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  • BKT140 australia br Introduction Fibrosis progression is the


    Introduction Fibrosis progression is the common consequence of most chronic liver diseases and histologic examination of a liver biopsy specimen is the reference standard for the assessment of liver fibrosis. However, liver biopsy is burdened by invasiveness and low degree of acceptance by patients, potentially lethal complications, sampling error, observer-dependent diagnostic variability and handling costs [1]. In the last decade, non-invasive and reproducible methodologies, with an acceptable level of diagnostic accuracy have been proposed for the non-invasive assessment of fibrosis [2], [3]. These mainly include the measurement of tissue elasticity by transient elastography and serum markers of liver fibrosis [4], [5]. The “indirect serum markers” are panels of clinical and biochemical parameters not directly related to extracellular matrix BKT140 australia while the “direct serum markers”, such as the serum levels of molecules diffused into the systemic circulation, are related to the metabolism of the extracellular matrix [6]. Currently, the ELF score is derived by the assessment of direct serum markers of fibrosis, namely hyaluronic acid, aminoterminal propeptide of type III collagen and tissue inhibitor of matrix metalloproteinase 1 [7]. All non-invasive fibrosis tests to date were developed and calibrated with reference to semi-quantitative histological scoring systems, such as Ishak’s or METAVIR, rather than quantitative histological measurement of fibrosis, which would be more accurate and appropriate. Indeed, existing scoring systems do not represent a measurement of quantitative fibrosis, but rather a categorical description of both architecture and fibrosis. Collagen proportionate area (CPA) is a validated method for the quantification of fibrosis by measuring hepatic collagen using digital image analysis [8], [9], [10], [11], [12], [13]. This method was first described by Calvaruso et al. [8], who determined relationships between computer–assisted digital analysis, Ishak score and HVPG. The authors found a significant relationship between CPA and HVPG, indicating that computer-assisted digital image analysis measurement of CPA has clinical relevance, because Focus formation could be useful to stratify prognostic groups. Based on these premises, the aims of this study was to evaluate the diagnostic accuracy of CPA for the diagnosis of fibrosis stages using a standard semi-quantitative method (Ishak’s score) and to provide a further validation of ELF by comparing ELF with a method (CPA) able to assess liver fibrosis quantitatively.
    Study design and methods The study was performed on 143 liver biopsy samples of available tissue blocks largely from patients with HCV-related chronic liver disease, obtained at the time of the original ELF study at the University of Florence University Hospitals (AOUC) in Florence, Italy, as a part of an international, multicenter, cross-sectional cohort study [7]. In the original ELF study [7], patients were considered eligible if they were due to undergo liver biopsy for the investigation of chronic liver disease, defined as abnormal biochemical liver function tests persisting for more than 6 months, ability to provide informed consent and age between 18 and 75 years. Patients were excluded from the study if their age fell outside of this range; for any disorder associated with extrahepatic fibrosis, including rheumatic, renal, or lung disease; for cardiovascular disease or cancer; for advanced cirrhosis with evidence of decompensation (Child–Pugh class C); for consumption of regular aspirin; or for hepatocellular carcinoma or drug-induced liver disease.