*Purpose: Ledipasvir/sofosbuvir (LDV/SOF) in combination with ribavirin (RBV) has shown excellent results post-liver transplant. However, due to the poor tolerability of RBV, it is commonly questioned whether LDV/SOF monotherapy would be equally as efficacious. Additionally, a short course of LDV/SOF has shown preliminary feasibility immediately post-transplant, however may be challenging to replicate. We aimed to compare the efficacy and safety of LDV/SOF monotherapy with LDV/SOF+RBV in patients post-liver transplant, as well as determine the ability of LDV/SOF monotherapy for 8 weeks at preventing recurrence if given within 90 days post-transplant.

*Methods: This was a multicenter, randomized, open-label, phase IV study in patients post-liver transplant with genotype 1 or 4 HCV. Patients within 90 days of transplant (Early Cohort) were randomized to receive either 8 or 12 weeks of LDV/SOF monotherapy (target N = 60) and patients more than 90 days out from transplant (Late Cohort) were randomized to LDV/SOF monotherapy or LDV/SOF+RBV for 12 weeks (target N = 170).

*Results: The Early Cohort was discontinued after 3 patients had been enrolled and the study was halted after 32 patients had been enrolled in the Late Cohort. One patient in the Early Cohort received 12 weeks of LDV/SOF and was included in the Late Cohort data. Two patients in the Early Cohort received 8 weeks of LDV/SOF, one of whom had virologic relapse with a newly detected NS5A mutation and one of whom died from a cause unrelated to treatment. Within the Late Cohort, there were no differences amongst baseline demographics between Late Cohort groups, although 2 patients in the LDV/SOF group had a mutation that predicted NS5A resistance, but were determined clinically insignificant by investigators (Table 1). Treatment outcomes were similar between groups, with 88% of the LDV/SOF cohort and 75% of the LDV/SOF+RBV cohort achieving SVR24 (Table 2). There was one death, unrelated to treatment, in the LDV/SOF cohort and one relapse. The relapse occurred in one of the two patients with a detected NS5A resistant mutation. In the LDV/SOF+RBV cohort, there was one patient that withdrew consent, one nonresponse, and two relapses. No patient that had virologic failure had a newly detected mutation predicting resistance. Treatment tolerability appeared to favor the LDV/SOF cohort over the LDV/SOF+RBV groups (Table 3 and 4).

*Conclusions: Due to changes in the national treatment atmosphere in the time it took to begin enrollment, there was a paucity of untreated HCV patients being transplanted. At any time post-liver transplant, ribavirin inclusion as part of the antiviral regimen leads to more overall and clinically significant adverse effects, and does not appear to improve treatment efficacy.

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