Evaluation of circulating CD4+CD25+ and liver-infiltrating Foxp3+ cells in HCV-associated liver disease.

In hepatitis C virus (HCV)-associated liver disease, the immune system is unable to clear the viral infection. Previous studies have raised the possibility of an involvement of regulatory T cells (Tregs). In this study, we analysed the peripheral blood from 30 patients with HCV-associated chronic liver disease and 20 healthy controls by flow cytometry for the evaluation of the Treg population [CD4⁺CD25hi forkhead box protein 3 (Foxp3)⁺], as well as the activated/effector CD4⁺ T cells (CD4⁺CD25low) and IFN-γ-secreting cells. We also analysed liver biopsies of the patients by immunohistochemical evaluation of Foxp3⁺ cells. Our results showed higher proportions of CD4⁺CD25low and IFN-γ⁺ cells in the patients than in the controls. By contrast, the proportions of peripheral CD4⁺CD25hi cells did not significantly differ. The 11 patients displaying Foxp3⁺ cells in the liver infiltrates showed significantly higher proportions of peripheral CD4⁺CD25low cells. Moreover, we found lower serum transaminase levels in the patients than in the controls, as shown by Foxp3⁺ immunohistochemistry, although these results were only statistically significant as regards alanine transaminase (ALT). In conclusion, these data suggest that the presence of Tregs infiltrating the liver is associated with high levels of activated/effector T cells in the peripheral blood and lower activity of hepatitis. Therefore, liver-infiltrating Tregs may play a role in limiting tissue damage and may thus support an effective immune response against HCV.

Relationship between circulating interleukin-10 and histological features in patients with chronic C hepatitis.

BACKGROUND AND OBJECTIVES: An imbalance in cytokine production may be involved in the pathogenesis of chronic C hepatitis. The aim of the study was to investigate circulating levels of interleukin-10 (IL-10) in a selected cohort of patients affected by chronic C hepatitis. DESIGN AND SETTING: Retrospective study based on consecutive hepatitis C virus patients, affected by chronic active hepatitis, attending the general hospital of hepatology unit from June to September 2009 PATIENTS AND METHODS: A total of 49 patients with chronic C hepatitis and 20 healthy control subjects similar in gender and age were examined. Circulating IL-10 was assessed by ELISA commercial kit (R and D Systems) in all investigated subjects. RESULTS: There was no significant difference in IL-10 values between controls and overall patients (P>.05). Nevertheless, among patients, subjects with more severe necroinflammation had higher values than others (P<.001). Moreover, a close relationship was found between IL-10 values and serum aspartate aminotransferase (r=0.61; P<.001). CONCLUSIONS: These findings suggest that IL-10 may be a useful additional marker to assess necroinflammation and to monitor the evolution of liver damage. They also argue for a potential pathophysiological role for IL-10 in the persistence and progression of hepatitis.

Liver immunolocalization and plasma levels of MMP-9 in non-alcoholic steatohepatitis (NASH) and hepatitis C infection.

Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic disease. Many issues related to the pathogenesis of this disease remain unresolved. Because of NASH association with the activation of liver fibrogenesis, we examined the plasma levels and liver immunolocalization of matrix metalloprotease-9 (MMP-9), a molecule involved in the remodelling processes of fibrogenesis. In addition, patients with chronic hepatitis C (HCV) were analyzed. Plasma concentrations of MMP-9 were determined by ELISA from peripheral blood and immunohistochemistry of the same protein was carried out in formalin-fixed and paraffin wax-embedded liver specimens. The mean value of circulating concentrations of MMP-9 in healthy controls was 39.7 ng/ml (SD: +/-4.6). In NASH and HCV-infected patients, MMP-9 concentrations were higher: 69.0 ng/ml (SD: +/-14.5) and 61.7 ng/ml (SD: +/-11.0), respectively. In NASH livers, MMP-9 was mainly immunolocalized on neutrophils, whereas in HVC-infected livers it was mainly localized over biliary canaliculi, bile ducts and hepatocyte cytoplasm. The different MMP-9 immunolocalization patterns in the examined diseases suggest the presence of a different pathophysiological involvement of this protease in the fibrogenesis underlying these diseases.