title: Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study.
abstract: Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa is highly effective, but can be associated with frequent side-effects. We investigated the safety and efficacy of an interferon-free regimen for treatment of acute HCV infection.
  
  
  
  In this prospective, open-label, multicentre, single-arm pilot study, we enrolled adults (≥18 years) with acute HCV genotype 1 monoinfection from ten centres in Germany. Patients were given ledipasvir (90 mg) plus sofosbuvir (400 mg) as a fixed-dose combination tablet once daily for 6 weeks. The primary efficacy outcome was the proportion of patients with sustained virological response (defined as undetectable HCV RNA 12 weeks after the end of treatment; other primary outcomes were safety and tolerability of ledipasvir plus sofosbuvir. The primary analysis population consisted of all patients who received at least one dose of study drug. Safety was also assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, number NCT02309918.
  
  
  
  Between Nov 19, 2014, and Nov 10, 2015, we enrolled 20 patients. Median HCV RNA viral load at baseline was 4·04 log10IU/mL (1·71-7·20); 11 patients were infected with HCV genotype 1a and nine patients with genotype 1b. All patients achieved a sustained virological response 12 weeks after the end of treatment (20 [100%] of 20 patients). Treatment was well tolerated; there were no drug-related serious adverse events. Up to 12 weeks after treatment, 22 possible or probable drug-related adverse events were reported. There was one serious adverse event, which was judged unrelated to the study drug; one patient was admitted to hospital for surgery of a ruptured cruciate ligament.
  
  
  
  Treatment for 6 weeks with ledipasvir plus sofosbuvir was well tolerated and highly effective in patients with acute HCV genotype 1 monoinfection. Short-duration treatment of acute hepatitis C might prevent the spread of HCV in high-risk populations.
  
  
  
  Gilead Sciences, HepNet Study-House/German Liver Foundation, and German Centre for Infection Research (DZIF).
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Deterding
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Spinner
authors.affiliation: Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
authors.affiliation: Department of Medicine, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Tania M
authors.initials: TM
authors.lastname: Welzel
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.affiliation: Department of Internal Medicine II, Division of Infectious Diseases, University of Würzburg Medical Center, Würzburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Klinker
authors.affiliation: Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.affiliation: Department of Gastroenterology and Rheumatology, Section of Hepatology, University of Leipzig, Leipzig, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Wiegand
authors.affiliation: Department of Internal Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze Zur Wiesch
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, University Clinic of Heidelberg, Heidelberg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Pathil
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Umgelter
authors.affiliation: Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Zöllner
authors.affiliation: Department of Medicine, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Hannover Clinical Trial Center, Hannover, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Papkalla
authors.affiliation: Department of Biostatistics, Hannover Medical School, Hannover, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Weber
authors.affiliation: HepNet Study-House, German Liver Foundation, Hannover, Germany; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Hardtke
authors.affiliation: Hannover Clinical Trial Center, Hannover, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: von der Leyen
authors.affiliation: Department of Biostatistics, Hannover Medical School, Hannover, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Koch
authors.affiliation: HepNet Study-House, German Liver Foundation, Hannover, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: von Witzendorff
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany. Electronic address: manns.michael@mh-hannover.de.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany. Electronic address: wedemeyer.heiner@mh-hannover.de.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D005858:Germany; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D000069474:Sofosbuvir / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D012367:RNA, Viral; C586541:ledipasvir; D000069474:Sofosbuvir