Page 11 - NON-INVASIVE TESTS FOR EVALUATION OF LIVER DISEASE SEVERITY AND PROGNOSIS
P. 11
Clinical Practice Guidelines evaluated patients with mixed chronic liver disease with viral
hepatitis being the predominant liver disease [166–177].
TE has also been investigated in NAFLD patients but in a smal- Similar to TE, pSWE/ARFI more accurately detects cirrhosis
ler number of studies [66,68,82,85,156–159] (Table 6). Like in (AUROC values: 0.81–0.99) than significant fibrosis (AUROC
viral hepatitis, TE performances are better for cirrhosis than for values: 0.77–0.94). The largest study evaluating pSWE/ARFI for
significant fibrosis with AUROCs ranging from 0.94 to 0.99 and staging of chronic hepatitis C was a retrospective pooled
from 0.79 to 0.99, respectively. However, the performance of TE analysis of 914 international patient data [178], part of which
in NAFLD deserves several comments: Firstly, these studies have were published in smaller single centre studies previously
been conducted in heterogeneous and special populations such [166,167,170,171,174,179]. It reported sensitivity and specificity
as Asian patients or children with low BMI (<28 kg/m2); secondly, of pSWE/ARFI for the diagnosis of significant fibrosis of 0.69 and
most of them are underpowered with small sample size 0.80 and for the diagnosis of liver cirrhosis of 0.84 and 0.76,
(<100 patients) and very few patients with cirrhosis; thirdly, the respectively [178].
histological scoring systems such as those proposed by Brunt
et al. [160] or Kleiner et al. [161] and endpoints (significant fibrosis Meta-analyzes have confirmed the better diagnostic perfor-
or severe fibrosis) were heterogeneous in most studies evaluating mance of pSWE/ARFI for cirrhosis than for fibrosis [180,181]. In
fibrosis by TE in NAFLD. These differences in the study designs are a pooled meta-analysis including 518 individual patients with
likely the explanation for the observed differences among pro- chronic liver disease (83% with viral hepatitis) mean AUROCs
posed cut-offs for a given endpoint (ranging for instance from were 0.87 for the diagnosis of significant fibrosis, and 0.93 for
10.3 to 22.3 kPa for cirrhosis) (Table 6), known as the spectrum the diagnosis of liver cirrhosis [180]. In a meta-analysis of 36
bias [16,17]. Finally, all these studies have been conducted in ter- studies (21 full paper publications and 15 abstracts) comprising
tiary referral centres with a higher proportion of patients with 3951 patients mean AUROCs were 0.84 (diagnostic odds ratio
severe fibrosis than in the general population, making it difficult [DOR]: 11.54) for the diagnosis of significant fibrosis, and 0.91
to extrapolate the performance of TE in detecting cirrhosis in large (DOR: 45.35) for the diagnosis of liver cirrhosis [181]. Cut-off val-
populations. Nevertheless, TE could be of interest to exclude con- ues suggested in the two meta-analyzes were 1.34–1.35 m/sec
fidently severe fibrosis and cirrhosis with high negative predictive for the diagnosis of significant fibrosis and 1.80–1.87 m/sec for
value (around 90%) in NAFLD patients [85]. the diagnosis of cirrhosis. Only few studies have evaluated
pSWE/ARFI in chronic hepatitis B [182,183] and reported com-
TE has also been evaluated in a variety of chronic liver dis- parable results as for chronic hepatitis C and mixed chronic liver
eases [56,144,162], as well as in primary biliary cirrhosis (PBC) disease.
and primary sclerosing cholangitis (PSC) [163,164], and ALD
[151,165] (Table 6). However, in the latter it has been suggested In a few studies pSWE/ARFI has also been investigated in
by several groups that the presence of alcoholic hepatitis may NAFLD [184–187]. Such as in viral hepatitis, pSWE/ARFI perfor-
influence LS results [74–76] and thus, TE should be ideally per- mances are better for severe fibrosis and cirrhosis than for signifi-
formed only after alcohol withdrawal in order to improve cant fibrosis with AUROCs ranging from 0.91 to 0.98 and from
diagnostic accuracy. 0.66 to 0.86, respectively. Interestingly, 80% of patients with
BMI between 30 and 40 kg/m2 and 58% of patients with BMI
Recommendations >40 kg/m2 could be successfully evaluated using pSWE/ARFI
[186]. Finally, pSWE/ARFI has also been evaluated in a variety
• TE can be considered the non-invasive standard for of chronic liver diseases (ALD, PBC, PSC, and autoimmune hepati-
the measurement of LS (A1) tis (AIH)). However, since most studies included mixed chronic
liver diseases with predominantly viral hepatitis, the value of
• TE is well validated in viral hepatitis with performance pSWE/ARFI for less common etiologies of chronic liver disease
equivalent in hepatitis B and C and in HIV-HCV needs further evaluation.
coinfection (A1)
2D-shear wave elastography
• TE is less well validated in NAFLD and in other chronic Only few studies [96,97,188,189] have evaluated 2D-SWE for the
liver diseases (A1) staging of liver fibrosis, two of which used liver biopsy as refer-
ence method [97,189]. In a pilot study in 121 patients with
• TE performs better for detection of cirrhosis than for chronic hepatitis C (METAVIR fibrosis stage 41% F0/F1, 27% F2,
detection of significant fibrosis (A1) 12% F3, and 20% F4), AUROCs of 2D-SWE for the diagnosis of sig-
nificant fibrosis and cirrhosis were 0.92 and 0.98, respectively
• TE is a reliable method for the diagnosis of cirrhosis [189]. In another study in 226 patients with chronic hepatitis B
in patients with chronic liver diseases, that generally (METAVIR fibrosis stage 17% F0, 23% F1, 25% F2, 20% F3, and
performs better at ruling out than ruling in cirrhosis 15% F4), 2D-SWE had AUROCS of 0.88 and 0.98 for the diagnosis
(with negative predictive value higher than 90%) (A1) of significant fibrosis and cirrhosis, respectively [97]. Sensitivities
and specificities were 85% and 92% for the diagnosis of significant
Performance of other techniques for staging liver fibrosis fibrosis using a cut-off of 7.1 kPa, and 97% and 93% for the diagno-
sis of cirrhosis using a cut-off of 10.1 kPa.
Point shear wave elastography using acoustic radiation force impulse
quantification Other elastography methods such as strain elastography (a
Performances of pSWE/ARFI (Siemens) for diagnosing significant quasi-static technique) are available, but data for the staging of
fibrosis and cirrhosis are summarized in Table 7. Most studies liver fibrosis are insufficient and seem to suggest that strain elas-
tography has a worse diagnostic performance as compared to
shear wave elastography [190].
10 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
hepatitis being the predominant liver disease [166–177].
TE has also been investigated in NAFLD patients but in a smal- Similar to TE, pSWE/ARFI more accurately detects cirrhosis
ler number of studies [66,68,82,85,156–159] (Table 6). Like in (AUROC values: 0.81–0.99) than significant fibrosis (AUROC
viral hepatitis, TE performances are better for cirrhosis than for values: 0.77–0.94). The largest study evaluating pSWE/ARFI for
significant fibrosis with AUROCs ranging from 0.94 to 0.99 and staging of chronic hepatitis C was a retrospective pooled
from 0.79 to 0.99, respectively. However, the performance of TE analysis of 914 international patient data [178], part of which
in NAFLD deserves several comments: Firstly, these studies have were published in smaller single centre studies previously
been conducted in heterogeneous and special populations such [166,167,170,171,174,179]. It reported sensitivity and specificity
as Asian patients or children with low BMI (<28 kg/m2); secondly, of pSWE/ARFI for the diagnosis of significant fibrosis of 0.69 and
most of them are underpowered with small sample size 0.80 and for the diagnosis of liver cirrhosis of 0.84 and 0.76,
(<100 patients) and very few patients with cirrhosis; thirdly, the respectively [178].
histological scoring systems such as those proposed by Brunt
et al. [160] or Kleiner et al. [161] and endpoints (significant fibrosis Meta-analyzes have confirmed the better diagnostic perfor-
or severe fibrosis) were heterogeneous in most studies evaluating mance of pSWE/ARFI for cirrhosis than for fibrosis [180,181]. In
fibrosis by TE in NAFLD. These differences in the study designs are a pooled meta-analysis including 518 individual patients with
likely the explanation for the observed differences among pro- chronic liver disease (83% with viral hepatitis) mean AUROCs
posed cut-offs for a given endpoint (ranging for instance from were 0.87 for the diagnosis of significant fibrosis, and 0.93 for
10.3 to 22.3 kPa for cirrhosis) (Table 6), known as the spectrum the diagnosis of liver cirrhosis [180]. In a meta-analysis of 36
bias [16,17]. Finally, all these studies have been conducted in ter- studies (21 full paper publications and 15 abstracts) comprising
tiary referral centres with a higher proportion of patients with 3951 patients mean AUROCs were 0.84 (diagnostic odds ratio
severe fibrosis than in the general population, making it difficult [DOR]: 11.54) for the diagnosis of significant fibrosis, and 0.91
to extrapolate the performance of TE in detecting cirrhosis in large (DOR: 45.35) for the diagnosis of liver cirrhosis [181]. Cut-off val-
populations. Nevertheless, TE could be of interest to exclude con- ues suggested in the two meta-analyzes were 1.34–1.35 m/sec
fidently severe fibrosis and cirrhosis with high negative predictive for the diagnosis of significant fibrosis and 1.80–1.87 m/sec for
value (around 90%) in NAFLD patients [85]. the diagnosis of cirrhosis. Only few studies have evaluated
pSWE/ARFI in chronic hepatitis B [182,183] and reported com-
TE has also been evaluated in a variety of chronic liver dis- parable results as for chronic hepatitis C and mixed chronic liver
eases [56,144,162], as well as in primary biliary cirrhosis (PBC) disease.
and primary sclerosing cholangitis (PSC) [163,164], and ALD
[151,165] (Table 6). However, in the latter it has been suggested In a few studies pSWE/ARFI has also been investigated in
by several groups that the presence of alcoholic hepatitis may NAFLD [184–187]. Such as in viral hepatitis, pSWE/ARFI perfor-
influence LS results [74–76] and thus, TE should be ideally per- mances are better for severe fibrosis and cirrhosis than for signifi-
formed only after alcohol withdrawal in order to improve cant fibrosis with AUROCs ranging from 0.91 to 0.98 and from
diagnostic accuracy. 0.66 to 0.86, respectively. Interestingly, 80% of patients with
BMI between 30 and 40 kg/m2 and 58% of patients with BMI
Recommendations >40 kg/m2 could be successfully evaluated using pSWE/ARFI
[186]. Finally, pSWE/ARFI has also been evaluated in a variety
• TE can be considered the non-invasive standard for of chronic liver diseases (ALD, PBC, PSC, and autoimmune hepati-
the measurement of LS (A1) tis (AIH)). However, since most studies included mixed chronic
liver diseases with predominantly viral hepatitis, the value of
• TE is well validated in viral hepatitis with performance pSWE/ARFI for less common etiologies of chronic liver disease
equivalent in hepatitis B and C and in HIV-HCV needs further evaluation.
coinfection (A1)
2D-shear wave elastography
• TE is less well validated in NAFLD and in other chronic Only few studies [96,97,188,189] have evaluated 2D-SWE for the
liver diseases (A1) staging of liver fibrosis, two of which used liver biopsy as refer-
ence method [97,189]. In a pilot study in 121 patients with
• TE performs better for detection of cirrhosis than for chronic hepatitis C (METAVIR fibrosis stage 41% F0/F1, 27% F2,
detection of significant fibrosis (A1) 12% F3, and 20% F4), AUROCs of 2D-SWE for the diagnosis of sig-
nificant fibrosis and cirrhosis were 0.92 and 0.98, respectively
• TE is a reliable method for the diagnosis of cirrhosis [189]. In another study in 226 patients with chronic hepatitis B
in patients with chronic liver diseases, that generally (METAVIR fibrosis stage 17% F0, 23% F1, 25% F2, 20% F3, and
performs better at ruling out than ruling in cirrhosis 15% F4), 2D-SWE had AUROCS of 0.88 and 0.98 for the diagnosis
(with negative predictive value higher than 90%) (A1) of significant fibrosis and cirrhosis, respectively [97]. Sensitivities
and specificities were 85% and 92% for the diagnosis of significant
Performance of other techniques for staging liver fibrosis fibrosis using a cut-off of 7.1 kPa, and 97% and 93% for the diagno-
sis of cirrhosis using a cut-off of 10.1 kPa.
Point shear wave elastography using acoustic radiation force impulse
quantification Other elastography methods such as strain elastography (a
Performances of pSWE/ARFI (Siemens) for diagnosing significant quasi-static technique) are available, but data for the staging of
fibrosis and cirrhosis are summarized in Table 7. Most studies liver fibrosis are insufficient and seem to suggest that strain elas-
tography has a worse diagnostic performance as compared to
shear wave elastography [190].
10 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
