Portal hypertension and esophageal varices complicating hepatitis C virus (HCV)-related chronic liver diseases are some of the most devastating sequelae. Angiogenesis is the hallmark of their pathogenesis. Apelin is one of the recently identified angiogenic and fibrogenic peptides. We studied apelin gene expression, apelin (rs3761581) single-nucleotide polymorphism (SNP), and serum apelin level in patients with chronic HCV, and their association with liver fibrosis and esophageal varices in 112 patients with HCV-related chronic liver disease (40 with liver cirrhosis [LC]/lowgrade varices, 33 with LC/high-grade varices, and 39 with fibrotic non-cirrhotic liver/no varices) and 80 healthy control subjects. Real-time polymerase chain reaction was used for apelin gene expression assay and apelin rs3761581 SNP analysis in peripheral blood samples. The serum apelin level was measured by ELISA. Apelin gene expression was undetectable in the studied samples. The SNP analysis revealed a greater frequency of the C (mutant) allele among patients compared with control subjects (P = 0.012; odds ratio, 3.67). The serum apelin level was significantly greater in patients with LC/varices (median, 31.6 ng/L) compared with patients without LC/varices (median, 2.9 ng/L; P < 0.001). A serum apelin level cutoff value of 16.55 ng/L predicted the presence of varices, with an area under the receiver operating characteristic curve value of 0.786. A positive correlation was found between serum apelin level and grade of liver fibrosis (r = 0.346, P < 0.001) and portal hypertension (r = 0.438, P < 0.001). In conclusion, the apelin rs3761581-C allele may be associated with the progression of HCV-related chronic liver disease and varices formation, and can be considered a potential therapeutic target to control fibrosis progression. The serum apelin level provided an accurate prediction of the presence of esophageal varices.
Background COVID-19 was identified in Wuhan, China, in December 2019, and rapidly spread worldwide, being declared global pandemic on the 11th of March 2020. Since its emergence, COVID-19 has raised global concerns associated with drastic measures that were never adopted in any previous outbreak, to contain the situation as early as possible. Main body The 2019 novel corona virus (2019-nCoV) or SARS-CoV-2 is the causative agent of COVID-19. 2019-nCoV genetic sequence was rapidly identified within few days since the first reported cases and RT-PCR kits became available for COVID-19 diagnosis. However, RT-PCR diagnosis carries a risk of false-negative results; therefore, additional serologic tests are needed. In this review, we summarize the clinical scenario that raises suspicion of COVID-19 and available laboratory diagnostics. Conclusion The most important approach in the battle against COVID-19 is rapid diagnosis of suspicious cases, timely therapeutic intervention and isolation to avoid community spread. Diagnosis depends mainly on PCR testing and serological tests. However, even in the context of negative lab test results and clinical suspicion of COVID-19 infection, clinical decision should be based on clinical suspicion.
The authors have no competing interests. Data available on request from the authors.
COVID-19 was identified in Wuhan, China in in December 2019, and rapidly spread worldwide, being declared global pandemic one month later on 30 January 2020. Since its emergence, COVID-19 has raised global concerns associated with drastic measures that were never adopted in any previous outbreak, to contain the situation as early as possible. The 2019 novel corona virus (2019-nCoV) or SARS-CoV-2 is the causative agent of COVID-19. 2019-nCoV genetic sequence was rapidly identified within few days since the first reported cases and RT-PCR kits became available for COVID-19 diagnosis. However, RT-PCR diagnosis carries a risk of false-negative results, therefore additional serologic test are needed. The most important approach in the battle against COVID-19 is rapid diagnosis of suspicious cases, timely therapeutic intervention and isolation to avoid community spread. In this review, we summarize the clinical scenario that raises suspicion of COVID-19 and available laboratory diagnostics.
IL-17 is a proinflammatory cytokine family produced by Th-17 cells and has been found to be implicated in the pathophysiology of many cancers including acute myeloid leukemia (AML). Since single nucleotide poly-morphism (SNP) alters the genetic functions and cancer susceptibility, we studied SNPs in two members of IL-17 family, IL-17A (rs2275913; G-197A) and IL-17F (rs763780; A7488G) which are the most common loci associated with IL-17 activity and cancer risk, and correlated the results to AML susceptibility and response to therapy. The study included 200 participants; 100 de novo AML patients and 100 age and sex matched healthy control subjects. SNPs in IL-17A (rs2275913; G-197A) and IL-17F (rs763780; A7488G) were studied using restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP). IL-17A homozygote mutation was more frequent in AML patients compared to control subjects (P = 0.034) and conferred 2.8 fold increased risk of AML (OR = 2.755 [95% CI: 1.078-7.042]). While IL-17F mutation showed no correlation with acute myeloid leukemia susceptibility. Also neither IL-17 A nor IL 17-F mutation showed significant correlation to therapy outcome. In conclusion, IL-17 A homozygote mutation may be associated with AML susceptibility.
Liver cirrhosis and hepatocellular carcinoma (HCC) are consequences of chronic hepatitis C virus (HCV) infection. HCC is one of the fastest rising causes of cancer-related mortality. This dismal prognosis is related to late diagnosis with currently available screening methods. The aim of our study was to evaluate the diagnostic power of serum growth differentiation factor (GDF) 15 in HCC detection and its ability to distinct HCC from cirrhosis in chronic hepatitis C Egyptian patients. Ninety participants were included in the study; 30 patients with HCV-cirrhosis, 30 patients with HCV-Cirrhosis and HCC, and 30 gender and age-matched healthy subjects as the control group. The patients were subjected to history taking, clinical examinations, routine laboratory analysis, and α-fetoprotein (AFP) determination. Serum GDF15 was measured using an enzyme-linked immunosorbent assay kit. The mean level of GDF15 in HCV-cirrhosis patients was 140.28±128.66 pg/ml, in HCV-HCC patients 154.45±123.74 pg/ml, and in the control group it was 81.19 ±42.53 pg/ml. Statistically significant difference in GDF15 level was found between HCV-HCC patients and controls, P=0.012, while no statistically significant difference was found on comparing HCV-cirrhosis patients to controls or to HCV-HCC patients, P=0.064 and 0.473, respectively. The cut-off value of GDF15 to discriminate HCV-HCC patients from controls was 122.3 pg/ml with 53.3% sensitivity and 86.7% specificity and an area under the receiver operating characteristic (AUROC) of 0.692. AFP at a cut-off value of 20.85 ng/l was able to discriminate HCV-HCC patients from HCV-cirrhosis patients with 73.3% sensitivity and 73.3% specificity and an AUROC of 0.744. AUROC for combined AFP and GDF15 showed lower performance than AFP alone in discrimination of HCV-HCC from HCV-cirrhosis patients (AUROC=0.642). GDF15 is not a potential diagnostic marker for the distinction of HCC from cirrhosis in chronic hepatitis C Egyptian patients.
Background High prevalence of hepatitis C virus (HCV) infection among patients with psoriasis has been reported. Interferons (IFNs) play pivotal roles in both the pathogenesis of psoriasis and the immunological response to HCV. Objective To study serum levels of IFN-α, IFN-γ, and IFN-λ2 in psoriatic patients with concomitant HCV infection in comparison with their levels in patients with psoriasis alone and in healthy control. Patients and methods The study included 20 patients with concomitant psoriasis vulgaris and chronic HCV infection, 25 patients with only psoriasis vulgaris, and 24 healthy controls. Serum levels of IFN-α, IFN-γ, and IFN-λ2 were assessed using enzyme-linked immunosorbent assay technique. Results Psoriatic patients with HCV infection showed significantly higher serum IFN-α, IFN-γ, and IFN-λ2 compared with controls (P=0.028, 0.001, and 0.007), higher serum IFN-λ2 levels compared with patients with psoriasis alone, yet significantly lower serum IFN-α and IFN-γ levels in comparison with psoriasis only patients. A significant positive correlation was found between IFN-α and IFN-λ2 levels in psoriatic patients with HCV (r=0.536, P=0.015). Conclusion IFN-α and IFN-γ play important roles in the pathogenesis of psoriasis, yet they are not likely to be the cause of development of psoriasis in chronic HCV-infected patients. High levels of IFN-λ2 among psoriatic patients with HCV infection but not in patients with psoriasis alone point to its possible safety in the treatment of HCV in psoriatic patients.
INTRODUCTION: Portal hypertension (PH) and esophageal varices complicating HCV-related chronic liver disease (CLD) are the most devastating sequelae. Angiogenesis is the hallmark of their pathogenesis. Apelin is one of the recently identified angiogenic and fibrogenic peptides. We studied apelin gene expression, apelin (rs3761581) SNP and serum apelin level in chronic HCV patients, and their association with hepatic fibrosis and esophageal varices. METHODS: 112 patients with HCV related CLD (40 having liver cirrhosis (LC)/low grade varices, 33 with LC/high grade varices and 39 with fibrotic non-cirrhotic liver/no varices), and 80 healthy control subjects were included. Real time PCR was used for apelin gene expression assay and apelin rs3761581 SNP analysis in peripheral blood samples. Serum apelin level was measured by ELISA. RESULTS: Apelin gene expression was undetectable in studied samples. SNP analysis revealed higher frequency of the C-(mutant)-allele among patients compared to controls (P = 0.012, odds ratio 3.67). Serum Apelin level was significantly higher in patients with hepatic cirrhosis/ varices (median 31.6 ng/L) compared to non-cirrhotic patients/ no varices (median 2.9 ng/L) (P < 0.001). Serum apelin level at cut off value 16.55 ng/L predicted the presence of varices with AUROC 0.786. Positive correlation was found between serum apelin level and grade of liver fibrosis (r=0.346, P < 0.001) and PH (r=0.438, P < 0.001). CONCLUSION: Apelin rs3761581 C-allele may be associated with progression of HCV-related CLD and varices formation, and can be considered as a potential therapeutic target to control fibrosis progression. Serum apelin level provided accurate prediction of the presence of esophageal varices.
Introduction and aim. The correlation between interleukin-28B (IL-28B) polymorphisms and chronic hepatitis C (CHC) progression is debatable. Here, we aimed to evaluate the relation between IL-28B C/T genotypes and the development of cirrhotic liver. Extracellular matrix (ECM) proteins, FibroScan and model for end-stage liver disease (MELD) were used to substantiate the severity of liver disease. Material and methods. IL-28B rs12979860, liver stiffness and ECM proteins were assessed in 272 CHC patients. Results. Cirrhosis percentage increased to 10%, 52% and 96% with the increasing number of T alleles (CC, CT and TT, respectively). Also, elevated ECM proteins levels were correlated with the increasing number of T alleles. Interestingly, among cirrhotic patients, liver stiffness, MELD and ECM proteins were significantly (P < 0.0001) higher in patients with TT more than CT genotype. FibroScan, hyaluronic acid, Laminin, Collagen IV and the N-terminal pro-peptide of collagen type III have high accuracy to differentiate liver status in CC from TT genotype. Area under receiver-operating characteristic curve (95% CI) were 1.0 (1.0-1.0), 0.97 (0.961.0), 0.93 (0.85-1.0), 0.98 (0.97-1.0) and 0.93 (0.91-0.97), respectively. Conclusion. This study suggests that IL-28B T allele affects the natural course of CHC type 4 and also suggests that carriage of the IL-28B C allele protects from unfavorable clinical outcomes in CHC as coexistence of C allele with T allele reduced cirrhosis severity.
Background: Acute myeloid leukemia (AML) is a potentially fatal hematological disease. Along with disease-related factors, patient-related factors, in particular age, are a strong predictor of outcome that influence treatment decisions. Many acute myeloid leukemia risk stratification models have been developed to predict the outcome of intensive chemotherapy. However, these models did not include physical function assessments. Methods: This study investigated the impact of several factors, namely the performance status, physical function and age on the short-term outcomes of intensive chemotherapy in a cohort of 50 Egyptian patients with de novo acute myeloid leukemia. Results: Complete remission after intensive chemotherapy in these myeloid leukemia patients at Day 28 was 56% and the mortality rate was 12% and 34% at Day 28 and Day 60, respectively. The pretreatment Eastern Cooperative Oncology Group score was significantly correlated with outcomes on Day 28 and Day 60 (p-value = 0.041 and p-value = 0.032, respectively). There were significant correlations between the two-minute walk test and outcomes of therapy on Day 28 and 60 (p-value = 0.032 and p-value = 0.047, respectively) and between grip strength test and outcomes of therapy on Day 28 and 60 (p-value = 0.046 and p-value = 0.047 respectively). Furthermore, there was a significant correlation between chair stand test and outcome of therapy on Day 28 (p-value = 0.023). Conclusion: Performance status and physical function assessments were strong predictors of outcome of intensive chemotherapy in acute myeloid leukemia and we recommend the incorporation of these variables in risk stratification models for the personalization of therapy before treating acute myeloid leukemia patients with intensive chemotherapy. (C) 2018 Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda.
Abstract Background: Fibrosis markers are useful for the prediction of cirrhosis but clinical scores such as King’s score, AST-Platelet ratio index (APRI), Biotechnology research center (BRC), Fibrosis routine test (FRT), Fibro-α score and Fibro-quotient (FibroQ) have limited accuracy for diagnosing significant fibrosis. We hypothesised that new markers (reflecting the balance between hepatic fibrogenesis and fibrolysis) together with other indirect fibrosis markers would together construct a more sensitive and specific score capable of identifying fibrosis than existing scores. Methods: Collagen IV, hyaluronic acid, platelet-derived growth factor (PDGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by ELISA, and AST, ALT, platelet count, albumin, total bilirubin, INR and AFP by routine methods in 148 patients with hepatitis C induced liver disease. Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were used to create a predictive score and compare it to others. Results: Patients with significant fibrosis (n = 100, F2–F4) showed 2.08, 2.14, 1.80 and 1.90-fold increase in collagen IV, hyaluronic acid, PDGF and TIMP-1, respectively, over patients with no or mild fibrosis (n = 48, F0/F1)(all p < 0.01). Significant independent predictors of F2–F4 were AFP (AUC 0.79), age (0.76), PDGF (0.74), collagen IV (0.78) and TIMP (0.75), which together formed a five-marker score ‘Fibro-Mark’ for predicting F2–F4. In comparison with other scores, AUC for Fibro-Mark was 0.89, BRC was 0.83, followed by FRT and King’s score (both 0.82), APRI (0.80), Fibro-α (0.70) and finally Fibro Q (0.63). Conclusions: The Fibro-Mark score provides better discrimination in hepatic-fibrosis staging in chronic hepatitis C patients than existing scores.
Worldwide, more than one million people die each year from hepatitis C virus (HCV) related diseases, and over 300 million people are chronically infected with hepatitis B or C. Egypt used to be on the top of the countries with heavy HCV burden. Some countries are making advances in elimination of HCV, yet multiple factors preventing progress; remain for the majority. These factors include lack of global funding sources for treatment, late diagnosis, poor data, and inadequate screening. Treatment of HCV in Egypt has become one of the top national priorities since 2007. Egypt started a national treatment program intending to provide cure for Egyptian HCV-infected patients. Mass HCV treatment program had started using Pegylated interferon and ribavirin between 2007 and 2014. Yet, with the development of highly-effective direct acting antivirals (DAAs) for HCV, elimination of viral hepatitis has become a real possibility. The Egyptian National Committee for the Control of Viral Hepatitis did its best to provide Egyptian HCV patients with DAAs. Egypt adopted a strategy that represents a model of care that could help other countries with high HCV prevalence rate in their battle against HCV. This review covers the effects of HCV management in Egyptian real life settings and the outcome of different treatment protocols. Also, it deals with the current and future strategies for HCV prevention and screening as well as the challenges facing HCV elimination and the prospect of future eradication of HCV.
Background and aim of work: Sickle cell disease (SCD) is an inherited disease of the beta globin gene. The beta(s) globin gene haplotypes are Senegal, Benin, Bantu, Cameroon, Arab-Indian and atypical haplotypes. In SCD, stroke is a life-threatening event in both adults and children. In light of paucity of studies on beta(s) globin gene haplotypes in Egypt, we aimed to determine beta(s) globin gene haplotypes in children with SCD and study their impact on stroke risk. Methods: Fifty-two SCD patients were included in the study, they were 26 males and 26 females with age range from 3 to 18 years old. The PCR-RFLP technique was used for the determination of beta(s) globin gene haplotypes. Transcranial Doppler (TCD) was done to identify patients at risk of stroke. Results: Benin/Benin was the most prevalent haplotype detected in 50% followed by Benin/ Bantu in 30.8% of studied patients. TCD study showed that 14/52 (26.9%) patients had abnormally high TCD flow velocities (TCD velocities >= 170 cm/s) and thus considered high stroke risk group, whereas 38/52 (73.1%) patients had TCD flow velocities <170 cm/s and are considered low stroke risk group. Stroke risk was not found to be associated with beta(s) globin gene haplotype (p = .532). Conclusion: This study provides a relevant contribution to our understanding of the anthropological and historical background of the population in Egypt where Benin haplotype is the commonest beta(s) globin gene haplotype and homozygous Benin/Benin is associated with higher stroke risk than other haplotypes.
Stage of liver fibrosis is critical for treatment decision and prediction of outcomes in chronic hepatitis C (CHC) patients. We evaluated the diagnostic accuracy of transient elastography (TE)-Fibroscan and noninvasive serum markers tests in the assessment of liver fibrosis in CHC patients, in reference to liver biopsy. One-hundred treatment-naive CHC patients were subjected to liver biopsy, TE-FibroScan, and eight serum biomarkers tests; AST/ALT ratio (AAR), AST to platelet ratio index (APRI), age-platelet index (AP index), fibrosis quotient (FibroQ), fibrosis 4 index (FIB-4), cirrhosis discriminant score (CDS), King score, and Goteborg University Cirrhosis Index (GUCI). Receiver operating characteristic curves were constructed to compare the diagnostic accuracy of these noninvasive methods in predicting significant fibrosis in CHC patients. TE-FibroScan predicted significant fibrosis at cutoff value 8.5kPa with area under the receiver operating characteristic (AUROC) 0.90, sensitivity 83%, specificity 91.5%, positive predictive value (PPV) 91.2%, and negative predictive value (NPV) 84.4%. Serum biomarkers tests showed that AP index and FibroQ had the highest diagnostic accuracy in predicting significant liver fibrosis at cutoff 4.5 and 2.7, AUROC was 0.8 and 0.8 with sensitivity 73.6% and 73.6%, specificity 70.2% and 68.1%, PPV 71.1% and 69.8%, and NPV 72.9% and 72.3%, respectively. Combined AP index and FibroQ had AUROC 0.83 with sensitivity 73.6%, specificity 80.9%, PPV 79.6%, and NPV 75.7% for predicting significant liver fibrosis. APRI, FIB-4, CDS, King score, and GUCI had intermediate accuracy in predicting significant liver fibrosis with AUROC 0.68, 0.78, 0.74, 0.74, and 0.67, respectively, while AAR had low accuracy in predicting significant liver fibrosis. TE-FibroScan is the most accurate noninvasive alternative to liver biopsy. AP index and FibroQ, either as individual tests or combined, have good accuracy in predicting significant liver fibrosis, and are better combined for higher specificity.
Insecticide resistance monitoring of mosquito field populations is a crucial for guide and select the rational application of this insecticide.Both, levels and mechanisms of resistance are important to select efficient insecticides for the control of disease vectors.Culex pipiens mosquitoes collected from three different Governorates in Egypt (El-Fayoum, Menofia and Giza), were tested for insecticides susceptibility against Lambda-cyhalothrin and DDT.The results showed high resistance to the tested insecticides among Menofia and Giza collected populations, whereas El-Fayoum population showed low level of resistance.a great precaution should be considered about the type of control measures in these areas, when using the same insecticide.The presented output is alarming to health sectors and vector control decision makers.Mosquito control programs may need considering alternative insecticide classes for control of C. pipiens in the monitored areas.
OBJECTIVE: Multiple genetic alterations with prognostic significance have been discovered in acute myeloid leukemia (AML). We studied the expression level of two genes, Meningioma1 (MN1) and Phosphatase and Tensin homolog (PTEN) to determine their expression in AML patients and their role as progno stic markers. METHODS: The study included 50 cytogenetic normal de novo AML cases and 10 controls, Their level was detected by Real time Reverse Transcription-Polymerase Chain Reaction. RESULT: Relative mRNA expression of MN1 was significantly higher (p value < 0.001) and PTEN expression was significantly lower (p value = 0.002). No correlation was found between neither MN1 nor PTEN mRNA expression and overall survival (p value = 0.212 and 0.310) respectively. CONCLUSION: Although our study suggests a role for MN1 gene and PTEN genes in AML, we could not recommend their use as routine diagnostic and prognostic markers for AML in Egyptian population.
Evaluation of liver fibrosis stage is crucial in the assessment of chronic HCV patients, regarding decision to start treatment and during follow-up. Our aim was to assess the validity of the enhanced liver fibrosis (ELF) score in discrimination of advanced stage of liver fibrosis in naïve chronic HCV patients. We prospectively evaluated liver fibrosis stage in one hundred eighty-one naïve chronic HCV Egyptian patients by transient elastography (TE)-FibroScan. Patients were categorized into mild to moderate fibrosis (≤F2) group and advanced fibrosis (≥F3) group. The ELF score components, hyaluronic acid (HA), amino-terminal propeptide of type-III-procollagen (PIIINP) and tissue inhibitor of metalloproteinase type-1 (TIMP-1), were done using ELISA test. The mean values of ELF and its individual components significantly correlated with the hepatic fibrosis stage as measured by TE-FibroScan (P value 0.001). ELF cutoff value of 9.8 generated a sensitivity of 77.8%, specificity of 67.1%, area under the receiver operator characteristic curve (AUROC) of 0.76 with 95% confidence interval [CI] (0.68–0.83) for detecting advanced fibrosis (F ≥ 3). ELF panel is a good, reliable noninvasive test and showed comparable results to TE-FibroScan in detecting liver fibrosis stage in treatment naïve chronic HCV patients.
Toll-like receptors (TLRs) are recognized as fundamental contributors to the immune system function against infections. Hepatitis C virus (HCV) infection represents a global health problem especially in Egypt having the highest HCV prevalence worldwide where HCV infection is a continuing epidemic. The aim of the present study was to investigate the possible association between genetic variation in TLR-3 and TLR-9 and HCV infection and hepatic fibrosis in chronic HCV-positive Egyptian patients. The present study included 100 naïve chronic HCV-positive patients and 100 age- and sex-matched healthy controls. Genotyping of TLR-3 (_7 C/A [rs3775296]), TLR-3 (c.1377C/T [rs3775290]) and TLR-9 (1237T/C [rs5743836]) were done by polymerase chain reaction restriction fragment length polymorphism technique. Frequency of polymorphic genotypes in TLR-3 (_7 C/A), TLR-3 (c.1377C/T) and TLR-9 (1237T/C) were not significantly different between studied HCV-positive patients and controls with P values 0.121, 0.112, and 0.683, respectively. TLR-3 c.1377 T-allele was associated with advanced stage of hepatic fibrosis (P = 0.003).
Hepatitis C virus (HCV) infection represents a worldwide health problem and has been for long an attractive point of research due to diversity among different genotypes regarding unique geographical distribution and diverse treatment outcome. HCV is considered a major cause of chronic liver disease and cirrhosis, which leads to liver failure and hepatocellular carcinoma requiring liver transplantation. Of the HCV genotypes identified, HCV genotype 4 (HCV-4) is the least studied. HCV-4 is responsible for ∼10% of HCV infections and is common in the Middle East and Africa; recently it is increasingly prevalent in European Countries. HCV-4 is a continuing epidemic in Egypt, having the highest prevalence of HCV worldwide. “Know your epidemic, know your response” concept necessitates better understanding of HCV-4 characteristics to control disease dissemination and progression, which compromises the life quality of chronic HCV-infected patients. In this review, we discuss the epidemiology, natural history, and treatment options for patients with HCV-4 infection.