Page 6 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 6
required with the use of sofosbuvir in patients with severe renal JOURNAL OF HEPATOLOGY
impairment, as the effect of impaired renal function on clearance
of sofosbuvir-derived metabolites is still being ascertained. The basis for evidence of progression, to reconsider the indication
combination of ritonavir-boosted paritaprevir, ombitasvir, and for treatment, and to discuss new therapies as they emerge or
dasabuvir is undergoing evaluation in patients with Child-Pugh become available and affordable.
B decompensated cirrhosis and is contra-indicated in patients
with Child-Pugh C decompensated cirrhosis. Studies are on-going Treatment is not recommended in patients with limited life
to assess the pharmacokinetics and safety of simeprevir in expectancy due to non–liver-related comorbidities.
decompensated cirrhosis.
Recommendations
Indications for treatment: who should be treated?
• All treatment-naïve and treatment-experienced patients
All treatment-naïve and –experienced patients with compen- with compensated or decompensated chronic liver
sated or decompensated chronic liver disease related to HCV, disease due to HCV should be considered for therapy
who are willing to be treated and who have no contra-indications (A1)
to treatment, should be considered for therapy. Because not every
HCV-infected patient can be treated within the next year or so, • Treatment should be prioritized for patients with
prioritization is necessary (Table 2). The panel acknowledges that significant fibrosis or cirrhosis (METAVIR score F3 to
priorities may be modulated according to local and/or societal F4) (A1)
considerations.
• Patients with decompensated cirrhosis (Child-Pugh
Treatment priority should be based on fibrosis stage, risk of B and C) should be urgently treated with an IFN-free
progression towards more advanced disease, presence of extra- regimen (A1)
hepatic manifestations of HCV infection and risk of HCV trans-
mission. Treatment should be prioritized in patients with • Treatment should be prioritized regardless of the
advanced fibrosis (METAVIR score F3 to F4), including patients fibrosis stage in patients with HIV or HBV coinfection,
with decompensated cirrhosis who have a contra-indication to patients in the pre- or post-liver transplant setting,
patients with clinically significant extra-hepatic
the use of IFN-a but can be safely treated with IFN-free regimens. manifestations (e.g. symptomatic vasculitis associated
with HCV-related mixed cryoglobulinaemia, HCV
Indeed, data from clinical trials and real-life cohorts indicate that immune complex-related nephropathy and non-Hodgkin
these patients could benefit more from a cure of HCV infection in B cell lymphoma), and patients with debilitating fatigue
the short-term, because substantial decreases in Child-Pugh and (A1)
MELD scores and reductions in the incidence of clinical events
have been observed. However, evidence for an improved outlook • Treatment should be prioritized regardless of the
is still limited in patients with Child-Pugh scores above 12 and fibrosis stage for individuals at risk of transmitting
MELD scores higher than 20. IFN-free treatment in patients with HCV, including active injection drug users, men who
decompensated disease should only be attempted in experienced have sex with men with high-risk sexual practices,
centres until further safety and efficacy data have accumulated. women of childbearing age who wish to get pregnant,
haemodialysis patients, and incarcerated individuals
High priority groups also include patients with HIV or HBV (B1)
coinfection, patients in the pre- or post-liver transplant setting,
patients with clinically significant extra-hepatic manifestations • Treatment is justified in patients with moderate fibrosis
(e.g. symptomatic vasculitis associated with HCV-related mixed (METAVIR score F2) (A2)
cryoglobulinaemia, HCV immune complex-related nephropathy
and non-Hodgkin B cell lymphoma), and patients with debilitat- • In patients with no or mild disease (METAVIR score
ing fatigue, regardless of their liver fibrosis stage. F0-F1) and none of the above-mentioned extra-hepatic
manifestations, the indication for and timing of therapy
Treatment should also be prioritized regardless of the fibrosis can be individualized (B1)
stage or extra-hepatic manifestations in individuals at risk of
transmitting HCV, including active injection drug users, men • Treatment is not recommended in patients with limited
who have sex with men with high-risk sexual practices, women life expectancy due to non-liver-related comorbidities
of childbearing age who wish to get pregnant, haemodialysis (B1)
patients, and incarcerated individuals. Injection drug users and
men who have sex with men with high-risk sexual practices Available drugs in the European Union in 2015
should be made aware of the risk of reinfection and should apply
preventative measures after successful treatment. The HCV drugs available in the European Union are listed in this
paragraph and in Table 3. Their known drug-drug interactions are
Treatment is justified in patients with moderate fibrosis also listed. For a more comprehensive listing of drug-drug inter-
(METAVIR score F2). The timing and nature of therapy for actions, see Tables 4A–F and www.hep-druginteractions.org.
patients with minimal or no fibrosis (METAVIR score F0–F1)
and no severe extra-hepatic manifestations is debatable, and PegIFN-a. PegIFN-a2a should be used at the dose of 180 lg/
informed deferral can be considered. The decision to defer treat- week, whereas PegIFN-a2b should be used at the weight-based
ment for a specific patient should consider the patient’s prefer- dose of 1.5 lg/kg/week.
ence and priorities, the natural history and risk of progression,
the presence of comorbidities, and the patient’s age. Patients
who have treatment deferred should be assessed on a regular
5
impairment, as the effect of impaired renal function on clearance
of sofosbuvir-derived metabolites is still being ascertained. The basis for evidence of progression, to reconsider the indication
combination of ritonavir-boosted paritaprevir, ombitasvir, and for treatment, and to discuss new therapies as they emerge or
dasabuvir is undergoing evaluation in patients with Child-Pugh become available and affordable.
B decompensated cirrhosis and is contra-indicated in patients
with Child-Pugh C decompensated cirrhosis. Studies are on-going Treatment is not recommended in patients with limited life
to assess the pharmacokinetics and safety of simeprevir in expectancy due to non–liver-related comorbidities.
decompensated cirrhosis.
Recommendations
Indications for treatment: who should be treated?
• All treatment-naïve and treatment-experienced patients
All treatment-naïve and –experienced patients with compen- with compensated or decompensated chronic liver
sated or decompensated chronic liver disease related to HCV, disease due to HCV should be considered for therapy
who are willing to be treated and who have no contra-indications (A1)
to treatment, should be considered for therapy. Because not every
HCV-infected patient can be treated within the next year or so, • Treatment should be prioritized for patients with
prioritization is necessary (Table 2). The panel acknowledges that significant fibrosis or cirrhosis (METAVIR score F3 to
priorities may be modulated according to local and/or societal F4) (A1)
considerations.
• Patients with decompensated cirrhosis (Child-Pugh
Treatment priority should be based on fibrosis stage, risk of B and C) should be urgently treated with an IFN-free
progression towards more advanced disease, presence of extra- regimen (A1)
hepatic manifestations of HCV infection and risk of HCV trans-
mission. Treatment should be prioritized in patients with • Treatment should be prioritized regardless of the
advanced fibrosis (METAVIR score F3 to F4), including patients fibrosis stage in patients with HIV or HBV coinfection,
with decompensated cirrhosis who have a contra-indication to patients in the pre- or post-liver transplant setting,
patients with clinically significant extra-hepatic
the use of IFN-a but can be safely treated with IFN-free regimens. manifestations (e.g. symptomatic vasculitis associated
with HCV-related mixed cryoglobulinaemia, HCV
Indeed, data from clinical trials and real-life cohorts indicate that immune complex-related nephropathy and non-Hodgkin
these patients could benefit more from a cure of HCV infection in B cell lymphoma), and patients with debilitating fatigue
the short-term, because substantial decreases in Child-Pugh and (A1)
MELD scores and reductions in the incidence of clinical events
have been observed. However, evidence for an improved outlook • Treatment should be prioritized regardless of the
is still limited in patients with Child-Pugh scores above 12 and fibrosis stage for individuals at risk of transmitting
MELD scores higher than 20. IFN-free treatment in patients with HCV, including active injection drug users, men who
decompensated disease should only be attempted in experienced have sex with men with high-risk sexual practices,
centres until further safety and efficacy data have accumulated. women of childbearing age who wish to get pregnant,
haemodialysis patients, and incarcerated individuals
High priority groups also include patients with HIV or HBV (B1)
coinfection, patients in the pre- or post-liver transplant setting,
patients with clinically significant extra-hepatic manifestations • Treatment is justified in patients with moderate fibrosis
(e.g. symptomatic vasculitis associated with HCV-related mixed (METAVIR score F2) (A2)
cryoglobulinaemia, HCV immune complex-related nephropathy
and non-Hodgkin B cell lymphoma), and patients with debilitat- • In patients with no or mild disease (METAVIR score
ing fatigue, regardless of their liver fibrosis stage. F0-F1) and none of the above-mentioned extra-hepatic
manifestations, the indication for and timing of therapy
Treatment should also be prioritized regardless of the fibrosis can be individualized (B1)
stage or extra-hepatic manifestations in individuals at risk of
transmitting HCV, including active injection drug users, men • Treatment is not recommended in patients with limited
who have sex with men with high-risk sexual practices, women life expectancy due to non-liver-related comorbidities
of childbearing age who wish to get pregnant, haemodialysis (B1)
patients, and incarcerated individuals. Injection drug users and
men who have sex with men with high-risk sexual practices Available drugs in the European Union in 2015
should be made aware of the risk of reinfection and should apply
preventative measures after successful treatment. The HCV drugs available in the European Union are listed in this
paragraph and in Table 3. Their known drug-drug interactions are
Treatment is justified in patients with moderate fibrosis also listed. For a more comprehensive listing of drug-drug inter-
(METAVIR score F2). The timing and nature of therapy for actions, see Tables 4A–F and www.hep-druginteractions.org.
patients with minimal or no fibrosis (METAVIR score F0–F1)
and no severe extra-hepatic manifestations is debatable, and PegIFN-a. PegIFN-a2a should be used at the dose of 180 lg/
informed deferral can be considered. The decision to defer treat- week, whereas PegIFN-a2b should be used at the weight-based
ment for a specific patient should consider the patient’s prefer- dose of 1.5 lg/kg/week.
ence and priorities, the natural history and risk of progression,
the presence of comorbidities, and the patient’s age. Patients
who have treatment deferred should be assessed on a regular
5
