Received: 02.12.2009 Accepted: 29.01.2010 J Gastrointestin Liver Dis June 2010 Vol.19 No 2, 169-174 Address for correspondence: Hadi Parsian Department of Biochemistry and Biophysics University of Medical Sciences Babol, Iran E-mail: hadiparsian@yahoo.com Serum Hyaluronic Acid and Laminin as Biomarkers in Liver Fibrosis Hadi Parsian 1 , Ali Rahimipour 2 , Mohammad Nouri 3 , Mohammad Hossein Somi 3 , Durdi Qujeq 1 , Mehrdad Kashi Fard 4 , Karim Agcheli 5 1) Department of Biochemistry and Biophysics, Babol University of Medical Sciences, Babol; 2) Department of Clinical Biochemistry, Shahid Beheshti University of Medical Sciences, Tehran; 3) Liver and Gastrointestinal Diseases Research Centre, Tabriz University of Medical Sciences, Tabriz; 4) Yahya Nezhad Hospital, Babol University of Medical Sciences, Babol; 5) Liver and Gastrointestinal Diseases Research Centre, Gorgan University of Medical Sciences, Gorgan, Iran Abstract Background and Aim: Non-invasive methods have been proposed as surrogate markers for liver biopsy. It was shown that serum hyaluronic acid (HA) and laminin (LN) levels increase with the development of liver ibrosis. The aim of this study was to determine serum HA and LN levels cut-off points for predicting liver fibrosis, highlighting their diagnostic value and their changes during treatment. Methods: Serum HA and LN levels in chronic hepatitis patients (n=62) and controls (n=20) were assessed by ELISA and liver histopathological parameters were evaluated by the modiied Knodell score. Results: Mean serum HA (113.4±59.2 ng/ml) and LN (91.9±20.9 ng/ml) concentrations in patients were greater than in controls (46.6±10.5 and 46.1±10.1 ng/ml, p<0.001). A strong correlation between serum HA and LN concentrations with hepatic necroinlammatory lesions was found (p<0.001). A cut-off point of 59.5 ng/ml HA and 52.0 ng/ml LN for the discrimination of patients with liver ibrosis from healthy controls and 102.0 ng/ml HA and 92.5 ng/ml LN for the discrimination of patients with mild from severe ibrosis showed acceptable AUC, sensitivity and speciicity. After six months of treatment, a gradual decrease in serum HA and LN levels was observed, however the levels were still higher than those of the controls (p<0.05). Conclusions: Serum hyaluronic acid and laminin concentrations increase in liver ibrosis and could be used as a noninvasive biomarker to discriminate between patients with liver ibrosis and healthy individuals. Key words Chronic hepatitis – hepatic ibrosis – hyaluronic acid – serum laminin – Knodell score. Introduction Liver ibrosis is a process involving production and deposition of various components that constitute the extracellular matrix (ECM). Some of these components are noncollagenous glycoproteins such as laminin (LN), hyaluronic acid (HA), and proteoglycans. Staging of liver ibrosis and evaluation of the inlammation grade is beneicial for estimating the progression rate of liver ibrosis, treatment selection and monitoring the disease. Liver biopsy is still the reference test for staging and grading hepatic ibrosis and inlammation. However, due to some limitations of the liver biopsy, noninvasive methods are now preferred [1]. In recent years, some studies proposed HA and LN as indices of the extent of liver ibrosis in chronic liver diseases [2]. Hyaluronic acid is a glycosaminoglycan distributed in the extracellular spaces. In the liver, HA is mostly synthesized by the hepatic stellate cells and degraded by the sinusoidal endothelial cells. An increase in serum HA levels was observed in chronic hepatitis C and in cirrhotic patients [2, 3]. One of the main glycoproteins of the basement membrane is LN, which is synthesized by hepatocytes and sinusoidal cells [4]. Stellate cells or lipocytes produce the largest amount of serum LN. Increased serum LN levels in advanced stages of ibrosis (in patients with hepatic disease) were observed [5]. Korner et al reported that LN serum concentration could be a sensitive screening test for hepatic ibrotic disease and portal hypertension if the test was assessed together with the serum level of HA [6]. In the Iranian population, there are few published studies concerning the relationship between HA and LN serum levels and liver ibrosis stage or inlammation grade in chronic hepatitis and the studies have been performed in chronic