Page 5 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 5
Clinical Practice Guidelines Recommendations
(bridging) fibrosis is of particular importance, as the post- • The causal relationship between HCV infection and liver
treatment prognosis depends on the stage of fibrosis. The disease should be established (A1)
absence of significant fibrosis may also have important impli-
cations for stratification of disease and possibly the timing of • The contribution of comorbid conditions to the
therapy. Assessment of the stage of fibrosis is not required progression of liver disease must be evaluated and
in patients with clinical evidence of cirrhosis. Patients with appropriate corrective measures implemented (A1)
cirrhosis need surveillance for HCC. Since significant fibrosis
may be present in patients with repeatedly normal ALT, eval- • Liver disease severity should be assessed prior to
uation of disease severity should be performed regardless of therapy. Identifying patients with cirrhosis is of particular
ALT levels. importance, as their prognosis is altered and their
treatment regimen may be adapted (A1)
Liver biopsy has been for many years the reference method for
grading the activity and histological progression (staging) of the • Fibrosis stage can be assessed by non-invasive
disease. In chronic hepatitis C, considerable evidence suggest that methods initially, with liver biopsy reserved for cases
non-invasive methods can now be used instead of liver biopsy to where there is uncertainty or potential additional
assess liver disease severity prior to therapy at a safe level of pre- aetiologies (A1)
dictability. Liver stiffness measurement can be used to assess
liver fibrosis in patients with chronic hepatitis C, provided that • HCV RNA detection and quantification should be made
consideration is given to factors that may adversely affect its per- by a sensitive assay with a lower limit of detection of
formance such as obesity. Well-established panels of biomarkers ≤15 IU/ml (A1)
of fibrosis can also be applied. Both liver stiffness measurement
and biomarkers perform well in the identification of cirrhosis or • The HCV genotype and genotype 1 subtype (1a/1b)
no fibrosis, but they perform less well in resolving intermediate must be assessed prior to treatment initiation and will
degrees of fibrosis. determine the choice of therapy (A1)
The combination of blood biomarkers or the combination of • IL28B genotyping has no role in the indication for
liver stiffness measurement and a blood test improve accuracy treating hepatitis C with the new DAAs (A1)
and reduce the need for liver biopsy to resolve uncertainty
[20,21]. These tests are of particular interest in patients with coa- • HCV resistance testing should not be performed prior
gulation disorders, though transjugular liver biopsy may also be to therapy, because the SVR rates are very high both
used safely in this situation with the bonus that portal pressure in patients without and with detectable amounts of
can also be assessed. In case of contradictory results with non- resistance-associated variants by means of population
invasive markers, liver biopsy may be indicated. Also, histology sequencing at baseline (with the exception of patients
may be required in cases of known or suspected mixed aetiolo- infected with subtype 1a who receive the combination of
gies (e.g. HCV infection with HBV infection, metabolic syndrome, PegIFN-α, ribavirin and simeprevir) (A1)
alcoholism or autoimmunity).
Contra-indications to therapy
HCV RNA detection/quantification and genotype determination
HCV RNA detection/quantification is indicated for the patient IFN-a and ribavirin
who may undergo antiviral treatment. HCV RNA quantification Treatment of chronic hepatitis C with PegIFN-a and ribavirin-
should be made by a reliable sensitive assay, and HCV RNA levels
should be expressed in IU/ml. containing regimens is absolutely contra-indicated in the follow-
ing patient groups: uncontrolled depression, psychosis or epi-
The HCV genotype, including genotype 1 subtype, should also lepsy; pregnant women or couples unwilling to comply with
be assessed prior to treatment initiation. Genotyping/subtyping adequate contraception; severe concurrent medical diseases
should be performed with an assay that accurately discriminates and comorbidities including retinal disease, autoimmune thyroid
subtype 1a from 1b [22]. disease; decompensated liver disease.
HCV resistance testing prior to first-line therapy is not The use of PegIFN-a is not recommended in patients with
required. Indeed, the presence of pre-existing resistance-associ-
ated variants as detected by population sequencing does not have absolute neutrophil counts <1500/mm3 and/or platelet counts
a major impact on the results of therapy and will not influence 690,000/mm3. Treatment of patients with advanced liver disease
the treatment decision (with the exception of the effect of the whose parameters fall outside of label recommendations may be
Q80K substitution in patients with subtype 1a infection treated feasible in experienced centres under careful monitoring and
informed consent.
with the combination of PegIFN-a, ribavirin, and simeprevir,
Approved DAAs
see below). Based on existing knowledge, no absolute contra-indications to
the DAAs approved in the EU region in 2015 exist. Caution is
Determination of host genetics
IL28B genotyping has lost predictive value with the new highly
efficacious IFN-free treatment regimens. Thus, IL28B genotyping
is useful only in settings where only PegIFN-a and ribavirin are
available or to select cost-effective treatment options in settings
with economical restrictions.
4
(bridging) fibrosis is of particular importance, as the post- • The causal relationship between HCV infection and liver
treatment prognosis depends on the stage of fibrosis. The disease should be established (A1)
absence of significant fibrosis may also have important impli-
cations for stratification of disease and possibly the timing of • The contribution of comorbid conditions to the
therapy. Assessment of the stage of fibrosis is not required progression of liver disease must be evaluated and
in patients with clinical evidence of cirrhosis. Patients with appropriate corrective measures implemented (A1)
cirrhosis need surveillance for HCC. Since significant fibrosis
may be present in patients with repeatedly normal ALT, eval- • Liver disease severity should be assessed prior to
uation of disease severity should be performed regardless of therapy. Identifying patients with cirrhosis is of particular
ALT levels. importance, as their prognosis is altered and their
treatment regimen may be adapted (A1)
Liver biopsy has been for many years the reference method for
grading the activity and histological progression (staging) of the • Fibrosis stage can be assessed by non-invasive
disease. In chronic hepatitis C, considerable evidence suggest that methods initially, with liver biopsy reserved for cases
non-invasive methods can now be used instead of liver biopsy to where there is uncertainty or potential additional
assess liver disease severity prior to therapy at a safe level of pre- aetiologies (A1)
dictability. Liver stiffness measurement can be used to assess
liver fibrosis in patients with chronic hepatitis C, provided that • HCV RNA detection and quantification should be made
consideration is given to factors that may adversely affect its per- by a sensitive assay with a lower limit of detection of
formance such as obesity. Well-established panels of biomarkers ≤15 IU/ml (A1)
of fibrosis can also be applied. Both liver stiffness measurement
and biomarkers perform well in the identification of cirrhosis or • The HCV genotype and genotype 1 subtype (1a/1b)
no fibrosis, but they perform less well in resolving intermediate must be assessed prior to treatment initiation and will
degrees of fibrosis. determine the choice of therapy (A1)
The combination of blood biomarkers or the combination of • IL28B genotyping has no role in the indication for
liver stiffness measurement and a blood test improve accuracy treating hepatitis C with the new DAAs (A1)
and reduce the need for liver biopsy to resolve uncertainty
[20,21]. These tests are of particular interest in patients with coa- • HCV resistance testing should not be performed prior
gulation disorders, though transjugular liver biopsy may also be to therapy, because the SVR rates are very high both
used safely in this situation with the bonus that portal pressure in patients without and with detectable amounts of
can also be assessed. In case of contradictory results with non- resistance-associated variants by means of population
invasive markers, liver biopsy may be indicated. Also, histology sequencing at baseline (with the exception of patients
may be required in cases of known or suspected mixed aetiolo- infected with subtype 1a who receive the combination of
gies (e.g. HCV infection with HBV infection, metabolic syndrome, PegIFN-α, ribavirin and simeprevir) (A1)
alcoholism or autoimmunity).
Contra-indications to therapy
HCV RNA detection/quantification and genotype determination
HCV RNA detection/quantification is indicated for the patient IFN-a and ribavirin
who may undergo antiviral treatment. HCV RNA quantification Treatment of chronic hepatitis C with PegIFN-a and ribavirin-
should be made by a reliable sensitive assay, and HCV RNA levels
should be expressed in IU/ml. containing regimens is absolutely contra-indicated in the follow-
ing patient groups: uncontrolled depression, psychosis or epi-
The HCV genotype, including genotype 1 subtype, should also lepsy; pregnant women or couples unwilling to comply with
be assessed prior to treatment initiation. Genotyping/subtyping adequate contraception; severe concurrent medical diseases
should be performed with an assay that accurately discriminates and comorbidities including retinal disease, autoimmune thyroid
subtype 1a from 1b [22]. disease; decompensated liver disease.
HCV resistance testing prior to first-line therapy is not The use of PegIFN-a is not recommended in patients with
required. Indeed, the presence of pre-existing resistance-associ-
ated variants as detected by population sequencing does not have absolute neutrophil counts <1500/mm3 and/or platelet counts
a major impact on the results of therapy and will not influence 690,000/mm3. Treatment of patients with advanced liver disease
the treatment decision (with the exception of the effect of the whose parameters fall outside of label recommendations may be
Q80K substitution in patients with subtype 1a infection treated feasible in experienced centres under careful monitoring and
informed consent.
with the combination of PegIFN-a, ribavirin, and simeprevir,
Approved DAAs
see below). Based on existing knowledge, no absolute contra-indications to
the DAAs approved in the EU region in 2015 exist. Caution is
Determination of host genetics
IL28B genotyping has lost predictive value with the new highly
efficacious IFN-free treatment regimens. Thus, IL28B genotyping
is useful only in settings where only PegIFN-a and ribavirin are
available or to select cost-effective treatment options in settings
with economical restrictions.
4
