Page 4 - EASL Recommendations on Treatment of Hepatitis C 2014
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Grading of evidence Notes Symbol High quality Further research is very unlikely to change our confdence in the estimate of effect A Moderate quality Further research is likely to have an important impact on our confdence in the estimate B of effect and may change the estimate Low or very low quality Further research is very likely to have an important impact on our confdence in the C estimate of effect and is likely to change the estimate. Any estimate of effect is uncertain Grading of recommendation Notes Symbol Strong recommendation warranted Factors infuencing the strength of the recommendation included the quality of the 1 evidence, presumed patient-important outcomes, and cost Weaker recommendation Variability in preferences and values, or more uncertainty: more likely a weak 2 recommendation is warranted Recommendation is made with less certainty; higher cost or resource consumption Table 1. Evidence grading used (adapted from the Grade system). aminotransferase [ALT] >10 times the upper limit of normal, Recommendations jaundice) in the absence of a history of chronic liver disease or other causes of acute hepatitis, and/or if a likely recent source of Recommendations transmission is identifiable. In all cases, HCV RNA can be detected during the acute phase although brief periods of undetectable HCV RNA may occur. • The goal of therapy is to eradicate HCV infection The diagnosis of chronic hepatitis C is based on the detection to prevent hepatic cirrhosis, decompensation of of both HCV antibodies and HCV RNA in the presence of signs cirrhosis, HCC, and death. The endpoint of therapy is of chronic hepatitis, either by elevated aminotransferases or by undetectable HCV RNA in a sensitive assay histological changes of chronic hepatitis C. Since, in the case of (<15 IU/ml) 12 and 24 weeks after the end of treatment a newly acquired HCV infection, spontaneous viral clearance is (i.e. an SVR) (Recommendation A1) very rare beyond four to six months of infection, the diagnosis of chronic hepatitis C can be made after that time period. • In patients with cirrhosis, HCV eradication reduces the rate of decompensation and will reduce, albeit not Recommendations abolish, the risk of HCC. In these patients surveillance for HCC should be continued (Recommendation A1) Recommendations • Anti-HCV antibodies are the first line diagnostic test for HCV infection (Recommendation A1) 4.3. Pre-therapeutic assessment • In the case of suspected acute hepatitis C or in The causal relationship between HCV infection and liver disease immunocompromised patients, HCV RNA testing should must be established, liver disease severity must be assessed, and be part of the initial evaluation (Recommendation A1) baseline virological parameters that will be useful to tailor therapy should be determined. • If anti-HCV antibodies are detected, HCV RNA should be determined by a sensitive molecular method 4.3.1. Search for other causes of liver disease (Recommendation A1) Other causes of chronic liver disease, or factors which are likely • Anti-HCV positive, HCV-RNA negative individuals should to affect the natural history or progression of liver disease, should be retested for HCV RNA 3 months later to confirm true be systematically investigated and all patients should be tested for convalescence (Recommendation A1) other hepatotropic viruses, particularly HBV, and for HIV. Alcohol consumption should be assessed and quantified, and specific counselling to stop any use of alcohol should be given. Possible co-morbidities, including alcoholism, autoimmunity, genetic or 4.2. Goals and endpoints of HCV therapy metabolic liver diseases (for instance genetic hemochromatosis, diabetes or obesity), and the possibility of drug-induced The goal of therapy is to eradicate HCV infection in order to hepatotoxicity should be assessed. prevent the complications of HCV-related liver and extra-hepatic diseases, including hepatic necro-inflammation, fibrosis, cirrhosis, decompensation of cirrhosis, HCC, and death. The endpoint of therapy is an SVR, defined by undetectable 4.3.2. Assessment of liver disease severity HCV RNA 12 weeks (SVR12) or 24 weeks (SVR24) after the end of therapy, as assessed by a sensitive molecular method with Assessment of liver disease severity is recommended prior to a lower limit of detection <15 IU/ml. Both SVR12 and SVR24 therapy. Identifying patients with cirrhosis or advanced (bridging) have been accepted as endpoints of therapy by regulators in the fibrosis is of particular importance, as the post-treatment US and Europe, given that their concordance is 99% [10]. Long- prognosis depends on the stage of fibrosis. The absence of term follow-up studies have shown that an SVR corresponds to a significant fibrosis may also have important implications for definitive cure of HCV infection in more than 99% of cases [11]. stratification of disease and possibly the timing of therapy. 2
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