Page 29 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 29
Clinical Practice Guidelines Recommendations
Treatment with PegIFN-a, ribavirin and sofosbuvir for 12 • In patients awaiting liver transplantation, antiviral
therapy is indicated, because it prevents graft infection
weeks is acceptable in patients with compensated (Child-Pugh (A1)
A) cirrhosis awaiting liver transplantation if IFN-free com-
binations are not available, based on a study in 164 genotype • Treatment should be initiated as soon as possible
1-infected patients, half treatment-experienced and in order to complete a full treatment course before
one-third with cirrhosis, who achieved SVR4 in 85% of cases transplantation and assess the effect of viral clearance
[13]. on liver function, because significant improvement in
liver function may lead to delisting selected cases (B1)
The combination of sofosbuvir and ledipasvir with ribavirin
for 12 or 24 weeks was assessed in genotype 1 and 4 patients • Patients awaiting liver transplantation should be treated
with compensated (Child-Pugh A) or decompensated (Child- with an IFN-free regimen, in principle for 12 or 24
Pugh B and C, up to 12 points) cirrhosis [89]. In Child-Pugh A weeks, practically up to transplantation, with ribavirin
patients, data from this and other studies showed SVR12 rates (A1)
above 95%, both in treatment-naïve and treatment-experienced
individuals, independent of treatment duration. In patients with • Patients with conserved liver function (Child-Pugh
decompensated cirrhosis, preliminary analysis showed SVR12 A) in whom the indication for transplantation is HCC
rates of 88% (50/57) and 88% (37/42) in Child-Pugh B and C can be treated with the combination of sofosbuvir
patients, respectively, independent of treatment duration [89]. and ribavirin for 16–20 weeks (genotype 2), with the
At week 4 post-treatment, the MELD scores had improved by 1 fixed-dose combination of sofosbuvir and ledipasvir
to 8 points in 64% (34/53) of Child-Pugh B patients and in 70% with ribavirin for 12 weeks (genotypes 1, 4, 5 or 6),
(28/40) of Child-Pugh C patients. Child-Pugh scores improved with the combination of ritonavir-boosted paritaprevir,
by 1 to 3 points in approximately two-thirds of patients. The ombitasvir and dasabuvir with ribavirin for 12 weeks
safety profile of this combination was good and most serious (genotype 1b) or 24 weeks (genotype 1a), with the
adverse events, including death, were unrelated to the study combination of ritonavir-boosted paritaprevir and
drugs. Although the study was not specifically designed to assess ombitasvir with ribavirin for 12 weeks (genotype 4),
the impact of antiviral therapy in patients awaiting liver trans- with the combination of sofosbuvir and simeprevir with
plantation, the data support the use of this combination in ribavirin for 12 weeks (genotypes 1 and 4), or with the
patients with compensated and decompensated cirrhosis on the combination of sofosbuvir and daclatasvir with ribavirin
waiting list. for 12 weeks (all genotypes) (B1)
Data on the efficacy and safety of the combination of • Treatment with PegIFN-α, ribavirin and sofosbuvir for
ritonavir-boosted paritaprevir, ombitasvir and dasabuvir with 12 weeks is acceptable in patients with compensated
ribavirin in compensated cirrhotic patients infected with geno- (Child-Pugh A) cirrhosis awaiting liver transplantation if
type 1 have been published [45]. Patients with compensated IFN-free combinations are not available (B2)
cirrhosis awaiting liver transplantation typically have more
advanced liver disease and portal hypertension than those • Patients with decompensated cirrhosis (Child-Pugh
included in this study; however, patients with low albumin B or C) awaiting liver transplantation can be treated
levels (<35 g/dl, 43 patients) and low platelet counts with the combination of sofosbuvir and ribavirin for 12
(<100,000 cells/ml, 78 patients) were included. In patients with weeks (genotype 2), with the fixed-dose combination
a platelet count <100,000 cells/ml, the SVR12 rates were 89% of sofosbuvir and ledipasvir with ribavirin for 12 weeks
and 97% in the 12- and 24-week treatment duration arms, (genotypes 1, 4, 5 or 6), or with the combination of
respectively. The SVR rates in patients with an albumin level sofosbuvir and daclatasvir with ribavirin for 12 weeks
<35 g/dl were 84% and 89%, respectively. Thus, this combination (all genotypes); however, data are limited in patients
can be considered in individuals with compensated cirrhosis with Child-Pugh C cirrhosis >12 points or
and HCC who are on the waiting list. with a MELD score >20 (A1)
The combination of sofosbuvir and simeprevir, with or with- • The optimal timing of treatment (i.e. before
out ribavirin, has been assessed in large real-life cohorts includ- transplantation or post-transplantation) to maximize
ing a significant number of patients with cirrhosis [13]. In survival is still debatable and requires individual
patients with HCV genotype 1 infection and compensated assessment (B2)
cirrhosis, the SVR4 rates were in the order of 90%. Preliminary
data in 81 genotype 1-infected patients with decompensated • Due to the limited amount of safety data reported
cirrhosis showed an SVR4 rate of 75%, with a good safety pro- in patients with decompensated cirrhosis awaiting
file. However, simeprevir is not indicated in patients with liver transplantation, frequent clinical and laboratory
decompensated cirrhosis, due to the higher drug concentrations assessment is necessary (B2)
observed.
28
Treatment with PegIFN-a, ribavirin and sofosbuvir for 12 • In patients awaiting liver transplantation, antiviral
therapy is indicated, because it prevents graft infection
weeks is acceptable in patients with compensated (Child-Pugh (A1)
A) cirrhosis awaiting liver transplantation if IFN-free com-
binations are not available, based on a study in 164 genotype • Treatment should be initiated as soon as possible
1-infected patients, half treatment-experienced and in order to complete a full treatment course before
one-third with cirrhosis, who achieved SVR4 in 85% of cases transplantation and assess the effect of viral clearance
[13]. on liver function, because significant improvement in
liver function may lead to delisting selected cases (B1)
The combination of sofosbuvir and ledipasvir with ribavirin
for 12 or 24 weeks was assessed in genotype 1 and 4 patients • Patients awaiting liver transplantation should be treated
with compensated (Child-Pugh A) or decompensated (Child- with an IFN-free regimen, in principle for 12 or 24
Pugh B and C, up to 12 points) cirrhosis [89]. In Child-Pugh A weeks, practically up to transplantation, with ribavirin
patients, data from this and other studies showed SVR12 rates (A1)
above 95%, both in treatment-naïve and treatment-experienced
individuals, independent of treatment duration. In patients with • Patients with conserved liver function (Child-Pugh
decompensated cirrhosis, preliminary analysis showed SVR12 A) in whom the indication for transplantation is HCC
rates of 88% (50/57) and 88% (37/42) in Child-Pugh B and C can be treated with the combination of sofosbuvir
patients, respectively, independent of treatment duration [89]. and ribavirin for 16–20 weeks (genotype 2), with the
At week 4 post-treatment, the MELD scores had improved by 1 fixed-dose combination of sofosbuvir and ledipasvir
to 8 points in 64% (34/53) of Child-Pugh B patients and in 70% with ribavirin for 12 weeks (genotypes 1, 4, 5 or 6),
(28/40) of Child-Pugh C patients. Child-Pugh scores improved with the combination of ritonavir-boosted paritaprevir,
by 1 to 3 points in approximately two-thirds of patients. The ombitasvir and dasabuvir with ribavirin for 12 weeks
safety profile of this combination was good and most serious (genotype 1b) or 24 weeks (genotype 1a), with the
adverse events, including death, were unrelated to the study combination of ritonavir-boosted paritaprevir and
drugs. Although the study was not specifically designed to assess ombitasvir with ribavirin for 12 weeks (genotype 4),
the impact of antiviral therapy in patients awaiting liver trans- with the combination of sofosbuvir and simeprevir with
plantation, the data support the use of this combination in ribavirin for 12 weeks (genotypes 1 and 4), or with the
patients with compensated and decompensated cirrhosis on the combination of sofosbuvir and daclatasvir with ribavirin
waiting list. for 12 weeks (all genotypes) (B1)
Data on the efficacy and safety of the combination of • Treatment with PegIFN-α, ribavirin and sofosbuvir for
ritonavir-boosted paritaprevir, ombitasvir and dasabuvir with 12 weeks is acceptable in patients with compensated
ribavirin in compensated cirrhotic patients infected with geno- (Child-Pugh A) cirrhosis awaiting liver transplantation if
type 1 have been published [45]. Patients with compensated IFN-free combinations are not available (B2)
cirrhosis awaiting liver transplantation typically have more
advanced liver disease and portal hypertension than those • Patients with decompensated cirrhosis (Child-Pugh
included in this study; however, patients with low albumin B or C) awaiting liver transplantation can be treated
levels (<35 g/dl, 43 patients) and low platelet counts with the combination of sofosbuvir and ribavirin for 12
(<100,000 cells/ml, 78 patients) were included. In patients with weeks (genotype 2), with the fixed-dose combination
a platelet count <100,000 cells/ml, the SVR12 rates were 89% of sofosbuvir and ledipasvir with ribavirin for 12 weeks
and 97% in the 12- and 24-week treatment duration arms, (genotypes 1, 4, 5 or 6), or with the combination of
respectively. The SVR rates in patients with an albumin level sofosbuvir and daclatasvir with ribavirin for 12 weeks
<35 g/dl were 84% and 89%, respectively. Thus, this combination (all genotypes); however, data are limited in patients
can be considered in individuals with compensated cirrhosis with Child-Pugh C cirrhosis >12 points or
and HCC who are on the waiting list. with a MELD score >20 (A1)
The combination of sofosbuvir and simeprevir, with or with- • The optimal timing of treatment (i.e. before
out ribavirin, has been assessed in large real-life cohorts includ- transplantation or post-transplantation) to maximize
ing a significant number of patients with cirrhosis [13]. In survival is still debatable and requires individual
patients with HCV genotype 1 infection and compensated assessment (B2)
cirrhosis, the SVR4 rates were in the order of 90%. Preliminary
data in 81 genotype 1-infected patients with decompensated • Due to the limited amount of safety data reported
cirrhosis showed an SVR4 rate of 75%, with a good safety pro- in patients with decompensated cirrhosis awaiting
file. However, simeprevir is not indicated in patients with liver transplantation, frequent clinical and laboratory
decompensated cirrhosis, due to the higher drug concentrations assessment is necessary (B2)
observed.
28
