Liver Fibrosis: A Compilation on the Biomarkers Status and Their Significance During Disease Progression

Abstract

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.

Effect of Non-alcoholic Fatty Liver Disease on the Risk of Synchronous Liver Metastasis: Analysis of 451 Consecutive Patients of Newly Diagnosed Colorectal Cancer

“…As reported previously, those patients with NFS higher than 0.676, FIB-4 higher than 1.30, APRI higher than 0.50 and the BRAD score of 2-4 were diagnosed as having an advanced fibrotic liver (29)(30)(31)(32)(33), patients in NAFLD group were grouped according to high-level (>0.676) or low-level (≤0.676) NFS, high-level (>1.30) or low-level (≤1.30) FIB-4, high-level (>0.50), or low-level (≤0.50) APRI and high-score (2-4 score) or low-score (0-1 score) BRAD. NFS, FIB-4, APRI, and BARD score were compared between the NAFLD patients with or without synCRLM.…”

Correlative Study of Hyaluronic Acid and YKL-40 with Conventional Markers for Cirrhosis of Liver

“…Elevated levels of HA in cirrhotic liver subjects is due to imbalance between synthesis from fibrogenesis and decrease in fibrolysis during the disease progression, dysfunction of sinusoidal endothelial cells leads to reduction in degradation of HA resulting in elevated levels in circulation [8,22]. Damaged hepatocytes release Reactive Oxygen Species (ROS) and fibrogenic mediators which in turn stimulate inflammatory cells leads to cell damage [3]. Decreased hepatic ATP and cell damage result in increased uric acid production which lead to histological liver injury [23].…”

“…Existing biomarkers for cirrhosis in clinical practice have narrow applicability; unable to predict etiology (specificity) and distinguish intermediate stages (sensitivity). Ideal biomarker should be organ specific, sensitive to indicate active damage, easily accessible in peripheral tissue, cost effective; should give insights for tailor made therapy for effective clinical management of the disease [3]. Hence, the present study aimed to correlate serum levels of uric acid, HA and YKL-40 with conventional markers of liver cirrhosis.…”

“…In cirrhotic liver, the Extra Cellular Matrix (ECM) produced by myofibroblasts which are trans-differentiated from activated Hepatic Stellate Cells (HSCs) differs qualitatively and quantitatively compared to normal liver. An increase in fibril and non fibril forming collagens along with glycoproteins, proteoglycans and glycosaminoglycans reflects ECM turnover and serve as direct biomarkers for severity of cirrhosis [3].Inflammatory factors [Tumor Necrosis Factor α (TNF-α) and interleukins] induced oxidative and apoptotic stress are important features for liver fibrosis/cirrhosis progression which results in uric acid production, an end product of purine metabolism [4]. Hyperuricemia, increased degradation of nuclear material cause endothelial dysfunction, insulin resistance, oxidative stress and systemic inflammation (metabolic syndrome) which are risk factors for hepatic damage [5].…”

“…Indirect biomarkers which are reflection of liver dysfunction have narrow applicability in clinical practice due to lack of sensitivity and specificity. Direct biomarkers which reflect ECM turnover needs validation in large population studies in diverse geographical settings [3]. Serum levels of HA and YKL-40 which are crucial components of ECM in disease progression may reflect severity of the disease [12].…”