A novel panel of blood markers to assess the degree of liver fibrosis†

Abstract

The objective was to develop new blood tests to characterize different fibrosis parameters in viral and alcoholic chronic liver diseases. Measurements included 51 blood markers and Fibrotest, Fibrospect, ELFG, APRI, and Forns scores. The clinically significant fibrosis was evaluated via Metavir staging (F2-F4), and image analysis was used to determine the area of fibrosis. In an exploratory step in 383 patients with viral hepatitis, the area under the receiving operator characteristic (AUROC) curve for stages F2-F4 in a test termed the "Fibrometer" test combining platelets, prothrombin index, aspartate aminotransferase, ␣2-macroglobulin (A2M), hyaluronate, urea, and age was 0.883 compared with 0.808 for the Fibrotest (P ‫؍‬ .01), 0.820 for the Forns test (P ‫؍‬ .005), and 0.794 for the APRI test (P < 10 ؊4 ). The Fibrometer AUROC curve was 0.892 in the validating step in 120 patients. The AUROC curve for stages F2-F4 in a test combining prothrombin index, A2M, hyaluronate, and age was 0.962 in 95 patients with alcoholic liver diseases. The area of fibrosis was estimated in viral hepatitis by testing for hyaluronate, ␥-glutamyltransferase, bilirubin, platelets, and apolipoprotein A1 ( a R 2 ‫؍‬ 0.645), and in alcoholic liver diseases by testing for hyaluronate, prothrombin index, A2M, and platelets ( a R 2 ‫؍‬ 0.836). In conclusion, the pathological staging and area of liver fibrosis can be estimated using different combinations of blood markers in viral and alcoholic liver diseases. Whereas the Fibrometer has a high diagnostic accuracy for clinically significant fibrosis, blood tests for the area of liver fibrosis provide a quantitative estimation of the amount of fibrosis, which is especially useful in cirrhosis. (HEPATOLOGY 2005;42:1373-1381

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL)

“…The six parameters required to calculate FibroMeter are platelets, PT index, AST, a-2-M, HA, and urea levels [22].…”

Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis C–related fibrosis: A systematic review

“…Serum biochemical tests, including direct and indi-rect markers of liver fibrosis, have been the most widely investigated. 8,9 Direct markers such as glycoproteins (for example, hyaluronic acid, laminin, YKL-40), collagens, the matrix metalloproteinases and their inhibitors, and cytokines (for example, transforming growth factor beta) have demonstrated associations with fibrosis, and some have been incorporated into panels available on a proprietary basis (for example, FibroSpect, 10 FibroMeter, 11 Hepascore, 12 the European Liver Fibrosis test 13 ). Although these markers are less expensive than liver biopsy, they are still costly and are not available in most clinical settings.…”

“…Subsequently, numerous studies have attempted to externally validate these findings, but results have been controversial. 11,17,48 Differences in patient populations, including the prevalence of significant fibrosis, and reference ranges for AST, may explain these discrepancies.…”

Non-Invasive Index for Predicting Significant Liver Fibrosis: Comparison of Diagnostic Performances in Patients with Chronic Hepatitis B and C

“…Individual serum markers of liver fibrosis are useful for the diagnosis or exclusion of liver cirrhosis, but have limited accuracy for the diagnosis of significant fibrosis [23]. Recently, some fibrosis scores which have been calculated from statistical models were described [8][9][10][14][15][16][17]. Some of the fibrosis scores include serum indices comprised of routine laboratory parameters, and other fibrosis scores require measurement of additional fibrosis markers.…”

“…To overcome the limitations of a liver biopsy, a variety of serum markers ranging from routine laboratory tests to more complex indices have been proposed [8][9][10][11][12][13][14][15][16][17], but no single test is sufficient to provide an accurate assessment on hepatic fibrosis for every clinical situation. Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting that multiple serum markers may be used in conjunction with liver biopsy to assess a range of chronic liver diseases.…”