Page 28 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 28
of liver function was reported 4 weeks after treatment interrup- JOURNAL OF HEPATOLOGY
tion. It will thus be important to assess the benefit of HCV elim-
ination on liver function and subsequent survival at later time evaluate the impact of highly effective IFN-free regimens on
points. These preliminary results suggest that patients with the risk of recurrent HCC following resection or ablation.
decompensated cirrhosis benefit from this treatment regimen.
The treatment indication should take into account the presence Recommendations
of comorbidities that may impact survival. Data in patients with
more advanced liver disease (Child-Pugh >12) are limited. • Although the long-term benefit of antiviral therapy to
reduce the risk of HCC in patients undergoing resection
Recommendations or ablation for HCV-associated HCC is unknown, these
patients frequently have advanced fibrosis and should
• Patients with decompensated cirrhosis (Child-Pugh B receive appropriate antiviral therapy for their liver
and Child-Pugh C, up to 12 points) not on the waiting disease, following the guidelines above (B2)
list for liver transplantation and without concomitant
comorbidities that could impact their survival can Patients with an indication for liver transplantation
be treated with the combination of sofosbuvir and
ribavirin for 16-20 weeks (genotype 2), the fixed-dose Liver transplantation is the treatment of choice for patients with
combination of sofosbuvir and ledipasvir (genotypes end-stage liver disease. However, hepatitis C recurrence due to
1, 4, 5 and 6), or the combination of sofosbuvir and graft infection is universal after transplantation in the absence
daclatasvir (all genotypes), with weight-based ribavirin, of prevention [93], and the life of the graft is reduced in patients
for 12 weeks (B1) with recurrent hepatitis C.
• Patients with decompensated cirrhosis with contra- Treatment of HCV infection in patients awaiting a liver
indications to the use of ribavirin or with poor tolerance transplantation has two complementary goals: preventing liver
to ribavirin on treatment should receive the fixed-dose graft infection after transplantation (in all cases) and improving
combination of sofosbuvir and ledipasvir (genotypes liver function before transplantation (in patients with decom-
1, 4, 5 or 6), or the combination of sofosbuvir and pensated liver disease). It might be argued that as treatment
daclatasvir (all genotypes) for 24 weeks without ribavirin of HCV infection can be achieved in the vast majority of
(B1) patients after transplantation, there is no need to treat HCV
infection prior to transplantation, especially because the dura-
Patients with HCC without an indication for liver transplantation tion of antiviral therapy cannot be predicted in a patient on
the waiting list. Nevertheless, prevention of liver graft infection
HCV is a leading cause of HCC worldwide and the morbidity and substantially facilitates post-transplant management. In
mortality from HCV-associated HCC is increasing, especially in addition, improvement of liver function implies delisting of
high-income areas. HCC occurs at an annual rate of 1–7% in some patients [94], an appropriate strategy in the current con-
patients with cirrhosis. The risk is related to the severity of fibro- text of organ shortage [89]. Also, the risk of HCC recurrence
sis among other factors. An SVR has been shown to be associated could theoretically be reduced by antiviral therapy after
with a reduction in all-cause mortality, liver mortality and a resection; thus, more patients could possibly be offered
reduction in the risk of HCC. Several metanalysis have examined resection.
the relationship between achievement of SVR and reduction in
the risk of HCC, which suggest that SVR is associated with a In a recently published study [95], 61 patients infected with
reduction in HCC [90,91]. However, most of these studies are genotypes 1 or 4 with Child-Pugh A cirrhosis were treated with
observational and retrospective and were based on SVR achieved sofosbuvir and ribavirin up to 48 weeks prior to trans-
with IFN-based treatments. plantation; 46 of them were transplanted. The per-protocol effi-
cacy population consisted of 43 patients with an HCV RNA level
As IFN has been shown to improve outcomes following abla- <25 IU/ml at the time of transplantation. Among them, 30 (70%)
tion or resection of HCV, it is possible that the high rates of SVR had post-transplantation SVR12, meaning no recurrence of
achieved with new IFN-free regimens could reduce the risk of infection. The duration of undetectable HCV RNA pre-transplant
recurrence following resection or ablation of HCC [92]. If the was the best predictor of response (undetectable HCV RNA for
incidence of recurrent HCC can be reduced via this strategy, more than 30 continuous days). This proof of concept study
higher rates of resection or ablation plus an SVR with antiviral demonstrated that an IFN-free regimen administered for a few
treatment could possibly reduce the subsequent need for trans- weeks before transplantation prevented HCV graft infection in
plantation for HCV-associated HCC. Further data is required to a majority of treated patients. In patients infected with geno-
type 2, the combination of sofosbuvir and ribavirin is the treat-
ment of choice, with very high SVR rates. For other genotypes,
this combination should be administered until liver trans-
plantation only if no other treatment choice is available.
27
tion. It will thus be important to assess the benefit of HCV elim-
ination on liver function and subsequent survival at later time evaluate the impact of highly effective IFN-free regimens on
points. These preliminary results suggest that patients with the risk of recurrent HCC following resection or ablation.
decompensated cirrhosis benefit from this treatment regimen.
The treatment indication should take into account the presence Recommendations
of comorbidities that may impact survival. Data in patients with
more advanced liver disease (Child-Pugh >12) are limited. • Although the long-term benefit of antiviral therapy to
reduce the risk of HCC in patients undergoing resection
Recommendations or ablation for HCV-associated HCC is unknown, these
patients frequently have advanced fibrosis and should
• Patients with decompensated cirrhosis (Child-Pugh B receive appropriate antiviral therapy for their liver
and Child-Pugh C, up to 12 points) not on the waiting disease, following the guidelines above (B2)
list for liver transplantation and without concomitant
comorbidities that could impact their survival can Patients with an indication for liver transplantation
be treated with the combination of sofosbuvir and
ribavirin for 16-20 weeks (genotype 2), the fixed-dose Liver transplantation is the treatment of choice for patients with
combination of sofosbuvir and ledipasvir (genotypes end-stage liver disease. However, hepatitis C recurrence due to
1, 4, 5 and 6), or the combination of sofosbuvir and graft infection is universal after transplantation in the absence
daclatasvir (all genotypes), with weight-based ribavirin, of prevention [93], and the life of the graft is reduced in patients
for 12 weeks (B1) with recurrent hepatitis C.
• Patients with decompensated cirrhosis with contra- Treatment of HCV infection in patients awaiting a liver
indications to the use of ribavirin or with poor tolerance transplantation has two complementary goals: preventing liver
to ribavirin on treatment should receive the fixed-dose graft infection after transplantation (in all cases) and improving
combination of sofosbuvir and ledipasvir (genotypes liver function before transplantation (in patients with decom-
1, 4, 5 or 6), or the combination of sofosbuvir and pensated liver disease). It might be argued that as treatment
daclatasvir (all genotypes) for 24 weeks without ribavirin of HCV infection can be achieved in the vast majority of
(B1) patients after transplantation, there is no need to treat HCV
infection prior to transplantation, especially because the dura-
Patients with HCC without an indication for liver transplantation tion of antiviral therapy cannot be predicted in a patient on
the waiting list. Nevertheless, prevention of liver graft infection
HCV is a leading cause of HCC worldwide and the morbidity and substantially facilitates post-transplant management. In
mortality from HCV-associated HCC is increasing, especially in addition, improvement of liver function implies delisting of
high-income areas. HCC occurs at an annual rate of 1–7% in some patients [94], an appropriate strategy in the current con-
patients with cirrhosis. The risk is related to the severity of fibro- text of organ shortage [89]. Also, the risk of HCC recurrence
sis among other factors. An SVR has been shown to be associated could theoretically be reduced by antiviral therapy after
with a reduction in all-cause mortality, liver mortality and a resection; thus, more patients could possibly be offered
reduction in the risk of HCC. Several metanalysis have examined resection.
the relationship between achievement of SVR and reduction in
the risk of HCC, which suggest that SVR is associated with a In a recently published study [95], 61 patients infected with
reduction in HCC [90,91]. However, most of these studies are genotypes 1 or 4 with Child-Pugh A cirrhosis were treated with
observational and retrospective and were based on SVR achieved sofosbuvir and ribavirin up to 48 weeks prior to trans-
with IFN-based treatments. plantation; 46 of them were transplanted. The per-protocol effi-
cacy population consisted of 43 patients with an HCV RNA level
As IFN has been shown to improve outcomes following abla- <25 IU/ml at the time of transplantation. Among them, 30 (70%)
tion or resection of HCV, it is possible that the high rates of SVR had post-transplantation SVR12, meaning no recurrence of
achieved with new IFN-free regimens could reduce the risk of infection. The duration of undetectable HCV RNA pre-transplant
recurrence following resection or ablation of HCC [92]. If the was the best predictor of response (undetectable HCV RNA for
incidence of recurrent HCC can be reduced via this strategy, more than 30 continuous days). This proof of concept study
higher rates of resection or ablation plus an SVR with antiviral demonstrated that an IFN-free regimen administered for a few
treatment could possibly reduce the subsequent need for trans- weeks before transplantation prevented HCV graft infection in
plantation for HCV-associated HCC. Further data is required to a majority of treated patients. In patients infected with geno-
type 2, the combination of sofosbuvir and ribavirin is the treat-
ment of choice, with very high SVR rates. For other genotypes,
this combination should be administered until liver trans-
plantation only if no other treatment choice is available.
27
