The enhanced liver fibrosis test: a clinical grade, validated serum test, biomarker of overall fibrosis in systemic sclerosis

Abignano, Giuseppina; Cuomo, Giovanna; Buch, Maya H; Rosenberg, William; Valentini, Gabriele; Emery, Paul; Galdo, Francesco Del

doi:10.1136/annrheumdis-2012-202843

Cited by 40 publications

(26 citation statements)

References 28 publications

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“…These data associated with the lack of correlation with capillaroscopic microvascular abnormalities are in agreement with a recent study4 suggesting the potential role of ELF test as a fibrosis index in overt SSc.…”

supporting

confidence: 92%

Fibrosis biomarkers in isolated Raynaud's phenomenon: too little, too soon?

et al. 2013

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supporting

confidence: 92%

Fibrosis biomarkers in isolated Raynaud's phenomenon: too little, too soon?

et al. 2013

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“…Our findings suggest potential for development of composite serum biomarkers for HICS response in SSc and could inform development of a more generic composite serum biomarker for SSc [17–19]. This would complement other markers that include serum variables and tests of other available markers such as the enhanced liver fibrosis (ELF) test [20] and confirm the feasibility of this approach. Our study has the particular strength of having longitudinal sampling and simultaneous assessment of MRSS.…”

Section: Discussionmentioning

confidence: 53%

Multiplex serum protein analysis reveals potential mechanisms and markers of response to hyperimmune caprine serum in systemic sclerosis

et al. 2017

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BackgroundHyperimmune caprine serum (HICS) is a novel biological therapy with potential benefit for skin in established diffuse cutaneous systemic sclerosis. Here we report multiplex protein analysis of blood samples from a placebo-controlled phase II clinical trial and explore mechanisms of action and markers of response.MethodsPatients were treated with HICS (n = 10) or placebo (n = 10) over 26 weeks, with follow-up open-label treatment to 52 weeks in 14 patients. Serum or plasma samples at baseline, 26 and 52 weeks were analysed using multiplex or individual immunoassays for 41 proteins. Patterns of change were analysed by clustering using Netwalker 1.0, Pearson coefficient and significance analysis of microarrays (SAM) correction.ResultsCluster analysis, SAM multiplex testing and paired comparison of individual analytes identified proteins that were upregulated or downregulated during treatment with HICS. There was upregulation of the hypothalamo-pituitary-adrenal axis after HICS treatment evidenced by increases in α-MSH and ACTH in cases treated with HICS. Interestingly, significant increase in PIIINP was associated with HICS treatment and improved MRSS suggesting that this may be a marker of extracellular matrix turnover. Other relevant factors reduced in HICS-treated patients compared with controls, although not reaching statistical significance included COMP, CCL2, IL6, TIMP2, Fractalkine and TGFβ1 levels.ConclusionsOur results suggest mechanisms of action for HICS, including upregulation of α-MSH, that has been shown to be anti-fibrotic in preclinical models, and possible markers to be included in future trials targeting skin in diffuse cutaneous systemic sclerosis.Trial registrationEudract, No. 2007-003122-24. ClinTrials.gov, No. NCT00769028. Registered 7 October 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1252-x) contains supplementary material, which is available to authorized users.

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“…Liver fibrosis was assessed by measuring HA levels and the ELF score in other populations as well. ELF was associated with lung and skin fibrosis, as well as HCV co-morbidity in systemic sclerosis patients (121). HA correlated with liver fibrosis in patients with Fontan circulation who underwent cardiac catheterisation (123).…”

Section: Other Liver Disease Populationsmentioning

confidence: 96%

“…There was a significant inverse relationship between serum Zn level and HA level (mean HA 244.1 ± 223.2 in patients with serum Zn ≤65 vs. 118.8 ± 117.9 ng/mL in patients with serum Zn >65 mg/dL, p<0.0001) (118). Table 5 describes studies in individuals with diseases to other organs that are also accompanied by liver involvement (119)(120)(121)(122)(123). HA levels were found to be elevated in a sample of 164 critically ill patients compared to 61 matched blood donors.…”

Section: Other Liver Disease Populationsmentioning

confidence: 99%

“…with mild fibrosis, 57.9 ± 24.9 in patients with moderate fibrosis and 71.9 ± 38.8 ng/mL in patients with severe fibrosis 51 48 chronic HBV patients 41 Higher mean HA levels associated with higher inspiratory-to-expiratory flow rate ratio of the portal vein, which indicates liver fibrosis Table 5: ALT: alanine aminotransaminase; AST: aspartate aminotransferase; ELF: enhanced liver fibrosis score; HA: hyaluronic acid; HCV: hepatitis C virus; IgG4-RD: immunoglobulin G4-related disease; γ-GTP: γ-glutamyl transpeptidase; NPV: negative predictive value; PPV: positive predictive value Serum HA measured by latex agglutination (Wako Chemicals GmbH) (HA reference value: 20.8 ± 7.4 ng/mL) (119); Serum HA measured by ELISA (R&D Systems, Minneapolis, MN) (122) and by latex agglutination-turbidimetric immunoassay (Fujirebio Inc., Tokyo, Japan) (123) ELF was assessed by Siemens Bayer ADVIA Centaur® CP Immunoassay System (Tarrytown, NY) (121) Fibrosis was assessed in biopsy by Metavir (120) Limited cutaneous systemic sclerosis (lcSSc) or diffuse cutaneous systemic sclerosis (dcSSc) was assessed; Disease activity was expressed as per the European Scleroderma Study Group activity index (EScSG-AI) (121).…”

mentioning

confidence: 99%

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