The involvement of the hepatitis C virus (HCV) in the severity of liver disease in chronic schistosomiasis was investigated in 215 Brazilian patients with S. mansoni infections, but without evidence of hepatitis B surface antigen (HBsAg). Forty-three had hepatointestinal (HIS) and 172 had hepatosplenic schistosomiasis (HSS), and 135 had compensated (HSSC), and 37 had decompensated (HSSD) liver disease. Fifty-two (24%) were found to have evidence of HCV infection (seropositive for anti-HCV antibodies and/or HCV-RNA). These comprised 35 (95%) of the 37 with HSSD, 16 (12%) of the 135 with HSSC, and 1 (2.4%) of the 43 with HIS, compared with only 1 (2%) of 50 control patients without S. mansoni. Testing of matched liver tissue and peripheral blood mononuclear cells (PBMCs) from 25 patients (6 HSSC and 19 HSSD) with HCV infections showed that 17 (68%) had "active" viral infections, in that negative strand HCV-RNA (the presumed replicative intermediate of the virus) could be detected in liver and/or PBMCs. Among these 25, negative strand HCV-RNA was found in 16 (84%) of the 19 with chronic active hepatitis, but in only 1 (17%) of the 6 with mild or inactive disease (P < 0.01). HCV-RNA was detected in matched spleen specimens from 9 of 10 patients (all of whom were also positive in PBMCs), suggesting that the spleen is an important extrahepatic reservoir of the virus.(ABSTRACT TRUNCATED AT 250 WORDS)

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