Page 33 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
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Clinical Practice Guidelines Active drug addicts and patients on stable maintenance substitution
Ageing cohorts of people who inject drugs (PWID) with chronic
transplant candidates [94]. For patients with established cirrhosis HCV and low treatment uptake are making a significant con-
and portal hypertension who fail (or are unsuitable for) HCV tribution to the population with advanced liver disease and to
antiviral treatment, isolated renal transplantation may be con- liver-related mortality [112,113]. The prevalence of HCV among
tra-indicated and consideration should be given to combined PWIDs is approximately 65% [114–116] and >80% among long-
liver and kidney transplantation [110]. As IFN-based treatment term PWIDs [114].
may lead to graft rejection, there is an urgent need to offer these
patients IFN-free regimens. It remains to be determined whether HCV treatment must be considered for PWIDs, provided they
patients with chronic hepatitis C without cirrhosis should opti- wish to receive treatment and are able and willing to maintain
mally proceed to renal transplantation, with the expectation that regular appointments. Guidelines for pre-therapeutic assessment
their hepatitis C can be cured post-transplant to improve the for HCV-infected individuals are available [5,117]. Modelling
outcome. studies suggest that implementation of HCV treatment for
PWIDs could reduce transmission [118,119]. Decisions to treat
Data on HCV infection after heart transplantation are scarce must be made on a case-by-case basis. PWIDs with on-going
and controversial, with studies showing unaltered or decreased social issues and/or with a history of psychiatric disease or with
survival rates in patients infected with HCV. No studies on the more frequent drug use during therapy are at risk of lower adher-
risks and benefits of antiviral therapy are available in these ence and reduced likelihood of achieving SVR and need to be
monitored closely during therapy, and also need more supporting
patients and the risk of graft rejection on IFN-a treatment measures.
remains unclear. In this context, treatment of chronic HCV infec- HCV treatment has been delivered successfully to drug users
tion in heart transplant recipients must be based on IFN-free regi- through various clinical models, including within general hospi-
mens and the indication should be assessed on a case-by-case tal liver disease and viral hepatitis clinics, drug detoxification
basis, if HCV infection is life-threatening. clinics, opioid substitution therapy clinics, prisons and com-
munity-based clinics. Strategies to enhance treatment adherence
International guidelines list chronic HCV infection as a contra- were discussed above.
indication to lung transplantation [111]. Treatment of lung trans-
plant candidates before transplantation has been recommended DAA clinical development programs have excluded individu-
by some authors, but there is limited experience with this als with active drug use, but many trials have included those
approach. No data are available on the impact of HCV infection on opioid substitution therapy. DAA-based safety and treatment
and its treatment after pancreas or small bowel transplantation. outcome data has not been presented on clinical trial sub-pop-
ulations of individuals on opioid substitution therapy. Drug-drug
Recommendations interaction studies have been undertaken with sofosbuvir and
simeprevir on the one hand, methadone [120] and buprenorphine
• HCV treatment before kidney transplantation may avoid [121] on the other hand, with no clinically important interactions
liver-related mortality in the post-transplant patient, observed. Interaction studies with daclatasvir and methadone/
and may prevent HCV-specific causes of renal graft buprenorphine are underway.
dysfunction. Where possible, antiviral therapy should
be given to potential transplant recipients before listing In addition to opioid substitution therapy, antidepressants,
for renal transplantation. These patients should receive antipsychotics and sedatives are frequently used in patients or
an IFN-free, if possible ribavirin-free regimen, for 12 used by patients with addiction problems. No significant drug-
weeks in patients without cirrhosis, for 24 weeks in drug interaction has been reported with sofosbuvir. Simeprevir
patients with compensated (Child-Pugh A) cirrhosis, increases blood concentrations of orally administered midazolam
following the above recommendations. However, no and potentially triazolam. Caution is thus warranted when these
safety and efficacy data is available in this population, drugs with a narrow therapeutic index are co-administered via
and the need for dose adjustments for the new the oral route. Little data is available with daclatasvir.
DAAs is unknown. These drugs should thus be used Pharmacokinetic studies on recreational and illicit drug use have
with extreme caution and sofosbuvir should not be not been performed.
administered to patients with an eGFR <30 ml/min/1.73
m2 or with end-stage renal disease until more data is
available (B1)
• In non-hepatic solid organ transplant recipients,
patients with an indication for anti-HCV therapy
should receive an IFN-free regimen, following the
above recommendations on treatment regimen and
management of drug-drug interactions with cyclosporine
and tacrolimus when appropriate (B2)
32
Ageing cohorts of people who inject drugs (PWID) with chronic
transplant candidates [94]. For patients with established cirrhosis HCV and low treatment uptake are making a significant con-
and portal hypertension who fail (or are unsuitable for) HCV tribution to the population with advanced liver disease and to
antiviral treatment, isolated renal transplantation may be con- liver-related mortality [112,113]. The prevalence of HCV among
tra-indicated and consideration should be given to combined PWIDs is approximately 65% [114–116] and >80% among long-
liver and kidney transplantation [110]. As IFN-based treatment term PWIDs [114].
may lead to graft rejection, there is an urgent need to offer these
patients IFN-free regimens. It remains to be determined whether HCV treatment must be considered for PWIDs, provided they
patients with chronic hepatitis C without cirrhosis should opti- wish to receive treatment and are able and willing to maintain
mally proceed to renal transplantation, with the expectation that regular appointments. Guidelines for pre-therapeutic assessment
their hepatitis C can be cured post-transplant to improve the for HCV-infected individuals are available [5,117]. Modelling
outcome. studies suggest that implementation of HCV treatment for
PWIDs could reduce transmission [118,119]. Decisions to treat
Data on HCV infection after heart transplantation are scarce must be made on a case-by-case basis. PWIDs with on-going
and controversial, with studies showing unaltered or decreased social issues and/or with a history of psychiatric disease or with
survival rates in patients infected with HCV. No studies on the more frequent drug use during therapy are at risk of lower adher-
risks and benefits of antiviral therapy are available in these ence and reduced likelihood of achieving SVR and need to be
monitored closely during therapy, and also need more supporting
patients and the risk of graft rejection on IFN-a treatment measures.
remains unclear. In this context, treatment of chronic HCV infec- HCV treatment has been delivered successfully to drug users
tion in heart transplant recipients must be based on IFN-free regi- through various clinical models, including within general hospi-
mens and the indication should be assessed on a case-by-case tal liver disease and viral hepatitis clinics, drug detoxification
basis, if HCV infection is life-threatening. clinics, opioid substitution therapy clinics, prisons and com-
munity-based clinics. Strategies to enhance treatment adherence
International guidelines list chronic HCV infection as a contra- were discussed above.
indication to lung transplantation [111]. Treatment of lung trans-
plant candidates before transplantation has been recommended DAA clinical development programs have excluded individu-
by some authors, but there is limited experience with this als with active drug use, but many trials have included those
approach. No data are available on the impact of HCV infection on opioid substitution therapy. DAA-based safety and treatment
and its treatment after pancreas or small bowel transplantation. outcome data has not been presented on clinical trial sub-pop-
ulations of individuals on opioid substitution therapy. Drug-drug
Recommendations interaction studies have been undertaken with sofosbuvir and
simeprevir on the one hand, methadone [120] and buprenorphine
• HCV treatment before kidney transplantation may avoid [121] on the other hand, with no clinically important interactions
liver-related mortality in the post-transplant patient, observed. Interaction studies with daclatasvir and methadone/
and may prevent HCV-specific causes of renal graft buprenorphine are underway.
dysfunction. Where possible, antiviral therapy should
be given to potential transplant recipients before listing In addition to opioid substitution therapy, antidepressants,
for renal transplantation. These patients should receive antipsychotics and sedatives are frequently used in patients or
an IFN-free, if possible ribavirin-free regimen, for 12 used by patients with addiction problems. No significant drug-
weeks in patients without cirrhosis, for 24 weeks in drug interaction has been reported with sofosbuvir. Simeprevir
patients with compensated (Child-Pugh A) cirrhosis, increases blood concentrations of orally administered midazolam
following the above recommendations. However, no and potentially triazolam. Caution is thus warranted when these
safety and efficacy data is available in this population, drugs with a narrow therapeutic index are co-administered via
and the need for dose adjustments for the new the oral route. Little data is available with daclatasvir.
DAAs is unknown. These drugs should thus be used Pharmacokinetic studies on recreational and illicit drug use have
with extreme caution and sofosbuvir should not be not been performed.
administered to patients with an eGFR <30 ml/min/1.73
m2 or with end-stage renal disease until more data is
available (B1)
• In non-hepatic solid organ transplant recipients,
patients with an indication for anti-HCV therapy
should receive an IFN-free regimen, following the
above recommendations on treatment regimen and
management of drug-drug interactions with cyclosporine
and tacrolimus when appropriate (B2)
32
