title: Plasma MicroRNA Levels Are Associated With Hepatitis B e Antigen Status and Treatment Response in Chronic Hepatitis B Patients.
abstract: Hepatitis B virus (HBV) modulates microRNA (miRNA) expression to support viral replication. The aim of this study was to identify miRNAs associated with hepatitis B e antigen (HBeAg) status and response to antiviral therapy in patients with chronic hepatitis B (CHB) , and to assess if these miRNAs are actively secreted by hepatoma cells.
  
  
  
  Plasma miRNA levels were measured by reverse-transcription quantitative polymerase chain reaction in healthy controls (n = 10) and pretreatment samples of an identification cohort (n = 24) and a confirmation cohort (n = 64) of CHB patients treated with peginterferon/nucleotide analogue combination therapy. Levels of HBV-associated miRNAs were measured in cells, extracellular vesicles, and hepatitis B surface antigen (HBsAg) particles of hepatoma cell lines.
  
  
  
  HBeAg-positive patients had higher plasma levels of miR-122-5p, miR-125b-5p, miR-192-5p, miR-193b-3p, and miR-194-5p compared to HBeAg-negative patients, and levels of these miRNAs were associated with HBV DNA and HBsAg levels. Pretreatment plasma levels of miR-301a-3p and miR-145-5p were higher in responders (combined response or HBsAg loss) compared to nonresponders. miR-192-5p, miR-193b-3p, and miR-194-5p were present in extracellular vesicles and HBsAg particles derived from hepatoma cells.
  
  
  
  We identified miRNAs that are associated with HBeAg status, levels of HBV DNA and HBsAg, and treatment response in CHB patients. We demonstrated that several of these miRNAs are present in extracellular vesicles and HBsAg particles secreted by hepatoma cells.
authors.affiliation: Departments of Gastroenterology and Hepatology and.|Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Meike H
authors.initials: MH
authors.lastname: van der Ree
authors.affiliation: Departments of Gastroenterology and Hepatology and.|Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Jansen
authors.affiliation: Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Zita
authors.initials: Z
authors.lastname: Kruize
authors.affiliation: Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ad C
authors.initials: AC
authors.lastname: van Nuenen
authors.affiliation: Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Karel A
authors.initials: KA
authors.lastname: van Dort
authors.affiliation: Departments of Gastroenterology and Hepatology and.
authors.forename: R Bart
authors.initials: RB
authors.lastname: Takkenberg
authors.affiliation: Departments of Gastroenterology and Hepatology and.|Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Hendrik W
authors.initials: HW
authors.lastname: Reesink
authors.affiliation: Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D035683:MicroRNAs
keywords: chronic hepatitis B patients; hepatitis B virus; microRNA; treatment outcome.