Page 7 - NON-INVASIVE TESTS FOR EVALUATION OF LIVER DISEASE SEVERITY AND PROGNOSIS
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Clinical Practice Guidelines availability of novel antiviral agents able to achieve sustained
virological response (SVR) rates above 90% with limited side
Recommendations effects, it is likely that significant fibrosis will no longer represent
an important decision making endpoint in HCV-infected patients.
• Non-invasive tests should always be interpreted (2) Detection of cirrhosis (METAVIR, F4 or Ishak, 5–6) indicates
by specialists in liver disease, according to the that patients should not only potentially be treated for longer
clinical context, considering the results of other tests duration/different regimens in HCV but also monitored for com-
(biochemical, radiological and endoscopic) and taking plications related to portal hypertension (PH) and regularly
into account the recommended quality criteria for each screened for hepatocellular carcinoma (HCC). In NAFLD,
test and its possible pitfalls (A1) representing another major etiology of chronic liver disease, the
presence of significant fibrosis does not represent a relevant end-
• Serum biomarkers can be used in clinical practice point in the absence of standardized treatment regimens.
due to their high applicability (>95%) and good inter- However, detection of septal (advanced) fibrosis-cirrhosis seems
laboratory reproducibility. However, they should be clinically more relevant in NAFLD patients. In alcoholic liver dis-
preferably obtained in fasting patients (particularly ease (ALD), cholestatic liver diseases, and other etiologies, cirrho-
those including hyaluronic acid) and following the sis represents the most relevant clinical endpoint.
manufacturer’s recommendations for the patented
tests (A1) Recommendations
• TE is a fast, simple, safe and easy to learn procedure • In patients with viral hepatitis (including HIV/HCV
that is widely available. Its main limitation is the coinfection), there are two clinically relevant endpoints:
impossibility of obtaining results in case of ascites or the detection of significant fibrosis and the detection
morbid obesity and its limited applicability in case of of cirrhosis. However, with the availability of highly
obesity and limited operator experience (A1) effective novel antiviral agents significant fibrosis
might no longer represent a relevant endpoint in HCV-
• TE should be performed by an experienced operator infected patients whereas detection of cirrhosis is still
(>100 examinations) following a standardized protocol important to guide treatment with novel antiviral agents
with the patient, fasting for at least 2 hours, in the (A1)
supine position, right arm in full abduction, on the mid-
axillary line with the probe-tip placed in the 9th to 11th • In patients with NAFLD, detection of cirrhosis
intercostal space with a minimum of 10 shots (A1) represents the most important endpoint. The clinical
importance of detecting milder stages of liver fibrosis in
• Correct interpretation of TE results in clinical practice NAFLD remains to be defined (A1)
must consider the following parameters:
- IQR/ median value (<30%), • In patients with other etiologies of chronic liver
- Serum aminotransferases levels (<5 x ULN), diseases, detection of cirrhosis represents the most
- BMI (use XL probe above 30 kg/m2 or if skin-to- relevant clinical endpoint (A1)
capsule distance is >25 mm),
- Absence of extra-hepatic cholestasis, • Detection of cirrhosis indicates that patients should be
- Absence of right heart failure, or other causes of monitored for complications related to PH and regularly
congestive liver screened for HCC (A1)
- Absence of ongoing excessive alcohol intake
(A1) Performance of serum biomarkers for staging liver fibrosis
• Although alternative techniques, such as pSWE/ARFI The diagnostic performances of serum biomarkers of fibrosis are
or 2D-SWE seem to overcome limitations of TE, their summarized in Table 4. Overall, biomarkers are less accurate in
quality criteria for correct interpretation are not yet well detecting intermediate stages of fibrosis than cirrhosis. The most
defined (A1) widely used and validated are the APRI (a free non-patented
index) and the FibroTestÒ (a patented test that is not widely
• At present correct interpretation of pSWE/ARFI results available), mainly in viral hepatitis C. A recent systematic review
in clinical practice should systematically take into including 172 studies conducted in hepatitis C [103] reported
account the potentially confounding parameter: median AUROCs of 0.79 and 0.86 for FibroTestÒ and of 0.77 and
- fasting for at least 2 hours, transaminases levels 0.84 for APRI, for significant fibrosis and cirrhosis, respectively.
(<5 x ULN), absence of extra-hepatic cholestasis and A meta-analysis by the developer [104] that analyzed data from
absence or right heart failure (B1) 6378 subjects (individual data from 3282 subjects) who received
the FibroTestÒ and biopsies (3501 with HCV infection and 1457
• MR elastography is currently too costly and time- with HBV) found that the mean standardized AUROC for diagno-
consuming for routine clinical practice use and seems sis of significant fibrosis was 0.84, without significant differences
more suited for research purposes (A1) between patients with HCV (0.85) and HBV (0.80). Another meta-
analysis [105] analyzed results from 6259 HCV patients from 33
Endpoints for staging liver fibrosis
In patients with viral hepatitis and HIV-HCV coinfection, the
clinically relevant endpoints are: (1) detection of significant
fibrosis (METAVIR, F P2 or Ishak, P3), which indicates that
patients should receive antiviral treatment. However, with the
6 Journal of Hepatology 2015 vol. xxx j xxx–xxx
Please cite this article in press as: EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J
Hepatol (2015), http://dx.doi.org/10.1016/j.jhep.2015.04.006
virological response (SVR) rates above 90% with limited side
Recommendations effects, it is likely that significant fibrosis will no longer represent
an important decision making endpoint in HCV-infected patients.
• Non-invasive tests should always be interpreted (2) Detection of cirrhosis (METAVIR, F4 or Ishak, 5–6) indicates
by specialists in liver disease, according to the that patients should not only potentially be treated for longer
clinical context, considering the results of other tests duration/different regimens in HCV but also monitored for com-
(biochemical, radiological and endoscopic) and taking plications related to portal hypertension (PH) and regularly
into account the recommended quality criteria for each screened for hepatocellular carcinoma (HCC). In NAFLD,
test and its possible pitfalls (A1) representing another major etiology of chronic liver disease, the
presence of significant fibrosis does not represent a relevant end-
• Serum biomarkers can be used in clinical practice point in the absence of standardized treatment regimens.
due to their high applicability (>95%) and good inter- However, detection of septal (advanced) fibrosis-cirrhosis seems
laboratory reproducibility. However, they should be clinically more relevant in NAFLD patients. In alcoholic liver dis-
preferably obtained in fasting patients (particularly ease (ALD), cholestatic liver diseases, and other etiologies, cirrho-
those including hyaluronic acid) and following the sis represents the most relevant clinical endpoint.
manufacturer’s recommendations for the patented
tests (A1) Recommendations
• TE is a fast, simple, safe and easy to learn procedure • In patients with viral hepatitis (including HIV/HCV
that is widely available. Its main limitation is the coinfection), there are two clinically relevant endpoints:
impossibility of obtaining results in case of ascites or the detection of significant fibrosis and the detection
morbid obesity and its limited applicability in case of of cirrhosis. However, with the availability of highly
obesity and limited operator experience (A1) effective novel antiviral agents significant fibrosis
might no longer represent a relevant endpoint in HCV-
• TE should be performed by an experienced operator infected patients whereas detection of cirrhosis is still
(>100 examinations) following a standardized protocol important to guide treatment with novel antiviral agents
with the patient, fasting for at least 2 hours, in the (A1)
supine position, right arm in full abduction, on the mid-
axillary line with the probe-tip placed in the 9th to 11th • In patients with NAFLD, detection of cirrhosis
intercostal space with a minimum of 10 shots (A1) represents the most important endpoint. The clinical
importance of detecting milder stages of liver fibrosis in
• Correct interpretation of TE results in clinical practice NAFLD remains to be defined (A1)
must consider the following parameters:
- IQR/ median value (<30%), • In patients with other etiologies of chronic liver
- Serum aminotransferases levels (<5 x ULN), diseases, detection of cirrhosis represents the most
- BMI (use XL probe above 30 kg/m2 or if skin-to- relevant clinical endpoint (A1)
capsule distance is >25 mm),
- Absence of extra-hepatic cholestasis, • Detection of cirrhosis indicates that patients should be
- Absence of right heart failure, or other causes of monitored for complications related to PH and regularly
congestive liver screened for HCC (A1)
- Absence of ongoing excessive alcohol intake
(A1) Performance of serum biomarkers for staging liver fibrosis
• Although alternative techniques, such as pSWE/ARFI The diagnostic performances of serum biomarkers of fibrosis are
or 2D-SWE seem to overcome limitations of TE, their summarized in Table 4. Overall, biomarkers are less accurate in
quality criteria for correct interpretation are not yet well detecting intermediate stages of fibrosis than cirrhosis. The most
defined (A1) widely used and validated are the APRI (a free non-patented
index) and the FibroTestÒ (a patented test that is not widely
• At present correct interpretation of pSWE/ARFI results available), mainly in viral hepatitis C. A recent systematic review
in clinical practice should systematically take into including 172 studies conducted in hepatitis C [103] reported
account the potentially confounding parameter: median AUROCs of 0.79 and 0.86 for FibroTestÒ and of 0.77 and
- fasting for at least 2 hours, transaminases levels 0.84 for APRI, for significant fibrosis and cirrhosis, respectively.
(<5 x ULN), absence of extra-hepatic cholestasis and A meta-analysis by the developer [104] that analyzed data from
absence or right heart failure (B1) 6378 subjects (individual data from 3282 subjects) who received
the FibroTestÒ and biopsies (3501 with HCV infection and 1457
• MR elastography is currently too costly and time- with HBV) found that the mean standardized AUROC for diagno-
consuming for routine clinical practice use and seems sis of significant fibrosis was 0.84, without significant differences
more suited for research purposes (A1) between patients with HCV (0.85) and HBV (0.80). Another meta-
analysis [105] analyzed results from 6259 HCV patients from 33
Endpoints for staging liver fibrosis
In patients with viral hepatitis and HIV-HCV coinfection, the
clinically relevant endpoints are: (1) detection of significant
fibrosis (METAVIR, F P2 or Ishak, P3), which indicates that
patients should receive antiviral treatment. However, with the
6 Journal of Hepatology 2015 vol. xxx j xxx–xxx
Please cite this article in press as: EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J
Hepatol (2015), http://dx.doi.org/10.1016/j.jhep.2015.04.006
