Suitability of using serum hialuronic acid concentrations in the diagnosis of canine liver fibrosis

Abstract

There are multiple dynamic changes associated with the metabolism of the extracellular matrix (ECM) which occur in the course of liver fibrosis. Therefore, the evaluation of parameters reflecting the deposition of ECM, the activity of myofibroblasts and the synthesis and degradation of collagen may aid in the diagnosis of liver fibrosis. Hyaluronic acid is considered to be a marker of ECM deposition. It is a glycosaminoglycan synthesized by hepatic stellate cells and degraded by hepatic sinusoidal endothelial cells. The aim of this study was to evaluate the concentration of hyaluronic acid in dogs with different degrees of liver fibrosis. The study was carried out on 29 dogs with liver disease. A core needle biopsy of the liver was performed in order to assess the degree of hepatic inflammation. Then, hyaluronic acid serum concentrations were measured. The dogs were divided into five groups based on the histopathological examination and the evaluation of the degree of hepatic fibrosis. The study showed that serum hyaluronic acid concentrations were low in patients with first stage liver fibrosis and in controls, while they were twice as high as control values in the group of dogs with second stage liver fibrosis. These concentrations were three-fold greater than control values in patients with third stage liver fibrosis, and seven-fold greater in patients with liver cirrhosis. Based on the results, it was concluded that serum hyaluronic acid is a useful marker of liver fibrosis and may aid in determining the degree of its advancement.

Evaluation of potential serum biomarkers of hepatic fibrosis and necroinflammatory activity in dogs with liver disease

“…Our study, as well as previously reported studies of liver biomarkers in dogs have enrolled relatively few dogs with cirrhosis. This is an important limitation because many biomarker studies in humans focus on distinguishing cirrhotic from non‐cirrhotic patients.…”

“…Serum concentrations of hyaluronic acid, which is produced by hepatic stellate cells, were significantly increased in dogs with cirrhosis, with only modest overlap in dogs without cirrhosis or with non‐hepatic diseases . In another study, serum hyaluronic acid concentrations were distinctly higher in dogs with stage 4 fibrosis, although statistical comparisons were not made . The same research group also reported significantly higher serum concentrations of type III procollagen aminopeptide (PIIINP) and a fragment of type IV collagen (PIVNP) in dogs with advanced liver fibrosis .…”

“…46 In another study, serum hyaluronic acid concentrations were distinctly higher in dogs with stage 4 fibrosis, although statistical comparisons were not made. 47 The same research group also reported significantly higher serum concentrations of type III procollagen aminopeptide (PIIINP) and a fragment of type IV collagen (PIVNP) in dogs with advanced liver fibrosis. 48,49 However, these findings for hyaluronic acid and PIIINP could not be replicated in another study.…”

The Endothelium as a Driver of Liver Fibrosis and Regeneration

“…As mentioned before, LSEC regulate HSC activation via an alteration of the balance of vasodilators/vasoconstrictors molecules. LSEC also contribute to HSC activation through additional ways: secreting fibronectin EIIIA [161,162], TGF-β and PDGF or activating signaling pathways such as Hh or Wntβcatenin, which can activate HSC in both a paracrine and an autocrine manner [72,[74][75][76][163][164][165][166][167][168][169][170].…”

Hepatic Fibrosis in Dogs

“…Some of these serum markers have been evaluated in dogs. Serum hyaluronic acid concentration is increased in dogs with hepatic disease, especially cirrhosis, and therefore holds some promise as a biomarker . Serum concentrations of TGFβ‐1, the 7S fragment of type IV collagen, and procollagen type III N‐terminal peptide also have been found to be increased in dogs with hepatic fibrosis.…”