Egyptian Hepatitis C Virus Patients Research Articles

Evaluation of Serum Level of IL-6 in Chronic Hepatitis C Virus Infected Egyptian Patients

Background: Hepatitis C virus (HCV) infection is a worldwide public health problem. The highest prevalence is in Egypt and constitute about 10-20% of the general population. IL-6 is a plieotropic cytokine that plays a role in the acute phase response; it is released from various cells, such as, Leukocytes, fibroblasts, macrophages and endothelia cells. IL-6 is produced by kupffer cells in the liver and leads to production of the acute phase proteins. Aims: This study was conducted to evaluate serum level of IL-6 as a marker of liver fibrosis in chronic hepatitis C virus infected Egyptian patients and to assess its correlation with the stages of liver fibrosis. Methods: A case control study was conducted on 40 Egyptian patients with chronic HCV infection (group1). Studied patients were divided according to the stage of fibrosis assessed by fibroscan into two sub-groups: Group Ia: 22 Patients with early fibrosis (F0, F1, F2) and Group Ib: 18 Patients with late fibrosis (F3, F4) compared to age matched 40 healthy controls (group 11). Routine laboratory investigations, Hepatitis markers including (HBsAg), HCV antibody and HCV RNA by real time polymerase chain reaction (PCR) and, serum Interleukin-6 and Abdominal ultrasonography were done for all studied groups and assessment of liver fibrosis by APRI score & FIB-4for patients and control but Fibro scan for patients only. Results: There were highly significant Elevation of serum level of IL-6 in group1 when compared to the control and This elevation was more significant in (group Ib) when compared to (group Ia) and There was highly significant positive correlation between serum IL-6 and each of serum ALT, AST and Fibro scan in group 1. Conclusion: The study concluded that a highly significant elevation of serum level of IL-6 in chronic HCV Egyptian patients and there was a highly significant positive correlation between IL-6 and stages of liver fibrosis assessed by fibroscan.

Chronic Hepatitis C Virus (HCV)-associated Cryoglobulinemia and its possible impact on the skin in Egyptian Patients

Background: Chronic hepatitis C virus (HCV) infection may have extremely variable clinical consequences and is more than just a liver disease; it has been associated with numerous extra-hepatic manifestations (EHM). According to various international studies Mixed Cryoglobulinemia (MC) was found to be the most common EHM, however its local prevalence in Egyptian HCV patients was not clearly studied. The aim of our study was to investigate the frequency of cryoglobulinaemia in sera of chronic HCV patients and their association with clinical symptoms especially, vasculitis. Method: One hundred patients with chronic HCV infection attending the outpatient clinic of the National Hepatology and Tropical Medicine Research Institute were interviewed. Patients with decompensated liver disease, on interferon therapy, having end-stage renal disease or coexisting viral infection like hepatitis B surface antigen positive patients were all excluded from the research. All patients were subjected to general and dermatological examination for liver affection signs; cryoglobulinemia related clinical manifestations and/or associated dermatoses. Cryoglobulins, CBC, LFT. AFP, ALP, KFT, ANA and RF were assessed. Results: Overall 15% of 100 patients were positive for presence of cryoglobulins in their sera. We found a relatively high incidence of clinical symptoms commonly accompanying cryoglobulinemic cases in the form of Purpura, Arthralgia, Generalized weakness, Peripheral Neuropathy and Reynaud’s phenomenon with prevalence of 26.67%, 46.67%, 53.33%, 40% and 6.67% respectively. Our data also demonstrated that 46.67% (7) of our 15 cryopositive patients had concomitant skin manifestations in the form of Pruritus 40% (6) and Vasculitis 26.67% (4) (P=0.004) which was significant in comparison with prevalence of vasculitis in all patients 4.7% (4 patients). Generalized weakness and fatigue, which is the most prevalent symptoms related to Chronic Hepatitis C (CHC) patients whether positive or negative for cryoglobulinemia, were present in 52% of all patients. Other associated dermatological diseases in all patients were Lichen Planus, Psoraiasis, Urticaria, Necrolytic Acral Erythema (NAE) and Vitiligo with prevalence of (1%), (1%), (5%), (1%) and (2%) respectively. The most common dermatological disease was pruritus 36% (36) of all patients and 40% (6) in cryopositive patients. Regarding liver condition there was no significant correlation between presence of cryoglobulins and biochemical parameters. However, we found a significant correlation between presence of cryoglobulinemia and presence of ANA in sera of HCV patients with incidence of 40%) in

Chronic Hepatitis C Virus (HCV)-associated Cryoglobulinemia and its possible impact on the skin in Egyptian Patients

Background: Chronic hepatitis C virus (HCV) infection may have extremely variable clinical consequences and is more than just a liver disease; it has been associated with numerous extra-hepatic manifestations (EHM). According to various international studies Mixed Cryoglobulinemia (MC) was found to be the most common EHM, however its local prevalence in Egyptian HCV patients was not clearly studied. The aim of our study was to investigate the frequency of cryoglobulinaemia in sera of chronic HCV patients and their association with clinical symptoms especially, vasculitis. Method: One hundred patients with chronic HCV infection attending the outpatient clinic of the National Hepatology and Tropical Medicine Research Institute were interviewed. Patients with decompensated liver disease, on interferon therapy, having end-stage renal disease or coexisting viral infection like hepatitis B surface antigen positive patients were all excluded from the research. All patients were subjected to general and dermatological examination for liver affection signs; cryoglobulinemia related clinical manifestations and/or associated dermatoses. Cryoglobulins, CBC, LFT. AFP, ALP, KFT, ANA and RF were assessed. Results: Overall 15% of 100 patients were positive for presence of cryoglobulins in their sera. We found a relatively high incidence of clinical symptoms commonly accompanying cryoglobulinemic cases in the form of Purpura, Arthralgia, Generalized weakness, Peripheral Neuropathy and Reynaud’s phenomenon with prevalence of 26.67%, 46.67%, 53.33%, 40% and 6.67% respectively. Our data also demonstrated that 46.67% (7) of our 15 cryopositive patients had concomitant skin manifestations in the form of Pruritus 40% (6) and Vasculitis 26.67% (4) (P=0.004) which was significant in comparison with prevalence of vasculitis in all patients 4.7% (4 patients). Generalized weakness and fatigue, which is the most prevalent symptoms related to Chronic Hepatitis C (CHC) patients whether positive or negative for cryoglobulinemia, were present in 52% of all patients. Other associated dermatological diseases in all patients were Lichen Planus, Psoraiasis, Urticaria, Necrolytic Acral Erythema (NAE) and Vitiligo with prevalence of (1%), (1%), (5%), (1%) and (2%) respectively. The most common dermatological disease was pruritus 36% (36) of all patients and 40% (6) in cryopositive patients. Regarding liver condition there was no significant correlation between presence of cryoglobulins and biochemical parameters. However, we found a significant correlation between presence of cryoglobulinemia and presence of ANA in sera of HCV patients with incidence of 40%) in

5′ UTR and NS5B-based genotyping of hepatitis C virus in patients from Damietta governorate, Egypt

Chronic hepatitis C virus (HCV) infection is a main health problem in Egypt causing high rates of mortalities. Egypt has the highest HCV prevalence in the world, with specific HCV subtypes epidemic and circulating extensively in the country. Different antiviral therapy protocols have been implemented for treating Egyptian HCV patients. Due to the limited data about HCV in Egypt, this study aimed to genotype HCV strains circulating in the Nile Delta Damietta governorate and to investigate the variation in the nonstructural 5B (NS5B) region targeted by the newly approved antiviral drugs. Thirty HCV samples from treatment-naïve patients were genotyped by restriction fragment length polymorphism. Some samples were genotyped by direct sequencing of their 5′ untranslated region (UTR) and NS5B regions. Phylogenetic analysis was also performed on the sequences of their NS5B regions. Fourteen new sequences have been deposited in the GenBank database. Results showed that subtype 4a was prevalent in addition to subtype 1g. None of the previously reported NS5B substitutions were detected in the sequenced isolates from treatment-naïve patients, which may be a good predictor for efficient treatment of HCV Egyptian patients with Sofosbuvir. Further studies on Sofosbuvir treated-HCV Egyptian patients are required to investigate whether any NS5B substitutions can confer resistance to treatment.

Study of the Humoral Immune Response towards HCV Genotype 4 Using a Bead-Based Multiplex Serological Assay.

Hepatitis C is one of the leading causes of hepatocellular carcinoma and remains at a high prevalence in Egypt and other resource-limited countries. Several hepatitis C virus (HCV) genotypes are distributed throughout the world, with genotype 4 being most common in North and Central Africa. We developed a multiplex serological assay for the detection of the HCV specific humoral immune response, with a focus on genotype 4. For the multiplex HCV assay we used twelve antigenic regions of different HCV proteins (core, and non-structural (NS) proteins NS3, NS4, NS5A, NS5B) and validated the assay technically and clinically. In comparison to a commercially available test, our assay revealed a higher sensitivity for genotype 4, and is therefore more suited for studying immune seroconversion in samples from acutely infected Egyptian HCV patients. Furthermore, our assay discriminates acutely and chronically infected HCV patients. Of 296 well characterized HCV patient samples, 83.9% of the acute samples and 86.5% of the chronic samples could be correctly classified. In sum, this newly developed serological HCV assay has a higher sensitivity for HCV genotype 4, and can thus improve diagnostic accuracy. Through the discrimination of acutely and chronically infected HCV patients the assay may be useful in supporting clinical management of HCV patients.

Real-life results of sofosbuvir based therapy in chronic hepatitis C -naïve and -experienced patients in Egypt.

BackgroundMore than ten million Egyptians are infected with HCV. Every one of them is going to infect about three to four persons every year. Treating those patients is a matter of national security. A dramatic improvement in hepatitis C virus (HCV) infection treatment was achieved in the last five years. A new era of direct-acting antivirals is now dawning in Egypt.Objective(s)We share in this report our clinical experience in treating chronic HCV Egyptian patients with Sofosbuvir based regimens to evaluate its safety and efficacy on real life practical ground.MethodsA total of 205 chronic HCV patients (195 naive and 15 experienced) were enrolled in the study. Patient were treated with Sofosbuvir+Ribavirin 24 weeks as standard of care. Two interferon eligible patients were treated with PEG-INF+ Sofosbuvir+Ribavirin for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response at 24 weeks after cessation of therapy.ResultsThe overall response rate was 97.1%. Sustained virological response rate did not differ among treatment-naive patients and patients with previous history of IFN-based therapy. Portal hypertension, prediabetes, and lack of early virologic response were predictors of non response. No clinically significant treatment-emergent adverse effects were noted. No treatment discontinuation was encountered.ConclusionIn the real-life setting, Sofosbuvir based regimens for 24 weeks has established an efficacious and well tolerated treatment in naïve and experienced patients with chronic HCV genotype 4 infection; although shorter treatment durations may be possible. However, patient follow up should extent to at least 6 months post-treatment and verifying viral load on yearly basis is warranted to track any late relapse.

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement.

BackgroundLiver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 pre-dominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM) improvement after successful HCV eradication.Patients and methodsThe study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA) treatment and after achieving sustained virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified into F0–F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4), p-value <0.05 was statistically significant.ResultsFollowing DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%), mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m2. Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of −5.8 occurred in F4 versus −2.79, −1.28 and +0.08 in F3, F2 and F0–F1 respectively (p<0.0001). At baseline, 41 patients were in the F4 group; only 16 (39%) regressed to non-cirrhotic range (<12.5 kPa), while 25 (61%) were still cirrhotic despite achieving SVR-24 (p<0.0001). Patients who achieved LSM improvement (n=64) have had significantly higher baseline aspartate transferase (AST) and alanine transaminase (ALT). Also, those patients showed significant improvement in AST, AST/platelets ratio index (APRI) and fibrosis-4 index (Fib-4) after achieving SVR; 91% showed AST improvement (p=0.01) and APRI improvement (p=0.01) and 81% showed Fib-4 improvement (p=0.04). Females, diabetics, patients with S3 steatosis and patients older than 50 years showed less LSM improvements than their counterparts. Baseline LSM ≥9 kPa, bilirubin ≥1 mg/dl, ALT ≥36 U/L and AST ≥31 U/L were significant predictors for LSM improvement.ConclusionSuccessful HCV genotype-4 eradication results in significant LSM improvement; the best improvement occurs in F4 patients. But as the majority of cirrhotics are still at risk for liver decompensation and hepatocellular carcinoma development despite achieving SVR-24, early detection and treatment are highly recommended.

The genetic association of cytokine genes, single nucleotide polymorphisms, and the incidence of liver cirrhosis in chronic hepatitis C Egyptian patients

Cytokines play a central role in regulating the anti-viral responses against hepatitis C virus (HCV). The objective of this study were to evaluate the effect of proinflammatory cytokines (IL-18 − 607 C/A, rs 1946518; IL-18 − 137 G/C, rs 187283; INF-γ + 874 T/A, rs 240561), SNPs, and the anti-inflammatory cytokine (IL-10 + 1082 G/A, rs 1800896) SNPs on the risk of development of hepatic cirrhosis in Egyptian patients and to evaluate the combined effect of the polymorphic variants that show an interrelation with the risk of hepatic cirrhosis. The study included 63 chronic HCV patients. The patients were stratified into two groups. Group 1 consisted of 33 cirrhotic chronic hepatitis C patients while the second group consisted of 30 non-cirrhotic chronic hepatitis C patients that were taken as a control group. Genotyping of IFN-γ (+ 874 T/A) and IL-10 (− 1082 G/A) SNPs was performed by allele-specific PCR technique (AS-PCR). Genotyping of IL-18 (− 607 C/A) and IL-18 (− 137 G/C) SNPs was determined by PCR-RFLP technique. Analysis of IFN-γ (+ 874 T/A) SNP revealed that the T allele and the TT genotype were significantly higher in cirrhotic patients’ group compared to non-cirrhotic group (P < 0.001 and P = 0.004, respectively). Analysis of IL-10 (− 1082 G/A) SNP revealed that the A allele and AA genotype were significantly higher in the cirrhotic patients’ group (P = 0.001 and P = 0.047, respectively). Regression analysis revealed that IFN-γ Hi/IL-10 Lo combined genotypes were significantly higher in liver cirrhosis patients compared to non-cirrhotic patients (P = 0.002). INF-γ (+ 874 T/A) and IL-10 (+ 1082 G/A) SNPs might be associated with occurrence of hepatic cirrhosis in chronic HCV Egyptian patients.

Incidence of HCV induced-Esophageal varices in Egypt: Valuable knowledge using data mining analysis.

Esophageal varices is one of the most important comorbidity related liver cirrhosis, patients usually presented with hematemesis, melena, or both, ultimately 20% is the mortality during the first attack, hence we aimed to investigate the incidence of such esophageal varices related chronic Hepatitis C virus (HCV) in randomized Egyptian population.One thousand eighteen Egyptian patients, aged between 17 and 58 years, positive for Hepatitis C virus genotype 4 (HCV-4) by enzyme linked immunosorbent assay Ab and HCV RNA-polymerase chain reaction were screened for the presence of esophageal varices.Incidence of esophageal varices was 62.3%; 635 patients, those with large Esophageal varices (LEVs) was 47.4%; 301 patients. Model for end-stage liver disease (MELD) score has not been significantly improved post variceal band ligation (VBL). Using 2D U/S was useful for EVs prediction.Incidence of esophageal varices in HCV Egyptian patients still high, valuable knowledge would be helpful in clinical field have been discovered by data mining computational intelligent analysis using in practical medicine to improve overall health care.

Gut microbiome alterations in patients with stage 4 hepatitis C.

BackgroundHepatitis C virus (HCV) causes debilitating liver diseases, which may progress to cirrhosis and cancer, and claims 500,000 annual lives worldwide. While HCV epidemiology, pathophysiology, and therapy are being deeply studied, rare attention is given to reciprocal interactions between HCV infection , HCV-induced chronic liver diseases, and the human gut microbiome. As Egypt has the world’s highest prevalence of HCV infections, we launched this study to monitor differences in the gut microbial community composition of Egyptian HCV patients that may affect, or result from, the patients’ liver state.ResultsTo this end, we analyzed stool samples from six stage 4-HCV patients and eight healthy individuals by high-throughput 16S rRNA gene sequencing using Illumina MiSeq. Overall, the alpha-diversity of the healthy persons’ gut microbiomes was higher than those of the HCV patients. Whereas members of phylum Bacteroidetes were more abundant in HCV patients, healthy individuals had higher abundance of Firmicutes, Proteobacteria, and Actinobacteria. Genus-level analysis showed differential abundance of Prevotella and Faecalibacterium (higher in HCV patients) vs. Ruminococcus and Clostridium (healthy group), indicating that the higher abundance of Bacteroidetes in HCV patients is most likely due to Prevotella overabundance. The probiotic genus, Bifidobacterium, was only observed in the microbiotas of healthy individuals.ConclusionsTo the best of our knowledge, this study provides a first overview of major phyla and genera differentiating stage 4-HCV patients from healthy individuals and suggests possible microbiome remodeling in chronic hepatitis C, possibly shaped by bacterial translocation as well as the liver’s impaired role in digestion and protein synthesis. Future studies will investigate the microbiome composition and functional capabilities in more patients while tracing some potential biomarker taxa (e.g., Prevotella, Faecalibacterium vs. Bifidobacterium).Electronic supplementary materialThe online version of this article (doi:10.1186/s13099-016-0124-2) contains supplementary material, which is available to authorized users.

PGI1 - A PILOT STUDY TO ASSESS THE EFFICACY AND SAFETY OF FOLIC ACID AND/OR VITAMIN B COMPLEX ON HEPATITIS C INFECTED PATIENTS TREATED WITH PEGYLATED INTERFERON AND RIBAVIRIN

Pegylated-interferon α-2a and ribavirin (PIFN/RBV), the current standard treatment for hepatitis C virus (HCV) infection in Egypt, is frequently associated with hematological adverse effects, leading to high treatment discontinuation rates. The objective of the present study is to explore the effectiveness of intervening with folic acid (F) and/or vitamin B complex (B) compared with placebo (C) in HCV-treatment Egyptian patients for the management of treatment-induced deterioration of health related quality of life (HRQOL) as well as hematological parameter. In a randomized controlled trial, one hundred and sixty subjects were randomly assigned to receive PIFN/RBV in addition to BF, B, F, or C. Blood samples were collected at different time points during 48 weeks and at 12 and 24 weeks post treatment for complete blood count and for HCV RNA real time PCR. Short form SF 36V2 questionnaire were used to assess HRQOL at various time during and post treatment. Egyptian HCV patients treated with PIFN/RBV showed deterioration of HRQOL which were correlated with deterioration in the measured hematological parameter. Supplementation with vitamin B complex plus folic acid significantly (P<0.001) decreased the deterioration observed in physical and mental health as well as complete blood count. Supplementation with either vitamin B complex or folic acid were also effective but with lower potency than their combination. BF supplementation can reduce adverse effects of PIFN/RBV therapy in chronic hepatitis C patients, which may improve patients’ HRQOL and their adherence to combination antiviral therapy.

Predictors of Virological Response in 3,235 Chronic HCV Egyptian Patients Treated with Peginterferon Alpha-2a Compared with Peginterferon Alpha-2b Using Statistical Methods and Data Mining Techniques

Despite the appearance of new oral antiviral drugs, pegylated interferon (PEG-IFN)/RBV may remain the standard of care therapy for some time, and several viral and host factors are reported to be correlated with therapeutic effects. This study aimed to reveal the independent variables associated with failure of sustained virological response (SVR) to PEG-IFN alpha-2a versus PEG-IFN alpha-2b in treatment of naive chronic hepatitis C virus (HCV) Egyptian patients using both statistical methods and data mining techniques. This retrospective cohort study included 3,235 chronic hepatitis C patients enrolled in a large Egyptian medical center: 1,728 patients had been treated with PEG-IFN alpha-2a plus ribavirin (RBV) and 1,507 patients with PEG-IFN alpha-2b plus RBV between 2007 and 2011. Both multivariate analysis and Reduced Error Pruning Tree (REPTree)-based model were used to reveal the independent variables associated with treatment response. In both treatment types, alpha-fetoprotein (AFP) >10 ng/mL and HCV viremia >600 × 10(3) IU/mL were the independent baseline variables associated with failure of SVR, while male gender, decreased hemoglobin, and thyroid-stimulating hormone were the independent variables associated with good response (P < 0.05). Using REPTree-based model showed that low AFP was the factor of initial split (best predictor) of response for either PEG-IFN alpha-2a or PEG-IFN alpha-2b (cutoff value 8.53, 4.89 ng/mL, AUROC = 0.68 and 0.61, P = 0.05). Serum AFP >10 ng/mL and viral load >600 × 10(3) IU/mL are variables associated with failure of response in both treatment types. REPTree-based model could be used to assess predictors of response.

Assessment of immunological, haematological and biochemical status after sofosbuvir-based combination therapy in HCV Egyptian patients from Menoufia Province

Chronic hepatitis C virus (HCV) is a serious health problem in Egypt. Although the effectiveness of pegylated interferon (peg-IFN) and ribavirin (RBV) combined therapy, poor response rates and lamentable tolerability were recorded in the chronically HCV infected patients. Sofosbuvir (SOF) target the highly conserved active site of the HCV-specific NS5B polymerase that affect directly the viral replication and has broad genotypic coverage. In the present study we investigated the efficacy of SOF-based combination therapy and its effects on the status of immune cells from chronically infected HCV Egyptian patients. HCV Patients were treated with a combination treatment of SOF, RBV and peg-IFN-α or SOF and RBV for either 12 or 24 weeks. Then biochemical, hematological parameters, immunological phenotyping, PBMCs proliferation and apoptosis were detected pre- and post-treatment. While SOF-based combination therapy improved the liver function, anemia, leucopenia and thrombocytopenia were detected especially after treatment with SOF, RBV and peg-IFN-α-2a. We observed significant reduction in the percentage of CD3+CD4+ and CD3+CD8+ cells post-treatment with either SOF and RBV or SOF, RBV and peg-IFN-α-2a as compared to the baseline. Moreover, SOF-based combination therapy altered the percentage of CD3-CD8+, CD14+ and CD20+ cells. The proliferative capacity of PBMCs was significantly decreased in both regimens, whilst the percentage of apoptotic cells was significantly augmented. SOF-based therapy regimens are efficacious in reducing HCV load in the current study with some adverse effects that include the reduction of the mononuclear cells from the blood periphery by apoptosis.

IP-10 Serum Level in Chronic Hepatitis C Virus Patients: Relation to Fibrosis and Response to Combined Interferon/Ribavirin Therapy.

Despite the appearance of the direct acting antiviral drugs, pegylated interferon/ribavirin (PEG-IFN/RBV) still has a place in the standard of care (SOC) therapy for chronic HCV4. Studies were conducted to find an accurate prediction in response to SOC therapy. Pretreatment serum interferon-γ-inducible protein-10 (IP-10) is an independent predictive factor of sustained virological response (SVR) in HCV1-infected patients. To assess whether the pretreatment serum level of IP-10 influences hepatic fibrosis and PEG-IFN/RBV therapy response, a study was conducted on 88 chronic Hepatitis C virus (HCV) patients who received PEG-IFN/RBV. Patients were subjected to a pretreatment routine laboratory evaluation, liver biopsy, and serum IP-10 assessment. They were followed up for 6 months after cessation of therapy (week 72). Patients were classified into 3 groups according to their response; nonresponders, relapsers, or sustained virological responders. The relation of pretreatment IP-10 with fibrosis and response was assessed. The studied groups were matched regarding their demographic data. There was no statistically significant association between the pretreatment IP-10 level and fibrosis (P=0.86) and no relation to response was found at week 12, 24, 48, and 72 (P=0.58, 0.8, 0.47, and 0.43, respectively). Pretreatment IP-10 could not predict either fibrosis or response to PEG-IFN/RIB therapy in chronic HCV Egyptian patients.

Association of Myxovirus Resistance Gene Promoter Polymorphism with Response to Combined Interferon Treatment and Progression of Liver Disease in Chronic HCV Egyptian Patients.

To evaluate the frequency of single-nucleotide polymorphism at the -88 myxovirus resistance (MxA) gene promoter region in relation to the status of hepatitis C virus (HCV) progression and response to combined interferon (IFN) in chronic HCV Egyptian patients. One hundred ten subjects were enrolled in the study; 60 HCV genotype 4-infected patients who underwent combined IFN therapy and 50 healthy individuals. All subjects were genotyped for -88 MxA polymorphism by the restriction fragment length polymorphism technique. There was an increasing trend of response to combined IFN treatment as 34.9% of GG, 64.3% of GT, and 66.7% of TT genotypes were sustained responders (P=0.05). The T allele was significantly affecting the response rate more than G allele (P=0.032). Moreover, the hepatic fibrosis score and hepatitis activity were higher in GG genotypes compared with the GT and TT genotypes. The multivariate analysis showed that the MxA GG genotype was an independent factor increasing the no response to IFN therapy (P=0.04, odds ratio [OR] 3.822, 95% confidence interval [CI] 1.056-11.092), also MxA G allele (P=0.0372, OR 2.905, 95% CI 1.066-7.919). MxA -88 polymorphism might be a potential biomarker to predict response to IFN and disease progression in chronic HCV-infected patients.

Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians.

Single-nucleotide polymorphisms (SNPs) around the interferon lambda 3 (IFNL3; also known as interleukin 28B; IL28B) gene are associated with spontaneous hepatitis C virus (HCV) clearance. Interferon lambda 4 (IFNL4).ss469415590, in linkage disequilibrium (LD) with IFNL3.rs12979860 among the Caucasian population, has recently been identified as a potential functional variant. Our objective was to assess the LD between IFNL3.rs12979860 and IFNL4.ss469415590 and to compare their effect on the outcome of HCV infection among Egyptians, mainly infected with HCV genotype 4. One-hundred and eighty-five Egyptian HCV patients (77 spontaneous resolvers and 108 chronic subjects), and 122 healthy controls were genotyped for both IL28B.rs12979860 and IFNL4.ss469415590. Logistic regression models including factors with univariate association with the outcome of infection were calculated for each genetic marker. The LD was also calculated for the 122 healthy controls. The CC genotype of IFNL3.rs12979860 was more frequent among individuals with HCV spontaneous resolution than among those with chronic infection (57 vs. 27%; adjusted OR 3.84; 95% CI 2.02-7.30; p < 0.0001). Also, the TT/TT genotype of IFNL4.ss469415590 was more frequent among individuals with spontaneous resolution (49 vs. 20%; adjusted OR 4.17; 95% CI 2.12-8.19; p < 0.0001). Both markers were in LD (D' = 0.96; r (2) = 0.84). The IFNL3.rs12979860 and IFNL4.ss469415590 variants have comparable effects on spontaneous resolution of HCV among Egyptians, for whom both markers are closely linked.

Factors Affecting the Response to Interferon Alpha Therapy in Egyptian HCV Patients

Hepatitis C Virus (HCV) infection is one of the main causes of chronic liver disease worldwide. Egypt has the highest prevalence of Hepatitis C Virus (HCV) in the world, estimated nationally at 14.7%. knowledge of the predictors of Sustained Viral Response (SVR) to Pegylated Interferon (PEG-INF) and Ribavirin (RBV) therapy in patients with chronic hepatitis C is crucial for selecting patients who would benefit most from therapy especially in developing country as Egypt where the highest percentage of treatment cost funded by government. This study was performed on Egyptian patients with chronic active hepatitis C who were prepared for receiving a course of treatment with: Interferon (PEG IFN) and ribavirin for 48 weeks. We aimed to find more predictive markers those can help clinicians to choose the most effective treatment program for each patient. Assessment of HLA-DRB1, HLA-DQB1 genes by Sequence Specific Primer (SSP) PCR, interleukin-10 (IL-10) by ELISA technique and Serum HCV RNA load by TaqMan Real Time RT-PCR technology were done. We found that sustained responders were significantly among DRB1*13 allele and DQB1*02 typing (p<0.001). DRB1*07 allele only appeared with responded patients. Relations were found between response to treatment and lower IL-10 level and lower Body Mass Index (BMI) but not sufficient to reach to significant value. In conclusion, we emphasize the importance of the use of pharmacogenomic data in the treatment of patients. HLA-DRB1*07, HLA-DRB1*13 and HLA-DQ02 alleles can predict the response to HCV combined therapy. The data generated from our study may be helpful in future for clinicians to predict the treatment outcome for HCV-seropositive individuals in Egypt.

Insulin resistance as a predictor of early virologic response to HCV therapy among chronic HCV Egyptian patients.

Prior assessment of insulin resistance by HOMA-IR is emerging as an important milestone in the treatment of patients with chronic hepatitis C. This cost-effective tool is recommended to individualize treatment duration, or to exclude those with low insulin sensitivity from being treated until ameliorating their state of insulin resistance (IR). The present work aims to elucidate further the effect IR state on early viral kinetic response to Chronic hepatitis C virus (HCV) therapy and the impact of HCV treatment and viral eradication on insulin sensitivity. Insulin sensitivity was assessed using the HOMA-IR method. All enrolled patients were treated with a dual therapy (pegylated interferon-alpha plus ribavirin) for 48 weeks and evaluated using qRT-PCR for early virologic response as well as the impact of treatment on insulin sensitivity throughout the early period of therapy. Of a total 392 chronic HCV cases, early virologic response was achieved by 318 (81.1%). IR was detected in 241 (61.5%) chronic HCV patient of which 73.4% responded to treatment. Early virologic response among patients with > 2.18 HOMA-IR value were significantly lower than those with HOMA-IR values ≤2.18 (P < 0.0001). IR was significantly associated with high baseline BMI. Steatosis and fibrosis correlated with IR but neither independently predicted early virologic response. Pretreatment IR < 2.18, low fasting blood glucose, low and intermediate HCV viral load, normal BMI, and non-smoking were independent factors associated with early virologic response. IR interferes with early virologic response to the antiviral care. Clinical application of pretreatment HOMA-IR assessment could help in predicting early treatment outcome and thus enable treatment regimens to be optimized and individually tailored.

New insight into HCV E1/E2 region of genotype 4a.

IntroductionHepatitis C virus (HCV) genome contains two envelope proteins (E1 and E2) responsible for the virus entry into the cell. There is a substantial lack of sequences covering the full length of E1/E2 region for genotype 4. Our study aims at providing new sequences as well as characterizing the genetic divergence of the E1/E2 region of HCV 4a using our new sequences along with all publicly available datasets.MethodsThe genomic segments covering the whole E1/E2 region were isolated from Egyptian HCV patients and sequenced. The resulting 36 sequences 36 were analyzed using sequence analysis techniques to study variability within and among hosts in the same time point. Furthermore, previously published HCV E1/E2 sequence datasets for genotype 4a were retrieved and categorized according to the geographical location and date of isolation and were used for further analysis of variability among Egyptian over a period of 15 years, also compared with non-Egyptian sequences to figure out region-specific variability.ResultsPhylogenetic analysis of the new sequences has shown variability within the host and among different individuals in the same time point. Analysis of the 36 sequences along with the Egyptian sequences (254 sequences in E1 in the period from 1997 to 2010 and 8 E2 sequences in the period from 2006 to 2010) has shown temporal change over time. Analysis of the new HCV sequences with the non-Egyptian sequences (182 sequences in E1 and 155 sequences in the E2) has shown region specific variability. The molecular clock rate of E1 was estimated to be 5E-3 per site per year for Egyptian and 5.38E-3 for non-Egyptian. The clock rate of E2 was estimated to be 8.48E per site per year for Egyptian and 6.3E-3 for non-Egyptian.ConclusionThe results of this study support the high rate of evolution of the Egyptian HCV genotype 4a. It has also revealed significant level of genetic variability among sequences from different regions in the world.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-014-0231-y) contains supplementary material, which is available to authorized users.

Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis

BackgroundChronic hepatitis C virus (HCV) represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphisms is associated with high rates of sustained virological response to pegylated interferon and ribavirin in HCV genotype-1 patients. Data on other genotypes are more limited. ObjectiveWe aim to evaluate the predictive power of the rs12979860 IL28B single nucleotide polymorphisms for treatment response at 3 and 6months in chronic HCV genotype 4 Egyptian patients in relation to other predictors. Patients and methodsThe study included 60 chronic HCV Egyptian patients receiving pegylated interferon and ribavirin therapy. Patients were classified into 2 groups; 30 patients with compensated cirrhosis, and 30 patients without cirrhosis. We analyzed selected pretreatment factors such as age, sex, HCV viral load, anti-schistosomal antibodies, insulin resistance, alpha fetoprotein, low and high density lipoproteins and single nucleotide polymorphisms of IL28B and tried to find out which of them influence sustained virological response. ResultsIn univariate analysis, CC genotype showed a significant association with sustained virological response at 6months among the cirrhotic patients (81.8% responders had the CC genotype, 58.3% had the CT/TT genotype) (p=0.009). While in multivariate analysis, the presence of cirrhosis showed higher risk of failed response at 3 and 6months (p=0.016 and 0.020 respectively). Also, positive schistosoma serology was an important negative predictor of response at 3 and 6months in both groups (p=0.003 and 0.001 respectively). ConclusionIn Egypt, where chronic HCV genotype 4 and schistosoma coinfection predominate, both schistosoma infection and cirrhosis are more potent than IL28B polymorphisms as strong baseline negative predictors of hepatitis C treatment response.