Page 20 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 20
daclatasvir. In settings where none of these options is available, JOURNAL OF HEPATOLOGY
the combination of PegIFN-a and ribavirin remains acceptable Comments: Ledipasvir is active against both genotype 5 and 6
in vitro. No data is available with this combination for genotype
[5]. 5. The combination of sofosbuvir and ledipasvir, administered
12 weeks without ribavirin in treatment-naïve and treatment-
Genotype 5 or 6, Option 1 experienced patients infected with genotype 6 yielded an SVR
rate of 96% (24/25) [56].
• Patients infected with HCV genotype 5 or 6 can be
treated with a combination of weekly PegIFN-α, daily Genotype 5 or 6, Option 3
weight-based ribavirin (1000 or 1200 mg in patients <75
kg or ≥75 kg, respectively), and daily sofosbuvir (400 • Patients infected with HCV genotype 5 or 6 can be
mg) 12 weeks (B1) treated with an IFN-free combination of daily sofosbuvir
(400 mg) and daily daclatasvir (60 mg) for 12 weeks
Comments: This combination has been evaluated in the (B1)
NEUTRINO Phase III trial in treatment-naïve patients [25]. The
single patient with genotype 5 and all 6 patients with genotype • Based on data with other combinations, adding daily
6 achieved an SVR. No data with this regimen has been presented weight-based ribavirin (1000 or 1200 mg in patients <75
in treatment-experienced patients. Whether longer treatment kg or ≥75 kg, respectively) is recommended in patients
duration would be needed in the most difficult-to-treat pop- with cirrhosis (B1)
ulation is unknown.
• In patients with cirrhosis with contra-indications to the
Genotype 5 or 6, Option 2 use of ribavirin, extending duration of treatment to 24
weeks must be considered (B1)
• Patients infected with HCV genotype 5 or 6 can be Comments: Daclatasvir is active in vitro against both genotype 5
treated with the IFN-free fixed-dose combination of and 6. No data is available with this combination for these rare
sofosbuvir (400 mg) and ledipasvir (90 mg) in a single genotypes.
tablet administered once daily (A1)
Treatment monitoring
• Patients without cirrhosis, including treatment-naïve
and treatment-experienced patients, should be treated Treatment monitoring includes monitoring of treatment efficacy
with this fixed-dose combination for 12 weeks without and of safety and side effects.
ribavirin (B1)
Monitoring of treatment efficacy
• Based on data in patients infected with HCV genotype
1, patients with compensated cirrhosis, including Monitoring of treatment efficacy is based on repeated measure-
treatment-naïve and treatment-experienced patients, ments of HCV RNA levels. A sensitive, accurate assay with a broad
should be treated with this fixed-dose combination for dynamic range of quantification should be used. The same assay,
12 weeks with daily weight-based ribavirin (1000 or ideally from the same laboratory, should be used in each patient
1200 mg in patients <75 kg or ≥75 kg, respectively) (B1) to measure HCV RNA at different time points, in order to assure
consistency of results [57–59].
• Patients with compensated cirrhosis with contra-
indications to the use of ribavirin or with poor tolerance In order to monitor treatment efficacy, HCV RNA level mea-
to ribavirin on treatment should receive the fixed-dose surements should be performed at specific time points.
combination of sofosbuvir and ledipasvir for 24 weeks Measurements should be made to assess patient adherence to
without ribavirin (B1) therapy. For some treatment regimens, the HCV RNA level results
obtained can determine whether treatment should be abandoned
• Based on data in patients infected with HCV genotype (the futility rule) or abbreviated (response-guided therapy). In all
1, treatment with the fixed-dose combination of cases, HCV RNA level monitoring indicates whether treatment
sofosbuvir and ledipasvir with ribavirin can be prolonged has been successful (end of treatment and post-treatment SVR
to 24 weeks in treatment-experienced patients with assessment). Little is known about the impact of the analytical
compensated cirrhosis and negative predictors of sensitivity and lower limits of detection or quantification of dif-
response, such as a platelet count <75 x 103/μl (B1) ferent HCV RNA assays for assessment of futility rules and deter-
mination of treatment duration.
19
the combination of PegIFN-a and ribavirin remains acceptable Comments: Ledipasvir is active against both genotype 5 and 6
in vitro. No data is available with this combination for genotype
[5]. 5. The combination of sofosbuvir and ledipasvir, administered
12 weeks without ribavirin in treatment-naïve and treatment-
Genotype 5 or 6, Option 1 experienced patients infected with genotype 6 yielded an SVR
rate of 96% (24/25) [56].
• Patients infected with HCV genotype 5 or 6 can be
treated with a combination of weekly PegIFN-α, daily Genotype 5 or 6, Option 3
weight-based ribavirin (1000 or 1200 mg in patients <75
kg or ≥75 kg, respectively), and daily sofosbuvir (400 • Patients infected with HCV genotype 5 or 6 can be
mg) 12 weeks (B1) treated with an IFN-free combination of daily sofosbuvir
(400 mg) and daily daclatasvir (60 mg) for 12 weeks
Comments: This combination has been evaluated in the (B1)
NEUTRINO Phase III trial in treatment-naïve patients [25]. The
single patient with genotype 5 and all 6 patients with genotype • Based on data with other combinations, adding daily
6 achieved an SVR. No data with this regimen has been presented weight-based ribavirin (1000 or 1200 mg in patients <75
in treatment-experienced patients. Whether longer treatment kg or ≥75 kg, respectively) is recommended in patients
duration would be needed in the most difficult-to-treat pop- with cirrhosis (B1)
ulation is unknown.
• In patients with cirrhosis with contra-indications to the
Genotype 5 or 6, Option 2 use of ribavirin, extending duration of treatment to 24
weeks must be considered (B1)
• Patients infected with HCV genotype 5 or 6 can be Comments: Daclatasvir is active in vitro against both genotype 5
treated with the IFN-free fixed-dose combination of and 6. No data is available with this combination for these rare
sofosbuvir (400 mg) and ledipasvir (90 mg) in a single genotypes.
tablet administered once daily (A1)
Treatment monitoring
• Patients without cirrhosis, including treatment-naïve
and treatment-experienced patients, should be treated Treatment monitoring includes monitoring of treatment efficacy
with this fixed-dose combination for 12 weeks without and of safety and side effects.
ribavirin (B1)
Monitoring of treatment efficacy
• Based on data in patients infected with HCV genotype
1, patients with compensated cirrhosis, including Monitoring of treatment efficacy is based on repeated measure-
treatment-naïve and treatment-experienced patients, ments of HCV RNA levels. A sensitive, accurate assay with a broad
should be treated with this fixed-dose combination for dynamic range of quantification should be used. The same assay,
12 weeks with daily weight-based ribavirin (1000 or ideally from the same laboratory, should be used in each patient
1200 mg in patients <75 kg or ≥75 kg, respectively) (B1) to measure HCV RNA at different time points, in order to assure
consistency of results [57–59].
• Patients with compensated cirrhosis with contra-
indications to the use of ribavirin or with poor tolerance In order to monitor treatment efficacy, HCV RNA level mea-
to ribavirin on treatment should receive the fixed-dose surements should be performed at specific time points.
combination of sofosbuvir and ledipasvir for 24 weeks Measurements should be made to assess patient adherence to
without ribavirin (B1) therapy. For some treatment regimens, the HCV RNA level results
obtained can determine whether treatment should be abandoned
• Based on data in patients infected with HCV genotype (the futility rule) or abbreviated (response-guided therapy). In all
1, treatment with the fixed-dose combination of cases, HCV RNA level monitoring indicates whether treatment
sofosbuvir and ledipasvir with ribavirin can be prolonged has been successful (end of treatment and post-treatment SVR
to 24 weeks in treatment-experienced patients with assessment). Little is known about the impact of the analytical
compensated cirrhosis and negative predictors of sensitivity and lower limits of detection or quantification of dif-
response, such as a platelet count <75 x 103/μl (B1) ferent HCV RNA assays for assessment of futility rules and deter-
mination of treatment duration.
19
