Page 4 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 4
JOURNAL OF HEPATOLOGY
Table 1. Evidence grading used (adapted from the GRADE system).
Evidence quality Notes Grading
High A
Moderate Further research is very unlikely to change our confidence in the estimate of effect B
Low Further research is likely to have an important impact on our confidence in the estimate of effect and may C
change the estimate
Recommendation Grading
Strong Further research is very likely to have an important impact on our confidence in the estimate of effect and 1
is likely to change the estimate. Any change of estimate is uncertain
Weak 2
Notes
Factors influencing the strength of the recommendation included the quality of the evidence, presumed
patient-important outcomes, and cost
Variability in preferences and values, or more uncertainty. Recommendation is made with less certainty,
higher cost or resource consumption
diagnostic tests (RDTs) can be used to screen for anti-HCV Recommendations
antibodies. RDTs use various matrices, including serum, plasma,
but also fingerstick capillary whole blood or, for some of them, • The goal of therapy is to cure HCV infection to prevent
oral (crevicular) fluid, facilitating screening without the need hepatic cirrhosis, decompensation of cirrhosis, HCC,
for venous puncture, tube centrifugation, freezing and skilled severe extra-hepatic manifestations and death (A1)
labour. RDTs are simple to perform at room temperature without
specific instrumentation or extensive training. • The endpoint of therapy is undetectable HCV RNA in a
sensitive assay (≤15 IU/ml) 12 weeks (SVR12) and 24
Recommendations weeks (SVR24) after the end of treatment (A1)
• Screening for HCV infection must be recommended • In patients with advanced fibrosis and cirrhosis, HCV
in targeted populations defined according to the local eradication reduces the rate of decompensation and
epidemiology of HCV infection, ideally within the will reduce, albeit not abolish, the risk of HCC. In these
framework of national plans (A1) patients surveillance for HCC should be continued (A1)
• Screening for HCV infection must be based on the • In patients with decompensated cirrhosis, HCV
detection of anti-HCV antibodies (A1) eradication reduces the need for liver transplantation.
Whether HCV eradication impacts mid- to long-term
• Rapid diagnostic tests can be used instead of classical survival in these patients is unknown (B2)
enzyme immunoassays to facilitate anti-HCV antibody
screening and improve access to care (B1) Pre-therapeutic assessment
• If anti-HCV antibodies are detected, HCV RNA should The causal relationship between HCV infection and liver disease
be determined by a sensitive molecular method to should be established, liver disease severity must be assessed,
identify patients with on-going infection (A1) and baseline virological parameters that will be useful for tailor-
ing therapy should be determined.
Goals and endpoints of HCV therapy
Search for other causes of liver disease
The goal of therapy is to cure HCV infection in order to prevent Other causes of chronic liver disease, or factors which are likely
the complications of HCV-related liver and extra-hepatic dis- to affect the natural history or progression of liver disease, should
eases, including hepatic necro-inflammation, fibrosis, cirrhosis, be systematically investigated and all patients should be tested
decompensation of cirrhosis, HCC, severe extra-hepatic mani- for other hepatotropic viruses, particularly hepatitis B virus
festations and death. (HBV), and for human immunodeficiency virus (HIV). Alcohol
consumption should be assessed and quantified, and specific
The endpoint of therapy is an SVR, defined by undetectable counselling to stop any use of alcohol should be given. Possible
HCV RNA 12 weeks (SVR12) or 24 weeks (SVR24) after the end comorbidities, including alcoholism, autoimmunity, genetic or
of therapy, as assessed by a sensitive molecular method with a metabolic liver diseases (for instance genetic hemochromatosis,
lower limit of detection 615 IU/ml. Both SVR12 and SVR24 diabetes or obesity) and the possibility of drug-induced hep-
have been accepted as endpoints of therapy by regulators in atotoxicity should be assessed.
the US and Europe, given that their concordance is 99% [18].
Long-term follow-up studies have shown that an SVR corre- Assessment of liver disease severity
sponds to a definitive cure of HCV infection in more than Assessment of liver disease severity is recommended prior to
99% of cases [19]. therapy. Identifying patients with cirrhosis or advanced
3
Table 1. Evidence grading used (adapted from the GRADE system).
Evidence quality Notes Grading
High A
Moderate Further research is very unlikely to change our confidence in the estimate of effect B
Low Further research is likely to have an important impact on our confidence in the estimate of effect and may C
change the estimate
Recommendation Grading
Strong Further research is very likely to have an important impact on our confidence in the estimate of effect and 1
is likely to change the estimate. Any change of estimate is uncertain
Weak 2
Notes
Factors influencing the strength of the recommendation included the quality of the evidence, presumed
patient-important outcomes, and cost
Variability in preferences and values, or more uncertainty. Recommendation is made with less certainty,
higher cost or resource consumption
diagnostic tests (RDTs) can be used to screen for anti-HCV Recommendations
antibodies. RDTs use various matrices, including serum, plasma,
but also fingerstick capillary whole blood or, for some of them, • The goal of therapy is to cure HCV infection to prevent
oral (crevicular) fluid, facilitating screening without the need hepatic cirrhosis, decompensation of cirrhosis, HCC,
for venous puncture, tube centrifugation, freezing and skilled severe extra-hepatic manifestations and death (A1)
labour. RDTs are simple to perform at room temperature without
specific instrumentation or extensive training. • The endpoint of therapy is undetectable HCV RNA in a
sensitive assay (≤15 IU/ml) 12 weeks (SVR12) and 24
Recommendations weeks (SVR24) after the end of treatment (A1)
• Screening for HCV infection must be recommended • In patients with advanced fibrosis and cirrhosis, HCV
in targeted populations defined according to the local eradication reduces the rate of decompensation and
epidemiology of HCV infection, ideally within the will reduce, albeit not abolish, the risk of HCC. In these
framework of national plans (A1) patients surveillance for HCC should be continued (A1)
• Screening for HCV infection must be based on the • In patients with decompensated cirrhosis, HCV
detection of anti-HCV antibodies (A1) eradication reduces the need for liver transplantation.
Whether HCV eradication impacts mid- to long-term
• Rapid diagnostic tests can be used instead of classical survival in these patients is unknown (B2)
enzyme immunoassays to facilitate anti-HCV antibody
screening and improve access to care (B1) Pre-therapeutic assessment
• If anti-HCV antibodies are detected, HCV RNA should The causal relationship between HCV infection and liver disease
be determined by a sensitive molecular method to should be established, liver disease severity must be assessed,
identify patients with on-going infection (A1) and baseline virological parameters that will be useful for tailor-
ing therapy should be determined.
Goals and endpoints of HCV therapy
Search for other causes of liver disease
The goal of therapy is to cure HCV infection in order to prevent Other causes of chronic liver disease, or factors which are likely
the complications of HCV-related liver and extra-hepatic dis- to affect the natural history or progression of liver disease, should
eases, including hepatic necro-inflammation, fibrosis, cirrhosis, be systematically investigated and all patients should be tested
decompensation of cirrhosis, HCC, severe extra-hepatic mani- for other hepatotropic viruses, particularly hepatitis B virus
festations and death. (HBV), and for human immunodeficiency virus (HIV). Alcohol
consumption should be assessed and quantified, and specific
The endpoint of therapy is an SVR, defined by undetectable counselling to stop any use of alcohol should be given. Possible
HCV RNA 12 weeks (SVR12) or 24 weeks (SVR24) after the end comorbidities, including alcoholism, autoimmunity, genetic or
of therapy, as assessed by a sensitive molecular method with a metabolic liver diseases (for instance genetic hemochromatosis,
lower limit of detection 615 IU/ml. Both SVR12 and SVR24 diabetes or obesity) and the possibility of drug-induced hep-
have been accepted as endpoints of therapy by regulators in atotoxicity should be assessed.
the US and Europe, given that their concordance is 99% [18].
Long-term follow-up studies have shown that an SVR corre- Assessment of liver disease severity
sponds to a definitive cure of HCV infection in more than Assessment of liver disease severity is recommended prior to
99% of cases [19]. therapy. Identifying patients with cirrhosis or advanced
3
