Gamma-glutamyl transpeptidase and alpha-fetoprotein: are they predictors of treatment response in patients with chronic hepatitis C?

Hepatitis C virus is a leading cause of chronic liver disease. Elevated serum alpha-fetoprotein [AFP] has been used as a marker for hepatic regeneration after the destruction of hepatocyte in viral hepatitis. Recently, gamma-glutamyl transpeptidase [GGT] has also been taken into account in the evaluation of patients with chronic hepatitis C [CHC]. This study aimed to examine the association between serum AFP and serum GGT levels, and treatment outcome in patients with CHC treated with pegylated interferon and ribavirin. We examined the association between AFP and GGT levels and sustained virological response [SVR] in 150 patients with CHC in whom antiviral therapy was initiated. Serum AFP, GGT, and hepatitis C virus RNA were tested for patients completing 48 weeks of treatment and patients who responded to treatment after 6 months. AFP and GGT levels were lesser in patients who achieved SVR than in those who did not achieve a response. The logistic regression model [univariate analysis] of factors associated with SVR showed a significant increase in SVR when AFP ranged from 2.8 to 9.9 micro g/ml, GGT less than or equal to 50 U/l, and Ishak fibrosis score less than or equal to F2. Serum AFP and GGTwere strongly correlated in multivariate analysis; only GGT less than or equal to 50 U/l and AFP from 2.8 to 9.9 micro g/ml were independent predictors of SVR, whereas Ishak score of fibrosis was a dependent predictor for SVR. AFP and GGT can be used as independent predictors of treatment response in patients with CHC receiving pegylated interferon and ribavirin

regulatory T cells in peripheral blood of Egyptian pade with hpatitis C infection and hatocellular carcinoma

Recent studies have suggested that CD4[+] CD25[+] regulatory T cells [Tregs] are increased and linked to compromised immune responses in patients with hepatocellular carcinoma [HCC]. The forkhead/winged helix transcription factor [FOXP3] is a useful marker for the presence of Tregs as it is required for their development and function. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen-reactive lymphocytes mediated by Treg cells; however, definitive evidence that Treg cells have an immunopathological role in human cancer is lacking. This study attempted to characterize CD4[+] CD25[+] FOXP3 Treg cells in peripheral blood of HCV and HCV related HCC patients and to understand how the Treg cells affect immune responses and contribute to disease progression. A total of 80 patients, 30 with HCV-related HCC, 25 with chronic hepatitis C virus [CHC] infection 25 HCV-related liver cirrhosis [LC] patients and 20 normal controls were enrolled randomly. Flow cytometric assay for quantification of CD4[+] CD25[+] T cells and real time PCR assay for analysis of FOXP3 were used. Our study showed that the frequency of Treg cells was significantly increased in HCC patients compared with controls, CHC and cirrhotic patients [p<0.001]. However, the frequency of Treg cells was not significantly different in CHC and cirrhotic patients, which suggests that they play a central role in tumor immunity. In addition, the level of Treg cells in peripheral blood of HCC patients was significantly higher with the extent of tumor burden [large tumor size, increased number. unclear margin and vascular involvement]. Our results suggest that CD4[+] CD25[+] FOXP3 Treg cells may impair the effector function of T cells in HCC patients, promote disease progression and represent both a potential prognostic marker and a therapeutic target for HCV-related HCC individuals. A better understanding of the mechanisms of the Treg increase in HCC may allow for future immunotherapeutic and diagnostic opportunities in this population