Two patients treated with pegylated interferon/ribavirin/telaprevir triple therapy for recurrent hepatitis C after living donor liver transplantation

Abstract

It is difficult to use protease inhibitors in patients with recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) due to interaction with immunosuppressive drugs. We report our experience with two patients treated with telaprevir (TVR) combined with pegylated interferon/ribavirin (PEG IFN/RBV) for recurrent HCV genotype 1 infection after LT. The first was a 63-year-old man with HCV-related liver cirrhosis, who failed to respond to IFN-β plus RBV after LT. Treatment was switched to PEG IFN-α-2b plus RBV and TVR was started. The donor had TT genotype of interleukin (IL)-28 single nucleotide polymorphisms (SNP) (rs8099917). The recipient had TT genotype of IL-28 SNP (rs8099917). Completion of 12-week triple therapy was followed by PEG IFN-α-2b plus RBV for 36 weeks. Finally, he had sustained viral response. The second was a 70-year-old woman with HCV-related liver cirrhosis and hepatocellular carcinoma. She failed to respond to PEG IFN-α-2b plus RBV after LT, and was subsequently switched to PEG IFN-α-2b/RBV/TVR. Genotype analysis showed TG genotype of IL-28 SNP for the donor, and TT genotype of IL-28 SNP for the recipient. Serum HCV RNA titer decreased below the detection limit at 5 weeks. However, triple therapy was withdrawn at 11 weeks due to general fatigue, which resulted in HCV RNA rebound 4 weeks later. Both patients were treated with cyclosporin, starting with a small dose to avoid interactions with TVR. TVR is a potentially suitable agent for LT recipients who do not respond to PEG IFN-α-2b plus RBV after LT.

Sustained virological response to antiviral therapy improves survival rate in patients with recurrent hepatitis C virus infection after liver transplantation

“…also compared the response to treatment with TVR plus cyclosporin with that of boceprevir in patients who had undergone LT . We have also reported our results on overall survival in patients with genotype 1 recurrent HCV treated with TVR in combination with PEG IFN/RBV after LT …”

“…35 The newly introduced triple therapy of protease inhibitors (telaprevir [TVR] plus PEG IFN/RBV) offers the prospect of better management of LT patients. Pungpapong et al also compared the response to treatment with TVR plus cyclosporin with that of boceprevir in patients who had undergone LT. 36 We have also reported our results on overall survival in patients with genotype 1 recurrent HCV treated with TVR in combination with PEG IFN/RBV after LT. 37 Simeprevir (SMV) is an investigational, single-pill, once-daily, oral HCV NS3/4A protease inhibitor currently in clinical development for the treatment of HCV infection with fewer reported side-effects than TVR, which is associated with anemia, renal failure and skin rash. 38 However, no study has evaluated SMV in patients with recurrent HCV infection after LT.…”

Use of simeprevir following pre‐emptive pegylated interferon/ribavirin treatment for recurrent hepatitis C in living donor liver transplant recipients: a 12‐week pilot study

“…The introduction of TVR and BOC was anticipated to greatly improve virologic effects, even in liver transplant recipients with recurrent hepatitis C. The efficacy of TVR-or BOC-based triple therapy, however, was somewhat unsatisfactory; approximately 50% of the patients receiving such treatment achieved SVR [9,[24][25][26][27]. TVR-or BOC-based triple therapy was also associated with challenges in controlling the CNI trough levels and unignorable adverse events, such as cytopenic events, renal impairment, or skin rash [9].…”

“…The HCV titer of the remaining patient remained around LLOQ at weeks 8 and 12 (Table 1). At the last follow up (median 22 [range [16][17][18][19][20][21][22][23][24][25][26][27] weeks since the initiation of triple therapy), HCV viral load of those with undetectable HCV-RNA at week 12 were sustained to be below detectable level, although those with positive HCV-RNA at week 12 were both positive then (1.4 and 7.5 log10 IU/ml). HCV-RNA levels in the five patients are shown in Figure 2.…”

Daily Low-dose Tacrolimus Is a Safe and Effective Immunosuppressive Regimen During Telaprevir-based Triple Therapy for Hepatitis C Virus Recurrence After Liver Transplant

“…3 The newly introduced protease inhibitor (PI)-based triple therapy now offers improved outcomes for patients with HCV also in the LT setting even after living-donor LT. 4 However, a serious therapeutic problem is the danger of increased toxicity because of drug-drug interactions between PIs and concurrently used immunosuppressants. Protease inhibitors, such as TVR, can significantly modify the trough levels of immunosuppressants, which are primarily metabolized by the cytochrome P450 3A4 pathway in the liver and, to a lesser extent, in the gut.…”