Reply: Outcome of recurrent hepatitis C virus after liver transplantation in a randomized trial of tacrolimus monotherapy versus triple therapy

Abstract

We read with interest the article by Manousou and colleagues,1 investigating the impact of tacrolimus monotherapy (MT) versus triple therapy (TT) on recurrent hepatitis C infection after liver transplantation. This study examined hepatic fibrosis progression in patients randomized to tacrolimus MT versus corticosteroid, tacrolimus, and azathioprine TT. Seventeen of 54 patients (31.4%) in the MT group and 10 of 49 patients (20.4%) in the TT group reached Ishak stage 4 (S4) over a median of 26 and 39 months, respectively. In multivariate analysis, randomization to MT (odds ratio = 0.7, 95% confidence interval = 0.066-0.847) and a diagnosis of acute hepatitis (odds ratio = 3.59, 95% confidence interval = 1.108-9.823) were associated with S4. Acute hepatitis was more common in the MT group (17/54) than in the TT group (8/49) over a median of 4.4 and 4.8 months, respectively. The authors concluded that TT prolongs graft survival. This may be an overinterpretation because the authors failed to demonstrate statistically significant differences in mortality (16.7% MT versus 12.2% TT) or retransplantation rates (9.6% with MT versus 7.8% with TT) between the groups. TT appeared to delay the progression to S4, but this did not translate into improved graft survival. In addition, we are uncertain from the present study whether delayed hepatic fibrosis progression is related to azathioprine or corticosteroid use. Five-year graft survival in hepatitis C virus-positive transplant recipients is poor (56%).2 A study by Berenguer et al.3 showed improved outcomes for hepatitis C virus recurrence after liver transplantation through the use of 2 immunosuppressants (calcineurin inhibitors with corticosteroids) with a slow tapering of corticosteroids over 9 to 12 months. The present findings of Manousou et al.1 are intriguing, but a study comparing the outcomes with low-dose prednisolone and tacrolimus versus the outcomes with TT is needed to determine which combination of immunosuppressive agents is best in this challenging group of patients. Dinesh Jothimani*, Timothy J. S. Cross*, * Southwest Liver Unit, Hepatology Department, Derriford Hospital, Plymouth Devon, United Kingdom.