A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy

Burton, James R.; O’Leary, Jacqueline G.; Verna, Elizabeth C.; Saxena, Varun; Dodge, Jennifer L.; Stravitz, R. Todd; Levitsky, Joshua; Trotter, James F.; Everson, Gregory T.; Brown, Robert S.; Terrault, Norah A.

doi:10.1016/j.jhep.2014.04.037

Cited by 75 publications

(77 citation statements)

References 26 publications

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“…32 We elected to use ribavirin in our transplant recipients because this agent historically has had a lower response rate to antiviral therapy. 7,8,11,12 It has been described that ribavirin has some activity against sofosbuvir-resistant strains. 33 Moreover, in human immunodeficiency viruscoinfected patients, addition of ribavirin to the sofosbuvir regimen resulted in a 76% SVR rate.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4][5][6] In the past, treatment of HCV after liver transplant with pegylated interferon and ribavirin, as well as with the addition of first-generation protease inhibitors (boceprevir and telaprevir), have resulted in sustained virologic response (SVR) rates of 20% to 60%. [7][8][9][10][11][12][13] These regimens have been hampered by numerous adverse effects, frequent dose adjustments, and need for intense immuno suppressive mo nitoring. [7][8][9][10][11][12][13] On the other hand, the newer regimens have better safety and efficacy profiles.…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9][10][11][12][13] These regimens have been hampered by numerous adverse effects, frequent dose adjustments, and need for intense immuno suppressive mo nitoring. [7][8][9][10][11][12][13] On the other hand, the newer regimens have better safety and efficacy profiles. Sofosbuvir, a potent inhibitor of the HCV NS5B polymerase inhibitor with pan-genotypic activity and high barrier to resistance, was approved for treatment of HCV in 2013.…”

Section: Introductionmentioning

confidence: 99%

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Nair

González

2017

Exp Clin Transplant

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Objectives: Recurrent hepatitis C is universal after liver transplant when viremia is present at the time of transplant, and this affects survival. Previous treatments with pegylated interferon and ribavirin with or without boceprevir or telaprevir have yielded modest sustained virologic response rates and frequent adverse effects. A combination of new antiviral agents has been used for recurrent hepatitis C. We aim to describe the outcomes of recurrent hepatitis C in liver transplant patients treated with simeprevir, sofosbuvir, and ribavirin. Materials and Methods: Fifty-three consecutive patients with recurrent hepatitis C genotype 1 were included. All patients had liver biopsy before enrollment if cirrhosis was not evident. Standard doses of simeprevir and sofosbuvir were used for 12 weeks. Ribavirin was adjusted based on hemoglobin levels. In 53 patients, 50 completed 12 weeks of treatment. Results: All 50 patients who completed 12 weeks of treatment achieved sustained virologic response. One patient who completed only 6 weeks also achieved sustained virologic response. Overall, the antiviral treatment was well tolerated, with no interactions with immunosuppressive drugs. Conclusions: The combination of simeprevir and sofosbuvir with or without ribavirin yields a high sustained virologic response rate of 96% in a historically difficult to treat patient population (recurrent hepatitis C genotype 1).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nair

González

2017

Exp Clin Transplant

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“…27,28 Triple therapy with NS3/4A protease inhibitors in conjunction with interferon and ribavirin can yield SVR rates of 50% to 63%, though this is attenuated in patients with prior nonresponse to PEG/RBV, and limited by discontinuation related to adverse events in 15% to 20% of patients. 29,30 As HCV treatment in middle-income countries may still use interferon in the near future, the use of CIFN instead of PEG may offer improved SVR, especially in difficult-totreat patient populations such as liver transplant recipients with prior nonresponse to PEG/RBV.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2015

Exp Clin Transplant

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Objectives: Hepatitis C virus infection universally recurs in liver transplant recipients. Peginterferon/-ribavirin achieves a sustained virologic response rate of 30% in recipients infected with hepatitis C virus genotype 1. Consensus-interferon plus ribavirin yields sustained virologic response rates to 30% in patients failing to achieve sustained virologic response with peginterferon/ribavirin pretransplant, but it has not been studied posttransplant. We sought to evaluate the efficacy and tolerability of consensus-interferon and ribavirin in treating posttransplant hepatitis C virus. Materials and Methods: Clinical, laboratory, and virologic data were collected retrospectively from all patients who received at least 1 dose of consensus-interferon after transplant between January 2008 and December 2011. A standardized treatment protocol was used. The primary aim was sustained virologic response defined by undetectable hepatitis C virus RNA at 24 weeks after completing therapy. Results: Twenty-three patients were treated with consensus-interferon/ribavirin; 15 with prior nonresponse (87%) or breakthrough (6.7%) during peginterferon/ribavirin, and 8 as initial therapy. The intention-to-treat sustained virologic response with consensus-interferon was 30%. Anemia, leukopenia, and growth factor requirement were similar between peginterferon and consensus-interferon cohorts. Conclusions: Consensus-interferon may rescue liver recipients who are nonresponders to peginterferonbased therapy. The efficacy of interferon-based treatment regimens may benefit from substitution of consensus-interferon for peginterferon.

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“…The addition of first generation protease inhibitors to therapy achieved SVR 12 rates of 50%-63%; however there was an increased incidence of SAEs requiring discontinuation of therapy. The most frequent AE was anemia reaching up to 72% in 1 study (59)(60)(61). The use of telaprevir and boceprevir after LT has high potential for toxicity and drug-drug interactions with calcineurin inhibitors (CNIs).…”

Section: Ifn-based Therapiesmentioning

confidence: 99%

New modalities in the treatment of HCV in pre and post - transplantation setting

Araz

Durand²,

Gürakar³

2015

Turk J Gastroenterol

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End-stage liver disease and hepatocellular carcinoma (HCC) secondary to hepatitis C virus (HCV) infection are the leading indications for liver transplantation (LT) in developed countries. Recurrence of HCV following LT is universal if the recipient has detectable serum HCV RNA at the time of LT. Recurrent HCV has an accelerated course and is associated with poor long term patient and graft survival. Interferon (IFN)-based regimens have achieved low Sustained Virological Rates (SVR) in this setting and are associated with a high rate of adverse events, resulting in treatment discontinuation. With advances in understanding the HCV life cycle, drugs targeting specific steps, particularly inhibiting the NS3/4A protease, NS5B RNA dependent RNA polymerase and the NS5A protein, have been developed. Sofosbuvir (SOF), a nucleotide analogue inhibitor of NS5B polymerase was the first compound to enter the market. Combinations of SOF with new HCV antivirals from other classes have allowed for IFN-free regimens with low rates of adverse events and SVR rates >90%. With the availability of newer agents, the approach to the treatment of HCV infection during the pre-and post-liver transplantation period has changed. We will hereby review the current status of HCV treatment and discuss the potential future therapies in the transplant setting.

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A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy

Cited by 75 publications

References 26 publications

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New modalities in the treatment of HCV in pre and post - transplantation setting

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