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Background and Aims Methods Results Conclusions 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. [ABSTRACT FROM AUTHOR]