Hepatic stellate cells in human schistosomiasis mansoni: a comparative immunohistochemical study with liver cirrhosis

Abstract

This study compares the populations of liver mesenchymal cells (LMCs) and their proliferative activity in schistosomal periportal fibrosis and in hepatitis C virus-induced cirrhosis. LMCs were evaluated by immunohistochemical double staining for proliferating cell nuclear antigen (PCNA) and alpha-smooth muscle actin (alpha-SMA) or glial fibrillary acid protein (GFAP) in liver biopsies from humans with schistosomal fibrosis (n=40), hepatitis C virus-induced cirrhosis (n=20), and normal controls (n=20). The number of LMCs was found to be higher in schistosomal fibrosis than in the normal liver, but lower than in cirrhosis. alpha-SMA- and GFAP-positive cells were increased in both diseases, but more so in cirrhosis. In cirrhotic liver, alpha-SMA-positive cells were highly predominant in relation to GFAP-positive cells. However, there was an inverted ratio between these cells in schistosomiasis as compared to cirrhosis. The PCNA labeling index was higher in alpha-SMA-positive cells than in GFAP-positive cells, and did not differ between pipe-stem fibrosis and liver cirrhosis regarding alpha-SMA- or GFAP-positive cells. The predominance of GFAP-positive cells observed in schistosomiasis suggests that hepatic stellate cells (HSCs) have a major role in connective tissue deposition in the human schistosomal liver. On the other hand, the smaller number of LMCs in schistosomal fibrosis in comparison to liver cirrhosis may be related to mild and limited injury due to the schistosomal egg-induced inflammatory response. The granulomatous inflammation around Schistosoma mansoni eggs appears to mobilize and activate a reduced number of mesenchymal cells in comparison to the scattered necro-inflammatory reaction produced by the hepatitis C virus.