Tuesday, April 4, 2017

Noninvasive tests for fibrosis - Editorial: combining elastography with blood test for fibrosis assessment in chronic hepatitis C

Invited Editorial

Editorial: combining elastography with blood test for fibrosis assessment in chronic hepatitis C Authors H. D. Trivedi, M. Lai

First published: 3 April 2017
DOI: 10.1111/apt.14011

Editorial: combining elastography with blood test for brosis assessment in chronic hepatitis C 
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The imprecision and invasive nature of the liver biopsy has led to the development of several validated non-invasive fibrosis markers, which have decreased the need for liver biopsy in chronic hepatitis C patients. In the realm of highly effective oral therapies, management is affected by the presence or absence of severe fibrosis, which would warrant surveillance screening for hepatocellular carcinoma and oesophageal varices. Vibration controlled transient elastography (VCTE) is a validated non-invasive modality that is widely used with an AUROC of 0.90 for detecting advanced fibrosis.[1] The limitation of VCTE is its potential overestimation of fibrosis, particularly in those with obesity or increased necroinflammatory activity.[2, 3] In contrast, serologic markers have historically led to underestimation of fibrosis levels.[4, 5] Combination of VCTE with other markers have shown favorable results[1] and have been proposed by national guidelines.[6, 7]

Calés et al. evaluated the performance of a serologic test (FibroMeterV2G) with VCTE (Fibroscan) as two separate constitutive tests, as well as a single combined test (FibroMeterVCTE2G), for the detection of severe fibrosis in hepatitis C patients.[8] They found increased accuracy with the combination test, compared to individual tests alone, especially when there was concordance between the tests, validating the recommendation of using combined tests. The authors conclude that if the constitutive tests are concordant, then the diagnosis can be accepted, and if discordant, FibroMeterVCTE2G should be pursued. However, in cases (3.2%) of strict discordance, the FibroMeterVCTE2G is unreliable for detecting severe fibrosis (accuracy of 44%) and requires alternative measures for fibrosis (i.e. liver biopsy). The authors projected a reduction in the liver biopsy rates from 28% to 1% with the use of this diagnostic algorithm.

This study validates EASL-ALEH and AASLD-IDSA recommendations to combine biomarkers with VCTE and shows the combined test to have improved accuracy, especially when there is concordance, eliminating the need for an invasive liver biopsy in the majority of patients. However, the claim that the liver biopsy rate is reduced from 28% to 1% should be taken with some caution as the authors did not provide the invalid and failure rate of VCTE, one of major components in their combination test. Although VCTE has revolutionised the non-invasive measurement of fibrosis, unreliable results and failure to obtain results have been reported in 3% and 16% of cases, respectively, mostly due to obesity and operator experience.[3] It would be important to see how the combined test performs in the United States population, which has a higher mean body mass index than this study cohort from France. While the accuracy of the FibroMeterVCTE2G is excellent, it still leaves 8% of patients misclassified, making it important that the clinician still thoroughly evaluates the patient's clinical, radiologic and laboratory data. The role of this combination test in monitoring the progression or regression of fibrosis, as well as its applicability to other chronic liver disease is an important avenue for research.

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