Page 13 - EASL Recommendations on Treatment of Hepatitis C 2015 - Summary
P. 13
Post-liver transplantation recurrence • When using the combination of ritonavir-boosted
paritaprevir, ombitasvir and dasabuvir, the tacrolimus
• All patients with post-transplant recurrence of HCV dose must be adjusted to 0.5 mg once weekly or 0.2
infection should be considered for therapy (A1) mg every 3 days, while cyclosporine A dose must be
adjusted to one-fifth of the daily dose given prior to HCV
• Acute cholestatic hepatitis or the presence of moderate treatment once daily; prednisone use at doses ≤5 mg/
to extensive fibrosis or portal hypertension one year day is permitted, but the use of mTOR inhibitors is not
after transplantation predict rapid disease progression recommended (A2)
and graft loss and indicate more urgent antiviral
treatment (A1) 13. Treatment of special groups
• Patients with post-transplant recurrence of HCV should HBV co-infection
be treated with an IFN-free regimen, for 12 or 24 weeks
with ribavirin (A1) • Patients should be treated with the same regimens,
following the same rules as HCV monoinfected patients
• Patients without cirrhosis or with compensated (Child- (B1)
Pugh A) cirrhosis post-transplant can be treated
with the combination of sofosbuvir and ribavirin • If HBV replicates at significant levels before, during
for 12 weeks (genotype 2), with the fixed-dose or after HCV clearance, concurrent HBV nucleoside/
combination of sofosbuvir and ledipasvir with ribavirin nucleotide analogue therapy is indicated (B1)
for 12 weeks (genotypes 1, 4, 5 or 6), or with the
combination of sofosbuvir and daclatasvir with ribavirin Immune complex-mediated manifestations of
for 12 weeks (all genotypes), without the need for chronic hepatitis C
immunosuppressant drug dose adjustments (A1)
• Treatment of HCV-associated lymphoma should utilise
• Patients without cirrhosis or with compensated (Child- new IFN-free regimens as appropriate, but the effect
Pugh A) cirrhosis post-transplant can be treated with the of an SVR on the overall prognosis is not yet known.
combination of ritonavir-boosted paritaprevir, ombitasvir The effect of new antiviral therapies together with B
and dasabuvir with ribavirin for 12 weeks (genotype cell depletion requires further study. An interdisciplinary
1b) or 24 weeks (genotype 1a with cirrhosis), with approach with close monitoring of liver function is
the combination of ritonavir-boosted paritaprevir and required (B1)
ombitasvir for 12 or 24 weeks with ribavirin (genotype
4 without or with cirrhosis, respectively), or with the • Appropriate antiviral therapy should be considered
combination of sofosbuvir and simeprevir with ribavirin for the treatment of mixed cryoglobulinemia and renal
for 12 weeks (genotypes 1 and 4), with the need for disease associated with chronic HCV infection. The
immunosuppressant drug dose adjustments or, in the role of rituximab in HCV-related renal disease requires
case of the sofosbuvir-simeprevir combination, the need evaluation. The more rapid inhibition of HCV replication
to avoid cyclosporine A (B1) and high SVR rates will need correlation with the
response of the renal injury and the cryoglublinemia.
• Patients with decompensated (Child-Pugh B or C) Careful monitoring for adverse events is mandatory
cirrhosis can be treated with the combination of (B1)
sofosbuvir and ribavirin for 12 weeks (genotype 2), with
the fixed-dose combination of sofosbuvir and ledipasvir Haemodialysis patients
with ribavirin for 12 weeks (genotypes 1, 4, 5 or 6), or
with the combination of sofosbuvir and daclatasvir with • Haemodialysis patients, particularly those who are
ribavirin for 12 weeks (all genotypes). In these patients, suitable candidates for renal transplantation, should be
ribavirin can be started at the dose of 600 mg daily and considered for antiviral therapy (B1)
the dose subsequently adjusted depending on tolerance
(B1) • Haemodialysis patients should receive an IFN-free, if
possible ribavirin-free regimen, for 12 weeks in patients
• No dose adjustment is required for tacrolimus or without cirrhosis, for 24 weeks in patients with cirrhosis
cyclosporine with sofosbuvir-ribavirin, sofosbuvir- (B1)
ledipasvir or sofosbuvir-daclatasvir (A2)
• Simeprevir, daclatasvir, and the combination of ritonavir-
• Because of significantly increased plasma boosted paritaprevir, ombitasvir and dasabuvir are
concentrations of simeprevir, the concomitant use of cleared by hepatic metabolism and can be used in
simeprevir and cyclosporine A is not recommended in patients with severe renal disease (A1)
liver transplant recipients. No simeprevir dose changes
are required with tacrolimus and sirolimus, but regular • Sofosbuvir should not be administered to patients with
monitoring of their blood concentrations should be an eGFR <30 ml/min/1.73 m2 or with end-stage renal
performed (A2) disease until more data is available (B2)
12 • The need for dose adjustments for the approved HCV
DAAs in patients on dialysis is unknown. No safety
dosing and efficacy data is available in this population.
paritaprevir, ombitasvir and dasabuvir, the tacrolimus
• All patients with post-transplant recurrence of HCV dose must be adjusted to 0.5 mg once weekly or 0.2
infection should be considered for therapy (A1) mg every 3 days, while cyclosporine A dose must be
adjusted to one-fifth of the daily dose given prior to HCV
• Acute cholestatic hepatitis or the presence of moderate treatment once daily; prednisone use at doses ≤5 mg/
to extensive fibrosis or portal hypertension one year day is permitted, but the use of mTOR inhibitors is not
after transplantation predict rapid disease progression recommended (A2)
and graft loss and indicate more urgent antiviral
treatment (A1) 13. Treatment of special groups
• Patients with post-transplant recurrence of HCV should HBV co-infection
be treated with an IFN-free regimen, for 12 or 24 weeks
with ribavirin (A1) • Patients should be treated with the same regimens,
following the same rules as HCV monoinfected patients
• Patients without cirrhosis or with compensated (Child- (B1)
Pugh A) cirrhosis post-transplant can be treated
with the combination of sofosbuvir and ribavirin • If HBV replicates at significant levels before, during
for 12 weeks (genotype 2), with the fixed-dose or after HCV clearance, concurrent HBV nucleoside/
combination of sofosbuvir and ledipasvir with ribavirin nucleotide analogue therapy is indicated (B1)
for 12 weeks (genotypes 1, 4, 5 or 6), or with the
combination of sofosbuvir and daclatasvir with ribavirin Immune complex-mediated manifestations of
for 12 weeks (all genotypes), without the need for chronic hepatitis C
immunosuppressant drug dose adjustments (A1)
• Treatment of HCV-associated lymphoma should utilise
• Patients without cirrhosis or with compensated (Child- new IFN-free regimens as appropriate, but the effect
Pugh A) cirrhosis post-transplant can be treated with the of an SVR on the overall prognosis is not yet known.
combination of ritonavir-boosted paritaprevir, ombitasvir The effect of new antiviral therapies together with B
and dasabuvir with ribavirin for 12 weeks (genotype cell depletion requires further study. An interdisciplinary
1b) or 24 weeks (genotype 1a with cirrhosis), with approach with close monitoring of liver function is
the combination of ritonavir-boosted paritaprevir and required (B1)
ombitasvir for 12 or 24 weeks with ribavirin (genotype
4 without or with cirrhosis, respectively), or with the • Appropriate antiviral therapy should be considered
combination of sofosbuvir and simeprevir with ribavirin for the treatment of mixed cryoglobulinemia and renal
for 12 weeks (genotypes 1 and 4), with the need for disease associated with chronic HCV infection. The
immunosuppressant drug dose adjustments or, in the role of rituximab in HCV-related renal disease requires
case of the sofosbuvir-simeprevir combination, the need evaluation. The more rapid inhibition of HCV replication
to avoid cyclosporine A (B1) and high SVR rates will need correlation with the
response of the renal injury and the cryoglublinemia.
• Patients with decompensated (Child-Pugh B or C) Careful monitoring for adverse events is mandatory
cirrhosis can be treated with the combination of (B1)
sofosbuvir and ribavirin for 12 weeks (genotype 2), with
the fixed-dose combination of sofosbuvir and ledipasvir Haemodialysis patients
with ribavirin for 12 weeks (genotypes 1, 4, 5 or 6), or
with the combination of sofosbuvir and daclatasvir with • Haemodialysis patients, particularly those who are
ribavirin for 12 weeks (all genotypes). In these patients, suitable candidates for renal transplantation, should be
ribavirin can be started at the dose of 600 mg daily and considered for antiviral therapy (B1)
the dose subsequently adjusted depending on tolerance
(B1) • Haemodialysis patients should receive an IFN-free, if
possible ribavirin-free regimen, for 12 weeks in patients
• No dose adjustment is required for tacrolimus or without cirrhosis, for 24 weeks in patients with cirrhosis
cyclosporine with sofosbuvir-ribavirin, sofosbuvir- (B1)
ledipasvir or sofosbuvir-daclatasvir (A2)
• Simeprevir, daclatasvir, and the combination of ritonavir-
• Because of significantly increased plasma boosted paritaprevir, ombitasvir and dasabuvir are
concentrations of simeprevir, the concomitant use of cleared by hepatic metabolism and can be used in
simeprevir and cyclosporine A is not recommended in patients with severe renal disease (A1)
liver transplant recipients. No simeprevir dose changes
are required with tacrolimus and sirolimus, but regular • Sofosbuvir should not be administered to patients with
monitoring of their blood concentrations should be an eGFR <30 ml/min/1.73 m2 or with end-stage renal
performed (A2) disease until more data is available (B2)
12 • The need for dose adjustments for the approved HCV
DAAs in patients on dialysis is unknown. No safety
dosing and efficacy data is available in this population.
