Phylogenetic analysis has led to the classification of hepatitis B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show heterogeneity in their global distribution. These attributes of the genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also makes them responsible for differences in the clinical outcome and response to antiviral treatment in different population groups. Africa is one of the highly endemic regions of HBV with five genotypes (A-E) identified. Almost all patients in the Mediterranean area are infected with genotype D. However, there is little information of genotype distribution in Egypt. A total of 140 Egyptian patients with hepatitis B surface antigen (HBsAg) positive were enrolled in this study. Of the 140 patients, only 100 patients were HBV DNA positive and only these were included in the study. They were classified into 20 patients with acute hepatitis (AH), 75 patients with chronic active hepatitis (CAH) and 5 patients with hepatocellular carcinoma (HCC). HBV genotypes were determined using INNO-LiPA methodology which is based on the reversed hybridization principle. This study showed that genotype D constituted 87% of the total infections (75 CAH cases, 7 AH cases and 5 HCC cases). The other 13% showed mixed infections of D/F. These findings show that the most prevalent genotype in Egypt is genotype D especially in CAH and HCC patients while the mixed type D/F is only encountered in AH.

BackgroundThe Fas receptor/ligand system including soluble forms is the most important apoptotic initiator in the liver. Dysregulation of this pathway may contribute to abnormal cell proliferation and cell death and is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells.ObjectivesTo analyze the role of Fas system Fas/ Fas ligand (Fas/ FasL) in the multi-step process of hepatic fibrosis/carcinogenesis, and to use of the serum markers as possible candidate biomarkers for early detection of hepatocellular carcinoma (HCC).Patients and MethodsNinety patients were enrolled: 30 cases of chronic hepatitis C (CHC) without cirrhosis, 30 cases of CHC with liver cirrhosis, and 30 cases of HCC and hepatitis V virus (HCV) infection. Ten wedge liver biopsies, taken during laparoscopic cholecystectomy, were served as normal controls. Serum soluble Fas (sFas) levels were measured using ELISA technique; Fas and FasL proteins were detected in hepatic tissue by indirect Immuno-histochemical technique (IHC); electron microscopic (EM) and immune electron microscopic examinations were performed for detection of Fas expression on lymphocytes.ResultsHepatic expression of both Fas and FasL as well as expression of Fas on separated lymphocytes were significantly increased in the diseased groups (P < 0. 01) compared to the control specimens. The highest expression was noticed in CHC specimens, particularly with the necro-inflammatory activity and advancement of the fibrosis. The sFas in cirrhotic patients and HCC were significantly higher than that in normal controls and CHC without cirrhosis group (P < 0.01).ConclusionsApoptosis and the Fas system were significantly involved in the process of converting liver cirrhosis into hepatocellular carcinoma. Down-regulation of Fas expression, up regulation of FasL expression in hepatocytes, and elevation of serum sFas levels were important in tumor evasion from immune surveillance, and in hepatic carcinogenesis.

IntroductionAltered neutrophil apoptosis might be responsible for recurrent bacterial infections encountered in hemodialysis (HD) and chronic kidney disease (CKD) patients. This work was designed to assess the neutrophil apoptotic activity and the impact of implementation of granulocyte macrophage colony stimulating factor (GM-CSF), as a survival factor, on neutrophil apoptosis among these patients.Material and methodsTwenty-five patients on regular HD along with 34 CKD patients on conservative treatment, as well as 15 healthy controls, were investigated for apoptotic rate via assessment of neutrophil expression of Annexin-V by flow cytometry, before and after 20 h culture in absence and presence of GM-CSF. Neutrophil viability was determined using light microscopy. The preservation of neutrophil activation in these patients was analyzed by flow cytometric CD18 neutrophil expression. Chronic inflammatory state was evaluated by estimating C-reactive protein (CRP) and soluble intercellular adhesion molecule-1 (sICAM-1). Obtained data were statistically analyzed.ResultsCompared to controls, both HD and CKD groups had a significant increase of Annexin-V and CD18 expression and significant decrease in neutrophil viability. Culture of their neutrophils with GM-CSF showed significant decrease of apoptosis accompanied by improvement of neutrophil viability compared to their cultured cells without GM-CSF. These patients also showed significant elevation of CRP and sICAM-1.ConclusionsGranulocyte macrophage colony stimulating factor demonstrated an evident impact on improving in vitro neutrophil survival and viability in HD and CKD patients. Therefore, this may represent promising preventive and/or therapeutic strategies against infection frequently observed in these patients and causing morbidity and mortality.

The aim of the study is to characterize the phenotypes of CD4+ CD25+ T regulatory cells within the liver granulomas and association with both Foxp-3 gene expression and splenic cytokines. Naïve C57BL/6 mice were intravenously injected with multiple doses of the soluble egg antigen (SEA) 7 days before cercarial infection. The immunized and infected control groups were sacrificed 8 and 16 weeks post-infection (PI). Histopathology, parasitological parameters, splenic phenotypes for T regulatory cells, the FOXP-3 expression in hepatic granuloma using real-time PCR, and the associated splenic cytokines were studied. Histopathological examination of the liver revealed remarkable increase in degenerated ova within hepatic granuloma which decreased in diameter at weeks 8 and 16 PI (P<0.01). The percentage of T regulatory cells (CD4+ CD25+) increased significantly (P<0.01) in the immunized group compared to the infected control at weeks 8 and 16 PI. The FOXP-3 expression in hepatic granulomas increased from 10 at week 8 to 30 fold at week 16 PI in the infected control group. However, its expression in the immunized group showed an increase from 30 at week 8 to 70 fold at week 16 PI. The splenic cytokine levels of pro-inflammatory cytokines, IFN-γ, IL-4, and TNF-α, showed significant decreases (P<0.05) compared to the infected control group. In conclusion, the magnitude and phenotype of the egg-induced effects on T helper responses were found to be controlled by a parallel response within the T regulatory population which provides protection in worm parasite-induced immunopathology.

BackgroundChronic viral hepatitis is histologically characterized by predominantly periportal infiltration of mononuclear cells, including lymphocytes and monocytes/macrophages. Intralobular infiltration of these inflammatory cells is an ominous sign of deterioration and a criterion for disease activity.ObjectiveTo assess the monocyte inflammatory milieu, monocytes adhesion molecules, their endothelial receptors, cytokines and chemokines in patients with HCV induced chronic liver disease, in an attempt to clarify the role of blood monocytes in induction of inflammation and fibrogenesis in chronic hepatitis C liver disease.Subjects and MethodsThe current study included 60 patients with chronic liver disease categorized into 2groups: Patients chronic hepatitis C (CHC) and patients with liver cirrhosis (LC), 15 patients each; 15 healthy subjects were included as normal controls. Immunophenotype characterization was carried out by flowcytometric analysis for identification of CD11a, CD11b and CD49d monocyte surface antigen expression in different groups studied. The circulating levels of the soluble adhesion molecules (sE-selectin, sICAM-1 and sVCAM-1), cytokines (TNF-α and IL-1) and chemokines (MCP-1) were also assessed by immunoassays.ResultsData demonstrated a significant increase (p<0.01) in the surface expression of CD11a on peripheral blood monocytes and in the circulating levels sE-selectins, sICAM-1, sVCAM-1 and TNF-α in both groups of patients compared to healthy subjects. Data also revealed a significant increase (p<0.01) in the surface expression of each of CD11b and CD49d on peripheral blood monocytes and in the circulating levels sICAM-1, sVCAM-1 and TNF-α in patients with LC compared to those with CHC. Moreover, data demonstrated that the increase in surface antigen expression of each CD11a (p<0.01), CD11b (p<0.05) and CD49d (p<0.01) on circulating peripheral blood monocytes is positively correlated with the increase in the circulating levels of each of sICAM-1 and sVCAM-1 in the both groups of patients.ConclusionsThese findings suggest that the modulation of monocyte-subset recruitment into the liver via adhesion molecules or cytokines/cytokine receptors may represent promising approaches for therapeutic interventions in human liver fibrosis. Measurement of serum soluble adhesion molecules may be useful for monitoring progression of liver inflammation and fibrosis during CHC.