Multicenter experience using telaprevir or boceprevir with peginterferon and ribavirin to treat hepatitis C genotype 1 after liver transplantation

Abstract

The safety, efficacy, and effect on immunosuppression levels of telaprevir (TVR) or boceprevir (BOC) in combination with peginterferon (PEG-IFN) and ribavirin (RBV) in recipients of liver transplantation (LT) with hepatitis C virus (HCV) genotype 1 have not been defined. We report our 3 centers' preliminary experiences with administering triple antiviral treatment protocols containing PEG-IFN, RBV, and TVR or BOC. Patients with biopsy-proven HCV recurrence (METAVIR grade 3 and/or stage 2) received TVR with PEG-IFN/RBV for 12 weeks and then PEG-IFN/RBV for 36 weeks or BOC with PEG-IFN/RBV for 44 weeks after 4 weeks of lead-in PEG-IFN/RBV. Maintenance immunosuppression was changed to cyclosporine whenever possible, and the levels were followed closely. PEG-IFN/RBV dose adjustments were based on patients' tolerance. Sixty patients started triple antiviral treatment, and they were followed for up to 66 weeks (mean 5 35 weeks); all were followed at least 12 weeks. Thirty of the 35 patients treated with TVR (86%) achieved undetectable HCV RNA levels after an average of 6 weeks, whereas 12 patients (48%) in the BOC-treated group achieved undetectable HCV RNA levels after a mean of 11 weeks. According to an intention-to-treat analysis, 14 of 21 TVR-treated patients (67%) and 10 of 22 patients who received BOC (45%) achieved undetectable HCV RNA levels at week 24 without viral breakthrough at the last follow-up. Cytopenias complicated both regimens; all patients required dose reductions of PEG-IFN and/or RBV or the administration of hematological growth factors. One death occurred in each group on triple antiviral treatment. In conclusion, TVR or BOC combined with PEG-IFN/RBV achieved ontreatment virological response rates of approximately 50% to 60% in patients with recurrent HCV after LT, but significant side effects were common. Liver Transpl 19:690-700, 2013. V C 2013 AASLD.Received November 1, 2012; accepted March 31, 2013. Hepatitis C virus (HCV) infection is the leading indication for liver transplantation (LT) in the UnitedStates.1 HCV recurrence is universal and occurs immediately after LT.2 Although the severity and clinical course of HCV infections after LT are variable, severe histological recurrence is the most common cause of death and graft loss in LT recipients with HCV infections and accounts for approximately half of

Telaprevir-based triple therapy for hepatitis C null responders among living donor liver transplant recipients

“…In contrast to several Western reports of the triple therapy demonstrating moderate success for genotype 1 recurrent hepatitis C after DDLT (3,15,16), the present results were discouraging, with an end-of-treatment response rate of only 25% (2/8). It is important to note, however, that all eight recipients indicated for the triple therapy in our study had been resistant to standard dual treatment with PEG-IFN and RBV.…”

“…In the present study, however, only 25% (2/8) of patients achieved HCV-negative status at the end of therapy. Accumulating reports from Western countries in a DDLT setting suggest the efficacy of triple therapy for recurrent hepatitis C with genotype 1b (3,15,16), but the present results demonstrated dismal results for non-responders to standard dual therapy. Documented drug-drug interactions with protease inhibitors have raised concerns about the safety of protease inhibitors in the post-transplant setting.…”

“…The dose reduction necessary to maintain the same trough level of CsA seems comparable to that recommended in Western DDLT populations (15). As emphasized in other studies using TVR in the treatment of recurrent HCV after liver transplantation (3,15,16), the high frequency of hematologic adverse events is a major concern of TVR-based triple therapy, and is higher than that in the non-transplant population and more severe than that in the standard dual treatment among transplant recipients. In our study, 63% (5/8) of patients developed anemia requiring a blood transfusion and 50% (4/8) of patients developed leukopenia requiring filgrastim.…”

“…It is important to note, however, that all eight recipients indicated for the triple therapy in our study had been resistant to standard dual treatment with PEG-IFN and RBV. In the aforementioned Western reports (3,15,16), triple therapy was used as the initial antiviral treatment for recurrent disease after liver transplantation. Unlike this report, Ikegami and colleagues reported that 82% of patients achieved SVR after LDLT, however, 18% (2/11) of patients did not have previous IFN treatment history (5).…”

“…Pungpapong and colleagues (15) reported that 67% (14/21) of patients receiving TVR-based triple therapy achieved undetectable HCV-RNA levels at 24 weeks after finishing treatment without viral breakthrough. Another study described an SVR rate of 56% (5/9) (17).…”