Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression.

Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of IL-10, IL-35 and B-cell activating factor (BAFF) and investigated their association with regulatory T cells (Tregs) and disease progression in HCV-related HCC. For comparative purposes, four groups were enrolled; chronic HCV (CHC group, n = 35), HCV-related liver cirrhosis (HCV-LC group, n = 35), HCV-related HCC (HCV-HCC group, n = 60) and an apparently healthy control (Control-group, n = 20). HCC diagnosis and staging were in concordance with the Barcelona Clinic Liver Cancer (BCLC) staging system. Analysis of the percentage of Breg cells and peripheral lymphocyte subsets (Treg) was performed by flow cytometry. Serum cytokine levels of IL-10, IL-35 and B-cell activating factor (BAFF) were measured by ELISA. The frequency of Bregs was significantly higher in the HCV-HCC group compared to the other groups and controls. A significant increase was noted in late-HCC versus those in the early stages. The frequency of Bregs was positively correlated with Tregs, serum IL-10, IL-35 and BAFF. In conclusion, Peripheral Bregs were positively correlated with the frequency of Tregs, IL-10, IL-35 and BAFF, and may be associated with HCV-related HCC progression.

Impact of interleukin IL-6 rs-1474347 and IL-10 rs-1800896 genetic polymorphisms on the susceptibility of HCV-infected Egyptian patients to hepatocellular carcinoma.

Hepatitis C virus (HCV) is considered leading cause of cirrhosis and hepatocellular carcinoma (HCC). We aimed to examine the association of IL-6 and IL-10 single-nucleotide polymorphisms with the progression of chronic HCV (CHC) infection to cirrhosis and HCC. For comparative purposes, four groups were enrolled; chronic HCV group (CHC, n = 22), HCV-related liver cirrhosis group (HCV-LC, n = 22), HCV-related HCC group (HCV-HCC, n = 54), and an apparently healthy control group (controls, n = 48). HCC diagnosis and staging were in concordance to Barcelona Clinic Liver Cancer (BCLC) staging system. IL-6 rs-1474347 and IL-10 rs-1800896 genotyping was performed by allelic (VIC- and FAM-labeled) discrimination method using assay-on-demand TaqMan real-time PCR assays. For IL-6 rs1474347, the AA genotype was more frequent in CHC, HCV-LC, and HCV-HCC compared to controls. Also, the IL-6 rs1474347 AC genotype was favorable for the progression of HCV chronic infection to cirrhosis and HCC. On the other hand, the IL-10 rs1800896 TT genotype was found to be prominent in the HCC group. Additionally, the IL-10 rs180096 TT genotype was favorable for the progression of chronic HCV infection to cirrhosis and HCC. Furthermore, higher levels of AFP were observed in HCC patients with IL-6 rs1474347 AA genotype and HCC patients with IL-10 rs1800896 CC and TT genotypes. Screening for IL-6 rs 1474347 AC genotype and IL-10 rs180096 TT genotype as well as the determination of AFP level showed to be good markers for examining the susceptibility of HCV Egyptian patients to develop cirrhosis and HCC.

Prognostic impact of toll-like receptors 2 and 4 expression on monocytes in Egyptian patients with hepatocellular carcinoma.

Toll-like receptors (TLRs) have a role in chronic inflammation. Still, little is known about the expression of TLRs in hepatocellular carcinoma (HCC). Herein, we tried to assess the prognostic value of TLR2 and TLR4 expression on circulating monocytes in HCC patients and correlate their levels with some clinical, laboratory data, and treatment outcomes. Forty patients with hepatic focal lesions diagnosed radiologically as HCC by triphasic multislice CT pelviabdominal and chest, and in some patients MRI diffusion and 38 age and sex matching healthy controls were enrolled in the study. Subjects were evaluated for liver functions, alpha-fetoprotein (AFP), imaging, response to different treatments, and overall survival. TLR2 and TLR4 expression by monocytes was detected by flow cytometry. The expression of both TLR2 and TLR4 on monocytes was significantly increased in HCC patients than the controls, in patients with more progressive HCC than those with lower progression and in patients with poor response to treatment than patients with better treatment response. Moreover, their levels showed positive correlations with ALT, AST, and AFP and inverse correlations with the overall survival of HCC patients. The results of the current study suggest that increased expression ofTLR2 and TLR4 on peripheral monocytes might reflect the development and progression of HCC and can be used to indicate poor prognosis. In addition, high expression of TLR2 correlated significantly with poor response to treatment, while high expression of both TLR2 and TLR4 were associated with poor survival. Our findings will help to design more studies on the role of TLRs in HCC pathogenesis and prognosis which may provide new therapeutic targets for HCC.