Early development of chronic active hepatitis in recurrent hepatitis C virus infection after liver transplantation: association with treatment of rejection

J Hepatol. 1998 May;28(5):756-63. doi: 10.1016/s0168-8278(98)80224-9.


Background/aims: We retrospectively studied 63 consecutive patients (mean age 54+/-8) with hepatitis C virus genotype 1b recurrence after liver transplantation and with a minimum histological follow-up of 1 year, in order to determine whether an early severe recurrence, defined as the development of chronic active hepatitis within the first 2 years post-liver transplantation, was associated with increased immunosuppression.

Methods: The 1st year immunosuppression data (rejection episodes, boluses of methyl-prednisolone, cumulative doses of prednisone and azathioprine, OKT3 use) were recorded, and evaluated as predictive of severe recurrence at 1 and 2 years post-liver transplantation. Chronic active hepatitis and rejection were defined by histological criteria. Immunosuppression consisted of cyclosporine, azathioprine and prednisone. The treatment of rejection was based on a "bolus" of 1 g methyl-prednisolone/3 days.

Results: At 1 year, 64% (40/63) of the patients had chronic active hepatitis, whereas of the 40 patients who had a 2nd year biopsy available, 75% had chronic active hepatitis at 2 years. At 1 year post-liver transplantation, no significant association was observed between immunosuppression and the development of chronic active hepatitis. In contrast, at 2 years, rejection (p=0.006), treatment of rejection (p=0.05), methyl-prednisolone boluses (p=0.013) and the number of rejection episodes (p=0.0034) occurring during the 1st year post-liver transplantation were significantly more common in patients with chronic active hepatitis. There was also a trend towards higher cumulative steroids (9447+/-3176.5 vs 7891.5+/-2111 mg) and higher cumulative azathioprine doses (13472+/-11154 vs 6233.5+/-5937 mg) in patients with chronic active hepatitis as compared to those who did not develop chronic active hepatitis.

Conclusions: Rejection and/or its treatment may accelerate the natural history of hepatitis C virus genotype 1b infection post-liver transplantation.

MeSH terms

  • Alanine Transaminase / blood
  • Azathioprine / therapeutic use
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Genome, Viral
  • Graft Rejection / drug therapy*
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C / surgery*
  • Hepatitis C, Chronic / epidemiology
  • Hepatitis C, Chronic / etiology
  • Hepatitis C, Chronic / physiopathology*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Muromonab-CD3 / therapeutic use
  • Prednisone / therapeutic use
  • Prognosis
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Time Factors


  • Immunosuppressive Agents
  • Muromonab-CD3
  • Cyclosporine
  • Alanine Transaminase
  • Azathioprine
  • Prednisone
  • Methylprednisolone