Patogenesis of pipe-stem fibrosis of the liver (experimental observation on murine Schistosomiasis)

Abstract

Mice infected with 30 cercariae of Schistosoma mansoni developed portal and septal fibrosis due to the massive and concentrated deposition of eggs in the periportal areas which occurred following the 16th week after infection. The lesion resembled pipe-stem fibrosis seen in human hepatosplenic schistosomiasis in the following characters: portal fibrosis interconnecting portal spaces as well as portal spaces and central canals; portal inflammation; periovular granulomas; vascular obstruction and telangiectasia. The liver parenchyma maintained its normal architecture. Vascular injection techniques with Indian ink and vinylite revealed that the portal system developed numerous dilated collateral venules coming from the large and medium-sized portal branches, about 10 weeks after schistosome infection. The lodging of schistosome eggs into these collaterals resulted in granulomatous inflammation and fibrosis along all the portal tracts, thus forming the pipe-stem lesion. Although not readily demonstrable grossly, the pipe-stem fibrosis of murine schistosomiasis has many similarities with the human lesion and can be considered to have the same basic pathogenesis.

Experimental models of Schistosoma mansoni infection

“…Portal fibrosis resembling Symmers' fibrosis in humans was first described in mice by Warren (1966). Andrade (1987) and Andrade et al (1997) described similar fibrosis in infected mice in which low intensity infections allowed gradual obstruction of peripheral portal venules with subsequent preferential shunting of eggs into the portal spaces surrounding larger veins. In infected persons it was also noted that eggs did not concentrate in the large portal spaces until pipestem fibrosis had already begun (Cheever 1969).…”

Manson's schistosomiasis in the undernourished mouse: some recent findings

“…1), as a consequence of a massive and continuous deposition of eggs along the dilated intra-hepatic venous portal branches (Andrade 1987, Andrade & Cheever 1993.…”

Malnutrition and hepatic fibrosis in murine schistosomiasis

“…Concerning Symmers' fibrosis (clay pipestem fibrosis), different experimental hosts have been tried (Cheever et al 2003), such as monkeys (Lichtemberg & Sadun 1968, Sadun et al 1970, Lichtemberg et al 1971, Damian et al 1976, Farah et al 2000, rabbits , pigs (Hurst et al 2000), and mice (Warren & DeWitt 1958, Andrade & Warren 1964, Cheever 1965, Warren 1968, Andrade 1987a, Andrade & Cheever 1993. In this last animal model, during mild (one to two pairs of worms) and prolonged (16 weeks or more) infections with Schistosoma mansoni, a picture mimicking "clay pipestem" fibrosis seen in humans with advanced schistosomiasis has been reproduced in outbred and in some strains of well-nourished inbred mice (Andrade & Cheever 1993), but not in undernourished outbred specimens (Coutinho et al 1997).…”