title: Clinical operational tolerance in liver transplantation: state-of-the-art perspective and future prospects.
abstract: BACKGROUND
  Liver transplantation is the definite treatment for end-stage liver diseases with satisfactory results. However, untoward effects of life-long immunosuppression prevent the development of alternative strategies to achieve better long-term outcome. Achieving clinical operational tolerance is the ultimate goal.
  
  
  METHODS
  A PubMed and Google Scholar search using terms: "immune tolerance", "liver transplantation", "clinical trial", "operational tolerance" and "immunosuppression withdrawal" was performed, and relevant articles published in English in the past decade were reviewed. Full-text publications relevant to the field were selected and relevant articles from reference lists were also included. Priority was given to those articles which are relevant to the review.
  
  
  RESULTS
  Because of the inherent tolerogenic property, around 20%-30% of liver transplantation recipients develop spontaneous operational tolerance after immunosuppression withdrawal, and the percentage may be even higher in pediatric living donor liver transplantation recipients. Several natural killer and gammadeltaT cell related markers have been identified to be associated with the tolerant state in liver transplantation patients. Despite the progress, clinical operational tolerance is still rare in liver transplantation. Reprogramming the recipient immune system by creating chimerism and regulatory cell therapies is among newer promising means to achieve clinical liver transplantation tolerance in the future.
  
  
  CONCLUSIONS
  Although clinical operational tolerance is still rare in liver transplantation recipients, ongoing basic research and collaborative clinical trials may help to decipher the mystery of transplantation tolerance and extend the potential benefits of drug withdrawal to an increasing number of patients in a more predictable fashion.
authors: Center for Organ Transplantation and Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors: Xi-Qiang
authors: XQ
authors: Liu
authors: Zhi-Qiu
authors: ZQ
authors: Hu
authors: Yao-Fei
authors: YF
authors: Pei
authors: Ran
authors: R
authors: Tao
mesh_terms: D058625:End Stage Liver Disease / Q000601:surgery*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007165:Immunosuppression Therapy; D016031:Liver Transplantation / Q000276:immunology* / Q000639:trends; D018183:Transplantation Chimera / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*