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

Maria Buti, Cihan Yurdaydin, Marion Muche, George Gherlan, Onur Keskin, Grazia A Niro, Adela Turcanu, Emanoil Ceausu, Cirley Lobato, Anika Wranke, Patrick Ingiliz, Markus Cornberg, Petra Dörge, Heiner Wedemeyer, Mathias Jachs, Minaam Abbas, Zaigham Abbas, Mario Rizzetto, George N Dalekos, Thomas Vanwolleghem

Journal: Liver international : official journal of the International Association for the Study of the Liver 2024;44(9):2442-2457

PMID: 38888267

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Abstract

BACKGROUND AND AIMS

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

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

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

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.

Address: 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.; Centro de Ciências de Saúde e do Desporto, Universidade Federal do Acre, Rio Branco, Brazil.; Infectious Diseases, Dr. Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest, Romania.; Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece.; Department of Internal Medicine-Gastroenterology, University of Torino, Torino, Italy.; Department of Gastroenterology, State University of Medicine "Nicolae Testemitanu", Chisinau, Republic of Moldova.; Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.; Medical Faculty, Ankara University, Ankara, Turkey.; Department of Hepatogastroenterology and Liver Transplantation, Ziauddin University Hospital Karachi, Karachi, Pakistan.; Centre for Infectiology Berlin (CIB), Berlin, Germany.; Department of Gastroenterology, Infectious Diseases and Rheumatology (including Clinical Nutrition), Charité, Berlin, Germany.; Liver Unit, Valle d'Hebron University Hospital and Ciberhed del Instituto CarlosIII, Barcelona, Spain.; Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.; 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.; 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.; Medical Faculty, Ankara University, Ankara, Turkey.; Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey.; 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.

DOI: 10.1111/liv.16006

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MeSH Terms: Humans, Male, Female, Middle Aged, Adult, Registries, Liver Cirrhosis, Hepatitis Delta Virus, Antiviral Agents, Liver Neoplasms, Follow-Up Studies, Liver Transplantation, Hepatitis D, Chronic, Carcinoma, Hepatocellular, Global Health