Abstract
The aim of the study was to assess serum hyaluronic acid (HA) and transforming growth factor beta 1 (TGF-β1) concentrations: 1) to differentiate hepatic fibrosis from other forms of liver disease, and 2) for the non-invasive staging of canine liver fibrosis. We also evaluated the association between serum HA concentration and the size of the shunt vessel as an indirect marker of decreased liver clearance in patients with single congenital vascular anomaly. Forty-one healthy client-owned dogs and forty dogs diagnosed with hepatobiliary disease were enrolled in the prospective study. Patients were divided into 4 subgroups: 1) congenital portosystemic shunts (CPSS); 2) parenchymal diseases (a. mild and moderate fibrosis, b. advanced fibrosis and cirrhosis); 3) hepatic neoplasia; 4) biliary tract disorders based on thorough clinical, ultrasound and histopathological examination. Serum HA and TGF-β1 concentrations were measured using ELISA. The HA concentration was significantly increased in patients with advanced liver fibrosis/cirrhosis (P < 0.001) and CPSS (P < 0.001) compared to healthy dogs. Using a cut-off HA concentration of 135.94 ng/ml, the sensitivity and specificity for diagnosis for advanced liver fibrosis/cirrhosis was 100% (95% CI, 50.6–100) and 90.8% (95% CI, 81.6–95.7), respectively. The TGF-β1 levels did not significantly differ among groups (P = 0.180). Negligible correlation was found between serum HA concentration and the size of portosystemic shunt vessel (rs = 0.07; P = 0.831). These findings suggest that serum HA concentration is a potential non-invasive biomarker for advanced liver fibrosis and/or cirrhosis in dogs. The utility of measuring serum concentration of TGF-β1 for diagnosing canine liver fibrosis was not supported.
Highlights
Non-invasive detection of hepatic fibrosis is important for initiation of anti-fibrotic treatment to prevent progression to irreversible cirrhosis
Subgroup 1 vascular disorders: 11 dogs with extrahepatic congenital portosystemic shunt (CPSS), 1 dog with intrahepatic CPSS; subgroup 2 parenchymal diseases, further subdivided into 2a, 5 dogs with chronic hepatitis and mild to moderate fibrosis; and 2b, 5 dogs with chronic hepatitis and advanced fibrosis and cirrhosis; subgroup 3 hepatic neoplasia: 4 dogs with lymphoma, 3 with hepatocellular carcinoma, 1 with metastatic mast cell tumour, 1 with metastatic insulinoma, 1 with metastatic intestinal carcinoid; subgroup 4 biliary tract disorders: 3 dogs with acute pancreatitis leading to extrahepatic biliary duct obstruction (EHBDO), 3 with biliary mucocele and 2 with emphysematous cholecystitis
Hyaluronic acid is the main component of extracellular matrix (ECM) and here it is evaluated as a potential marker of increased fibrotic tissue accumulation as it is in humans (Lee et al 2010)
Summary
Non-invasive detection of hepatic fibrosis is important for initiation of anti-fibrotic treatment to prevent progression to irreversible cirrhosis. Liver fibrosis is characterized by excessive accumulation of extracellular matrix (ECM) which results from both increased synthesis and decreased degradation of ECM and is observed in most types of chronic liver diseases (Liu et al 2012). High serum levels of HA in humans correspond to increased production of ECM by HSCs 2004) and appear to be the most reliable individual test reflecting increased ECM in human patients with chronic hepatitis C and alcoholic liver disease (Wong et al 1998; Stickel et al 2003). Serum TGF-β1 concentrations have a lower diagnostic accuracy for fibrosis than HA (67% and 86%, respectively) (Oberti et al 1997)
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