title: Hepatitis E virus genotype 3 infection in a tertiary referral center in the Netherlands: Clinical relevance and impact on patient morbidity.
abstract: BACKGROUND
  Hepatitis E virus (HEV) genotype 3 infections can have important clinical consequences.
  
  
  OBJECTIVE
  To evaluate patients at risk and the effect of treatment strategies, we studied the clinical course and treatment outcome in patients diagnosed with HEV viremia in our hospital.
  
  
  METHODS
  Between January 2008 and March 2015 we included all patients with HEV genotype 3 (HEV-3) infections diagnosed by means of quantitative real-time reverse transcription-polymerase chain reaction test (RT-PCR). Clinical data were evaluated retrospectively.
  
  
  RESULTS
  In total 79 patients were included. Forty-nine patients (62%) were male, median age of all patients was 52 years (range 13-79). Sixty-one (77%) patients were immunocompromised. Three patients (3.8%) had only transient viremia, forty-three (54.5%) cleared the infection within six months and twenty-six (32.9%) developed chronic infection. Five patients (6.3%) were lost to follow-up. All patients developing chronic infection were immunocompromised. Overall, thirteen (16%) patients within this cohort died. Three patients had pre-existent liver diseases and died of liver-related causes. Time between diagnosis and death was shorter for patients with pre-existent liver diseases (p=0.03). Twenty-eight percent of patients on immunosuppressive medication achieved viral clearance after reducing the dose of immunosuppressive therapy. Thirty patients (38.0%) were treated with off-label ribavirin in which 25 (83.3%) a sustained viral response has been documented.
  
  
  CONCLUSIONS
  HEV genotype 3 viremia mainly presents in patients with underlying chronic liver diseases or an impaired immune system. Patients with pre-existent liver diseases are at high risk for complications and even death. The off-label use of ribavirin can cure HEV infection.
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Gastroenterology and Hepatology, PO Box 2040, 3000CA Rotterdam, The Netherlands.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Nijskens
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Viroscience, PO Box 2040, 3000CA Rotterdam, The Netherlands.
authors.forename: Suzan D
authors.initials: SD
authors.lastname: Pas
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Haematology, PO Box 2040, 3000CA Rotterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Cornelissen
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Cardiology, PO Box 2040, 3000CA Rotterdam, The Netherlands.
authors.forename: Kadir
authors.initials: K
authors.lastname: Caliskan
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Pulmonology, PO Box 2040, 3000CA Rotterdam, The Netherlands.
authors.forename: Rogier A S
authors.initials: RA
authors.lastname: Hoek
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Internal Medicine, PO Box 2040, 3000CA Rotterdam, The Netherlands.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Viroscience, PO Box 2040, 3000CA Rotterdam, The Netherlands.
authors.forename: Annemiek A
authors.initials: AA
authors.lastname: van der Eijk
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Gastroenterology and Hepatology, PO Box 2040, 3000CA Rotterdam, The Netherlands. Electronic address: r.deman@erasmusmc.nl.
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D016751:Hepatitis E / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000821:virology*; D016752:Hepatitis E virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D016019:Survival Analysis; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents
keywords: Chronic disease; HEV; Hepatitis E; Pre-existent liver disease; Ribavirin; Solid organ transplant