Complete weaning off immunosuppression in HCV liver transplant recipients is feasible and favourably impacts on the progression of disease recurrence

J Hepatol. 2006 Apr;44(4):702-9. doi: 10.1016/j.jhep.2005.11.047. Epub 2006 Jan 4.

Abstract

Background/aims: HCV-related disease recurrence progresses rapidly after liver transplantation. We hypothesised that withdrawal of immunosuppression might favourably impact on disease progression.

Methods: Weaning off immunosuppression was attempted in 34 HCV-RNA positive patients (mean age 62+/-6.4 years) transplanted 63.5+/-20.1 months earlier, under cyclosporine A monotherapy. Patients were followed for 3 years including yearly protocol liver biopsies. Primary endpoints were feasibility of weaning off immunosuppression and its impact on disease progression. Secondary endpoint was to identify predictors of an immunosuppression-free state and fibrosis progression.

Results: Complete and permanent immunosuppression withdrawal was achieved in 8 patients (23.4%), whereas 14 (41.2%) developed rejection within eight months despite an initial response and 12 (35.2%) rejected during tapering. After a mean follow-up 45.5+/-5.8 months weaned patients showed stabilisation/improvement of histological fibrosis (P<0.01), lower necro-inflammation (P<0.02) and improved liver function (P<0.05) compared to weaning-intolerants. Multiple logistic regression identified low blood cyclosporine A trough levels during the first post-transplant week (P=0.004) and initial steroid-free immunosuppression (P<0.008) as independent predictors of sustained weaning. Achievement of immunosoppression freedom (P=0.02) and baseline staging score (P<0.0001) were independently associated with stabilisation/improvement of histological fibrosis.

Conclusions: Reconstitution of immune-competence in the host improves the natural history of HCV recurrence in the graft.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Cyclosporine / immunology
  • Cyclosporine / therapeutic use
  • Disease Progression
  • Female
  • Hepacivirus / genetics
  • Hepacivirus / immunology
  • Hepatitis C / drug therapy*
  • Hepatitis C / surgery*
  • Humans
  • Immunocompetence / physiology
  • Immunosuppression / methods*
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / immunology
  • Liver / chemistry
  • Liver / pathology
  • Liver / physiopathology
  • Liver / virology
  • Liver Transplantation / immunology*
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • RNA, Viral / analysis
  • Recurrence
  • Regression Analysis

Substances

  • Immunosuppressive Agents
  • RNA, Messenger
  • RNA, Viral
  • Cyclosporine