Methods of diagnosing liver fibrosis

Abstract

The present invention provides a method of diagnosing the presence or severity of liver fibrosis in an individual by detecting α2-macroglobulin (α2-MG) in sample from the individual; detecting hyaluronic acid (HA) in a sample from the individual; detecting tissue inhibitor of a metalloproteinases-1 (TIMP-1) in a sample from the individual; and diagnosing the presence or severity of liver fibrosis in the individual based on the presence or level of α-MG, HA and TIMP-1.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] The present invention relates generally to the fields of hepatology and fibrosis and, more specifically, to a panel of serological markers which together are diagnostic of liver fibrosis. [0003] 2. Background Information [0004] Progressive fibrosis of the liver, kidney, lungs and other organs frequently results in organ failure that leads to organ transplantation or death, affecting millions in the United States and worldwide. Hepatic fibrosis, for example, is the leading non-malignant gastrointestinal cause of death in the United States, and the progression of fibrosis is the single most important determinant of morbidity and mortality in patients with chronic liver disease. Furthermore, the process of fibrosis is common to liver diseases of many etiologies, including chronic viral hepatitis B and C, autoimmune liver disease such as autoimmune hepatitis, alcoholic liver disease, fatty liver disease; primary biliary...

AI Technical Summary

Benefits of technology

"The present invention provides a method for diagnosing the presence or severity of liver fibrosis in an individual by detecting α2-MG, HA, and TIMP-1 proteins in a sample from the individual. This method can be used to differentiate no or mild liver fibrosis from moderate to severe liver fibrosis. The detection of these proteins can be done using specific binding agents or enzyme-linked assays. The method can be practiced using a single sample or multiple samples from the individual. The invention also provides a method for diagnosing the presence or severity of liver fibrosis by detecting α2-MG, HA, TIMP-1, and YKL-40 in a sample from the individual."

Problems solved by technology

Progressive fibrosis of the liver, kidney, lungs and other organs frequently results in organ failure that leads to organ transplantation or death, affecting millions in the United States and worldwide.

Untreated, fibrosis of the liver leads to cirrhosis and eventually end-stage liver disease or cancer.

Diagnosis of the presence or severity of fibrotic liver disease is difficult, with liver biopsy currently the most reliable method available.

Unfortunately, liver biopsy has several limitations: pain in about 30% of patients; the risk of severe complications such as hemorrhage or infection; a death rate of 3 in 10,000; and the cost of hospitalization (Nord, Gastrointest. Endosc. 28:102-104 (1982); Cadranel et al., Hepatology 32:47-481 (2000); and Poynard et al., Can. J. Gastroenterol. 14:543-548 (2000)).

Furthermore, slowly progressive diseases such as hepatitis C require repeated biopsies for continual assessment of disease progression, thus compounding the risks and costs of the procedure.

Finally, biopsy can fail to detect disease because of the heterogeneous distribution of pathological changes in the liver; it is not surprising, then, that false negatives are seen in a significant percentage of cases biopsied (Nord, supra, 1982).

However, the performance of any single marker has not been good enough to substitute for the biopsy procedure in detecting or staging fibrosis.

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