Page 31 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 31
Clinical Practice Guidelines • Patients with decompensated (Child-Pugh B or C)
cirrhosis can be treated with the combination of
Recommendations sofosbuvir and ribavirin for 12 weeks (genotype 2), with
the fixed-dose combination of sofosbuvir and ledipasvir
• All patients with post-transplant recurrence of HCV with ribavirin for 12 weeks (genotypes 1, 4, 5 or 6),
infection should be considered for therapy (A1) or with the combination of sofosbuvir and
daclatasvir with ribavirin for 12 weeks (all genotypes).
• Acute cholestatic hepatitis or the presence of moderate In these patients, ribavirin can be started at the dose
to extensive fibrosis or portal hypertension one year of 600 mg daily and the dose subsequently adjusted
after transplantation predict rapid disease progression depending on tolerance (B1)
and graft loss and indicate more urgent antiviral
treatment (A1) • No dose adjustment is required for tacrolimus or
cyclosporine with sofosbuvir-ribavirin, sofosbuvir-
• Patients with post-transplant recurrence of HCV should ledipasvir or sofosbuvir-daclatasvir (A2)
be treated with an IFN-free regimen, for 12 or 24 weeks
with ribavirin (A1) • Because of significantly increased plasma
concentrations of simeprevir, the concomitant use of
• Patients without cirrhosis or with compensated (Child- simeprevir and cyclosporine A is not recommended in
Pugh A) cirrhosis post-transplant can be treated liver transplant recipients. No simeprevir dose changes
with the combination of sofosbuvir and ribavirin are required with tacrolimus and sirolimus, but regular
for 12 weeks (genotype 2), with the fixed-dose monitoring of their blood concentrations should be
combination of sofosbuvir and ledipasvir with ribavirin performed (A2)
for 12 weeks (genotypes 1, 4, 5 or 6), or with the
combination of sofosbuvir and daclatasvir with ribavirin • When using the combination of ritonavir-boosted
for 12 weeks (all genotypes), without the need for paritaprevir, ombitasvir and dasabuvir, the tacrolimus
immunosuppressant drug dose adjustments (A1) dose must be adjusted to 0.5 mg once weekly or 0.2
mg every 3 days, while cyclosporine A dose must be
• Patients without cirrhosis or with compensated (Child- adjusted to one-fifth of the daily dose given prior to HCV
Pugh A) cirrhosis post-transplant can be treated with the treatment once daily; prednisone use at doses ≤5 mg/
combination of ritonavir-boosted paritaprevir, ombitasvir day is permitted, but the use of mTOR inhibitors is not
and dasabuvir with ribavirin for 12 weeks (genotype recommended (A2)
1b) or 24 weeks (genotype 1a with cirrhosis), with
the combination of ritonavir-boosted paritaprevir and
ombitasvir for 12 or 24 weeks with ribavirin (genotype
4 without or with cirrhosis, respectively), or with the
combination of sofosbuvir and simeprevir with ribavirin
for 12 weeks (genotypes 1 and 4), with the need for
immunosuppressant drug dose adjustments or, in
the case of the sofosbuvir-simeprevir combination,
the need to avoid cyclosporine A (B1)
Treatment of special groups Recommendations
HBV coinfection • Patients should be treated with the same regimens,
following the same rules as HCV monoinfected patients
In patients with HCV-HBV coinfection, the HBV DNA level is (B1)
often low or undetectable, although it may fluctuate widely,
and HCV is usually the main driver of chronic hepatitis activity. • If HBV replicates at significant levels before, during
Patients should be carefully characterized for the replicative sta- or after HCV clearance, concurrent HBV nucleoside/
tus of both HBV and HCV, and hepatitis delta virus infection nucleotide analogue therapy is indicated (B1)
should be sought. When HCV is replicating and causes liver dis-
ease, it should be treated following the same rules as applied to Immune complex-mediated manifestations of chronic hepatitis C
HCV monoinfected patients. There is a potential risk of HBV Several severe systemic immune complex-mediated mani-
reactivation during or after HCV clearance [108]. In that case, festations of chronic HCV infection have been described.
or if HBV replication is detectable at a significant level, Mixed cryoglobulinemia underlain by B lymphocyte expansion
concurrent HBV nucleoside/nucleotide analogue therapy is indi-
cated. Simeprevir increases exposure to tenofovir. Thus, in
patients receiving tenofovir as anti-HBV treatment, the eGFR
and tubular function should be monitored frequently during
treatment and tenofovir doses should be consequently
adjusted.
30
cirrhosis can be treated with the combination of
Recommendations sofosbuvir and ribavirin for 12 weeks (genotype 2), with
the fixed-dose combination of sofosbuvir and ledipasvir
• All patients with post-transplant recurrence of HCV with ribavirin for 12 weeks (genotypes 1, 4, 5 or 6),
infection should be considered for therapy (A1) or with the combination of sofosbuvir and
daclatasvir with ribavirin for 12 weeks (all genotypes).
• Acute cholestatic hepatitis or the presence of moderate In these patients, ribavirin can be started at the dose
to extensive fibrosis or portal hypertension one year of 600 mg daily and the dose subsequently adjusted
after transplantation predict rapid disease progression depending on tolerance (B1)
and graft loss and indicate more urgent antiviral
treatment (A1) • No dose adjustment is required for tacrolimus or
cyclosporine with sofosbuvir-ribavirin, sofosbuvir-
• Patients with post-transplant recurrence of HCV should ledipasvir or sofosbuvir-daclatasvir (A2)
be treated with an IFN-free regimen, for 12 or 24 weeks
with ribavirin (A1) • Because of significantly increased plasma
concentrations of simeprevir, the concomitant use of
• Patients without cirrhosis or with compensated (Child- simeprevir and cyclosporine A is not recommended in
Pugh A) cirrhosis post-transplant can be treated liver transplant recipients. No simeprevir dose changes
with the combination of sofosbuvir and ribavirin are required with tacrolimus and sirolimus, but regular
for 12 weeks (genotype 2), with the fixed-dose monitoring of their blood concentrations should be
combination of sofosbuvir and ledipasvir with ribavirin performed (A2)
for 12 weeks (genotypes 1, 4, 5 or 6), or with the
combination of sofosbuvir and daclatasvir with ribavirin • When using the combination of ritonavir-boosted
for 12 weeks (all genotypes), without the need for paritaprevir, ombitasvir and dasabuvir, the tacrolimus
immunosuppressant drug dose adjustments (A1) dose must be adjusted to 0.5 mg once weekly or 0.2
mg every 3 days, while cyclosporine A dose must be
• Patients without cirrhosis or with compensated (Child- adjusted to one-fifth of the daily dose given prior to HCV
Pugh A) cirrhosis post-transplant can be treated with the treatment once daily; prednisone use at doses ≤5 mg/
combination of ritonavir-boosted paritaprevir, ombitasvir day is permitted, but the use of mTOR inhibitors is not
and dasabuvir with ribavirin for 12 weeks (genotype recommended (A2)
1b) or 24 weeks (genotype 1a with cirrhosis), with
the combination of ritonavir-boosted paritaprevir and
ombitasvir for 12 or 24 weeks with ribavirin (genotype
4 without or with cirrhosis, respectively), or with the
combination of sofosbuvir and simeprevir with ribavirin
for 12 weeks (genotypes 1 and 4), with the need for
immunosuppressant drug dose adjustments or, in
the case of the sofosbuvir-simeprevir combination,
the need to avoid cyclosporine A (B1)
Treatment of special groups Recommendations
HBV coinfection • Patients should be treated with the same regimens,
following the same rules as HCV monoinfected patients
In patients with HCV-HBV coinfection, the HBV DNA level is (B1)
often low or undetectable, although it may fluctuate widely,
and HCV is usually the main driver of chronic hepatitis activity. • If HBV replicates at significant levels before, during
Patients should be carefully characterized for the replicative sta- or after HCV clearance, concurrent HBV nucleoside/
tus of both HBV and HCV, and hepatitis delta virus infection nucleotide analogue therapy is indicated (B1)
should be sought. When HCV is replicating and causes liver dis-
ease, it should be treated following the same rules as applied to Immune complex-mediated manifestations of chronic hepatitis C
HCV monoinfected patients. There is a potential risk of HBV Several severe systemic immune complex-mediated mani-
reactivation during or after HCV clearance [108]. In that case, festations of chronic HCV infection have been described.
or if HBV replication is detectable at a significant level, Mixed cryoglobulinemia underlain by B lymphocyte expansion
concurrent HBV nucleoside/nucleotide analogue therapy is indi-
cated. Simeprevir increases exposure to tenofovir. Thus, in
patients receiving tenofovir as anti-HBV treatment, the eGFR
and tubular function should be monitored frequently during
treatment and tenofovir doses should be consequently
adjusted.
30
