Page 19 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 19
Clinical Practice Guidelines Comments: This recommendation is based on the results of the
PEARL-I trial, in which treatment-naïve and treatment-experi-
IFN-free options enced patients infected with genotype 4 treated for 12 weeks
with ritonavir-boosted paritaprevir and ombitasvir (without
Genotype 4, IFN-free Option 1 dasabuvir) with ribavirin achieved SVR12 in 100% (42/42) and
100% (49/49) of cases, respectively [55]. Importantly, this study
• Patients infected with HCV genotype 4 can be treated included only non-cirrhotic patients. An on-going study will con-
with the IFN-free fixed-dose combination of sofosbuvir clude as to the duration of treatment needed with this regimen
(400 mg) and ledipasvir (90 mg) in a single tablet for patients infected with genotype 4 with cirrhosis.
administered once daily (A1)
Genotype 4, IFN-free Option 3
• Patients without cirrhosis, including treatment-naïve
and treatment-experienced patients, should be treated • Patients infected with HCV genotype 4 can be treated
with this fixed-dose combination for 12 weeks without with an IFN-free combination of daily sofosbuvir (400
ribavirin (A1) mg) and daily simeprevir (150 mg) 12 weeks (B2)
• Based on data in patients infected with HCV genotype • Based on data with other combinations, adding daily
1, patients with compensated cirrhosis, including weight-based ribavirin (1000 or 1200 mg in patients <75
treatment-naïve and treatment-experienced patients, kg or ≥75 kg, respectively) is recommended in patients
should be treated with this fixed-dose combination for with cirrhosis (B2)
12 weeks with daily weight-based ribavirin (1000 or
1200 mg in patients <75 kg or ≥75 kg, respectively) (B1) • In patients with cirrhosis with contra-indications to the
use of ribavirin, extending duration of treatment to 24
• Patients with compensated cirrhosis with contra- weeks must be considered (B2)
indications to the use of ribavirin or with poor tolerance
to ribavirin on treatment should receive the fixed-dose Comments: There is no data with this combination in patients
combination of sofosbuvir and ledipasvir for 24 weeks infected with HCV genotype 4. Nevertheless, given the antiviral
without ribavirin (B1) effectiveness of both sofosbuvir and simeprevir against this geno-
type, it is likely that the results of the COSMOS trial in patients
• Based on data in patients infected with HCV genotype infected with genotype 1 can be extrapolated [11].
1, treatment with the fixed-dose combination of
sofosbuvir and ledipasvir with ribavirin can be prolonged Genotype 4, IFN-free Option 4
to 24 weeks in treatment-experienced patients with
compensated cirrhosis and negative predictors of • Patients infected with HCV genotype 4 can be treated
response, such as a platelet count <75 x 103/μl (B1) with an IFN-free combination of daily sofosbuvir (400
mg) and daily daclatasvir (60 mg) for 12 weeks (B2)
Comments: The SYNERGY trial assessed the efficacy and safety of
the combination of sofosbuvir and ledipasvir without ribavirin in • Based on data with other combinations, adding daily
patients with genotype 4 infection. After 12 weeks of therapy, weight-based ribavirin (1000 or 1200 mg in patients <75
95% (20/21) of them achieved an SVR (the remaining patient kg or ≥75 kg, respectively) is recommended in patients
withdrew consent at week 4) [54]. It is unclear whether treat- with cirrhosis (B2)
ment duration can be shortened to 8 weeks (as in certain patients
infected with genotype 1 based on the ION-3 study results) • In patients with cirrhosis with contra-indications to the
because of the lack of data with genotype 4. use of ribavirin, extending duration of treatment to 24
Genotype 4, IFN-free Option 2 weeks must be considered (B2)
• Patients infected with HCV genotype 4 without cirrhosis Comments: There is no data with this combination in patients
can be treated with an IFN-free regimen comprising infected with HCV genotype 4. Nevertheless, given the antiviral
the fixed-dose combination of ombitasvir (75 mg), effectiveness of both sofosbuvir and daclatasvir against this geno-
paritaprevir (12.5 mg) and ritonavir (50 mg) in one type in vitro, it is likely that the results in patients infected with
single tablet (two tablets once daily with food), for 12 genotype 1 can be extrapolated.
weeks with daily weight-based ribavirin (1000 or 1200
mg in patients <75 kg or ≥75 kg, respectively), without Treatment of HCV genotype 5 or 6 infection
dasabuvir (B1)
The three treatment options for patients infected with HCV
• Patients infected with HCV genotype 4 with cirrhosis
should be treated with the fixed-dose combination genotypes 5 or 6 are the triple combination of PegIFN-a,
of ombitasvir (75 mg), paritaprevir (12.5 mg) and
ritonavir (50 mg) in one single tablet (two tablets once ribavirin and sofosbuvir, the IFN-free combination of sofosbuvir
daily with food), for 24 weeks with daily weight-based and ledipasvir, and the IFN-free combination of sofosbuvir and
ribavirin (1000 or 1200 mg in patients <75 kg or ≥75 kg,
respectively), without dasabuvir, pending further data
(B1)
18
PEARL-I trial, in which treatment-naïve and treatment-experi-
IFN-free options enced patients infected with genotype 4 treated for 12 weeks
with ritonavir-boosted paritaprevir and ombitasvir (without
Genotype 4, IFN-free Option 1 dasabuvir) with ribavirin achieved SVR12 in 100% (42/42) and
100% (49/49) of cases, respectively [55]. Importantly, this study
• Patients infected with HCV genotype 4 can be treated included only non-cirrhotic patients. An on-going study will con-
with the IFN-free fixed-dose combination of sofosbuvir clude as to the duration of treatment needed with this regimen
(400 mg) and ledipasvir (90 mg) in a single tablet for patients infected with genotype 4 with cirrhosis.
administered once daily (A1)
Genotype 4, IFN-free Option 3
• Patients without cirrhosis, including treatment-naïve
and treatment-experienced patients, should be treated • Patients infected with HCV genotype 4 can be treated
with this fixed-dose combination for 12 weeks without with an IFN-free combination of daily sofosbuvir (400
ribavirin (A1) mg) and daily simeprevir (150 mg) 12 weeks (B2)
• Based on data in patients infected with HCV genotype • Based on data with other combinations, adding daily
1, patients with compensated cirrhosis, including weight-based ribavirin (1000 or 1200 mg in patients <75
treatment-naïve and treatment-experienced patients, kg or ≥75 kg, respectively) is recommended in patients
should be treated with this fixed-dose combination for with cirrhosis (B2)
12 weeks with daily weight-based ribavirin (1000 or
1200 mg in patients <75 kg or ≥75 kg, respectively) (B1) • In patients with cirrhosis with contra-indications to the
use of ribavirin, extending duration of treatment to 24
• Patients with compensated cirrhosis with contra- weeks must be considered (B2)
indications to the use of ribavirin or with poor tolerance
to ribavirin on treatment should receive the fixed-dose Comments: There is no data with this combination in patients
combination of sofosbuvir and ledipasvir for 24 weeks infected with HCV genotype 4. Nevertheless, given the antiviral
without ribavirin (B1) effectiveness of both sofosbuvir and simeprevir against this geno-
type, it is likely that the results of the COSMOS trial in patients
• Based on data in patients infected with HCV genotype infected with genotype 1 can be extrapolated [11].
1, treatment with the fixed-dose combination of
sofosbuvir and ledipasvir with ribavirin can be prolonged Genotype 4, IFN-free Option 4
to 24 weeks in treatment-experienced patients with
compensated cirrhosis and negative predictors of • Patients infected with HCV genotype 4 can be treated
response, such as a platelet count <75 x 103/μl (B1) with an IFN-free combination of daily sofosbuvir (400
mg) and daily daclatasvir (60 mg) for 12 weeks (B2)
Comments: The SYNERGY trial assessed the efficacy and safety of
the combination of sofosbuvir and ledipasvir without ribavirin in • Based on data with other combinations, adding daily
patients with genotype 4 infection. After 12 weeks of therapy, weight-based ribavirin (1000 or 1200 mg in patients <75
95% (20/21) of them achieved an SVR (the remaining patient kg or ≥75 kg, respectively) is recommended in patients
withdrew consent at week 4) [54]. It is unclear whether treat- with cirrhosis (B2)
ment duration can be shortened to 8 weeks (as in certain patients
infected with genotype 1 based on the ION-3 study results) • In patients with cirrhosis with contra-indications to the
because of the lack of data with genotype 4. use of ribavirin, extending duration of treatment to 24
Genotype 4, IFN-free Option 2 weeks must be considered (B2)
• Patients infected with HCV genotype 4 without cirrhosis Comments: There is no data with this combination in patients
can be treated with an IFN-free regimen comprising infected with HCV genotype 4. Nevertheless, given the antiviral
the fixed-dose combination of ombitasvir (75 mg), effectiveness of both sofosbuvir and daclatasvir against this geno-
paritaprevir (12.5 mg) and ritonavir (50 mg) in one type in vitro, it is likely that the results in patients infected with
single tablet (two tablets once daily with food), for 12 genotype 1 can be extrapolated.
weeks with daily weight-based ribavirin (1000 or 1200
mg in patients <75 kg or ≥75 kg, respectively), without Treatment of HCV genotype 5 or 6 infection
dasabuvir (B1)
The three treatment options for patients infected with HCV
• Patients infected with HCV genotype 4 with cirrhosis
should be treated with the fixed-dose combination genotypes 5 or 6 are the triple combination of PegIFN-a,
of ombitasvir (75 mg), paritaprevir (12.5 mg) and
ritonavir (50 mg) in one single tablet (two tablets once ribavirin and sofosbuvir, the IFN-free combination of sofosbuvir
daily with food), for 24 weeks with daily weight-based and ledipasvir, and the IFN-free combination of sofosbuvir and
ribavirin (1000 or 1200 mg in patients <75 kg or ≥75 kg,
respectively), without dasabuvir, pending further data
(B1)
18
