The Outcome of BNT162b2, ChAdOx1-Sand mRNA-1273 Vaccines and Two Boosters: A Prospective Longitudinal Real-World Study.

To date, the effectiveness of COVID-19 vaccines and booster doses has yet to be evaluated in longitudinal head-to-head studies. This single-center longitudinal study assessed the effectiveness of ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273 vaccines and assessed two BNT162b2 boosters in 1550 participants, of whom 26% had comorbidities. In addition, the SARS-CoV-2 antibody dynamics was monitored. A group of 1500 unvaccinated subjects was included as the controls. The study's endpoint was the development of virologically-proven COVID-19 cases after vaccine completion, while the secondary endpoint was hospitalizations due to severe COVID-19. Overall, 23 (4.6%), 16 (3%), and 18 (3.8%) participants vaccinated with ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273, respectively, developed COVID-19 after vaccine completion, with an effectiveness of 89%, 92%, and 90%. Ten COVID-19 cases were reported in participants with comorbidities, three of whom were hospitalized. No hospitalizations occurred after boosters. SARS-CoV-2 antibody levels peaked 2-4 weeks after the second vaccine dose but declined after a mean of 28.50 ± 3.48 weeks. Booster doses significantly enhanced antibody responses. Antibody titers ≤ 154 U/mL were associated with a higher risk of COVID-19 emergence. Thus, COVID-19 vaccines effectively reduced COVID-19 and prevented severe disease. The vaccine-induced SARS-CoV-2 antibody responses declined after 28-32 weeks. Booster doses induced significant maintained responses. SARS-CoV-2 antibody levels may help determine the timing and need for vaccine booster doses.

Application of Mathematical Modeling in Prediction of COVID-19 Transmission Dynamics.

The entire world has been affected by the outbreak of COVID-19 since early 2020. Human carriers are largely the spreaders of this new disease, and it spreads much faster compared to previously identified coronaviruses and other flu viruses. Although vaccines have been invented and released, it will still be a challenge to overcome this disease. To save lives, it is important to better understand how the virus is transmitted from one host to another and how future areas of infection can be predicted. Recently, the second wave of infection has hit multiple countries, and governments have implemented necessary measures to tackle the spread of the virus. We investigated the three phases of COVID-19 research through a selected list of mathematical modeling articles. To take the necessary measures, it is important to understand the transmission dynamics of the disease, and mathematical modeling has been considered a proven technique in predicting such dynamics. To this end, this paper summarizes all the available mathematical models that have been used in predicting the transmission of COVID-19. A total of nine mathematical models have been thoroughly reviewed and characterized in this work, so as to understand the intrinsic properties of each model in predicting disease transmission dynamics. The application of these nine models in predicting COVID-19 transmission dynamics is presented with a case study, along with detailed comparisons of these models. Toward the end of the paper, key behavioral properties of each model, relevant challenges and future directions are discussed.

Influence of Nutrition on Disease Severity and Health-related Quality of Life in Adults with Sickle Cell Disease: A Prospective Study.

BACKGROUND & AIMS: Sickle cell disease (SCD), a genetic disorder resulting from the presence of a mutated hemoglobin S (HbS), has a worldwide distribution and causes significant morbidity and mortality in children and adults. Few studies addressed the determinants of SCD severity in adults; therefore, we investigated the impact of nutrition on the outcome of SCD and health-related quality of life (HRQoL) in adult patients. METHODS: In this longitudinal study, we recruited and prospectively followed 62 adults with SCD (aged ≥18 years) for a median of 93 months. At entry and follow-up, patients provided medical and dietary history, had a physical examination and anthropometric measurements, assessed protein-energy intake, measurement of micronutrient levels, estimation of SCD severity score, and determination of the HRQoL (SF-26v2). The study outcome was a composite of hospitalization due to SCD crises or death. RESULTS: At baseline, 42 (67.74%) patients had macro and, or micro-undernutrition (Group A), and 20 (32.26%) were well nourished. (Group B). The BMI and most anthropometric measurements were significantly lower in SCD patients compared to control subjects. Seventy percent of SCD patients had vitamin D, vitamin B12, and zinc deficiencies. Thirty-six under-nourished patients (86%) had gastrointestinal disorders. During follow-up, 46 patients (74.19%) developed one or more vaso-occlusive pain crises or other SCD related complications that required hospitalization. Significant differences in most SF-36v2 domains existed between well-nourished and undernourished SCD patients. Protein-energy and micronutrient deficiencies were independent predictors of severe SCD and mortality. Correction of undernutrition and hydroxyurea therapy improved SCD severity scores and HRQoL. CONCLUSIONS: Patients with sickle cell disease have various degrees of macro and micro deficiencies, which increase SCD severity and hospitalizations and reduce the health-related quality of life. Early diagnosis and prompt correction of macro and micronutrient deficiencies need to be incorporated in the standard of care of SCD patients to improve the disease outcomes.

The Course of Hepatitis C Infection and Response to Anti-viral Therapy in Patients with Thalassemia major and Hepatitis C Infection: A Longitudinal, Prospective Study.

BACKGROUND: The course of hepatitis C infection (HCV) in patients with thalassemia has not been adequately studied, and management has not been optimized. The current prospective longitudinal study assessed the clinical course, outcome, progression, and management of recently acquired HCV in patients with transfusion-dependent thalassemia major versus acute HCV without thalassemia. METHODS: A well-characterized cohort of patients with thalassemia and recent HCV infection or recent HCV without thalassemia were enrolled and prospectively followed. The blood transfusion needs and chelating agents were determined. Liver functions tests, HCV-RNA, iron, and ferritin levels were measured. Patients with chronic HCV evolution received treatment for HCV. The fibrosis progression rate was determined in chronic HCV patients with or without thalassemia by paired liver biopsies or serial transient elastography (TE), or serum markers of liver fibrosis. Liver iron content (LIC) was assessed by R2 MRI. RESULTS: Self-limited acute HCV was observed in 17% of patients with acute HCV and thalassemia versus 35% of patients without thalassemia (P=0.031). The fibrosis progression rates were significantly higher in patients with chronic HCV and thalassemia compared to those with chronic HCV alone (1.14±0.48) and (0.35±0.14) (P<0.0001), respectively. A direct linear correlation was observed between the fibrosis progression rate and each of LIC (R=+0.67; P=0.01) and ferritin (R=0.77; P<0.01). In patients with chronic HCV and thalassemia, the sustained virologic response (SVR) to pegylated interferon-based therapy and direct antiviral agents (DAAS) were 33% and 82% respectively (P<0.0001), while in chronic HCV patients without thalassemia, the SVR rates to PEG-IFN/RBV and DAAs were 51% and 92% respectively. Five patients with concomitant HCV and thalassemia died during the study due to cardiac causes (n=3) and liver cancer (n=2). CONCLUSIONS: Patients with acute HCV and thalassemia have low rates of spontaneous resolution of HCV infection, and the majority develop chronic HCV. Direct-acting antiviral combinations are associated with high SVR rates and low adverse event in treatment naïve and experienced patients with chronic HCV and thalassemia. Liver fibrosis is accelerated in thalassemia patients with chronic HCV; therefore, early diagnosis, treatment with DAAs, adequate iron chelation, and non-invasive monitoring liver status are recommended to prevent cirrhosis and hepatocellular carcinoma.

The frequency, clinical course, and health related quality of life in adults with Gilbert's syndrome: a longitudinal study.

BACKGROUND: Gilbert syndrome (GS) is an autosomal recessive inherited disorder of bilirubin glucuronidation which has not been investigated in Egypt. This longitudinal study investigated the frequency, clinical course, genetic profile and health related quality of life in Egyptian adults. METHODS: An initial cross-sectional study was conducted to assess the frequency of Gilbert syndrome among Egyptian adults. Subjects fulfilling the criteria of GS were enrolled into the study and prospectively followed for the clinical features, risk factors for hyperbilirubinemia, health related quality of life [Short form-36 Health Survey version 2 (SF-36v2) and Chronic Liver Disease Questionnaire (CLDQ)], vitamins assessment and UGT1A1 polymorphisms. RESULTS: One hundred and one subjects fulfilled the criteria of GS with a prevalence of 8.016%. Recurrent jaundice was the only presentation in 47 (56.627%) GS subjects and jaundice was associated with abdominal pain, dyspepsia or loss of appetite in 54 (53.465%) subjects. A significant difference in 25-Hydroxyvitamin D3 levels was detected between GS patients and control subjects (P <  00001). Twelve subjects with GS developed significant unconjugated bilirubinemia during direct antiviral therapy (DAAs) therapy for HCV despite achieving sustained virologic response. Pregnancy was associated with significant exacerbation of unconjugated bilirubin which persisted through pregnancy. Risk factors for clinical jaundice included general anesthesia, pregnancy, fasting > 12 h, pregnancy, and low calorie weight losing plans, systemic infections, and intensive physical effort. During jaundice attacks, subjects with GS had significant differences in vitality, role emotional, social functioning, worry and general health domains of the SF-36v2 and CLDQ compared to controls. The homozygous polymorphism A(TA)7TAA was the most frequent polymorphism in Egyptians with GS. CONCLUSION: Gilbert syndrome is a frequent inherited disorder in Egypt. In a substantial percentage of subjects with GS, episodes of jaundice are associated with other symptoms and nutritional deficiencies which result in impairment of HRQOL. Screening, counseling, monitoring and individualized health care are recommended for subjects with GS in the setting of anesthesia, pregnancy, treatment with DAAs, deliveries, surgery and weight loss plans.

Clinicopathological and immunological characteristics and outcome of concomitant coeliac disease and non-alcoholic fatty liver disease in adults: a large prospective longitudinal study.

OBJECTIVE: Concomitant non-alcoholic fatty liver disease (NAFLD) and coeliac disease (CD) have not been adequately studied. This study investigated the frequency of CD among NAFLD patients and the clinicopathological and immunological patterns and outcome of concomitant NAFLD and CD. DESIGN: This prospective longitudinal study screened patients with NAFLD for CD (tissue transglutaminase antibodies (TTGA); anti-TTGA and antiendomysial antibodies (EMA)). Patients with concomitant NAFLD and CD and patients with either NAFLD or CD were enrolled and followed. Duodenal biopsy, transient elastography, tumour necrosis factor (TNF)-alpha, transforming growth factor-beta, interleukins (ILs) 1, 6, 10, 15 and 17, folic acid and vitamins B12 and D were performed at baseline and 1 year after gluten-free diet (GFD). RESULTS: CD was confirmed in 7.2% of patients with NAFLD. Refractory anaemia and nutritional deficiencies were frequent in patients with concomitant NAFLD and CD who had advanced intestinal and hepatic lesions, higher levels of TNF-α, IL-15 and IL-17 compared with patients with CD and NAFLD. Patients concomittant CD and NAFLD showed clinical response to GFD, but intestinal histological improvement was suboptimal. Combining EMA-IgA or anti-TTGA with either IL-15 or IL-17 enhances the prognostic performance of both tests in predicting histological response to GFD. CONCLUSION: Concomitant NAFLD and CD is not uncommon. Recurrent abdominal symptoms, refractory anaemia, nutritional deficiencies in patients with NAFLD warrant screening for CD. The study has important clinical implications since failure in diagnosing CD in patients with NAFLD patients results in marked intestinal and hepatic damage and suboptimal response to GFD that can be alleviated by early diagnosis and initiation of GFD.

Estimation of ultrasound reference values for the lower limb peripheral nerves in adults: A cross-sectional study.

The objective of this study is to estimate the reference values for the lower limb peripheral nerves in adults.The demographics and physical characteristics of 69 adult healthy volunteers were evaluated and recorded. The estimated reference values and their correlations with the age, weight, height, body mass index (BMI) were evaluated.The cross sectional area reference values were obtained at 5 predetermined sites for 3 important lower limb peripheral nerves. Our CSA values correlated significantly with age, weight, and BMI. The normal reference values for each nerve were as follows: Tibial nerve at the popliteal fossa 19 mm ±â€Š6.9, tibial nerve at the level of the medial malleolus 12.7 mm ±â€Š4.5, common peroneal nerve at the popliteal fossa 9.5 mm ±â€Š4, common peroneal nerve fibular head 8.9 mm ±â€Š3.2, sural nerve 3.5 mm ±â€Š1.4.The reference values for the lower limb peripheral nerves were identified. These values could be used for future management of peripheral nerve disorders.

Serum soluble receptor of advanced glycation end products and risk of metabolic syndrome in Egyptian obese women.

Obesity is one of the diagnostic criteria of metabolic syndrome (MS). It is correlated with insulin resistance (IR) and high vascular risk as well. Advanced glycation end products (AGEs) and their receptor (RAGE) play an important role in abnormal metabolic components in obese women. This study aimed to explore the serum levels of sRAGE in Egyptian obese women and compare with healthy non-obese controls and investigate the relationship between serum sRAGE, metabolic parameters, and obesity complications. The soluble form of receptor for advanced glycation end products (sRAGE), anthropometry, metabolic and biochemical biomarkers were measured in 100 obese women and 100 age-matched healthy control non-obese women. The homeostasis model assessment estimate of insulin resistance (HOMA-IR) has been determined from serum insulin and glucose values. Serum sRAGE levels were significantly lower in obese cases than controls and inversely correlated with obesity and metabolic parameters. Results of univariate and multivariate analyses for determinants of serum sRAGE levels in obese cases showed that parameters statistically and significantly related were body mass index (BMI), waist circumference (WC), LDL-C, TG, BP, HOMA-IR, ALT and AST. sRAGE is a novel biomarker for metabolic dysfunction in Egyptian obese women and might predict the future cardio-metabolic events.

Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome.

AIM: To investigate the association of peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala polymorphism with polycystic ovary syndrome (PCOS) and its effect on the metabolic parameters in PCOS women. METHODS: The study used PCR to identify the presence of the PPARG Pro12Ala polymorphism in 100 PCOS women and 120 age-matched healthy women. All participants were subjected to anthropometry, biochemical and metabolic evaluation. RESULTS: Significant difference in the genotypes distributions of PPARG Pro12Ala polymorphism was observed among PCOS women and controls (p = 0.03). The frequency of the polymorphic allele Ala was significantly higher in PCOS cases than that in the controls (OR = 2.01, p = 0.01). The carries of the variant allele Ala in PCOS women showed significant higher values in body mass index (BMI), systolic and diastolic blood pressure, waist circumference, waist to hip ratio, sum of skin folds, fasting blood glucose, fasting blood insulin, HOMA-IR, fasting triglycerides, total cholesterol and low-density lipoprotein than non-carriers. CONCLUSION: The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications.

Association of vitamin D receptor gene polymorphism (VDR) with vitamin D deficiency, metabolic and inflammatory markers in Egyptian obese women.

Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance. The aim of this study is to analyze the associations between Vitamin D receptor (VDR) gene polymorphism, serum 25-hydroxy vitamin D, metabolic and inflammatory biomarkers in Egyptian obese women. The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels. Their age ranged between 25 and 35 years. Inflammatory biomarkers (interleukin-6 and C-reactive protein) and serum 25(OH) D were measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was determined by the homeostasis model assessment of insulin resistance (HOMA-IR).Vitamin D receptor (VDR) gene polymorphisms of FokI, ApaI, and TaqI were studied by PCR using the restriction fragment length polymorphism (RFLP) technique. Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls. Multivariable-logistic regression showed associations between 25(OH) D deficiency and metabolic components when comparing cases with controls. Moreover, cases carrying polymorphic alleles showed significant lower levels of serum 25(OH) D and higher HOMA-IR, blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency. Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers. Moreover, VDR polymorphisms play important role in immune and inflammation status.

Serum apelin levels and metabolic risk markers in obese women.

BACKGROUND: Adipose tissue hormones, Adipokines, play an important role in obesity-associated complications. Apelin has recently been added to the family of adipokines. The aim of this study was to evaluate the relationship between serum apelin levels and metabolic abnormal parameters in Egyptian obese women. MATERIALS AND METHODS: The study included 400 unrelated women; they were 200 obese women and 200 non- obese matched healthy women. All participants underwent clinical, anthropometric and biochemical examinations. Insulin resistance (IR) was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). Serum apelin levels and obesity biomarkers were measured using enzyme-linked immunoassay (ELISA) kits. Fat mass was measured by Tanita Body Composition Analyzer. RESULTS: Obese women showed significant higher levels of serum apelin, leptin, triglycerides, LDL-C, total cholesterol, fasting insulin HOMA-IR and blood pressure levels than controls. Significant positive correlations between apelin and leptin levels with abnormal metabolic markers were noted in obese women. CONCLUSION: The present study suggests the significant role that might be mediated by apelin for developing abnormal metabolic parameters among Egyptian obese women.

Estimation of ultrasound reference values for the upper limb peripheral nerves in adults: A cross-sectional study.

The objective of this study is to estimate the reference values for the upper limb peripheral nerves in adults.The demographics and physical characteristics of 69 adult healthy volunteers were evaluated and recorded. In addition, the side to side differences of the estimated reference values and their correlations with the age, weight, height, and body mass index (BMI) were evaluated.Cross-sectional area reference values of the upper limb nerves did not correlate with height; however, they correlated with age, weight, and BMI in some scanned sites.The data obtained in this study could be helpful in future diagnosis of peripheral nerve disorders of the upper limb.

The Validity of Body Adiposity Indices in Predicting Metabolic Syndrome and Its Components among Egyptian Women.

AIM: To assess the associations between the body adiposity indices and risk of metabolic syndrome (MS) and its components in Egyptian women and to evaluate their predictive power. MATERIALS AND METHODS: This was a cross-sectional analysis performed on 180 Egyptian women aged between 25-35 years. They were 90 women with MS diagnosed by International Diabetes Federation (IDF) and 90 healthy age matched controls. Body adiposity index (BAI), body mass index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) were calculated and serum samples were analyzed for metabolic parameters. Receiver operating characteristic curves (ROC) was used to determine the discriminatory capacity of BAI, WHR WHtR and BMI for MS. RESULTS: Area under the curve (AUC) was highest for BIA, followed by WHR, WHtR and then BMI. All adiposity indices were significantly correlated with metabolic components and BAI had the highest correlation coefficients compared to other indices. CONCLUSION: BAI is a practical predictor for MS and has satisfactory diagnostic accuracy for diagnosing MS among Egyptian women and can be used in addition to WHR, WHtR and BMI for identifying MS in the field studies.

Potential host-related risk factors for recurrent urinary tract infection in Saudi women of childbearing age.

INTRODUCTION AND HYPOTHESIS: Risk factors for recurrent urinary tract infection (rUTI) in women may differ between individuals, age, and the community. This study aimed to evaluate host related risk factors for rUTI in sexually active Saudi women during the childbearing period. METHODS: A case-control study was conducted in five healthcare centers and included married, nonpregnant women aged 18-40 years. A total of 217 women had rUTI (cases) and 252 did not (controls). A validated questionnaire, with a face-to-face interview, was applied to assess various demographic, behavioral, medical, and sexual data. Additionally, a thorough physical examination, saliva and blood analyses, uroflowmetry, and genitourinary ultrasonography were performed. Multivariate logistic regression analysis was used to identify the significant host related risk factors associated with rUTI. RESULTS: In multivariate analysis, attributable risks for rUTI were a history of childhood UTI [odds ratio (OR) = 6.8)] back-to-front douching/wiping after bowel movement (OR = 2.6), younger age at first intercourse (OR = 6.3), increased frequency of sexual intercourse (OR = 4.8), obstructed urinary flow (OR = 1.9), and genital prolapse (OR = 3.4). A total of 9.68 % of cases and none of the controls had high postvoid residual urine (positive predictive value for rUTI = 100 %). CONCLUSIONS: This is the first reported study to evaluate host related risk factors for rUTI in childbearing-age women in Saudi Arabia. Study findings indicate the association between rUTI and various factors that have been already established, with addition of improper rectal hygiene as a potential risk for recurrence.

Indicators of the metabolic syndrome in obese adolescents.

INTRODUCTION: To assess the prevalence of metabolic risk indicators for the metabolic syndrome (MS) in a sample of obese Egyptian adolescents and to compare anthropometric and biochemical parameters in subjects with one or two parameters of the MS with those who meet MS criteria. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted on 300 obese adolescents, with a mean age of 15.45 ±2.54 years. Variables examined included body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), systolic and diastolic blood pressure (BP), fasting blood glucose, cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoproteins (LDL), insulin and insulin resistance (IR) measured by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Receiver operating characteristic (ROC) curve analysis was used to determine the predictive powers of anthropometric parameters associated with increased risk for the MS. RESULTS: The overall prevalence of the MS was 20%. Individuals meeting 3 or more MS criteria had significantly higher levels of BP, TG, glucose, insulin and HOMA-R and low HDL levels compared with those who had 1 or 2 MS criteria. Area under the curve (AUC) for identifying the MS risk factors was the highest for WHR, followed by WC and BMI in both genders (p < 0.001). CONCLUSIONS: The most prevalent metabolic risk factors that compose the MS were arterial hypertension, low HDL and hypertriglyceridemia; BMI tended to be the weakest index for identifying MS risk factors, while WHR was the best predictive index in both genders.

Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents.

Hepatitis C virus (HCV) has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world's population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL28B) gene and natural clearance of HCV infection or after PEGylated interferon-alpha and ribavirin treatment with and without direct antiviral agents. This paper synthesizes the recent advances in the pharmacogenetics of HCV infection in the era of triple therapies.

Association of serum paraoxonase enzyme activity and oxidative stress markers with dyslipidemia in obese adolescents.

OBJECTIVES: The aim of the present study was to investigate the serum paraoxonase 1 (PON1) concentration and oxidative stress markers and assess its relations with the biochemical parameters in obese adolescents. MATERIALS AND METHODS: One hundred and fifty obese adolescents (range 16-18 years) and 150 healthy age- and sex-matched controls were enrolled in the study. The data were extracted from a project entitled "Obesity among Youth: Lifestyle and Genetic Factors" funded by the Science and Technology Development Fund, Egypt. Serum paraoxonase 1 (PON1), nitric oxide (NO), and malonaldehyde were measured. Anthropometry, fasting glucose, insulin concentrations, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, triglycerides, systolic and diastolic blood pressure (BP) were measured. Insulin resistance was determined by Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Diagnostic accuracy of oxidative markers to identify dyslipidemia was calculated with ROC analysis. RESULTS: The study showed that PON1 activity was significantly lower in obese adolescents than controls. Obese adolescents had significant lower NO level and significant increased MA values as compared to controls. PON1 was negatively correlated with MAD and body mass index in obese subjects. Obese adolescents showed dyslipidemia and increased blood pressure and HOMA-IR values. PON1 had high area under the curve in ROC analysis for identifying dyslipidemia in obese subjects. CONCLUSIONS: Our results indicate that obese subjects have increased oxidative stress and decreased PON1 activity. The lower paraoxonase level might contribute to the greater risk of dyslipidemia, insulin resistance, high blood pressure that are considered as important components in the pathogenesis of the metabolic syndrome in obese adolescents.

Host and viral determinants of the outcome of exposure to HCV infection genotype 4: a large longitudinal study.

OBJECTIVES: The objective of this study was to characterize the factors that influence the outcome of exposure to hepatitis C virus (HCV) genotype 4 (HCV-G4) and the course of recent infection. METHODS: In this longitudinal study, we prospectively assessed the clinical, genetic, virological, and immunological parameters and retrospectively determined single-nucleotide polymorphisms at interleukin-28B (IL-28B) rs12979860 in a well-characterized large cohort recently exposed to HCV-G4. RESULTS: A total of 136 subjects with acute HCV (new viremia, seroconversion, and HCV-specific T-cell responses) were identified. Forty-eight subjects (35%) had spontaneous viral clearance and 88 subjects developed chronic HCV of which 42 subjects were treated with pegylated interferon monotherapy, with a sustained virologic response (SVR) rate of 88%. Twenty-six subjects developed HCV-specific T-cell immune responses without detectable viremia or seroconversion. IL-28B-CC (odds ratio (OR) 14.22; P<0.0001), multispecific T-cell responses (OR=11.66; P<0.0001), >300 IU/l alanine aminotransferase (ALT) decline within 4 weeks (OR=6.83; P<0.0001), jaundice (OR=3.54; P=0.001), female gender (OR=2.39; P=0.007), and >2.5 log10 HCV-RNA drop within 8 weeks (OR=2.48; P=0.016) were independently associated with spontaneous clearance. ALT normalization and undetectable HCV-RNA predicted SVR. Exposed apparently uninfected participants had a higher frequency of IL-28B-CC than patients with unresolved acute HCV (P<0.001). IL-28B-CC was associated with multispecific T-cell response (r(2)=0.0.835; P<0.001). CONCLUSIONS: IL-28B-CC genotype, multispecific HCV T-cell responses, rapid decline in ALT, and viral load predict spontaneous clearance and response to acute HCV-G 4 therapy. IL-28B-CC genotype correlates with developing early multispecific T-cell responses. These findings have important implications for predicting the outcome of HCV exposure and acute infection and identifying patients likely to benefit from therapy.

Enhanced efficacy of pegylated interferon alpha-2a over pegylated interferon and ribavirin in chronic hepatitis C genotype 4A randomized trial and quality of life analysis.

AIM: The therapy of chronic hepatitis C genotype 4 (HCV-4) has not been optimized yet. This randomized, prospective, parallel-group clinical trial compared the efficacy and safety of pegylated interferon α-2a (PEG-IFN α-2a) plus ribavirin and PEG-IFN α-2b plus ribavirin and assessed the health-related quality of life (HRQOL) in patients with chronic HCV-4. METHODS: Eligible patients with proven chronic HCV-4 were randomized to receive either a weekly dose of PEG-IFN α-2a (180 µg) or PEG-IFN α-2b (1.5 µg/kg) and a daily dose of ribavirin (1000-1200 mg) for 48 weeks with 24 weeks post-treatment follow-up. The primary end point was sustained virological response (SVR) defined by undetectable HCV RNA 24 weeks after treatment. The Short form-36 Health Survey version 2 (SF-36v2) and the Chronic Liver Disease questionnaires (CLDQ) were assessed before, during and after therapy. RESULTS: The overall SVR rate of the entire cohort was 59.9%. The SVR rates were significantly higher in patients treated with PEG-IFN α-2a and ribavirin (Group A; n=109) compared with those treated with PEG-IFN α-2b and ribavirin (Group B; n=108, 70.6 vs. 54.6%, respectively; P=0.017). The relapse rates were 5.1% for PEG-IFN α-2a and 15.7% for PEG-IFN α-2b (P=0.0019). The SF-36v2 and CLDQ were low during therapy and improved significantly after therapy successful therapy. CONCLUSION: Pegylated interferon α-2a plus ribavirin was significantly more effective than PEG-IFN α-2b and ribavirin therapy in the treatment of chronic HCV-4 patients. The tolerability and adverse events were comparable between the two regimens. The HRQOL improved significantly after successful PEG-IFN α-2a plus ribavirin therapy.

Hepatitis C virus genotype 4 therapy: progress and challenges.

The hepatitis C virus genotype 4 (HCV-4) is prevalent in Egypt, the Middle East and Africa. Recently, the epidemiology of HCV-4 has changed and this genotype has begun to cross borders and spread to several regions in Europe through immigration and injection drug use. HCV-4 has been considered a difficult-to-treat genotype based on the low sustained virological response (SVR) rates obtained with conventional interferon (IFN)-based regimens. Pegylated interferons (PEG-IFN) plus ribavirin therapy for chronic HCV-4 has been associated with increased SVR rates of more than 60%. Shorter treatment of chronic HCV-4 patients with rapid and early virological responses has been associated with high SVR rates, better compliance, fewer adverse events and lower costs. Despite this progress, the treatment of HCV-4 non-responders, injection drug users, patients coinfected with human immunodeficiency virus, thalassaemic patients, patients on haemodialysis and patients with HCV-4 recurrence after liver transplantation still represents a significant therapeutic challenge. Treatment of HCV-4 has markedly improved, with higher sustained response rates and the possibility of shorter regimens. Despite the recent progress in the treatment of HCV-4, more research is required to optimize current therapy and include genotype 4 patients in clinical trials on emerging therapies such as specifically targeted antiviral therapy for HCV with protease and/or polymerase inhibitors.