Applicability, Tolerability and Efficacy of Preemptive Antiviral Therapy in Hepatitis C-Infected Patients Undergoing Liver Transplantation

Abstract

Preliminary studies suggest preemptive anti-HCV therapy in liver transplant recipients may enhance the rates of viral clearance, but the applicability and tolerability of preemptive therapy has not been evaluated in a contemporary cohort. In this randomized study, the safety and tolerability of preemptive standard (IFN) or pegylated (peg-IFN) interferon alfa-2b (3 MU thrice weekly or 1.5 lg/kg weekly), or IFN/peg-IFN plus ribavirin (600 mg increased to 1.0-1.2 g daily) was initiated 2-6 weeks post-transplantation and continued for a total of 48 weeks. Only 51 (41%) of 124 transplant recipients were eligible for preemptive treatment; eligible patients had lower model for end-stage liver disease (MELD) and Childs-Pugh scores pre-transplantation and were more frequently live donor transplant recipients than ineligible patients. Dose reductions and discontinuations were required in 85% and 37% of patients, respectively, and 27% experienced serious adverse events. Growth factor (GF) use (erythropoietin and GCSF) in the latter half of the study did not significantly affect the frequency of dose reductions. Only 15% of patients were able to achieve full-dose treatment during treatment. End-of-treatment and sustained virological responses were 13.6% and 9.1%, respectively, with most responders in the combination therapy group. We conclude that preemptive antiviral therapy is applicable to only a portion of transplant recipients, with 'sicker' patients less likely to be managed by this approach. Living donor liver transplant recipients were more frequently eligible for treatment than deceased donor recipients. Virological response rates are low, likely related to the poor tolerability of therapy and the lack of achievement of target drug doses. Future studies should focus on alternative dosing schedules with more aggressive use of adjuvant therapies, including GFs.

Treatment of recurrent hepatitis C virus infection in patients after liver transplantation

“…With a combined early treatment consisting of interferon-α-2b and ribavirin and lasting for 1 year, Mazzaferro et al [40] attained sustained virological response in 33% of patients; however, the dosage had to be reduced in 47% of patients. Pre-emptive antiviral treatment was tolerated better by patients who underwent transplantation with a lower MELD/Child score [41].…”

“…HCV titres were lower and histological alterations of the liver were milder in the treated groups [41,42]. Reduction of dosage and occurrence of side effects were common, however.…”

Treatment of hepatitis C virus infection: Updated Swedish Consensus recommendations

“…Currently, no studies indicate that early HCV treatment, so-called pre-emptive therapy, prevents histological recurrence [70]. Therefore, it is recommended that combination therapy for HCV should only be initiated following histological evidence of recurrence.…”

The prediction of immunological dysfunction during antiviral therapy for HCV after liver transplantation: can we improve outcomes?

“…However, 30 % of patients do not tolerate this treatment well, and half of the patients require drug dose reduction [7]. One randomized trial evaluated the efficacy of preemptive anti-HCV therapy and found that only 9 % of patients achieved SVR [8]. The treatment of established HCV recurrence can involve patients who are most likely to achieve the benefit from antiviral therapy, whereas patients without HCV recurrence can avoid the side effects.…”