This result was supported by a separate analysis, which found that the median number of consecutive days with undetectable
HCV-RNA level before transplantation was 5.5 days (range, 0–88 days) for patients with observed recurrence compared with 99.5 days (range, 1–473 days) for patients with pTVR (P < .001, 2-sided Wilcoxon rank sum test). Outcomes did not appear to correlate with donor age or other donor characteristics, although given the small numbers of patients with recurrence and incomplete donor information for all patients, this observation is Ruxolitinib datasheet preliminary. Baseline population sequencing detected the presence of 2 variants associated with resistance to nucleotide inhibitors: L159F in 4 patients and N142T in 1 patient. Resistance analysis by deep sequencing was performed for 29 of
61 patients who showed virologic failure before transplantation or recurrence after transplantation with HCV-RNA level greater than 1000 IU/mL. Ipilimumab No NS5B mutant S282T was detected in any patient samples analyzed. Twelve of 29 patients developed other nucleoside inhibitor resistance–associated variants and only as minor subpopulations (<10% of population) in 11 of 12 patients (Table 4). All 4 patients with L159F at baseline relapsed and had the L159F variant at the time of relapse. The patient Methisazone with N142T at baseline achieved SVR12. Phenotypic testing of the patient samples and site-directed mutants of the variants (N142T, L159F, V321A, and L320F) did not show any change in susceptibility to sofosbuvir (sofosbuvir fold-change, <2.0; data not shown). Observed minor variants, S282R and S282G, also were introduced by site-directed mutagenesis in replicons but failed to replicate in vitro precluding phenotypic analysis. No ribavirin treatment-associated mutations, M390I or F415Y, developed in patients who qualified for resistance testing. Eighty-nine percent of the 61 patients
receiving at least 1 dose of drug reported an adverse event (Table 3). The most common events were fatigue (38% of patients), headache (23% of patients), anemia (21% of patients), nausea (16% of patients), and rash (15% of patients). Two subjects discontinued treatment because of adverse events (pneumonitis and sepsis/acute renal failure). Eleven patients (18%) experienced serious adverse events; 3 of those events occurred in more than 1 patient: progression of hepatocellular carcinoma, obstructive umbilical hernia, and pyrexia (Supplementary Table 5 shows the full list of treatment-emergent serious adverse events). One treatment-emergent death as a result of sepsis occurred 15 days after the last dose of study drug.