Interferon lambda 4 gene [IFNL4] linked to hepatitis c virus clearance, treatment

Background: A designated IFNL4 gene, encoding the interferon-X4 protein [IFNL4], which is moderately similar to IFNL3, is more strongly associated with HCV clearance in individuals of African ancestry, whereas it provides comparable information in Europeans and Asians

Aim of the work: The study was attempted for the identification of interferon Lambda 4 [IFNL4] gene expression in the liver biopsy and the recombinant IFNL4 protein in the serum of CHCV patients

Patients and methods: Eighty five patients with chronic hepatitis C virus infection [CHCV], whose age ranged between 19 and 57 years, were selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, before chronic HCV therapy, during the preparation of patients, and ten healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigations, CBCs. Liver biopsy was done to all patients and controls. Patients revealed mild fibrosis [Metavir fibrosis from Fl to F3]. Using freshly frozen liver biopsies to identify gene [IFNL4] by real time-PCR and the detection of its serum protein levels by EL1SA

Results: Patients with CHCV have higher hepatic expression of IFNL4 before treatment and also recombinant IFNL4 protein expression was detectable in serum with high levels

Conclusion: An inducible human protein-coding gene IFNL4, which is related to, known IFNs have been identified in genotype 4 CHCV patients

Recommendations: The therapeutic inhibition of IFNL4 might represent a novel biological target for the treatment of HCV and HBV infection and possibly other diseases

role of vitamin D during therapy in chronic hepatitis C virus infection and its relation to CYP 27 B1-1260 promoter polymorphism

Objective: vitamin D is a potent immunomodulator. A number of genetic polymorphisms in the vitamin D pathway have been shown to affect vitamin D signaling, and stratification according to such polymorphisms has already being implemented in randomized controlled clinical intervention studies

Aim of the work: the study was attempted to examine whether vitamin D improved viral response and predicted treatment outcome in patients with chronic hepatitis C virus [CHCV] infection

Patients and methods: ninety two patients with CHCV, whose age ranged between 20 and 56 years, were selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, before and after the treatment with pegylated interferon [PEG-IFN], ribavirin [RBV] and vitamin D supplementation drops; 2000 IU/day, 10 drops/day, six patients whom received identical therapy without vitamin D were included to serve as controls. All the patients had body mass index [BMI]

Results: the treatment group with vitamin D had BMI

Conclusion: our study suggests a role of vitamin D in the response to treatment of chronic HCV patients. However, serum concentration is not a suitable predictor of treatment outcome. VDR had a predictive positive treatment outcome. CYP27B1-1260 was found to be an independent predictor of sustained virologic response [SVR]

Recommendations: The level of recommended supplementation of vitamin D depends on the patient's individual deficiency, although 2000 IU daily is a common dose. Patients taking vitamin D supplements should have serum measurements made after starting therapy to determine whether they are reaching target levels

fundamental role played by cell cycle proteins in controlling cell proliferation in chronic hepatitis C virus infection

Background: examining the alteration of cell cycle genes in early hepatitis C virus [HCV] found that altered expression of mitotic checkpoint genes, MAD2L1, KNTC1, CDC16 and CDC34, KNTC1 known as "rough deal protein" [ROD] is part of a complex involved in elaborating an inhibitory signal due to improper chromosomal aligment during cell division

Aim of the work: attempt for the identification of proteins [genes], which act as predictive factors to identify patients with high risk of cell transformation and HCC development

Patients and Methods: fifty three patients with chronic HCV infection, age ranged between 18 and 58 years, time of assessment was before starting therapy of hepatitis C at the National Hepatology and Tropical Medicine Research Institute. Ten healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography, and collection of blood samples for routine laboratory investigation; CBCs. Liver biopsy was done to all patients and controls, patients revealed mild fibrosis [Metavir fibrosis scores from F1 to F3]. Also, we used freshly frozen liver biopsies mRNA levels with perspective protein levels of four genes: P27, P15, KNTC1, MAD2L1

Results: significant association of P27, P15, KNTC1 and MAD2L-1 with the progression of liver fibrosis in chronic HCV liver biopsy was found

Conclusion: there is altered gene expression in HCV-associated liver disease

Recommendations: The emerging interest of hepatologists in the influence of genetic factors in HCV. Evaluation of the expression of key proteins related to the cell cycle and apoptosis in chronically infected patients with HCV would be of significance to understand disease pathogenesis, and will help in identifying novel prognostic indicators

IFN-stimulated genes upregulation pattern in Chronic Hepatitis C

Background: The development of effective tools for the large-scale analysis of gene expression has provided new insights into the involvement of gene networks and regular pathways in various disease processes. The chemokine receptor CXCR3 is a G protein-coupled receptor found predominantly on T cells that is activated by three ligands as follow: CXCL9 [Mig], CXCL10 [IP-10] and CXCL11 [I- TAC], and play a key role in immune and inflammatory responses by promoting recruitment and activation of different subpopulations of leukocytes. Aim of the work: The study is a logical functional approach for the development of serum markers chemokines that bind to CXC chemokine receptor 3 to determine whether they play a role in the future of immune system to clear HCV, these chemokines: CXCL9, CXCL10 and CXCL11

Patients and methods: 131 male and female patients with chronic hepatitis C virus [CHCV] infection, their age ranges between 22 and 55 years,selected from the National Hepatology and Tropical Medicine Research Institute. The included patients were divided to two groups, the first group: 80 patients were investigated for the predictive values of CXCL9,10,11 and CXCR3 chemokines in peripheral blood mononuclear cells [PBMCs], the second group were fifty one patients analyzed for the expression of surface markers on CD8+T cells. Twenty healthy individuals were included to serve as controls for each group. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation and serological assay

Results: Chemokine CXCL9, CXCL10, CXCL11 and their receptor CXCR3 expression levels are induced in PBMCs during CHCV infection, associated with increased the expression levels of CD8+T cells in CHCV patients

Conclusion: The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection

Recommendations: The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver, the blocking of chemokines and chemokine receptor engagement is a therapeutic strategy that should be explored in the near future for non-responders to current anti-HCV therapy

Tumor necrosis factor-alpha [TNF - alpha] gene expression in chronic hepatitis B virus infection

Background: Tumor necrosis-alpha [TNF-alpha] is produced by macrophages, neutrophils, T-cells and NK-cells after stimulation. In turn, TNF-alpha can stimulate secretion, increase the expression of adhesion molecules as well as active neutrophils. Hence, it fulfills the role as a principal mediator of cellular immune response and inflammation, and may play an important role in non-cytopathic and cytolytic clearance of hepatitis B virus [HBV]. The clearance of HBV is a complex process which may be influenced by many factors including polymorphisms in the tumor necrosis [TNF-] gene promoter

Aim of the work: The study aimed to determine the TNF-alpha as a gene expressed in chronic hepatitis B virus infection and its role in outcome of the virus

Patients and methods: Ninety four patients with chronic HBV infection, their age between 19 and 59 years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during treatment and twenty healthy individuals were included to serve as controls. All the patients and controls were subjected to the following; history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, and serological assay for HBsAg, HBsAb, HBeAg, HBeAb, HBV DNA [quantitative], and TNF-alpha promoter polymorphisms in two sites 238 and 308

Results: The prevalence of the variant at position -308 GA was similar in all investigated groups [patients and controls]. An association was found between the TNF-alpha promoter polymorphism at position -238 and the development of chronic HBV infection with sensitivity of 93% and specificity of 75%

Conclusion: TNF-alpha-308 GA was significantly associated with clearance, showing protective antibody and persistent HBV infection. The promoter variant of TNF-alpha at position 238 GA, GG appears to be linked to defective viral clearance, controls had higher TNF-alpha-238 GG,GA, AA as compared to cases with significant difference

Recommendations: The variation in the genes governing the levels of constitutive and inducible TNF-alpha might be an important factor, which might explain the variable outcome of HBV infection

CD8+T cell activation associated with viral replication in chronic infection

PD-1 expression is controlled during T-cell activation. PD-1 has an important role in regulating immune response as well as tolerance. During chronic hepatitis C virus [HCV] infection there is high level of PD-1 expression on exhausted CD8+T cells. There is also reduced expression of T-bet. T-bet is identified as a transcriptional repressor of Pdcd1. The study will attempt to find out the level of expression of PD-1 on peripheral CD8 + T-cells, associated with chronic HCV infection. Fifty patients with chronic hepatitis C virus infection [CHCV], whose age ranged between [16-59] years, were selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, before Interferon and ribavirin therapy, and fifteen healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigations. CBCs and analysis of the expression of surface markers on CD8+T cells and PD-1. Our results suggested that increased expression of PD-1 cells was an additional inhibitory mechanism that contributed to virus-specific CD8 + T cell exhaustion in chronic hepatitis C virus [CHCV] infected patients. Our study concluded that there's significant increase in PD-1 expression of circulating HCV-specific CD8 + T cells in CHCV patients. The blockade of the inhibitory receptors [PD-1] programmed cell death is considered as a novel strategy for the treatment of chronic HCV infection

Neutropenia in chronic hepatitis C during Interferon and ribavirin therapy

Neutropenia is a condition characterized by an abnormally low number of a type of white blood cells called Neutrophils, up to 25% of people who take pegylated interferon, ribavirin and an HCV protease inhibitor experience Neutropenia. The study will be intended to analyze neutrophil counts and associated conditions of the liver and spleen, platelet count, liver enzymes and infections, during Interferon and Ribavirin therapy. One hundred forty two patients with chronic hepatitis C virus infection, their age between [18-59] years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during Interferon and Ribavirin therapy. All the patients were subjected to the following history, through clinical examination, abdominal ultrasonography and collection of blood samples for routine investigations, CBCs and serological assay for ALT, Bilirubin. Our results revealed presence of 32.4% anaemia, 18.3% Thrombocytopenia, 16.9% elevated ALT, 2.8% elevated bilirubine, 16.9% coarse liver, 25.4% hepatomegaly, 16.2% splenomegaly, and 16.9% of cases complained different shapes of infection, associated with Neutropenia in patients of chronic hepatitis C during interferon and ribavirin therapy. Our study concluded that the prevalence of Neutropenia in chronic hepatitis C virus infection patients 23.8% during interferon and ribavirin therapy but it is not usually associated with infection. Neutropenia is a complicated process that requires expert guidance from a medical provider

combination anti-HBV regimen using lamivudine and other agents in treatment of resistant chronic hepatitis B

Several difficulties remain in formulating treatment for chronic hepatitis B [CHB], 350 million people are chronically infected with HBV, Chronic infection with hepatitis B virus accounts for an enormous burden of disease worldwide, including up to half of all cases of cirrhosis, end stage liver disease, and hepatocellular carcinoma. To maximize the elimination of the viral infection while minimizing or preventing damage to the liver cells and tissues and development of viral resistance to more antivirals. Eighty eight patients of chronic hepatitis B virus infection with resistance to lamivudine treatment as proved by quantitative PCR [more than 200 IU/ ml]. Their age between [20-60] years, [85 males, and 3 females] were selected from the National Hepatology and Tropical Medicine Research Institute and were included in this study. The included patients were two groups, the first group 42 patients, were receiving Lamivudine, plus [Baraclude] Entecavir [tablet 0.5mg / day] treatment at the time of assessment. The second group 46 patients were receiving [Hepsera tablet 10 mg / day] Adefovir dipivoxil plus lamivudine [tablet]. All the patients were subjected to the following: thorough history and clinical examination, abdominal ultrasonography and collection of blood samples for routine liver and kidney function investigations and serological assay for HBsAg, HBsAb, HBeAg, HBeAb, HBcAb quantitative HBV DNA [PCR]. Our results revealed significant differences between the two groups of patients of CHBV infection, resistant to Lamivudine drug, the first group were higher in response to a combination between Lamivudine + [Baraclude] Entecavir, than the second group who were receiving Lamivudine + [Hepsera] Adefovir dipivoxil combination therapy. Our study concluded that the clinical benefit is apparent with high percentage after a combination regimen using Lamivudine + Entecavir than a combination regimen using Lamivudine + Adefovir dipivoxil for the treatment of resistant chronic hepatitis B virus who were treated with Lamivudine only before. Optimal management of chronic hepatitis B, that may require long-term and sometimes lifelong treatment to maintain its clinical benefit is challenging. It is important to initiate treatment with a drug that has the least potential for induction of drug resistance as sequential monotherapy which may result in selection of multidrug resistant HBV mutatants