The prevalence of previously undiagnosed and untreated HCV infection in inner city African Americans, discovered through screening individuals from the community in their usual state of health, was 27%. This was a cross-sectional study of persons without a past history of HCV infection, and so we cannot comment on the chronicity of the infection.
HCV seropositivity in this study was not associated with anemia, thrombocytopenia or other changes in the complete blood count except for a trend to higher lymphocyte counts. Nor were the serum ferritin concentration or transferrin saturation influenced by HCV seropositivity. These observations are in contrast to reports of hemolytic anemia, thrombocytopenia and other cytopenias, and increased iron stores in association with untreated HCV infection [5
], and they indicate that the hematologic manifestations of HCV infection in previously undiagnosed individuals from the community may differ from those of symptomatic individuals presenting for medical care. Alcohol consumption estimated by dietary questionnaire also did not have a discernable effect on the complete blood count.
HCV seropositivity was associated with significant increases in AST, ALT and GGT, and with changes in serum proteins consistent with a chronic inflammatory process, i.e., increase in the globulin fraction and decrease in albumin concentration. Other aspects of the inflammatory response were lacking. In particular, the erythrocyte sedimentation was not increased, the serum iron was not decreased, the transferrin concentration was increased rather than decreased, and the CRP concentration was decreased rather than increased.
The anemia of chronic inflammation [20
] was noticeably absent in the patients with untreated HCV in this study, and this observation along with a lack of inflammatory changes in erythrocyte sedimentation rate, iron, transferrin and CRP raises the possibility that HCV may have certain properties in suppressing certain aspects of the systemic inflammatory response. Our finding of reduced rather than increased CRP concentrations in the present cohort parallels recent reports that co-infection with HCV is associated with reduced CRP concentrations in HIV infected patients [21
C-reactive protein is an acute phase plasma protein produced by hepatocytes under the transcriptional control of the pro-inflammatory cytokine, interleukin 6 [12
]. Some investigators have reported that HCV infection is associated with increased expression of interleukin-6 [23
], while others have not observed increased expression [27
]. One study indicated that the interleukin-6 response to stimulation of toll like receptors 3 and 4 is compromised in HCV infection [29
]. Lack of increased CRP expression in association with HCV seropositivity is not likely to be due simply to poor functioning of hepatocytes, for there was increased expression of transferrin. Transferrin is ordinarily a negative acute phase reactant, but in the present study serum levels were increased in association with HCV in tandem with decreased serum CRP concentration.
Interleukin 6 not only promotes the transcription of CRP by hepatocytes but also that of of hepcidin [30
]. Hepcidin is a peptide hormone that regulates iron absorption by enterocytes and iron release by macrophages; decreased hepcidin levels lead to increased iron absorption [31
]. Ferroportin is an iron exporter present on the surface of absorptive enterocytes, macrophages, hepatocytes and placental cells that also serves as a receptor for hepcidin. The binding of hepcidin leads to internalization and degradation of ferroportin, thereby decreasing export of cellular iron [31
]. Relatively low hepcidin expression has been reported in HCV infection [8
], and this might help to explain a failure to observe hypoferremia in association with HCV infection in the present study.