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LECT2, A Novel and Direct Biomarker of Liver Fibrosis in Patients With CHB.

ABSTRACT: Chronic hepatitis B (CHB) patients with severe liver fibrosis would be more likely to progress to a poorer prognosis. Treatment is considered once the liver fibrosis reaches significant liver fibrosis (≥S2). Leukocyte cell-derived chemotaxin-2 (LECT2) has been shown to contribute to liver fibrosis progression. No research has focused on the role of LECT2 in liver fibrosis in CHB patients. This study enrolled 227 CHB patients and divided them into the training group (n = 147) and validation group (n = 80), respectively. The expression of LECT2 in serum, protein and mRNA of the human liver tissues was detected to analyze the possible associations between LECT2 and liver fibrosis. A receiver operating characteristic curve (ROC) was used to estimate the efficacy of LECT2 for predicting liver fibrosis. The data showed that there was a positive relationship between LECT2 and the progression of liver fibrosis. In the training group, LECT2 was demonstrated to have better effectiveness than APRI and FIB-4. The AUC was 0.861, 0.698, and 0.734 for significant liver fibrosis, and 0.855, 0.769, and 0.752 for advanced liver fibrosis. Besides, the efficacy of LECT2 in different statuses of patients with CHB was examined and the effectiveness of LECT2 had also been confirmed in the validation group. All the results confirmed that LECT2 could act as a perfect predictor and thus offers a novel and direct biomarker to estimate liver fibrosis more accurately.

SUBMITTER: Xu H

PROVIDER: S-EPMC8492992 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: In more than 90% of chronic viral hepatitis C (HCV) patients treated with direct-acting antiviral agents (DAAs), a sustained viral response (SVR) was observed. Unfortunately, there are subgroups of subjects who display enduring liver fibrosis and are at high risk of developing hepatocellular carcinoma (HCC). Thus, liver fibrosis evaluation during the follow-up of these patients plays a pivotal role. The gold standard to evaluate hepatic fibrosis is liver biopsy, which is an invasive procedure. Imaging techniques and serum biomarkers have been proposed as safer and cheaper procedures. Objectives: In this study, we evaluated the concordance of transient elastography (TE) with ELF score ( enhanced liver fibrosis) in a cohort of patients with HCV before and after direct-acting antiviral (DAAs) treatment. ELF score has been validated in other chronic liver diseases; the evidence is not available in HCV patients treated with DAAs. Study design: We prospectively recruited all consecutive HCV patient candidates for DAAs therapy at the University of Naples "Federico II" between April 2015 and July 2016. TE and ELF scores were assessed at baseline, at SVR24, and at SVR48. Results: One-hundred-nineteen patients were treated with DAAs, and 94.1% of them reached SVR. A total of 55.5% of patients were males with a mean age of 64.7 ± 9.6 years. TE results revealed that 12 patients (10%) had F1-2 mild/moderate fibrosis, and 107 (90%) had F3-4 advanced fibrosis. At baseline, SVR24, and SVR48, the concordance between ELF test and TE was poor: 0.11 (p = 0.086), 0.15 (p = 0.124), and 0.034 (p = 0.002), respectively. However, at SVR24 and SVR48, both methods showed a significant amelioration of liver fibrosis compared to baseline (p < 0.001). In addition, both ELF index and TE were significantly associated with portal hypertension at baseline, but not with varices and ascites. Conclusions: Our findings suggested that ELF test could predict changes in liver fibrosis, independently of TE. In case of TE unavailability, ELF score could represent an appropriate tool. Notably, in the context of the COVID-19 pandemic, ELF testing should be encouraged to reduce unnecessary access to the hospital and prolonged physical contact.

Project description:BackgroundLiver biopsy is the reference standard for assessing liver fibrosis and no reliable non-invasive diagnostic approach is available to discriminate between the intermediate stages of fibrosis. Therefore suitable serological biomarkers of liver fibrosis are urgently needed. We used proteomics to identify novel fibrosis biomarkers in hepatitis C patients with different degrees of liver fibrosis.Methodology/principal findingsProteins in plasma samples from healthy control individuals and patients with hepatitis C virus (HCV) induced cirrhosis were analysed using a proteomics technique: two dimensional gel electrophoresis (2-DE). This technique separated the proteins in plasma samples of control and cirrhotic patients and by visualizing the separated proteins we were able to identify proteins which were increasing or decreasing in hepatic cirrhosis. Identified markers were validated across all Ishak fibrosis stages and compared to the markers used in FibroTest, Enhanced Liver Fibrosis (ELF) test, Hepascore and FIBROSpect by Western blotting. Forty four candidate biomarkers for hepatic fibrosis were identified of which 20 were novel biomarkers of liver fibrosis. Western blot validation of all candidate markers using plasma samples from patients across all Ishak fibrosis scores showed that the markers which changed with increasing fibrosis most consistently included lipid transfer inhibitor protein, complement C3d, corticosteroid-binding globulin, apolipoprotein J and apolipoprotein L1. These five novel fibrosis markers which are secreted in blood showed a promising consistent change with increasing fibrosis stage when compared to the markers used for the FibroTest, ELF test, Hepascore and FIBROSpect. These markers will be further validated using a large clinical cohort.Conclusions/significanceThis study identifies 20 novel fibrosis biomarker candidates. The proteins identified may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.

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LECT2, A Novel and Direct Biomarker of Liver Fibrosis in Patients With CHB.

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