A New Algorithm Shows Superior Ability to Discriminate Liver Fibrosis Stages in Chronic Hepatitis C

Stefania Varchetta; Dalila Mele; Roberta D'Ambrosio; Riccardo Perbellini; Andrea Lombardi; Angela Rojas; Stefania Paolucci; Fausto Baldanti; Barbara Oliviero; Stefania Mantovani; Carmine Tinelli; Annalisa De Silvestri; Manuel Romero Gomez; Pietro Lampertico; Mario U. Mondelli


J Viral Hepat. 2021;28(10):1443-1451. 

In This Article

Abstract and Introduction


Previous evidence suggests that sialic acid-binding Ig-like lectin 7 (Siglec-7) protein is significantly increased in patients with chronic hepatitis C virus (HCV) infection and directly correlates with clinical parameters of liver inflammation and fibrosis. The aim of this study was to determine the diagnostic value of Siglec-7 as a non-invasive tool to assess liver fibrosis in patients with chronic hepatitis C in a cross-sectional study. Serum levels of Siglec-7 were retrospectively tested in 1007 consecutive patients with chronic HCV infection recruited at three different European sites and data examined by the 'imperfect gold-standard' statistical analysis. Liver stiffness obtained by transient elastography (TE) was considered the standard reference. Liver fibrosis was staged according to published cut-offs of liver stiffness measurement by TE. Accuracy of detection of liver fibrosis stage was not increased by Siglec-7 alone. However, we developed a new index (SiGAP) including Siglec-7, γ-glutamyl transferase, age and platelet count which showed increased sensitivity and specificity in predicting fibrosis compared with APRI or FIB4 indices. The AUROC of SiGAP for the diagnosis of significant (≥F2) and advanced liver fibrosis (≥F3) showed significantly higher values than those of APRI and FIB-4. Siglec-7 may be useful as a complementary tool to assess liver fibrosis stage in patients with chronic hepatitis C when included in a specifically designed algorithm, which showed high level of accuracy in the detection of F2 and F3 fibrosis stage.


Liver fibrosis is the consequence of a chronic damage inflicted to the liver, leading to the formation of collagen scars in liver tissue.[1] It may be caused by different conditions, metabolic (dysfunction)-associated liver disease (MAFLD), chronic hepatitis B (CHB) and chronic hepatitis C (CHC), or alcoholic liver disease (ALD), to cite but a few of the commonest aetiologies. Liver fibrosis progression may lead to cirrhosis, a condition of substantial disruption of the liver architecture predisposing to the possible occurrence of hepatocellular carcinoma.[2] It is therefore important to accurately determine its severity, possibly by non-invasive procedures. Intriguingly, it has been shown that fibrosis may significantly decrease or even reverse[3] following the removal of the cause of liver damage, supporting the importance of assessing the severity of liver injury to determine the need of an appropriate therapeutic management.

Sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is a transmembrane protein expressed on human natural killer (NK) cells, monocytes and a small subset of CD8+ T cells, that transmits inhibitory signals upon interaction with its natural ligand, α2,8-disialyl residues.[4–6] Different variants of Siglec-7 can be produced, including a soluble isoform that can be detected in serum and has been correlated with clinical data of fibrosis and inflammation during CHB and CHC[7] and was associated with increased in-hospital mortality among patients with cirrhosis and acute kidney injury.[8] Furthermore, soluble Siglec-7 has been identified as an independent marker of advanced fibrosis in MAFLD patients.[9] To better understand the significance of serum Siglec-7 in hepatitis C, we determined its possible role as a biomarker of fibrosis in a retrospective cohort of patients with CHC recruited at three different clinical centres in Europe.