Minimal liver injury in chronic hepatitis C virus infection is associated with low levels of soluble TNF-alpha/Fas receptors and acquisition in childhood

Background/Aims: The rate of progression to cirrhosis of chronic hepatitis C might be related to an upregulation of TNF-alpha /Fas pathways. Methods: The serum levels of soluble TNF-alpha. type II receptor (sTNFr-II) and solu ble Fas antigen (sFas) were analyzed in patients with different histologica l outcomes of chronic parenterally acquired HCV infection of similar durati on. Results: One hundred and forty-five HCV-infected patients had a known d uration of infection, Twelve (8.3%) patients had minimal changes and were a ssigned to the case group. The control group was selected from the 24 (17%) patients with cirrhosis and the 54 (37%) with chronic active hepatitis (CA H). Two controls, one with CAH and one with cirrhosis, were paired with the cases following these criteria: duration of infection, transmission route and sex. The proportions of genotype 1 b and HCV RNA serum levels were simi lar among the groups. the median serum levels of sTNFr-II and sFas were sig nificantly lower in the case group than in the control groups. The cases we re significantly younger when they became infected than the control groups. Indeed, most cases were infected within the first 10 years of life. sTNFr- II and age at infection were independently associated with the minimal inju ry case group. When sTNFr-II was excluded from the logistic regression mode l, sFas and age at infection were independently associated with the case gr oup. Conclusion: The rate of progression of parenterally acquired chronic h epatitis C to end-stage liver disease might be related to an upregulation o f the TNF-alpha /Fas pathways and an age-dependent host response.