Page 17 - NON-INVASIVE TESTS FOR EVALUATION OF LIVER DISEASE SEVERITY AND PROGNOSIS
P. 17
Clinical Practice Guidelines Use of non-invasive methods for monitoring treatment response in
viral hepatitis
screening, that community based physicians, infectious disease
physicians and internists may treat HCV [250]. In this situation, HCV including HIV-HCV
the role of non-invasive tests is also very important for A major advantage of non-invasive tests, compared with liver
determination of appropriate referral of patients with more biopsy, is that they can be easily repeated over time in patients
advanced liver disease to specialists for appropriate disease receiving antiviral therapy and that they could be used to moni-
monitoring [81]. tor response to treatment and to evaluate fibrosis regression.
Several studies reported a significant decrease in LS and
Recommendations biomarkers values, compared with baseline values, in patients
with HCV who achieved SVR [254–263], consistent with signifi-
• Non-invasive tests, using either TE or serum cant histologic improvement documented in studies of paired
biomarkers, are adequate for diagnosis of severe liver biopsies from HCV patients who achieved SVR [264,265].
fibrosis/cirrhosis in HCV and HIV-HCV coinfected However, the changing levels of ALT and inflammation of suc-
patients and can be used to prioritize patients for HCV cessfully treated HCV patients can confound results of TE or bio-
therapy based on disease stage (A1) markers. Indeed, the major component of the significant
decrease observed in LS and biomarkers values is not just rever-
• For the diagnosis of significant fibrosis a combination sal of fibrosis but also reduction in liver injury, edema and
of tests with concordance may provide the highest inflammation.
diagnostic accuracy (A2)
There are two important clinical questions about the use of
• Non-invasive tests should be utilized prior to therapy by non-invasive tests after antiviral treatment. First, what is the evi-
treating non-specialists to make sure that patients with dence of fibrosis and particularly cirrhosis reversal by non-inva-
severe fibrosis/cirrhosis are referred for appropriate sive tests? The reversal of cirrhosis has important consequences
disease specific specialist evaluation (A1) in that it may alter long-term prognosis particularly for HCC
occurrence in HCV patients and change the approach to screening
HBV and surveillance for HCC after SVR. This leads into the second
Liver cirrhosis is the most important risk factor for liver-related question, what are the cut-off thresholds post SVR for determina-
complications and HCC in chronic hepatitis B. According to all tion of decreased risk of liver-related outcomes?
regional guidelines, patients with liver cirrhosis and significant
viraemia (HBV DNA >2000 IU/ml) should receive antiviral treat- In HCV, there is only one study that has examined reversal of
ment regardless of the ALT levels [251–253]. Hence, non-invasive cirrhosis in 33 patients with cirrhosis with pre- and post-treat-
assessment of liver fibrosis can be considered in all patients in ment liver biopsies and TE after SVR [266]. There was reversal
whom liver cirrhosis is suspected. Among hepatitis B patients of cirrhosis by biopsy in 19 patients with 11 of the 19 being
who have elevated ALT but not yet reached two times ULN, liver METAVIR F3 and the remainder F1 or F2. Using a cut-off of
fibrosis assessment can assist the decision of antiviral therapy. 12 kPa, TE had a sensitivity of 61% and a specificity of 95%. The
Patients who have significant liver fibrosis and HBV DNA low sensitivity makes TE a poor tool to be utilized clinically as
>2000 IU/ml should be considered for antiviral therapy even if evidence of cirrhosis regression. Non-invasive tests, including
their ALT levels are below two times ULN [251,252]. Among TE and serum biomarkers, have been shown to predict liver-re-
patients who have persistently elevated ALT >2 times ULN and lated outcomes in HCV patients [267,268]. In both these studies
HBV DNA >2000 IU/ml, all regional guidelines recommend com- clinical cut-offs of LS between 9.5 and 10.5 kPa were able to strat-
mencement of antiviral therapy and liver fibrosis assessment ify patients at increased risk of clinical liver-related outcome. The
may not be necessary. best timing for repeated assessment of LS after therapy has not
been established yet.
Recommendations
Recommendations
• Non-invasive assessment of liver fibrosis, using either • Routine use of non-invasive tests during treatment
serum biomarkers or TE, should be considered for or after SVR in non-cirrhotic patients does not add to
patients with significant viraemia (HBV DNA >2000 IU/ clinical disease management (A1)
ml) when liver cirrhosis is suspected (A1)
• Routine use of non-invasive tests after SVR in patients
• Among patients who have HBV DNA >2000 IU/ml, with HCV cirrhosis has a high false negative rate and
antiviral therapy should be considered for patients who cannot be used to determine which patients no longer
have advanced fibrosis or cirrhosis as determined by need HCC screening or for the diagnosis of cirrhosis
non-invasive assessment of liver fibrosis, either by reversal (A2)
serum biomarkers or TE, regardless of the ALT levels
(A1) • Routine use of non-invasive tests after SVR has not
yet established thresholds that predict low risk of liver-
related events (A1)
16 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
viral hepatitis
screening, that community based physicians, infectious disease
physicians and internists may treat HCV [250]. In this situation, HCV including HIV-HCV
the role of non-invasive tests is also very important for A major advantage of non-invasive tests, compared with liver
determination of appropriate referral of patients with more biopsy, is that they can be easily repeated over time in patients
advanced liver disease to specialists for appropriate disease receiving antiviral therapy and that they could be used to moni-
monitoring [81]. tor response to treatment and to evaluate fibrosis regression.
Several studies reported a significant decrease in LS and
Recommendations biomarkers values, compared with baseline values, in patients
with HCV who achieved SVR [254–263], consistent with signifi-
• Non-invasive tests, using either TE or serum cant histologic improvement documented in studies of paired
biomarkers, are adequate for diagnosis of severe liver biopsies from HCV patients who achieved SVR [264,265].
fibrosis/cirrhosis in HCV and HIV-HCV coinfected However, the changing levels of ALT and inflammation of suc-
patients and can be used to prioritize patients for HCV cessfully treated HCV patients can confound results of TE or bio-
therapy based on disease stage (A1) markers. Indeed, the major component of the significant
decrease observed in LS and biomarkers values is not just rever-
• For the diagnosis of significant fibrosis a combination sal of fibrosis but also reduction in liver injury, edema and
of tests with concordance may provide the highest inflammation.
diagnostic accuracy (A2)
There are two important clinical questions about the use of
• Non-invasive tests should be utilized prior to therapy by non-invasive tests after antiviral treatment. First, what is the evi-
treating non-specialists to make sure that patients with dence of fibrosis and particularly cirrhosis reversal by non-inva-
severe fibrosis/cirrhosis are referred for appropriate sive tests? The reversal of cirrhosis has important consequences
disease specific specialist evaluation (A1) in that it may alter long-term prognosis particularly for HCC
occurrence in HCV patients and change the approach to screening
HBV and surveillance for HCC after SVR. This leads into the second
Liver cirrhosis is the most important risk factor for liver-related question, what are the cut-off thresholds post SVR for determina-
complications and HCC in chronic hepatitis B. According to all tion of decreased risk of liver-related outcomes?
regional guidelines, patients with liver cirrhosis and significant
viraemia (HBV DNA >2000 IU/ml) should receive antiviral treat- In HCV, there is only one study that has examined reversal of
ment regardless of the ALT levels [251–253]. Hence, non-invasive cirrhosis in 33 patients with cirrhosis with pre- and post-treat-
assessment of liver fibrosis can be considered in all patients in ment liver biopsies and TE after SVR [266]. There was reversal
whom liver cirrhosis is suspected. Among hepatitis B patients of cirrhosis by biopsy in 19 patients with 11 of the 19 being
who have elevated ALT but not yet reached two times ULN, liver METAVIR F3 and the remainder F1 or F2. Using a cut-off of
fibrosis assessment can assist the decision of antiviral therapy. 12 kPa, TE had a sensitivity of 61% and a specificity of 95%. The
Patients who have significant liver fibrosis and HBV DNA low sensitivity makes TE a poor tool to be utilized clinically as
>2000 IU/ml should be considered for antiviral therapy even if evidence of cirrhosis regression. Non-invasive tests, including
their ALT levels are below two times ULN [251,252]. Among TE and serum biomarkers, have been shown to predict liver-re-
patients who have persistently elevated ALT >2 times ULN and lated outcomes in HCV patients [267,268]. In both these studies
HBV DNA >2000 IU/ml, all regional guidelines recommend com- clinical cut-offs of LS between 9.5 and 10.5 kPa were able to strat-
mencement of antiviral therapy and liver fibrosis assessment ify patients at increased risk of clinical liver-related outcome. The
may not be necessary. best timing for repeated assessment of LS after therapy has not
been established yet.
Recommendations
Recommendations
• Non-invasive assessment of liver fibrosis, using either • Routine use of non-invasive tests during treatment
serum biomarkers or TE, should be considered for or after SVR in non-cirrhotic patients does not add to
patients with significant viraemia (HBV DNA >2000 IU/ clinical disease management (A1)
ml) when liver cirrhosis is suspected (A1)
• Routine use of non-invasive tests after SVR in patients
• Among patients who have HBV DNA >2000 IU/ml, with HCV cirrhosis has a high false negative rate and
antiviral therapy should be considered for patients who cannot be used to determine which patients no longer
have advanced fibrosis or cirrhosis as determined by need HCC screening or for the diagnosis of cirrhosis
non-invasive assessment of liver fibrosis, either by reversal (A2)
serum biomarkers or TE, regardless of the ALT levels
(A1) • Routine use of non-invasive tests after SVR has not
yet established thresholds that predict low risk of liver-
related events (A1)
16 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
