Clinical diagnosis of hepatic fibrosis using a novel panel of low abundant human plasma protein biomarkers

Abstract

The inventors have proposed a novel panel of human plasma protein biomarkers for diagnosing hepatic fibrosis and cirrhosis. Presently there is no reliable non-invasive way of assessing liver fibrosis. A 2D-PAGE based proteomics study was used to identify potential fibrosis biomarkers. Plasma from patients with hepatic cirrhosis induced by infection with the hepatitis C virus (HCV) were analysed. Several proteins associated with liver scarring and potentially also related to viral infection were identified. These proteins include 14-3-3 protein zeta / delta, adiponectin, afamin, alpha-1-antitrypsin, alpha-2-HS-glycoprotein, apolipoprotein C-M, apolipoprotein E, C4b-binding protein beta chain, intact / cleaved complement C3dg, corticosteroid-binding globulin, fibrinogen gamma chain, beta haptoglobin at pH 5.46-5.49, haptoglobin-related protein, hemopexin, immunoglobulin J chain, leucine-rich alpha-2-glycoprotein, lipid transfer inhibitor protein, retinol-binding protein 4, serum paraoxonase / arylesterase 1, sex hormone-binding globulin and zinc-alpha-2-glycoprotein.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a Divisional of U.S. application Ser. No. 12 / 779,349, filed May 13, 2010, which claims priority from U.S. Provisional Application No. 61 / 178,334, filed May 14, 2009.FIELD[0002]The present application relates generally to methods for diagnosing hepatic fibrosis or cirrhosis using a panel of antibodies targeted against a novel panel of very low abundant hepatic scarring biomarkers. These novel proteins may also serve as biomarkers for hepatitis, hepatocellular carcinoma (HCC) as well as drug targets for hepatic scarring, hepatitis and HCC.BACKGROUND[0003]Hepatic Fibrosis.[0004]Hepatic fibrosis (liver fibrosis) is a wound healing response characterized by the excessive accumulation of scar tissue (i.e. extracellular matrix) in the liver. Normal structural elements of tissues are replaced with excessive amounts of non-functional scar tissue. Needle liver biopsy is the primary tool for the diagnosis and assessment of fibros...

AI Technical Summary

Benefits of technology

The present invention provides methods for detecting fibrosis and cirrhosis using biomarkers such as HF-ASSOCIATED polypeptides. These methods can be used to diagnose and prognosis fibrotic diseases such as hepatic fibrosis, renal fibrosis, cardial fibrosis, skin fibrosis, pancreatic fibrosis and others. The biomarkers can be detected using 2D-PAGE and compared to control levels or using immunoglobulin antibodies. The invention also provides a kit for detecting HF-ASSOCIATED polypeptides and a method for determining the prognosis of fibrosis by measuring the level of the polypeptides in a biological sample.

Problems solved by technology

Normal structural elements of tissues are replaced with excessive amounts of non-functional scar tissue.

Needle liver biopsy is the primary tool for the diagnosis and assessment of fibrosis yet there are a number of well-documented limitations and disadvantages to this technique including patient discomfort, pain, bleeding, and death in rare cases.

Furthermore, a biopsy can be unreliable if fibrosis is not homogenous throughout the liver.

In rare cases, HCV infection causes clinically acute disease and even liver failure.

About 20% of individuals with HCV who do develop cirrhosis will develop end-stage liver disease and have an increased risk of developing primary liver cancer.

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