Fibrosis markers in hepatitis C (original) (raw)
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Direct Markers of Liver Fibrosis
2019
AbstractLiver fibrosis is a chronic condition that originates as a result of prolonged hepatic injury. Liver fibrosis is caused mainly by Schistosomiasis, chronic hepatitis C and B viral infections, non-alcoholic fatty liver disease, alcoholic liver disease, cholestatic and autoimmune liver diseases. Hepatic stellate cells are the master cells in the fibrosis process regardless of the cause. HSCs activation involves two separate stages: the initiation stage and the perpetuation stage. The activated HSCs up-regulate gene expression of extracellular matrix elements, matrix-degrading enzymes, and their inhibitors. The components of fibrotic ECM or inflammatory mediators implicated in either the process of fibrosis or degradation of scar tissue could be used as direct markers of fibrosis. Direct indices of fibrosis are classified into direct markers associated with matrix deposition such as HA and laminin, direct markers associated with matrix degradation such as MMPs and TIMPs, and Cyt...
Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients
Clinical Chemistry, 2007
Background: Liver biopsy is currently the gold standard for assessing liver fibrosis, and no reliable noninvasive diagnostic approach is available. Therefore a suitable serologic biomarker of liver fibrosis is urgently needed. Methods: We used a proteomics method based on 2-dimensional gel electrophoresis to identify potential fibrosis biomarkers. Serum samples from patients with varying degrees of hepatic scarring induced by infection with the hepatitis C virus (HCV) were analyzed and compared with serum from healthy controls. Results: We observed the most prominent differences when we compared serum samples from cirrhotic patients with healthy control serum. Inter-␣-trypsin inhibitor heavy chain H4 (ITIH4) fragments, ␣1 antichymotrypsin, apolipoprotein L1 (Apo L1), prealbumin, albumin, paraoxonase/arylesterase 1, and zinc-␣2-glycoprotein were decreased in cirrhotic serum, whereas CD5 antigen-like protein (CD5L) and 2 glycoprotein I (2GPI) were increased. In general, ␣2 macroglobulin (a2M) and immunoglobulin components increased with hepatic fibrosis, whereas haptoglobin and complement components (C3, C4, and factor H-related protein 1) decreased. Novel proteins associated with HCV-induced fibrosis included ITIH4 fragments, complement factor H-related protein 1, CD5L, Apo L1, 2GPI, and thioester-cleaved products of a2M. Conclusions: Assessment of hepatic scarring may be performed with a combination of these novel fibrosis biomarkers, thus eliminating the need for liver biopsy. Further evaluation of these candidate markers needs to be performed in larger patient populations. Diagnosis of fibrosis during early stages will allow early treatment, thereby preventing fibrosis progression.
Future Science OA, 2018
Liver fibrosis occurs in response to different etiologies of chronic liver injury. Diagnosing degree of liver fibrosis is a crucial step in evaluation of severity of the disease. An invasive liver biopsy is the gold standard method associated with pain and complications. Biomarkers to detect liver fibrosis include direct markers of extracellular matrix turnover and indirect markers as a reflection of liver dysfunction. Although a single marker may not be useful for successful management, a mathematical equation combining tests might be effective. The main purpose of this review is to understand the diagnostic accuracy of biomarkers and scoring systems for liver fibrosis. Advances in-omics approach have generated clinically significant biomarker candidates for liver fibrosis that need further evaluation.
Annals of hepatology
Background and rationale for the study. The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decision. This study was concerned with determining the levels of collagen III and its degrading enzyme matrix metalloproteinase-1 (MMP-1) as direct and complementary markers for liver fibrosis staging. Results. A total of 269 chronic hepatitis C patients constituted this study. Western blotting was used for identifying collagen III and MMP-1 in serum samples. As a result, collagen III and MMP-1 were identified, respectively, at 70 and 245 kDa using their respective mono-specific antibodies. These two markers were quantified in sera of patients using ELISA. Next, Fibro-check was constructed combining collagen III and MMP-1 together with other indirect markers which reflect alteration in hepatic functions that proved useful to stage liver fibrosis. Fibro-check produced area under the receiver-operating characteristic curve (AUC) 0.91 and...
New Concepts on Pathogenesis and Diagnosis of Liver Fibrosis; A Review Article
Middle East Journal of Digestive Diseases, 2016
Liver fibrosis is a potentially reversible response to hepatic insults, triggered by different chronic diseases most importantly viral hepatitis, alcoholic, and nonalcoholic fatty liver disease. In the course of the chronic liver disease, hepatic fibrogenesis may develop, which is attributed to various types of cells, molecules, and pathways. Activated hepatic stellate cell (HSC), the primary source of extracellular matrix (ECM), is fundamental in pathophysiology of fibrogenesis, and thus is the most attractable target for reversing liver fibrosis. Although, liver biopsy has long been considered as the gold standard for diagnosis and staging of hepatic fibrosis, assessing progression and regression by biopsy is hampered by its limitations. We provide recent views on noninvasive approaches including serum biomarkers and radiologic techniques.
PLoS ONE, 2012
Background: Liver 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 Findings: Proteins 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/Significance: This study identifies 20 novel fibrosis biomarker candidates. The proteins identified may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.
Objective: To compare various biochemical markers i.e. APRI (AST to platelet ratio index), aspartate aminotransferase (AST) alanine aminotransferase (ALT) ratio, FIB-4 (AST, platelet, AST and age) with biopsy for assessing the severity of hepatic fibrosis in patients with hepatitis C. Study Design: Descriptive study. Place and Duration Methodology: Consecutive hepatitis C virus RNA positive and previously untreated patients were studied. Liver biopsy with histological evaluation and AST/ALT ratio, AST to platelet ratio index and FIB-4 were assessed in all patients. Receiver operative curves were developed. Results: There were 158 patients (109 males, 49 females). On histological grounds non-advanced fibrosis (F0-1) was present in 74 (46.5%) of cases, whereas 84 (53.5%) patients had advanced (F2-4) fibrosis. The area under the receiver operating characteristic curves of APRI < 0.05-1 and FIB-4 < 1.45 were 0.7 and 0.74 respectively, which means that APRI < 1 and FIB-4 < 1.45 will exclude advanced fibrosis in 70% and 74% of patients respectively. An APRI of > 1 and FIB-4 will predict advanced fibrosis in 87% and 98% of patients respectively. AST/ALT ratio was inferior to both of these biomarkers. Conclusion: Both APRI and FIB-4 not only exclude minimal fibrosis but can predict advanced fibrosis in the majority of the patients. The simultaneous use of several indirect markers of liver fibrosis does not improve their diagnostic accuracy.