Page 23 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 23
Clinical Practice Guidelines to increase adherence are interdisciplinary. They include HCV
education and monitoring services and, particularly, the help of
Treatment dose reductions a dedicated nurse [69,70]. For foreign patients, the language
and comprehension difficulties should be addressed before start-
The PegIFN-a dose should be reduced in case of severe side ing treatment.
effects, such as clinical symptoms of severe depression, and if To maximize the likelihood of benefit for patients who begin
the absolute neutrophil count falls below 750/mm3, or the plate- new HCV treatment regimens, resources should be devoted to
patient pretreatment assessment and preparation, as well as to
let count falls below 50,000/mm3. When using PegIFN-a2a, the on treatment adherence monitoring and support, which is
dose can be reduced from 180 lg/week to 135 lg/week, and then becoming easier with the new therapeutic regimens.
to 90 lg/week. When using PegIFN-a2b, the dose can be reduced
from 1.5 lg/kg/week to 1.0 lg/kg/week and then to 0.5 lg/kg/ Alcohol consumption has an impact on treatment adherence
week. PegIFN-a should be stopped in case of marked depression, [71]. Patients should therefore be advised to stop or to reduce
alcohol consumption before start of treatment. Treatment for
if the neutrophil count falls below 500/mm3 or the platelet count patients not able to abstain from alcohol should be fitted to
falls below 25,000/mm3. If and when neutrophil or platelet the individual, focussing on their ability to adhere to medication
counts rise from those nadir values, treatment can be restarted, and appointments. Hepatitis C patients with on-going alcohol
but at a reduced dose. IFN treatment interruptions should be as consumption during treatment profit from additional
brief as possible. Switch to IFN-free options should be considered support during antiviral therapy [71–74]. Pharmacists should
in patients who need to stop IFN administration. advise on potential drug-drug interactions.
If significant anaemia occurs (haemoglobin <10 g/dl), the dose Recommendations
of ribavirin should be adjusted downward by 200 mg at decre-
ments. A more rapid reduction of dose may be required for • HCV treatment should be delivered within a
patients with rapidly declining haemoglobin, particularly if the multidisciplinary team setting, with experience in HCV
baseline haemoglobin was low. Ribavirin administration should assessment and therapy (A1)
be stopped if the haemoglobin level falls below 8.5 g/dl [60–68].
• HCV-infected patients should be counselled on the
Treatment should be promptly stopped in case of a hepatitis importance of adherence for attaining an SVR (A1)
flare (ALT levels above 10 times normal, if not already present
at the time of starting treatment) or if a severe bacterial infection • In patients with socioeconomic disadvantages and
occurs at any site, regardless of neutrophil count. Any visual in migrants, social support services should be a
symptoms should be assessed and fundoscopic examination per- component of HCV clinical management (B2)
formed during treatment.
• In persons who actively inject drugs, access to harm
No dose adjustments are recommended for sofosbuvir, reduction programs is mandatory (A1)
simeprevir, daclatasvir, sofosbuvir-ledipasvir or ritonavir-
boosted paritaprevir/ombitasvir/dasabuvir. Treatment must be • Peer-based support should be evaluated as a means to
stopped in case of severe adverse events, such as sepsis in improve HCV clinical management (B2)
patients with decompensated cirrhosis. The effects on efficacy
and the number of allowable days for pausing treatment, and • Patients should be counselled to abstain from alcohol
duration of retreatment in patients who restart after interrup- during antiviral therapy. Patients with on-going alcohol
tion of IFN-free therapy are unknown. consumption during treatment should receive additional
support during antiviral therapy (A1)
Measures to improve treatment adherence
• HCV treatment can be considered also for patients
Full adherence to all drugs is associated with high SVR rates. In actively using drugs, provided they wish to receive
contrast, suboptimal exposure to therapy is associated with treatment and are able and willing to maintain regular
virological breakthrough or post-treatment relapse and the appointments. Also, the potential for drug-drug
emergence of resistance-associated variants, especially during interactions involving prescribed and non-prescribed
the early phase of treatment. Simple measures to enhance drugs needs to be considered (A1)
adherence to treatment should thus be implemented.
Post-treatment follow-up of patients who achieve an SVR
Before starting antiviral therapy, patients must be instructed
about the daily schedule and the likely side effects (of both Non-cirrhotic patients who achieve an SVR should be retested for
IFN- and ribavirin-containing and IFN-free regimens) to be HCV RNA at 48 weeks post-treatment. If HCV RNA is still not
expected during treatment. Patients should also be instructed detected, the infection can be considered as definitely cured
about the preventive and therapeutic measures to ameliorate and HCV RNA need not be retested. As hypothyroidism may occur
these side effects, for example by using antipyretics, analgesics, after stopping IFN therapy, thyroxin and TSH levels should also be
or antidepressants if they receive IFN. Regular follow-up visits assessed 1 and 2 years after treatment if the patient has received
must be scheduled so that treatment progress and management IFN. Patients with pre-existing cofactors for liver disease
of side effects can be discussed. Patient recall procedures in cases
of missed appointments should be instituted.
The key element of effective HCV clinical management is
access to a multidisciplinary team, generally including clinician
and nursing clinical assessment and monitoring, virology, drug
and alcohol services, HIV infection services, psychiatric support
for selected cases, pharmacy, and social work and other social
support services (including peer support, if available). Measures
22 Journal of Hepatology 2015 vol. xxx j xxx–xxx
education and monitoring services and, particularly, the help of
Treatment dose reductions a dedicated nurse [69,70]. For foreign patients, the language
and comprehension difficulties should be addressed before start-
The PegIFN-a dose should be reduced in case of severe side ing treatment.
effects, such as clinical symptoms of severe depression, and if To maximize the likelihood of benefit for patients who begin
the absolute neutrophil count falls below 750/mm3, or the plate- new HCV treatment regimens, resources should be devoted to
patient pretreatment assessment and preparation, as well as to
let count falls below 50,000/mm3. When using PegIFN-a2a, the on treatment adherence monitoring and support, which is
dose can be reduced from 180 lg/week to 135 lg/week, and then becoming easier with the new therapeutic regimens.
to 90 lg/week. When using PegIFN-a2b, the dose can be reduced
from 1.5 lg/kg/week to 1.0 lg/kg/week and then to 0.5 lg/kg/ Alcohol consumption has an impact on treatment adherence
week. PegIFN-a should be stopped in case of marked depression, [71]. Patients should therefore be advised to stop or to reduce
alcohol consumption before start of treatment. Treatment for
if the neutrophil count falls below 500/mm3 or the platelet count patients not able to abstain from alcohol should be fitted to
falls below 25,000/mm3. If and when neutrophil or platelet the individual, focussing on their ability to adhere to medication
counts rise from those nadir values, treatment can be restarted, and appointments. Hepatitis C patients with on-going alcohol
but at a reduced dose. IFN treatment interruptions should be as consumption during treatment profit from additional
brief as possible. Switch to IFN-free options should be considered support during antiviral therapy [71–74]. Pharmacists should
in patients who need to stop IFN administration. advise on potential drug-drug interactions.
If significant anaemia occurs (haemoglobin <10 g/dl), the dose Recommendations
of ribavirin should be adjusted downward by 200 mg at decre-
ments. A more rapid reduction of dose may be required for • HCV treatment should be delivered within a
patients with rapidly declining haemoglobin, particularly if the multidisciplinary team setting, with experience in HCV
baseline haemoglobin was low. Ribavirin administration should assessment and therapy (A1)
be stopped if the haemoglobin level falls below 8.5 g/dl [60–68].
• HCV-infected patients should be counselled on the
Treatment should be promptly stopped in case of a hepatitis importance of adherence for attaining an SVR (A1)
flare (ALT levels above 10 times normal, if not already present
at the time of starting treatment) or if a severe bacterial infection • In patients with socioeconomic disadvantages and
occurs at any site, regardless of neutrophil count. Any visual in migrants, social support services should be a
symptoms should be assessed and fundoscopic examination per- component of HCV clinical management (B2)
formed during treatment.
• In persons who actively inject drugs, access to harm
No dose adjustments are recommended for sofosbuvir, reduction programs is mandatory (A1)
simeprevir, daclatasvir, sofosbuvir-ledipasvir or ritonavir-
boosted paritaprevir/ombitasvir/dasabuvir. Treatment must be • Peer-based support should be evaluated as a means to
stopped in case of severe adverse events, such as sepsis in improve HCV clinical management (B2)
patients with decompensated cirrhosis. The effects on efficacy
and the number of allowable days for pausing treatment, and • Patients should be counselled to abstain from alcohol
duration of retreatment in patients who restart after interrup- during antiviral therapy. Patients with on-going alcohol
tion of IFN-free therapy are unknown. consumption during treatment should receive additional
support during antiviral therapy (A1)
Measures to improve treatment adherence
• HCV treatment can be considered also for patients
Full adherence to all drugs is associated with high SVR rates. In actively using drugs, provided they wish to receive
contrast, suboptimal exposure to therapy is associated with treatment and are able and willing to maintain regular
virological breakthrough or post-treatment relapse and the appointments. Also, the potential for drug-drug
emergence of resistance-associated variants, especially during interactions involving prescribed and non-prescribed
the early phase of treatment. Simple measures to enhance drugs needs to be considered (A1)
adherence to treatment should thus be implemented.
Post-treatment follow-up of patients who achieve an SVR
Before starting antiviral therapy, patients must be instructed
about the daily schedule and the likely side effects (of both Non-cirrhotic patients who achieve an SVR should be retested for
IFN- and ribavirin-containing and IFN-free regimens) to be HCV RNA at 48 weeks post-treatment. If HCV RNA is still not
expected during treatment. Patients should also be instructed detected, the infection can be considered as definitely cured
about the preventive and therapeutic measures to ameliorate and HCV RNA need not be retested. As hypothyroidism may occur
these side effects, for example by using antipyretics, analgesics, after stopping IFN therapy, thyroxin and TSH levels should also be
or antidepressants if they receive IFN. Regular follow-up visits assessed 1 and 2 years after treatment if the patient has received
must be scheduled so that treatment progress and management IFN. Patients with pre-existing cofactors for liver disease
of side effects can be discussed. Patient recall procedures in cases
of missed appointments should be instituted.
The key element of effective HCV clinical management is
access to a multidisciplinary team, generally including clinician
and nursing clinical assessment and monitoring, virology, drug
and alcohol services, HIV infection services, psychiatric support
for selected cases, pharmacy, and social work and other social
support services (including peer support, if available). Measures
22 Journal of Hepatology 2015 vol. xxx j xxx–xxx
