{
  "abstract": "Background Chronic hepatitis delta (CHD) causes severe chronic viral hepatitis.Objective This study examines the predictors and outcomes of CHD course in a large contemporary cohort.Design CHD patients with ≥3 years follow-up from the multicentre retrospective D-SOLVE and hepatitis D virus (HDV)-1000 database (6 European centres) were enrolled. Longitudinal changes in biochemical and laboratory markers were analysed. Time-to-event analysis was performed and predictors of liver-related events (LREs) were assessed with univariable and multivariable Cox regression analysis.Results Among a total of 1004 patients, 565 (56%) with ≥3 years follow-up were included. Patients had a mean (SD) age of 45 (12) years, with 55% men and 60% of European origin. At baseline, 77.8% were HDV RNA+, 39.8% had cirrhosis and 45% had previous interferon therapy. During a median (IQR) follow-up of 55 (46–62) months, 48 patients progressed to cirrhosis at 1, 3 and 5-year cumulative incidence of 1.8%, 5.6% and 13.6%, respectively. De-novo LREs occurred in 47 (9%) patients at 1, 3 and 5-year cumulative incidence of 0.8%, 2.4% and 10.8%, respectively. Cox regression analysis showed that anti-hepatitis C virus+ (adjusted hazard ratio (aHR)=1.72, 95% CI 1.22 to 5.88) and elevated gamma-glutamyl transferase (GGT) (aHR=2.77, 95% CI 1.22 to 6.27) at baseline were significantly associated with cirrhosis onset, while older age (aHR=1.03, 95% CI 1.00 to 1.07), elevated GGT (aHR=4.38, 95% CI 1.81 to 10.57), detectable HDV RNA (aHR=10.32, 95% CI 1.34 to 79.53) and cirrhosis diagnosis (aHR=2.23, 95% CI 1.03 to 4.84) correlated with LREs. The risk for LREs increased from HDV RNA ≥1000 IU/mL, while hepatitis B surface antigen (HBsAg) levels did not correlate with disease progression.Conclusions In a large real-life cohort of CHD patients, older age, GGT elevation, cirrhosis and detectable HDV RNA were the main determinants of liver-related outcomes, with worse prognosis noted from HDV RNA ≥1000 IU/mL.",
  "authors": [
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden",
        "Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Habiba Kamal"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy"
      ],
      "name": "Elisabetta Degasperi"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Institutul de Boli Infectioase, Bucharest, Romania"
      ],
      "name": "Monica Radu"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy"
      ],
      "name": "Dana Sambarino"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), Site Hannover-Braunschweig, Hannover, Germany",
        "German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany"
      ],
      "name": "Anika Wranke"
    },
    {
      "affiliations": [
        "Institute of Liver Studies, King's College Hospital, London, UK"
      ],
      "name": "Ivana Carey"
    },
    {
      "affiliations": [
        "Lyon Hepatology Institute (IHU EVEREST)",
        "UMR PaThLiv U1350",
        "Université Claude Bernard Lyon 1, INSERM, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Miroslava Subic-Levrero"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden",
        "Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Karin Lindahl"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), Site Hannover-Braunschweig, Hannover, Germany",
        "Excellence Cluster RESIST, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Lisa Sandmann"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "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"
      ],
      "name": "Petra Dörge"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "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",
        "Centre for Individualized Infection Medicine (CiiM), c/o CRC, Hannover, Germany"
      ],
      "name": "Julia Kahlhöfer"
    },
    {
      "affiliations": [
        "Lyon Hepatology Institute (IHU EVEREST)",
        "UMR PaThLiv U1350",
        "Université Claude Bernard Lyon 1, INSERM, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Fabien Zoulim"
    },
    {
      "affiliations": [
        "Institute of Liver Studies, King's College Hospital, London, UK"
      ],
      "name": "Kosh Agarwal"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden",
        "Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Soo Aleman"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Institutul de Boli Infectioase, Bucharest, Romania"
      ],
      "name": "Florin Alexandru Caruntu"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy",
        "CRC \"A. M. and A. Migliavacca\" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy"
      ],
      "name": "Pietro Lampertico"
    },
    {
      "affiliations": [
        "D-SOLVE: EU-Funded Network on Individualized Management of Hepatitis D, Hannover, Germany",
        "Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany",
        "German Centre for Infection Research (DZIF), Site Hannover-Braunschweig, Hannover, Germany",
        "Excellence Cluster RESIST, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Heiner Wedemeyer"
    },
    {
      "affiliations": [],
      "name": "D-SOLVE CONSORTIUM"
    }
  ],
  "title": "Course and clinical outcomes of chronic hepatitis delta: a longitudinal analysis of 565 patients from the D-SOLVE and HDV-1000 consortia",
  "uid": "7c2cf5a5-9e65-5223-a8c3-59847556ad87"
}