of hepatitis delta in Karachi. World J Gastroenterol. 2007;13:2604‐2607.
Su CW, Huang YH, Huo TI, et al. Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients. Gastroenterology. 2006;130:1625‐1635.
Koh C, Heller T, Glenn JS. Pathogenesis of and new therapies for hepatitis D. Gastroenterology. 2019;156:461‐476.e1.
Sagnelli C, Sagnelli E, Russo A, Pisaturo M, Occhiello L, Coppola N. HBV/HDV Co‐infection: epidemiological and clinical changes, recent knowledge and future challenges. Life (Basel). 2021;11:169. doi:10.3390/life11020169
Fallon BS, Cooke EM, Hesterman MC, Norseth JS, Akhundjanov SB, Weller ML. A changing landscape: tracking and analysis of the international HDV epidemiology 1999‐2020. PLOS Glob Public Health. 2023;3:e0000790.
Karimzadeh H, Usman Z, Frishman D, Roggendorf M. Genetic diversity of hepatitis D virus genotype‐1 in Europe allows classification into subtypes. J Viral Hepat. 2019;26:900‐910.
Coppola N, Masiello A, Tonziello G, et al. Factors affecting the changes in molecular epidemiology of acute hepatitis B in a southern Italian area. J Viral Hepat. 2010;17:493‐500.
Lazarus JV, Al‐Rifai A, Sanai FM, et al. Hepatitis delta virus infection prevalence, diagnosis and treatment in the Middle East: a scoping review. Liver Int. 2023;43(Suppl 1):116‐123.
Tharwani A, Hamid S. Elimination of HDV: epidemiologic implications and public health perspectives. Liver Int. 2023;43(Suppl 1):101‐107.
Vanwolleghem T, Armstrong PA, Buti M, et al. The elimination of hepatitis D as a public health problem: needs and challenges. J Viral Hepat. 2024;31:47‐50.
Scheller L, Hilgard G, Anastasiou O, et al. Poor clinical and virological outcome of nucleos(t)ide analogue monotherapy in HBV/HDV co‐infected patients. Medicine (Baltimore). 2021;100:e26571.

Auteurs

Anika Wranke (A)

Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany.

Cirley Lobato (C)

Centro de Ciências de Saúde e do Desporto, Universidade Federal do Acre, Rio Branco, Brazil.

Emanoil Ceausu (E)

Infectious Diseases, Dr. Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania.

George N Dalekos (GN)

Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece.

Mario Rizzetto (M)

Department of Internal Medicine-Gastroenterology, University of Torino, Torino, Italy.

Adela Turcanu (A)

Department of Gastroenterology, State University of Medicine "Nicolae Testemitanu", Chisinau, Republic of Moldova.

Grazia A Niro (GA)

Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Onur Keskin (O)

Medical Faculty, Ankara University, Ankara, Turkey.

George Gherlan (G)

Infectious Diseases, Dr. Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania.

Minaam Abbas (M)

Department of Hepatogastroenterology and Liver Transplantation, Ziauddin University Hospital Karachi, Karachi, Pakistan.

Patrick Ingiliz (P)

Centre for Infectiology Berlin (CIB), Berlin, Germany.

Marion Muche (M)

Department of Gastroenterology, Infectious Diseases and Rheumatology (including Clinical Nutrition), Charité, Berlin, Germany.

Maria Buti (M)

Liver Unit, Valle d'Hebron University Hospital and Ciberhed del Instituto CarlosIII, Barcelona, Spain.

Mathias Jachs (M)

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Thomas Vanwolleghem (T)

Faculty of Medicine and Health Sciences, Laboratory of Experimental Medicine and Pediatrics, Viral Hepatitis Research group, University of Antwerp, Antwerp, Belgium.
European Reference Network RARE-LIVER.

Markus Cornberg (M)

Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany.
D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D.
Centre for Individualized Infection Medicine (CiiM), c/o CRC, Hannover, Germany.

Zaigham Abbas (Z)

Department of Hepatogastroenterology and Liver Transplantation, Ziauddin University Hospital Karachi, Karachi, Pakistan.

Cihan Yurdaydin (C)

Medical Faculty, Ankara University, Ankara, Turkey.
Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey.

Petra Dörge (P)

Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany.

Heiner Wedemeyer (H)

Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany.
D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D.
Centre for Individualized Infection Medicine (CiiM), c/o CRC, Hannover, Germany.
Hannover Medical School, Excellence Cluster RESIST, Hannover, Germany.

Classifications MeSH