Septal fibrosis is a common form of hepatic fibrosis, but its etiology and pathogenesis are poorly understood. Rats infected with the helminth Capillaria hepatica constitute a good experimental model of such fibrosis. To investigate the pathogenetic contribution of the several parasitic factors involved, the following procedures were performed in rats: a) regarding the role of eggs, these were isolated and injected either into the peritoneal cavity or directly into the liver parenchyma; b) for worms alone, 15-day-old infection was treated with mebendazole, killing the parasites before oviposition started; c) for both eggs and worms, rats at the 30th day of infection were treated with either mebendazole or ivermectin. Eggs only originated focal fibrosis from cicatricial granulomas, but no septal fibrosis. Worms alone induced a mild degree of perifocal septal fibrosis. Systematized septal fibrosis of the liver, similar to that observed in the infected controls, occurred only in the rats treated with mebendazole or ivermectin, with dead worms and immature eggs in their livers. Thus, future search for fibrogenic factors associated with C. hepatica infection in rats should consider lesions with both eggs and worms.

Septal fibrosis commonly occurs during chronic diseases of the liver. It is experimentally reproduced in a proportion of rats treated with pig-serum, and in 100% of rats infected with Capillaria hepatica. These models have only been used in relatively short-term studies. To contribute to the natural history and significance of hepatic septal fibrosis it is important to disclose its fate after prolonged observation, and following partial or total withdrawal of its inciting cause. Adult Wistar rats were sacrificed 3, 6, 9 and 12 months following inoculation of 800 embryonated eggs of C. hepatica. Besides routine histology, liver sections were submitted to immunohistochemical, immunofluorescence and ultrastructural techniques for the identification of cells and extracellular matrix components present in the fibrous septa. Septal blood vessels were studied after portal vein perfusion with India-ink, while the hepatic functional profile and levels of anti-C. hepatica antibodies were determined in collected sera. Results revealed that all parasites were already dead 2 months from inoculation, and the accumulated eggs in the liver lost their capacity to embryonate around the 4th-6th month, when progressive reduction in the number of cells and in the amount of collagen occurred in the septa. Septal fibrosis persisted throughout the time of experimentation (12 months). This fibrosis was seen as a supporting stroma for septal vessels that conducted portal blood directly to the sinusoids. Thus, persistence of fibrosis was probably related to its morphological and functional association with blood vessels.

Septal fibrosis is an important, frequent, and non-specific type of fibrosis associated with chronic liver diseases, but its pathogenesis is still poorly understood. An interesting model of septal fibrosis occurs in rats infected with the nematode Capillaria hepatica. This model was used to investigate the pathogenesis, site of origin, structure, and cell-types of septal fibrosis. Forty young adult Wistar rats were inoculated with 800 embryonated eggs of C. hepatica. Daily liver samples were obtained from the 20th to the 39th day after inoculation to cover the critical period when septal fibrosis usually starts. Routine histology, electron microscopy, immunohistochemistry, and indirect immunofluorescence were applied to the study of liver sections. Septal blood vessels were demonstrated by India ink perfusion of the portal vein system. Prominent angiogenesis was observed to precede collagen deposition. Besides angiogenesis and mesenchymal-cell mobilization, septal fibrosis was seen to originate from portal spaces and to course through acinar zone I in between sinusoids, inducing no alterations in them, with no evident participation of stellate hepatic cells. Septal fibrosis appeared as an adaptative type of response of the liver to chronic injury, which resulted in a new structure that is normal to other species and creates accessory vessels that drain portal blood into hepatic sinusoids.

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