title: Specific immunotherapy in hepatocellular cancer: A systematic review.
abstract: OBJECTIVE
  In recent years, several novel immunotherapeutic approaches were developed and investigated in patients with hepatocellular carcinoma (HCC). We designed this systematic review, to evaluate clinical efficacy of specific immunotherapy in patients with HCC, according to the guidelines of Border of Immune Tolerance Education and Research Network (BITERN) and Cochrane collaboration.
  
  
  METHODS
  We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey, and ProQuest through the 9th of December 2015. One author reviewed and retrieved citations from these seven databases for irrelevant and duplicate studies, and two other authors independently extracted data from the studies and rated their quality. We collated study findings and calculated a weighted treatment effect across studies using Review Manager.
  
  
  RESULTS
  We found 12144 references in seven databases of which 21 controlled studies with 1885 HCC patients in different stages were included in this systematic review after the primary and secondary screenings. Overall, patients undergoing specific immunotherapy had significantly higher overall survival than those in control group (HR = 0.59; 95% CI = 0.47-0.76, P < 0.0001). There was a significant difference in recurrence-free survival between patients undergoing specific immunotherapy and patients in control groups and patients in immunotherapy groups overall had less recurrence than control group (HR = 0.54; 95% CI = 0.46-0.63, P < 0.00001).
  
  
  CONCLUSIONS
  Results of this systematic review based on the available literature suggest that overall specific immunotherapeutic approaches could be beneficiary for the treatment of patients with HCC. This further supports the current and ongoing evaluations of specific immunotherapies in the field.
authors.affiliation: Border of Immune Tolerance Education and Research Network (BITERN), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
authors.forename: Behnoud
authors.initials: B
authors.lastname: Baradaran Noveiry
authors.affiliation: Border of Immune Tolerance Education and Research Network (BITERN), Universal Scientific Education and Research Network (USERN), Tehran, Iran.|Molecular Immunology Research Center, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Armin
authors.initials: A
authors.lastname: Hirbod-Mobarakeh
authors.affiliation: Border of Immune Tolerance Education and Research Network (BITERN), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Khalili
authors.affiliation: Border of Immune Tolerance Education and Research Network (BITERN), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Hourshad
authors.affiliation: Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Tim F
authors.initials: TF
authors.lastname: Greten
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, USA.|Weill Cornell Medical College, New York, USA.
authors.forename: Ghassan K
authors.initials: GK
authors.lastname: Abou-Alfa
authors.affiliation: Border of Immune Tolerance Education and Research Network (BITERN), Universal Scientific Education and Research Network (USERN), Tehran, Iran.|Molecular Immunology Research Center, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.|Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Sheffield, UK.
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D016206:Databases, Bibliographic; D018572:Disease-Free Survival; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008113:Liver Neoplasms / Q000401:mortality / Q000628:therapy*; D017410:Practice Guidelines as Topic; D015996:Survival Rate
keywords: active immunotherapy; clinical outcomes; hepatocellular carcinoma; immunotherapy; meta-analysis; passive immunotherapy; systematic review; vaccines