Chronic liver diseases of differing etiologies are among the leading causes of mortality and morbidity worldwide. Establishing accurate staging of liver disease is very important for enabling both therapeutic decisions and prognostic evaluations. A liver biopsy is considered the gold standard for assessing the stage of hepatic fibrosis, but it has many limitations. During the last decade, several noninvasive markers for assessing the stage of hepatic fibrosis have been developed. Some have been well validated and are comparable to liver biopsy. This paper will focus on the various noninvasive biochemical markers used to stage liver fibrosis. 1. Introduction Chronic liver diseases of differing etiologies are among the leading causes of morbidity and mortality worldwide [1–5]. Chronic liver disease progresses through different pathological stages that vary from mild hepatic inflammation without fibrosis to advanced hepatic fibrosis and cirrhosis [6–8]. Assessment of the stage of liver disease is important for diagnosis, treatment, and follow-up both during treatment and after cessation of treatment. A liver biopsy is the oldest and most accurate method used to evaluate liver histology and the progression of chronic liver disease. Furthermore, different histological scoring systems have been developed and modified [9–12]. A liver biopsy is considered the gold standard for assessing liver histology [7, 12–14]. During the pathological progression of liver fibrosis, excessive amounts of extracellular matrix build up; furthermore, serum levels of various biomarkers change, in addition to the appearance of new biomarkers in the serum during the different stages of fibrosis [7, 8, 15]. Recently many noninvasive markers (NIMs) for assessing liver fibrosis have been developed, and they are frequently used in clinical practice. They have been validated in different studies, and some were found to be highly accurate in the assessment of liver fibrosis compared with liver biopsies [16–19], which have always been used as the standard reference method for evaluating the accuracy of noninvasive methods. 2. Is the Liver Biopsy Really the Gold Standard and Reference Method for Evaluating Hepatic Fibrosis? 2.1. The Following Are Limitations of the Liver Biopsy (1) The liver biopsy does not efficiently reflect the fibrotic changes occurring in the entire liver because an optimally sized biopsy contains 5–11 complete portal tracts and reflects only 1/50000 the volume of the liver. (2) The process of hepatic fibrosis is not linear, and biopsies from different areas have shown
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