Background and Aim Forkhead box protein P3 (FoxP3)+ regulatory T (Treg) cells play a fundamental role in maintaining the balance between the tissue-damaging and protective immune response to chronic hepatitis C (CHC) infection. Herein, we investigated the frequency of Treg cells in the colon and their potential relationship to the various CHC outcomes and hepatic histopathology. Methods Colonic biopsies were collected from three groups with CHC: treatment naïve (TN; n = 20), non-responders (NR; n = 20), sustained virologic response (SVR; n = 20), and a fourth healthy control group (n = 10). The plasma viral loads and cytokines levels were determined by quantitative real-time polymerase chain reaction, and ELISA, respectively. Liver biopsies were examined to assess inflammatory score and fibrosis stage. Colonic Treg frequency was estimated by immunohistochemistry using confocal microscopy. Results A significant increase in the frequency of colonic Treg was found in TN, and NR groups compared with the control and SVR group. The frequency of colonic Treg, plasma interleukin (IL)-10 and IL-4 levels were significantly positively correlated with viral load and negatively correlated with METAVIR inflammatory score, and fibrosis stages. Conclusion Colonic Treg cells are negatively correlated with liver inflammation and hepatitis C virus (HCV) viral load, which suggests a strong linkage between gut-derived Treg cell populations and HCV infection.

The IL28B gene is associated with spontaneous or treatment-induced HCV viral clearance. However, the mechanism by which the IL28B single nucleotide polymorphism (SNP) affects the extra-hepatic HCV immune responses and its relationship to HCV pathogenesis have not been thoroughly investigated. To examine the mechanism by which IL28B affects HCV clearance. Forty Egyptian patients with chronic HCV infection receiving an Interferon/ribavirin treatment regimen were enrolled into this study. There were two groups: non-responders (NR; n = 20) and sustained virologic responders (SVR; n = 20). The initial plasma HCV viral loads prior to treatment and IL28B genotypes were determined by quantitative RT-PCR and sequencing, respectively. Liver biopsies were examined to determine the inflammatory score and the stage of fibrosis. Colonic regulatory T cell (Treg) frequency was estimated by immunohistochemistry. No significant association between IL28B genotypes and response to therapy was identified, despite an odds ratio of 3.4 to have the TT genotype in NR compared to SVR (95 % confidence interval 0.3–35.3, p = 0.3). Patients with the TT-IL28Brs12979860 genotype (unfavorable genotype) have significantly higher frequencies of colonic Treg compared to the CT (p = 0.04) and CC (p = 0.03) genotypes. The frequency of colonic Treg cells in HCV-infected patients had a strong association with the IL-28B genotype and may have a significant impact on HCV clearance.

Extra-hepatic compartments might contribute to hepatitis C virus (HCV) persistence and extrahepatic manifestations. Therefore, we investigated HCV infection in colonic tissue in patients with chronic hepatitis C (CHC) and its relationship with HCV pathogenesis. Colonic biopsies were collected from three groups with CHC infection: treatment naïve (TN; n=12), non-responders (NR; n=10) to anti-HCV therapy (pegylated interferon-a and ribavirin) and sustained virologic response (SVR; n=10) and from a fourth healthy control group (n=10). Liver biopsies were examined to assess inflammation and fibrosis. HCV infection and colonic T regulatory (T reg ) frequency were detected by immunohistochemistry. HCV core and NS3 proteins were detected in B cells and macrophage/monocytes of 42 % and 25 % of TN and 50 % and 30 % of NR, respectively, but not in SVR or control group. The numbers of cells expressing HCV proteins were positively correlated with both HCV viral load and colonic T reg frequency. A significant negative correlation between HCV-expressing cells with both liver inflammation and fibrosis was identified. Our study provides evidence that HCV can infect B cells and macrophages of the colon. The correlations between HCV infection in colonic tissue and HCV viral load and liver pathology underline the significance of this extra-hepatic infection in HCV pathogenesis and response to therapy.

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AIM: This study aimed to evaluate the efficacy and safety of sofosbuvir (SOF)/ribavirin (RBV) and SOF/daclatasvir (DAC)/ RBV in Egyptian patients with hepatitis C virus (HCV)-related cirrhosis and to demonstrate the effects of these treatments on their haematological and biochemical profiles. PATIENTS AND METHODS: A prospective study was performed on 200 patients with HCV-related cirrhosis. Group 1 received SOF and RBV for 24 weeks, and Group 2 received SOF, DAC and RBV for 12 weeks. RESULTS: A sustained virological response (SVR) was achieved in 75 (75%) and 96 (96%) patients in Groups 1 and 2, respectively. The mean haemoglobin (Hb) level and platelet count decreased significantly at the end of treatment in both groups, and the percent decrease was significantly higher in Group 1 than in Group 2. The mean albumin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels decreased significantly at the end of treatment in both groups. There was a significant increase in the mean total bilirubin level in both groups at the end of treatment. The percent increase in the mean indirect bilirubin level was significantly higher in Group 2 than in Group 1. There was improvement in the Fibrosis-4 (FIB-4) score at the end of treatment in both groups. This improvement was maintained to SVR 12 in both groups. CONCLUSION: Patients with cirrhosis who received SOF, DAC and RBV for 12 weeks had a significantly higher SVR12 rate than those who received SOF and RBV for 24 weeks. In patients who achieved SVR, there was improvement in liver function parameters and the FIB4 score at the time of SVR12 in compared to baseline values.