Diversity of clinical presentation and virological characteristics of hepatitis delta: The hepatitis Delta International network (HDIN)

Background and Aims: The hepatitis delta virus (HDV) causes the most severe form of chronic viral hepatitis associated with fibrosis progression and an increased risk for developing liver-related clinical complications. The clinical and virological presentation of hepatitis delta patients varies largely between different regions and countries. The hepatitis Delta International network (HDIN) was established in 2011 to realize a previously unmet research need as there was no international platform to systematically collect data from hepatitis delta patients. The primary aim of the HDIN registry is to define the course of hepatitis delta and response to antiviral therapy in the context of different HDV and HBV genotypes and diverse host genetic and environmental backgrounds.

Methods: The registry was designed by the HepNet Study-House of the German Liver Foundation in close collaboration with clinicians and researchers in Europe, Asia, North and South America. The HDIN is funded by the German Center for Infection research DZIF. A structured eCRF optimized for hepatitis delta was implemented and 14 centers world-wide are participating. A central data monitoring process has been established. We here report data of more than 1300 patients included until Nov 1st 2015.

Results: Patients were mainly male (64%) with a median age of 37 years. 81% of patients were HDV RNA positive and 76% were HBeAg-negative. Hematological and biochemical parameters widely varied. The severity of hepatitis delta was confirmed as 447 patients (33%) had liver cirrhosis and about one quarter of patients presented low platelet counts, elevated INR and/or low albumin. Furthermore 18% of patients were icteric. Previous decompensation defined as ascites, oesophageal bleeding and encephalopathy occurred in 219 patients (16%). Hepatocellular carcinoma was detected in only 37 patients (2.7%). Liver transplantation was necessary in 70 patients (5%). Patients were divided according to the country of birth into Eastern Mediterranean EM (13%), Eastern Europe and Central Asia EE/CA (42%), Central and Southern Europe CE (5%), South Asian SAS (mainly Pakistan; 21%) and South America SA (19%). Patients from EE were the youngest and had the highest biochemical disease activity. While patients from SA showed the lowest platelet counts and the highest INR. In SA over half of the patients developed a clinical event, whereas in other regions endpoints were developed in about 15% of patients only. Previous antiviral therapy was reported for only 27% of patients with large differences between the regions with treatment rates between 62% in SA and 33 – 35% in EM and EE and only 11% in SAS. The majority of patients were treated with IFN (63%).

Conclusions: The HDIN registry highlights the diversity of patient characteristics in different regions world-wide and confirms the severity of chronic hepatitis delta. There is an urgent need for new treatment possibilities but also probably requiring different management strategies.