Page 32 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 32
may cause a systemic vasculitis in which multiple organs are JOURNAL OF HEPATOLOGY
involved as a result of vascular deposition of immune com-
plexes. The treatment of mixed cryoglobulinemia relies on cau- cause of death in dialysis patients irrespective of HCV status. As
sal (antiviral) therapy and/or immunosuppressive therapy. in all settings, the candidacy of a dialysis patient for antiviral
Rituximab, an anti-CD20 monoclonal antibody, has been used therapy requires special consideration of co-morbid conditions,
for both skin and organ involvement. since the liver disease may have little impact on predicted mor-
bidity and mortality of that patient. HCV-associated liver damage
There is a significant association between hepatitis C and B may be accelerated by immunosuppression. For this reason,
cell non-Hodgkin lymphoma. Diffuse large B cell lymphoma is antiviral therapy should be considered for all haemodialysis
the most common. The disease is treated with standard of care patients who will be candidates for renal transplantation.
R-CHOP regimens; the outcome with rituximab appears to be
enhanced albeit that rituximab may enhance viral replication. The use of ribavirin is problematic in this setting.
Rituximab has been associated with the possibility of Individualized ribavirin dosing of 200 mg/day or 200 mg/every
hepatic toxicity and transaminase elevations although the risk other day or 200 mg thrice weekly after haemodialysis is
is low. recommended, and substantial hematopoietic support is essen-
tial. There are no published data to describe the pharmacoki-
The association of chronic HCV infection and chronic renal netics, dosing safety and efficacy of current IFN-free anti-HCV
disease is well-established. A spectrum of histopathological regimens in haemodialysis patients. This is an urgent unmet
lesions has been reported but the most frequent is type I mem- need.
brano-proliferative glomerulonephritis, usually in the context of
type II mixed cryoglobulinemia. Focal segmental glomeru- Recommendations
losclerosis, vasculitic involvement and interstitial nephritis
may also occur. Approaches to therapy of HCV-associated renal • Haemodialysis patients, particularly those who are
disease include antiviral therapy, corticosteroids and cyclophos- suitable candidates for renal transplantation, should be
phamide, B cell depletion therapy to prevent the formation of considered for antiviral therapy (B1)
immune complexes, or plasma exchange. It is possible but
unproven that the more effective and rapid antiviral response • Haemodialysis patients should receive an IFN-free, if
observed with new IFN-free antiviral regimens will improve possible ribavirin-free regimen, for 12 weeks in patients
outcome. Some evidence for rituximab in the management of without cirrhosis, for 24 weeks in patients with cirrhosis
HCV-induced renal disease exists. However, there are questions (B1)
regarding its safe and optimal use together with rapidly acting
DAAs that need to be addressed. An interdisciplinary approach • Simeprevir, daclatasvir, and the combination of ritonavir-
is recommended. boosted paritaprevir, ombitasvir and dasabuvir are
cleared by hepatic metabolism and can be used in
Recommendations patients with severe renal disease (A1)
• Treatment of HCV-associated lymphoma should utilise • Sofosbuvir should not be administered to patients with
new IFN-free regimens as appropriate, but the effect an eGFR <30 ml/min/1.73 m2 or with end-stage renal
of an SVR on the overall prognosis is not yet known. disease until more data is available (B2)
The effect of new antiviral therapies together with B
cell depletion requires further study. An interdisciplinary • The need for dose adjustments for the approved HCV
approach with close monitoring of liver function is DAAs in patients on dialysis is unknown. No safety
required (B1) dosing and efficacy data is available in this population.
These drugs should thus be used with extreme caution
• Appropriate antiviral therapy should be considered in patients with severe renal disease, and only in
for the treatment of mixed cryoglobulinemia and renal extreme life-threatening situations for patients on
disease associated with chronic HCV infection. The dialysis (B1)
role of rituximab in HCV-related renal disease requires
evaluation. The more rapid inhibition of HCV replication Non-hepatic solid organ transplant recipients
and high SVR rates will need correlation with the HCV infection in kidney transplant recipients may be associated
response of the renal injury and the cryoglublinemia. with an increased rate of liver fibrosis progression. Most studies
Careful monitoring for adverse events is mandatory of kidney transplant cohorts show that HCV positivity is associ-
(B1) ated with impaired renal graft and patient survival. Impaired
graft survival partly reflects increased patient mortality. In addi-
Patients with comorbidities tion, specific HCV-related causes such as glomerulonephritis and
increased risk of diabetes will affect graft outcome. HCV positiv-
Haemodialysis patients. ity is associated with increased all-cause and liver-related mor-
HCV infection is prevalent in the haemodialysis population and is tality, though cardiovascular disease remains the main cause of
associated with an increased risk for all-cause and liver-related patient death [109]. As cirrhosis is an important predictor of poor
mortality. Cardiovascular disease remains, however, the main post-transplant survival after kidney transplantation, it is advis-
able to assess the stage of liver fibrosis in all HCV-positive kidney
31
involved as a result of vascular deposition of immune com-
plexes. The treatment of mixed cryoglobulinemia relies on cau- cause of death in dialysis patients irrespective of HCV status. As
sal (antiviral) therapy and/or immunosuppressive therapy. in all settings, the candidacy of a dialysis patient for antiviral
Rituximab, an anti-CD20 monoclonal antibody, has been used therapy requires special consideration of co-morbid conditions,
for both skin and organ involvement. since the liver disease may have little impact on predicted mor-
bidity and mortality of that patient. HCV-associated liver damage
There is a significant association between hepatitis C and B may be accelerated by immunosuppression. For this reason,
cell non-Hodgkin lymphoma. Diffuse large B cell lymphoma is antiviral therapy should be considered for all haemodialysis
the most common. The disease is treated with standard of care patients who will be candidates for renal transplantation.
R-CHOP regimens; the outcome with rituximab appears to be
enhanced albeit that rituximab may enhance viral replication. The use of ribavirin is problematic in this setting.
Rituximab has been associated with the possibility of Individualized ribavirin dosing of 200 mg/day or 200 mg/every
hepatic toxicity and transaminase elevations although the risk other day or 200 mg thrice weekly after haemodialysis is
is low. recommended, and substantial hematopoietic support is essen-
tial. There are no published data to describe the pharmacoki-
The association of chronic HCV infection and chronic renal netics, dosing safety and efficacy of current IFN-free anti-HCV
disease is well-established. A spectrum of histopathological regimens in haemodialysis patients. This is an urgent unmet
lesions has been reported but the most frequent is type I mem- need.
brano-proliferative glomerulonephritis, usually in the context of
type II mixed cryoglobulinemia. Focal segmental glomeru- Recommendations
losclerosis, vasculitic involvement and interstitial nephritis
may also occur. Approaches to therapy of HCV-associated renal • Haemodialysis patients, particularly those who are
disease include antiviral therapy, corticosteroids and cyclophos- suitable candidates for renal transplantation, should be
phamide, B cell depletion therapy to prevent the formation of considered for antiviral therapy (B1)
immune complexes, or plasma exchange. It is possible but
unproven that the more effective and rapid antiviral response • Haemodialysis patients should receive an IFN-free, if
observed with new IFN-free antiviral regimens will improve possible ribavirin-free regimen, for 12 weeks in patients
outcome. Some evidence for rituximab in the management of without cirrhosis, for 24 weeks in patients with cirrhosis
HCV-induced renal disease exists. However, there are questions (B1)
regarding its safe and optimal use together with rapidly acting
DAAs that need to be addressed. An interdisciplinary approach • Simeprevir, daclatasvir, and the combination of ritonavir-
is recommended. boosted paritaprevir, ombitasvir and dasabuvir are
cleared by hepatic metabolism and can be used in
Recommendations patients with severe renal disease (A1)
• Treatment of HCV-associated lymphoma should utilise • Sofosbuvir should not be administered to patients with
new IFN-free regimens as appropriate, but the effect an eGFR <30 ml/min/1.73 m2 or with end-stage renal
of an SVR on the overall prognosis is not yet known. disease until more data is available (B2)
The effect of new antiviral therapies together with B
cell depletion requires further study. An interdisciplinary • The need for dose adjustments for the approved HCV
approach with close monitoring of liver function is DAAs in patients on dialysis is unknown. No safety
required (B1) dosing and efficacy data is available in this population.
These drugs should thus be used with extreme caution
• Appropriate antiviral therapy should be considered in patients with severe renal disease, and only in
for the treatment of mixed cryoglobulinemia and renal extreme life-threatening situations for patients on
disease associated with chronic HCV infection. The dialysis (B1)
role of rituximab in HCV-related renal disease requires
evaluation. The more rapid inhibition of HCV replication Non-hepatic solid organ transplant recipients
and high SVR rates will need correlation with the HCV infection in kidney transplant recipients may be associated
response of the renal injury and the cryoglublinemia. with an increased rate of liver fibrosis progression. Most studies
Careful monitoring for adverse events is mandatory of kidney transplant cohorts show that HCV positivity is associ-
(B1) ated with impaired renal graft and patient survival. Impaired
graft survival partly reflects increased patient mortality. In addi-
Patients with comorbidities tion, specific HCV-related causes such as glomerulonephritis and
increased risk of diabetes will affect graft outcome. HCV positiv-
Haemodialysis patients. ity is associated with increased all-cause and liver-related mor-
HCV infection is prevalent in the haemodialysis population and is tality, though cardiovascular disease remains the main cause of
associated with an increased risk for all-cause and liver-related patient death [109]. As cirrhosis is an important predictor of poor
mortality. Cardiovascular disease remains, however, the main post-transplant survival after kidney transplantation, it is advis-
able to assess the stage of liver fibrosis in all HCV-positive kidney
31
