The giant liver fluke (Fascioloides magna) is a parasite which, contrary to other liver flukes of ruminants, exists as parasite in the hepatic parenchyma of domestic and wild ruminants, where it inflicts damage to all liver structures with the consequent development of liver fibrosis and cirrhosis. The giant liver fluke originates from North America, from where it spread to other regions through imports of deer game. It occurs sporadically in Central Europe, and its spreading to Serbia is probably connected with the course of the Danube River, as its flooding spreads the intermediate host, the dwarf pond snail Galba truncatula[1–5].
Through its penetration and spreading through the liver in the early stage of the disease, the giant liver fluke causes changes in the liver parenchyma that are characterized by findings of cystic spaces. These cystoid formations are filled with brown mucous fluid which contains parasites of oval leaf-like shape, around 50–70 × 30-40 mm in diameter and dark red in colour, without a cephalic cone, and with a clearly expressed mouth sucker. The thin-walled cystoid formations partly communicate with the bile pathways through which the liver fluke releases eggs which are disseminated into the outer environment by faeces. In addition to the presence of the liver fluke, there is also visible pigmentation in the form of black spots in the liver parenchyma, the portal lymph node, the peritoneum, diaphragm, and omentum . The microscopic finding in the liver of infected deer includes the presence of large quantities of connective tissue that forms wider or narrower stripes that are wound around groups of degenerated and regenerated liver lobuli which are irregular in shape and of unequal size. Connective tissue septa are often seen to contain lymphocytes, macrophages which often contain brown pigment – parasite hematin, which is also present in the parenchyma. The bile duct walls are thickened, and desquamated cells, parasite eggs and brown pigment are present in their lumen [1, 6–9].
These changes are somewhat similar to those described in the liver of domestic ruminants in connection with infection with the big liver fluke Fasciola hepatica. In chronic form, changes in infections with F. hepatica include stenosis of portal blood vessels, hyperplasia of blood vessels tunica media and a large number of newly-created blood vessels in the connective tissue stripes. Liver fibrosis and cirrhosis develop as the ultimate result of chronic liver damage caused by F. hepatica [10–13].
As it is known, hepatic fibrosis and cirrhosis develop following chronic damage to parenchymatous cells caused by infective agents, toxins, drugs, chemicals, malnutrition, metabolites, and hypoxia [14–17]. During the process of fibrosis and cirrhosis development, the loss of hepatocytes leads to fibroblast proliferation and transdifferentiation [18–27]. Accordingly, myofibroblast-dependent progressive fibrogenesis is sustained by at least three main pro-fibrogenic mechanisms: 1) chronic activation of the wound healing response, 2) radical oxygen system and other oxidative stress-related reactive mediators, 3) dearangement of epithelial-mesenchymal interaction and epithelial-mesenchymal transition detected in chronic cholangiopathies [28, 29]. Based on location and immunohistochemical profile three myofibroblasts (MF) subpopulations were described. These comprise 1) portal or septal MFs, present in the portal areas or in newly formed fibrous septa, 2) interface MFs, present at the interface between parenchyma and stroma of the portal areas or newly formed fibrous septa, and 3) the perisinusoidally located hepatic stellate cells (HSCs) [22, 28]. All types have fibrogenic potential, but many investigators regard HSCs as the principal fibrocompetent cell in the liver. Depending on the primary site of injury the resulting fibrosis may be restricted to the portal areas, as in most biliary diseases, or may be present in the hepatic parenchyma as seen in chronic hepatitis and cirrhosis. Although incompletely understood, the activation or transdifferentiation of MFs is a key event in liver tissue repair. Activated HSC express α-SMA and desmin and in humans and rats are without doubt the most important cells that are involved in the creation of extracellular matrix which occurs within liver fibrosis [30–40].
The behaviour of hepatic MFs during the process of development of parasitic liver cirrhosis in connection with natural infection of fallow deer (Dama dama) with the giant liver fluke (Fascioloides magna) is not known. This fact was the reason why the distribution and localization of hepatic MFs have been described and their role discussed in this paper, in addition to the descriptions of histological characteristics of parasitic liver cirrhosis in fallow deer.