Direct Acting Antiviral Therapy After Liver Transplantation

Paul Y. Kwo

Disclosures

Curr Opin Gastroenterol. 2016;32(3):152-158. 

In This Article

Ledipasvir/Sofosbuvir/Ribavirin

The combination of ledipasvir and sofosbuvir with ribavirin has been studied both prior to transplant in a decompensated cohort as well as post-OLT in the North American SOLAR-1 cohort.[13] In the posttransplant cohort, a total of 223 genotype 1 and 4 individuals were randomized to receive 12 or 24 weeks of ledipasvir and sofosbuvir with weight-based ribavirin (1000/1200 mg) for compensated patients (F0–F3 and Child–Turcotte–Pugh A cirrhosis study participants) with a decompensated cohort (posttransplant Child–Turcotte–Pugh B and C patients) receiving an initial dose of 600 mg of ribavirin with ledipasvir and sofosbuvir for 12 or 24 weeks. In this study, there were broad inclusion criteria, including those with platelet counts included down to 30 000/μl, total bilirubin level of less than 10 mg/dl and a hemoglobin greater than 10 g/dl and similar to sofosbuvir and ribavirin, a broad range of immunosuppressive agents were included. There were 111 post-OLT individuals who were F0 to F3, 51 who were Child–Turcotte–Pugh A, 52 Child–Turcotte–Pugh B, and 9 Child–Turcotte–Pugh C patients. The vast majority of the cohort was treatment experienced and in the posttransplant cirrhotic cohort, the majority of MELD scores were below 15. The overall SVR rates were comparable between the 12 and 24-week arms with an SVR rate in the F0 to F3 cohort of 96–98% (12 or 24 weeks), 96% in Child–Turcotte–Pugh A cohort with Child–Turcotte–Pugh B and C cohorts having lower sustained response rates of 83–85%, and 60–67%, respectively. Twenty-four weeks of ledipasvir/sofosbuvir with ribavirin did not confer benefit over a 12-week duration and thus 12 weeks of ledipasvir/sofosbuvir and ribavirin should be used to treat posttransplant genotype 1 individuals. There were only two patients post-OLT with genotype 4, one achieved SVR, the other died because of decompensated liver disease post-OLT during therapy. Improvements in MELD score were seen in both the Child–Turcotte–Pugh A and B cohorts posttransplant and this regimen was well tolerated at a low rate of serious adverse events. Importantly, there were no on treatment virologic failures and no treatment discontinuations occurred because of ledipasvir or sofosbuvir. Because of the lack of drug–drug interactions, no dose adjustments were required for any of the immunosuppressive agents, including cyclosporine, tacrolimus, and others. Similar results have been demonstrated in the European SOLAR-2 study, which has an identical study design to SOLAR-1 with ledipasvir or sofosbuvir being given for posttransplant for 12 and 24 weeks. Sustained response rates were seen in the genotype 1 cohort of 96% to 98% in the F0 to F3 in Child–Turcotte–Pugh A group cohort. Child–Turcotte B and C achieved SVR rates of 88% and 89% in the 12 and 24-week arms.[14] In the genotype 4 cohort, slightly lower SVR rates were seen though the sample size was much smaller than the genotype 1 cohort. The post-OLT Child–Turcotte–Pugh B SVR rate ranged from 95 to 100% with the Child–Turcotte C cohorts being small with SVR rates in one out of two and three out of four individuals. The final results of this cohort have yet to be reported.

The combination of ledipasvir/sofosbuvir with ribavirin for 12 weeks is highly effective for genotype 1 hepatitis C post-OLT.

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