Page 30 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
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Post-liver transplantation recurrence JOURNAL OF HEPATOLOGY
HCV infection recurrence is universal in patients with detectable Preliminary data from an on-going clinical trial assessing the
HCV RNA at the time of liver transplantation [93]. The course of efficacy and safety of the fixed-dose combination of sofosbuvir
HCV-related liver disease is accelerated in liver transplant recipi- and ledipasvir with ribavirin for 12 or 24 weeks were presented
ents and approximately one-third of them develop cirrhosis [104]. The patients included treatment-naïve and mostly treat-
within 5 years following transplantation [96,97]. Patients with ment-experienced patients with genotype 1 or 4 infection, with
acute cholestatic hepatitis and patients with moderate to exten- all fibrosis stages (F0 to F4) including patients with Child-Pugh
sive fibrosis or portal hypertension one year after transplantation B and C decompensated cirrhosis. The SVR rates were 97% (108/
are at high risk of graft loss, and must urgently receive antiviral 111) in F0-F3 patients, 96% (49/51) in Child-Pugh A patients,
therapy [98,99]. and 84% (37/44) in Child-Pugh B patients. Data were available
in only 8 Child-Pugh C patients, 5 of whom (62%) achieved an
Treatment with PegIFN-a and ribavirin yields low SVR rates SVR. There were no differences in efficacy between 12 and
24 weeks of therapy and the combination had an excellent
and is poorly tolerated in liver transplant recipients. The addition safety profile. As in immunocompetent patients, MELD
of telaprevir or boceprevir increases the SVR rates to 60–70% in scores at week 4 post-treatment improved in the majority of
patients infected with genotype 1, but at the cost of frequent sev- Child-Pugh A and B patients who achieved viral clearance
ere adverse events. Moreover, adjustments in the doses of cal- [104].
cineurin inhibitors are necessary to avoid toxicity due to drug-
drug interactions. Nevertheless, HCV clearance has been shown The antiviral efficacy and safety of the combination of
to have a positive impact on both graft and patient survival ritonavir-boosted paritaprevir, ombitasvir and dasabuvir with
[100,101]. ribavirin for 24 weeks was tested in 34 HCV genotype 1 liver
transplant recipients [105]. All of them were treatment-naïve
The first study assessing the safety and efficacy of an IFN-free post-transplantation and had F0 to F2 fibrosis. All but one
regimen in HCV-infected liver transplant recipients used a com- achieved SVR12, while only 6% of patients reported severe
bination of sofosbuvir and ribavirin for 24 weeks [102]. The cohort adverse events, 17% anaemia, and 1 patient had to
included 40 patients, of whom 40% had cirrhosis and 88% were discontinue therapy. Due to drug-drug interactions with riton-
non-responders to an IFN-based treatment. This regimen yielded avir and paritaprevir, tacrolimus or cyclosporine dose adjust-
an SVR12 rate of 70%, with an excellent safety profile (severe ments were required during the treatment period. In patients
adverse events in 15% of patients, anaemia in 20% and treatment with more advanced liver disease, data must be extrapolated
discontinuations in 5%). Calcineurin inhibitor dose adjustments from patients not in the post-transplant recurrence setting.
were not required due to the lack of significant interactions of
sofosbuvir with tacrolimus or cyclosporine. The beneficial impact Data from real-life cohorts with a combination of sofosbuvir
of HCV clearance on liver function and patient survival post-liver and simeprevir with or without ribavirin for 12 weeks were
transplantation is supported by data from the sofosbuvir compas- reported. SVR12 was achieved in 91% (60/66) of patients infected
sionate use program, which included patients with severe hepati- with genotype 1, most of whom were treatment-experienced
tis C recurrence and a life expectancy without antiviral therapy of with one-third having advanced fibrosis or compensated cirrho-
less than 12 months [103]. Patients received up to 48 weeks of sis. The SVR rate was slightly lower in genotype 1a patients with
advanced fibrosis [28]. In the TARGET real-life cohort study, in
sofosbuvir and ribavirin, with or without PegIFN-a. The SVR12 rate which most patients were treatment-experienced and more than
half had cirrhosis, the combination of sofosbuvir and simeprevir
was 59%. Fifty-seven percent of patients had a significant clinical yielded a 90% (61/68) SVR4 rate [106].
improvement at the last study visit, whereas 22% were unchanged,
3% had worsened their clinical status and 13% died. These results Little data is available with the combination of sofosbuvir and
suggest that HCV clearance impacts survival in these very sick daclatasvir in the post-transplant setting, mostly from small real-
patients, particularly those with severe early recurrence. In real- life cohorts. Overall, SVR is achieved in more than 90% of cases,
life patients infected with genotype 2, the combination of sofosbu- including in patients with fibrosing cholestatic hepatitis [107],
vir and ribavirin post-liver transplant yielded a very high SVR rate with this well tolerated regimen.
in the TARGET study [13].
29
HCV infection recurrence is universal in patients with detectable Preliminary data from an on-going clinical trial assessing the
HCV RNA at the time of liver transplantation [93]. The course of efficacy and safety of the fixed-dose combination of sofosbuvir
HCV-related liver disease is accelerated in liver transplant recipi- and ledipasvir with ribavirin for 12 or 24 weeks were presented
ents and approximately one-third of them develop cirrhosis [104]. The patients included treatment-naïve and mostly treat-
within 5 years following transplantation [96,97]. Patients with ment-experienced patients with genotype 1 or 4 infection, with
acute cholestatic hepatitis and patients with moderate to exten- all fibrosis stages (F0 to F4) including patients with Child-Pugh
sive fibrosis or portal hypertension one year after transplantation B and C decompensated cirrhosis. The SVR rates were 97% (108/
are at high risk of graft loss, and must urgently receive antiviral 111) in F0-F3 patients, 96% (49/51) in Child-Pugh A patients,
therapy [98,99]. and 84% (37/44) in Child-Pugh B patients. Data were available
in only 8 Child-Pugh C patients, 5 of whom (62%) achieved an
Treatment with PegIFN-a and ribavirin yields low SVR rates SVR. There were no differences in efficacy between 12 and
24 weeks of therapy and the combination had an excellent
and is poorly tolerated in liver transplant recipients. The addition safety profile. As in immunocompetent patients, MELD
of telaprevir or boceprevir increases the SVR rates to 60–70% in scores at week 4 post-treatment improved in the majority of
patients infected with genotype 1, but at the cost of frequent sev- Child-Pugh A and B patients who achieved viral clearance
ere adverse events. Moreover, adjustments in the doses of cal- [104].
cineurin inhibitors are necessary to avoid toxicity due to drug-
drug interactions. Nevertheless, HCV clearance has been shown The antiviral efficacy and safety of the combination of
to have a positive impact on both graft and patient survival ritonavir-boosted paritaprevir, ombitasvir and dasabuvir with
[100,101]. ribavirin for 24 weeks was tested in 34 HCV genotype 1 liver
transplant recipients [105]. All of them were treatment-naïve
The first study assessing the safety and efficacy of an IFN-free post-transplantation and had F0 to F2 fibrosis. All but one
regimen in HCV-infected liver transplant recipients used a com- achieved SVR12, while only 6% of patients reported severe
bination of sofosbuvir and ribavirin for 24 weeks [102]. The cohort adverse events, 17% anaemia, and 1 patient had to
included 40 patients, of whom 40% had cirrhosis and 88% were discontinue therapy. Due to drug-drug interactions with riton-
non-responders to an IFN-based treatment. This regimen yielded avir and paritaprevir, tacrolimus or cyclosporine dose adjust-
an SVR12 rate of 70%, with an excellent safety profile (severe ments were required during the treatment period. In patients
adverse events in 15% of patients, anaemia in 20% and treatment with more advanced liver disease, data must be extrapolated
discontinuations in 5%). Calcineurin inhibitor dose adjustments from patients not in the post-transplant recurrence setting.
were not required due to the lack of significant interactions of
sofosbuvir with tacrolimus or cyclosporine. The beneficial impact Data from real-life cohorts with a combination of sofosbuvir
of HCV clearance on liver function and patient survival post-liver and simeprevir with or without ribavirin for 12 weeks were
transplantation is supported by data from the sofosbuvir compas- reported. SVR12 was achieved in 91% (60/66) of patients infected
sionate use program, which included patients with severe hepati- with genotype 1, most of whom were treatment-experienced
tis C recurrence and a life expectancy without antiviral therapy of with one-third having advanced fibrosis or compensated cirrho-
less than 12 months [103]. Patients received up to 48 weeks of sis. The SVR rate was slightly lower in genotype 1a patients with
advanced fibrosis [28]. In the TARGET real-life cohort study, in
sofosbuvir and ribavirin, with or without PegIFN-a. The SVR12 rate which most patients were treatment-experienced and more than
half had cirrhosis, the combination of sofosbuvir and simeprevir
was 59%. Fifty-seven percent of patients had a significant clinical yielded a 90% (61/68) SVR4 rate [106].
improvement at the last study visit, whereas 22% were unchanged,
3% had worsened their clinical status and 13% died. These results Little data is available with the combination of sofosbuvir and
suggest that HCV clearance impacts survival in these very sick daclatasvir in the post-transplant setting, mostly from small real-
patients, particularly those with severe early recurrence. In real- life cohorts. Overall, SVR is achieved in more than 90% of cases,
life patients infected with genotype 2, the combination of sofosbu- including in patients with fibrosing cholestatic hepatitis [107],
vir and ribavirin post-liver transplant yielded a very high SVR rate with this well tolerated regimen.
in the TARGET study [13].
29
