Hepatic stellate cells in hepatitis C patients: relationship with liver iron deposits and severity of liver disease.
OBJECTIVE
To determine the relationship between hepatic stellate cell (HSC) populations and severity of liver disease and liver iron deposits in patients with chronic hepatitis C virus (HCV). We also studied the relationship between iron cellular distribution and HSC population and the role of HFE mutations in the determination of iron deposits.


METHODS
Forty-nine chronic HCV patients with varying degrees of liver damage and liver iron deposits were studied. A liver biopsy was scored for histology activity index (HAI), fibrosis and iron deposits. The number of HSC in the liver was evaluated by an immunohistochemical double-staining method to identify glial fibrillary acid protein (GFAP) and smooth muscle alpha-actin (alpha-SMA).


RESULTS
The HSC population was significantly higher in HCV patients than in normal controls and was predominant in zones 1 and 3. Liver iron deposits were observed in 49% of patients and were mild/moderate in most cases. We found a significantly higher number of GFAP and alpha-SMA positive cells in patients with liver iron deposits compared with those without iron deposits, and a positive correlation between liver iron scores and number (%) of GFAP and alpha-SMA positive cells. We observed a significantly higher number of GFAP and alpha-SMA positive cells in moderate/severe hepatitis than in minimal/mild hepatitis, and a positive correlation between GFAP and alpha-SMA positive cells and HAI and fibrosis scores.


CONCLUSIONS
Liver iron deposits in chronic HCV are common and are associated with activation of HSC. Thus, even mild iron deposits might stimulate HSC and contribute to liver damage.
Martinelli
Ana L C
AL
Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto, SP, Brazil. adlcmart@fmrp.usp.br
Ramalho
Leandra N Z
LN
Zucoloto
Sergio
S
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006526:Hepatitis C / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D007501:Iron