Direct Comparison of the Specialised Blood Fibrosis Tests FibroMeterV2G and Enhanced Liver Fibrosis Score in Patients With Non-alcoholic Fatty Liver Disease From Tertiary Care Centres

Maeva Guillaume; Valerie Moal; Cyrielle Delabaudiere; Floraine Zuberbuhler; Marie-Angèle Robic; Adrien Lannes; Sophie Metivier; Frederic Oberti; Pierre Gourdy; Isabelle Fouchard-Hubert; Janick Selves; Sophie Michalak; Jean-Marie Peron; Paul Cales; Christophe Bureau; Jerome Boursier

Disclosures

Aliment Pharmacol Ther. 2019;50(11):1214-1222. 

In This Article

Discussion

In this work, we directly compared the diagnostic accuracy of two specialized blood fibrosis tests, the ELF and the FibroMeterV2G, both tests having shown very good accuracy for the non-invasive evaluation of liver fibrosis in NAFLD in previous works.[20,26] Our results show that both ELF and FibroMeterV2G performed significantly better than the simple fibrosis tests FIB4 and NFS, and that the accuracies of these two specialized blood fibrosis tests were not significantly different. The strengths of our work are the large sample size of our cohort and the good balance of the whole spectrum of fibrosis stages.

Each of the direct markers of liver fibrosis evaluated (alpha2-macroglobulin, hyaluronic acid, PIIINP and TIMP-1) was as accurate as the simple blood fibrosis tests NFS and FIB4 which are the result of the combination of several indirect markers of liver fibrosis. Moreover, combining several direct markers of liver fibrosis in the specialized blood tests ELF and FibroMeterV2G further improved the accuracy for the diagnosis of advanced liver fibrosis. These results highlight the importance of deciphering the pathophysiological processes of fibrogenesis and fibrolysis in the liver to identify new biomarkers highly correlated to fibrosis. Very recently, the pro-C3 which indicates the formation of type III collagen has been shown to be well correlated with fibrosis stages.[41,42] Further works should evaluate whether the addition of such new direct markers of liver fibrosis makes an even greater improvement in the diagnostic accuracy of specialized blood fibrosis tests.

Regardless of the method used (AUROC; Obuchowski index; threshold corresponding to the highest Youden index, 90% sensitivity or 90% specificity), we found no significant difference between the accuracies of FibroMeterV2G and ELF. The ELF test requires only one tube during blood sampling and the results (from individual markers and the ELF score combining these individual results) are automatically delivered by the analytical platform. On the other hand, the ELF test is an exclusivity from Siemens company which requires the use of its automated systems (ADVIA Centaur or the new Atellica Solution systems), whereas FibroMeter has shown excellent reproducibility between laboratories using different analytical platforms.[43]

Compared to a single diagnostic cut-off, using a low and a high threshold optimizes the diagnostic indices of non-invasive fibrosis tests (Table 5). However, such an approach results in a grey zone with an indeterminate diagnosis which included approximately 40% of the patients for both ELF and FibroMeterV2G in our cohort. This rate is expected to be lower in clinical practice because, compared to our study population, the prevalence of advanced fibrosis is lower when the context is the general population of NAFLD patients.[44] Nevertheless, the existence of such a grey zone highlights the need for a second-line evaluation to refine the diagnosis. In this context, elastography devices are a very interesting option with very good accuracy for the diagnosis of advanced fibrosis, as shown in a recent meta-analysis where AUROCs ranged from 0.85 to 0.96.[12] The concept of test combination to increase accuracy has been largely explored in chronic viral hepatitis C,[45–48] but it remains poorly evaluated in NAFLD.[49] The FibroMeter tests include the FibroMeterVCTE which is a combination of blood markers with the Fibroscan result (Echosens) in a single formula (Table S1 and Table 1). Recent studies have demonstrated that the combinatory FibroMeterVCTE outperforms blood fibrosis tests and Fibroscan for the non-invasive evaluation of liver fibrosis in NAFLD.[18,32,50] Used as second-line procedure after blood fibrosis tests or Fibroscan, the FibroMeterVCTE decreases the rate of patients with undetermined diagnosis by twofold.[32]

Due to the very large population to evaluate, it would appear more appropriate to start the non-invasive evaluation of liver fibrosis in NAFLD with a simple blood fibrosis test such as FIB4 or NFS, which are less expensive than specialized blood tests. However, because they are less accurate and have a larger grey zone compared to specialized blood tests, simple blood tests induce more second-line specialized evaluations of liver fibrosis.[20] Cost-effectiveness analyses are mandatory to determine whether the best approach in NAFLD is to use a simple or a specialized blood test as first-line evaluation, and to evaluate the price at which specialized blood tests could become cost-effective compared to simple blood tests.

In conclusion, the diagnostic accuracy of FibroMeterV2G and ELF test is not significantly different in a population of NAFLD patients from tertiary care centres. These two specialized blood fibrosis tests including direct biomarkers of liver fibrosis perform significantly better than simple blood fibrosis tests such as FIB4 and the NFS.

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