European multicentre study validates enhanced liver fibrosis test as biomarker of fibrosis in systemic sclerosis

Abignano, Giuseppina; Blagojević, Jelena; Bissell, Lesley-Anne; Dumitru, Raluca B; Eng, Sookhoe; Allanore, Yannick; Avouac, Jérôme; Bosello, Silvia Laura; Denton, Christopher P.; Distler, Oliver; Ferraccioli, Gianfranco; Jordan, Suzana; Matucci‐Cerinic, Marco; Ong, Voon H; Messenger, Michael; Hutchinson, Michelle; Buch, Maya H; Emery, Paul; Galdo, Francesco Del

doi:10.1093/rheumatology/key271

Cited by 17 publications

(15 citation statements)

References 13 publications

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“…We show that serum markers that have been validated as cross sectional markers of skin fibrosis [8] have remarkably different trajectories of change between ANA subgroups, specifically the two dominant ANA reactivities, ATA and ARA.. Given our findings, despite the well-established correlation of the ELF test with MRSS and FVC [12], interpretation on a group level in early dcSSc with a mixed ANA profile, and especially over time, may be misleading. Unlike previous work on circulating markers of collagen turnover [13,14], we did not identify clear differences between markers of collagen degradation (C1M, C4M, C6M) between disease subgroups [15].…”

Section: Discussionmentioning

confidence: 66%

Molecular basis for clinical diversity between autoantibody subsets in diffuse cutaneous systemic sclerosis

Clark¹,

Campochiaro²,

Csomor

et al. 2021

Ann Rheum Dis

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ObjectivesClinical heterogeneity is a cardinal feature of systemic sclerosis (SSc). Hallmark SSc autoantibodies are central to diagnosis and associate with distinct patterns of skin-based and organ-based complications. Understanding molecular differences between patients will benefit clinical practice and research and give insight into pathogenesis of the disease. We aimed to improve understanding of the molecular differences between key diffuse cutaneous SSc subgroups as defined by their SSc-specific autoantibodiesMethodsWe have used high-dimensional transcriptional and proteomic analysis of blood and the skin in a well-characterised cohort of SSc (n=52) and healthy controls (n=16) to understand the molecular basis of clinical diversity in SSc and explore differences between the hallmark antinuclear autoantibody (ANA) reactivities.ResultsOur data define a molecular spectrum of SSc based on skin gene expression and serum protein analysis, reflecting recognised clinical subgroups. Moreover, we show that antitopoisomerase-1 antibodies and anti-RNA polymerase III antibodies specificities associate with remarkably different longitudinal change in serum protein markers of fibrosis and divergent gene expression profiles. Overlapping and distinct disease processes are defined using individual patient pathway analysis.ConclusionsOur findings provide insight into clinical diversity and imply pathogenetic differences between ANA-based subgroups. This supports stratification of SSc cases by ANA antibody subtype in clinical trials and may explain different outcomes across ANA subgroups in trials targeting specific pathogenic mechanisms.

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Section: Discussionmentioning

confidence: 66%

Molecular basis for clinical diversity between autoantibody subsets in diffuse cutaneous systemic sclerosis

Clark¹,

Campochiaro²,

Csomor

et al. 2021

Ann Rheum Dis

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“…The ELF panel has been used as a surrogate marker of liver fibrosis allowing a minimally invasive blood sampling method to be used instead of obtaining a liver biopsy (Tanwar et al, 2017). ELF score and PIIINP levels were also shown to be correlated with skin and lung fibrosis in patients with systemic sclerosis (Abignano et al, 2019).…”

Section: Other Diseases-mentioning

confidence: 90%

Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases

Kuivaniemi

Tromp

2019

Gene

227

184

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Collagen alpha-1(III) chain, also known as the alpha 1 chain of type III collagen, is a protein that in humans is encoded by the COL3A1 gene. Three alpha 1 chains are required to form the type III collagen molecule which has a long triple-helical domain. Type III collagen, an extracellular matrix protein, is synthesized by cells as a pre-procollagen. It is found as a major structural component in hollow organs such as large blood vessels, uterus and bowel. Other functions of type III collagen include interaction with platelets in the blood clotting cascade and it is also an important signalling molecule in would healing. Mutations in the COL3A1 gene cause the vascular type of Ehlers-Danlos syndrome (vEDS; OMIM 130050). It is the most serious form of EDS, since patients often die suddenly due to a rupture of large arteries. Inactivation of the murine Col3a1 gene leads to a shorter life span in homozygous mutant mice. The mice die prematurely *

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“…While some studies suggest that TE can overestimate fibrosis in the presence of steatosis, 12–14 ELF performs well in the presence of steatohepatitis 15,16 . The impact of extrahepatic fibrosis has yet to be fully quantified 17 …”

Section: Introductionmentioning

confidence: 99%

Systematic review: Accuracy of the enhanced liver fibrosis test for diagnosing advanced liver fibrosis and cirrhosis

Sharma

Cococcia

Ellis

et al. 2021

J of Gastro and Hepatol

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Background and Aims: The rising incidence of chronic liver disease (CLD) has increased the need for early recognition. This systematic review assesses the diagnostic accuracy of the enhanced liver fibrosis (ELF) test in cases of advanced fibrosis and cirrhosis due to multiple etiologies in at-risk populations. Methods: Studies evaluating the ELF accuracy in identifying advanced fibrosis or cirrhosis, defined as METAVIR stage F ≥ 3 and F = 4 or equivalent, in patients with non-alcoholic fatty liver disease (NAFLD), alcohol liver disease (ALD), or viral hepatitis were included. Liver biopsy was used as the reference standard. Medline and Embase databases were searched. The QUADAS-2 tool was used as a framework to assess risk of bias and applicability. The area under the receiver operator curve (AUROC) was extracted as a summary measure of diagnostic accuracy. Results: Thirty-six studies were included: 11 hepatitis C, 4 hepatitis B, 9 NAFLD, 2 ALD, and 10 mixed. The ELF test showed good diagnostic performance in detecting advanced fibrosis in patients with viral hepatitis (AUROC 0.69 to 0.98) and excellent performance in NAFLD (AUROC 0.78 to 0.97) and ALD (AUROC from 0.92 to 0.94). There is also evidence of good diagnostic performance for detecting cirrhosis in patients with viral hepatitis (AUROC 0.63 to 0.99), good performance in NAFLD (AUROC 0.85 to 0.92), and excellent performance in patients with ALD (AUROC 0.93 to 0.94). Conclusion:This systematic review supports the use of the ELF test across a range of CLD as a possible alternative to liver biopsy in selected cases. BackgroundTarget condition. Chronic liver disease (CLD) is a leading cause of death globally, with liver-related deaths increasing in England compared with other major killers. 1 The commonest causes of CLD are alcohol, obesity, and viral hepatitis. CLD can lead to liver fibrosis characterized by increased synthesis and altered deposition of extracellular matrix. Fibrosis is usually silent until cirrhosis leads to complications of portal hypertension including variceal bleeding, ascites, and hepatocellular carcinoma. Many patients with CLD present when it is too late to prevent these complications, and they can only be ameliorated. There is a need for tests to detect the presence of fibrosis before it causes irreversible damage, to stratify which patients might benefit from specialist care, and to target surveillance for complications. 2 Liver biopsy is the reference test for assessing liver fibrosis, but its accuracy is limited by sampling error and inter-observer and intra-observer variation. 3,4 Additionally, it is invasive and can

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European multicentre study validates enhanced liver fibrosis test as biomarker of fibrosis in systemic sclerosis

Abstract: Between the first and this validation studies, the value of the ELF score as independent marker of skin and lung involvement in SSc is confirmed in 457 patients. A longitudinal study is on-going to identify an SSc specific algorithm with predictive value for skin and lung progression.

Cited by 17 publications

References 13 publications

Molecular basis for clinical diversity between autoantibody subsets in diffuse cutaneous systemic sclerosis

Molecular basis for clinical diversity between autoantibody subsets in diffuse cutaneous systemic sclerosis

Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases

Systematic review: Accuracy of the enhanced liver fibrosis test for diagnosing advanced liver fibrosis and cirrhosis

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