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Cousien, Anthony, Dorothée Obach, Sylvie Deuffic-Burban, Aya Mostafa, Gamal Esmat, Valérie Canva, Mohamed El Kassas, Mohammad El-Sayed, Wagida A. Anwar, Arnaud Fontanet et al. "Is expert opinion reliable when estimating transition probabilities? The case of HCV-related cirrhosis in Egypt." BMC medical research methodology 14 (2014): 39. Abstract

BACKGROUND: Data on HCV-related cirrhosis progression are scarce in developing countries in general, and in Egypt in particular. The objective of this study was to estimate the probability of death and transition between different health stages of HCV (compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma) for an Egyptian population of patients with HCV-related cirrhosis.

METHODS: We used the "elicitation of expert opinions" method to obtain collective knowledge from a panel of 23 Egyptian experts (among whom 17 were hepatologists or gastroenterologists and 2 were infectiologists). The questionnaire was based on virtual medical cases and asked the experts to assess probability of death or probability of various cirrhosis complications. The design was a Delphi study: we attempted to obtain a consensus between experts via a series of questionnaires interspersed with group response feedback.

RESULTS: We found substantial disparity between experts' answers, and no consensus was reached at the end of the process. Moreover, we obtained high death probability and high risk of hepatocellular carcinoma. The annual transition probability to death was estimated at between 10.1% and 61.5% and the annual probability of occurrence of hepatocellular carcinoma was estimated at between 16.8% and 58.9% (depending on age, gender, time spent in cirrhosis and cirrhosis severity).

CONCLUSIONS: Our results show that eliciting expert opinions is not suited for determining the natural history of diseases due to practitioners' difficulties in evaluating quantities. Cognitive bias occurring during this type of study might explain our results.

Ismail, Sohair, Hanan Abdel Hafez, Samar K. Darweesh, Kamal Hassan Kamal, and Gamal Esmat. "Virologic response and breakthrough in chronic hepatitis B Egyptian patients receiving lamivudine therapy." Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology 27, no. 4 (2014): 380-386. Abstract

BACKGROUND: Lamivudine monotherapy is effective in suppressing hepatitis B virus (HBV) replication to undetectable levels by PCR, in ameliorating liver disease and to some extent in achieving HBsAg seroconversion. This study aimed at assessing the virological and biochemical responses as well as breakthrough in HBeAg-negative chronic HBV (CHB) Egyptian patients receiving lamivudine therapy.

METHODS: This retrospective study included 140 CHB patients with positive serum HBV-DNA by quantitative PCR assays and negative HBeAg who had never received prior anti-viral therapy for HBV. According to duration of lamivudine therapy (100 mg/day) patients were grouped into: group I (n=59) who received lamivudine for 1 year, group II (n=50) who received lamivudine for 2 years, and group III (n=31) who received lamivudine for 3 years.

RESULTS: In group I, 76.3% patients had virologic response but this was reduced in group II and group III to 72% and 67.7% respectively. None of the patients in group I developed virologic breakthrough, whereas 12% and 25.8% in groups II and III respectively developed breakthrough. In group I, 25% of patients having high pre-treatment viremia showed virologic response compared to 84.6% and 83.3% having mild and moderate viremia respectively (P<0.01). However, in groups II and III, there was no significant relationship between pre-treatment viremia and virologic response. No significant relationship was found between pre-treatment viral load and incidence of breakthrough within each group.

CONCLUSION: Lamivudine remains one of the antiviral therapies for HBeAg negative CHB patients. The rates of maintained virologic and biochemical responses to lamivudine decrease in time due to selection of drug-resistant mutants and, hence, breakthrough.

Obach, Dorothée, Sylvie Deuffic-Burban, Gamal Esmat, Wagida A. Anwar, Sahar Dewedar, Valérie Canva, Anthony Cousien, Wahid Doss, Aya Mostafa, Stanislas Pol et al. "Effectiveness and cost-effectiveness of immediate versus delayed treatment of hepatitis C virus-infected patients in a country with limited resources: the case of Egypt." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 58, no. 8 (2014): 1064-71. Abstract

BACKGROUND: Because of logistical and economic issues, in Egypt, as in other resource-limited settings, decision makers should determine for which patients hepatitis C virus (HCV) treatment should be prioritized. We assessed the effectiveness and cost-effectiveness of different treatment initiation strategies.

METHODS: Using a Markov model, we simulated HCV disease in chronically infected patients in Egypt, to compare lifetime costs, quality-adjusted life expectancy (QALE), and the incremental cost-effectiveness ratio (ICER) of different treatment initiation strategies.

RESULTS: Immediate treatment of patients at stages F1/F2/F3 was less expensive and more effective than delaying treatment until more severe stages or not providing treatment (in patients diagnosed at F1: QALE = 18.32 years if treatment at F1 vs 18.22 if treatment at F2). Treatment of F4 patients was more effective than no treatment at all (QALE = 10.33 years vs 8.77 years) and was cost-effective (ICER = $1915/quality-adjusted life-year [QALY]). When considering that affordable triple therapies, including new direct-acting antivirals, will be available starting in 2016, delaying treatment until stage F2, then treating all patients regardless of their disease stage after 2016, was found to be cost-effective (ICER = $33/QALY).

CONCLUSIONS: In Egypt, immediate treatment of patients with fibrosis stage F1-F3 who present to care is less expensive and more effective than delaying treatment. However, immediate treatment at stage F1 is only slightly more effective than waiting for disease to progress to stage F2 before starting treatment and is sensitive to the forthcoming availability of new treatments. Treating patients at stage F4 is highly effective and cost-effective. In Egypt, decision makers should prioritize treatment for F4 patients and delay treatment for F1 patients who present to care.

Shehab, H., I. Elattar, T. Elbaz, M. Mohey, and G. Esmat. "CUFA algorithm: assessment of liver fibrosis using routine laboratory data." Journal of viral hepatitis 21, no. 12 (2014): 956-64. Abstract

Staging of liver fibrosis is an integral part of the management of HCV. Liver biopsy is hampered by its invasiveness and possibility of sampling error. Current noninvasive methods are disadvantaged by their cost and complexity. In this study, we aimed at developing a noninvasive method for the staging of liver fibrosis based only on routine laboratory tests and clinical data. Basic clinical and laboratory data and liver biopsies were collected from 994 patients presenting for the evaluation of HCV. Logistic regression was used to create a model predictive of fibrosis stages. A sequential test was then developed by combining our new model with APRI. In the training set (497) a model was created by logistic regression for the prediction of significant fibrosis (≥F2), it included platelets, AST and age (PLASA). The areas under the curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 0.753, 66.8, 71.4, 69.8, 68.4, respectively, while in the validation set (497), they were 0.777, 66.7, 72.8, 68.6 and 71, respectively. These were the best performance indicators when compared to APRI, FIB-4, King's score, platelets, fibrosis index, age-platelet index and Lok index in the same set of patients. A sequential test was then developed including APRI followed by PLASA [Cairo University Fibrosis Assessment (CUFA) algorithm], this allowed saving 20% and 34% of liver biopsies for patients being tested for significant fibrosis and cirrhosis, respectively. In conclusion, the CUFA algorithms at no cost allow saving a significant proportion of patients from performing a liver biopsy or a more complex costly test. These algorithms could be used as the first step in the assessment of liver fibrosis before embarking on the more costly advanced serum markers, Fibroscan or liver biopsy.

Esmat, Gamal, Mohamed El Kassas, Mohamed Hassany, Mohamed Gamil, and Maissa El Raziky. "Optimizing treatment for HCV genotype 4: PEG-IFN alfa 2a vs. PEG-IFN alfa 2b; the debate continues." Liver international : official journal of the International Association for the Study of the Liver 34 Suppl 1 (2014): 24-8. Abstract

Hepatitis C virus (HCV) remains one of the leading causes of morbidity and mortality worldwide. Combined therapy with pegylated interferon (PEG-IFN) and ribavirin is the current standard of care treatment for HCV genotype 4. Two types of PEG-IFN are commercially available. The limited number of trials that were conducted for HCV genotype 4 and the few head to head comparisons make it impossible to know which is the best option? In this article we review all available PEG-IFN trials performed worldwide for HCV genotype 4 since 2004. Unless another molecule is developed as a standalone for the treatment of HCV, PEG-IFN will continue to be a source of debate.

Fawzy, Injie O., Mohamed Negm, Rasha Ahmed, Gamal Esmat, Nabila Hamdi, and Ahmed I. Abdelaziz. "Tamoxifen downregulates MxA expression by suppressing TLR7 expression in PBMCs of males infected with HCV." Journal of medical virology 86, no. 7 (2014): 1113-9. Abstract

Gender discrepancies in immune response to HCV infections and during HCV therapy exist and previous findings including those from this research team indicate the female sex hormone, 17β-estradiol (E2), to be one probable cause of such inconsistencies. Also, it was recently demonstrated that estrogen receptor modulator Tamoxifen (TAM) exerts an upmodulating/enhancing effect on the TLR7 and JAK-STAT pathways in PBMCs of premenopausal females infected with HCV. Pursuing this work, a discrepancy was noticed in the results from male patients, therefore this study aimed to determine whether the effects of TAM previously observed in the PBMCs of women would hold true in PBMCs from males infected with HCV. Isolated PBMCs were pooled and relative expression of the TLR7 was quantified using RTqPCR. Sets of PBMCs were treated with exogenous interferon alpha (IFNα) or the TLR7 ligand, Imiquimod; these stimulations were performed with and without E2 and TAM pretreatment and the relative gene expressions of TLR7 and MxA were measured. Pretreatment with E2 and IFNα downregulated TLR7 (**P = 0.0080) and TAM further decreased this expression significantly (*P = 0.0284). TAM pretreatment also caused a significant downregulation in MxA expression in Imiquimod-stimulated PBMCs (*P = 0.0218). In conclusion, TAM displays several paradoxical effects in PBMCs of males infected with HCV compared to those of females. Contrary to the previous study involving premenopausal females, in PBMCs of infected males TAM may decrease IFNα release as indicated by reduced MxA expression possibly via the suppression of TLR7 expression.

Esmat, Gamal, Maissa El Raziky, Aisha Elsharkawy, Dina Sabry, Mohamed Hassany, Amal Ahmed, Noha Assem, Mohamad El Kassas, and Wahid Doss. "Impact of Vitamin D Supplementation on Sustained Virological Response in Chronic Hepatitis C Genotype 4 Patients Treated by Pegylated Interferon/Ribavirin." Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (2014). Abstract

The current standard of care therapy (SOC) for chronic HCV is pegylated interferon/ribavirin (Peg-IFN/RBV). Many reports showed the possible role of vitamin D supplementation in augmenting the response to SOC. The aim of this study was to assess the role of vitamin D supplementation on the response to treatment in chronic HCV genotype 4 patients. One hundred and one chronic HCV patients were classified into two groups (Group 1): 51 patients received the SOC therapy consisting of Peg-interferon alfa-2b plus ribavirin, (Group 2): 50 patients received the SOC therapy+vitamin D3 (Cholecalciferol) in a dose of 15,000 IU/week during the treatment course. Vitamin D deficiency was found in 95% of patients. No correlation was found between vitamin D levels and stage of fibrosis in the whole population. Vitamin D supplementation had no positive impact on treatment outcome where sustained virological response (SVR) was achieved in 51.2% in group 2 and 71.4% in group 1 by per-protocol analysis and in 44% in group 2 and in 68.6% in group 1 by intention to treat analysis (P value 0.22 and 0.220 respectively). Despite its role in other genotypes, vitamin D supplementation has no significant impact on SVR in HCV Genotype 4 patient. No correlation was found between vitamin D levels and stage of liver fibrosis.

Alboraie, Mohamed, Marwa Khairy, Marwa Elsharkawy, Noha Asem, Aisha Elsharkawy, and Gamal Esmat. "Value of Egy-Score in diagnosis of significant, advanced hepatic fibrosis and cirrhosis compared to aspartate aminotransferase-to-platelet ratio index, FIB-4 and Forns' index in chronic hepatitis C virus." Hepatology research : the official journal of the Japan Society of Hepatology (2014). Abstract

AIM: Serum markers and developed scores are of rising importance in non-invasive diagnosis of hepatic fibrosis. Aspartate aminotransferase-to-platelet ratio index (APRI), FIB-4 and Forns' index are validated scores used for diagnosis of liver fibrosis. The Egy-Score is a newly developed score for detection of hepatic fibrosis with promising results. We aimed to assess the accuracy of the Egy-Score in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis compared to APRI, FIB-4 and Forns' in chronic hepatitis C virus (HCV) patients.

METHODS: A retrospective study including 100 chronic hepatitis C naïve Egyptian patients was performed. Patients were classified according to stages of fibrosis into three groups: significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4). Egy-Score, APRI, FIB-4 and Forns' index were calculated. Regression analysis and receiver-operator curves were plotted to assess the sensitivity, specificity and predictive values for the significant scores with the best cut-off for diagnosis.

RESULTS: An Egy-Score of 3.28 or more was superior to APRI, FIB-4 and Forns' index for detecting advanced fibrosis with a sensitivity of 91% and specificity of 78%. An Egy-Score of 3.67 or more was superior to APRI, FIB-4 and Forns' index for detecting cirrhosis with a sensitivity of 82% and specificity of 87%. Forns' index was superior to Egy-Score, FIB-4 and APRI for detecting significant fibrosis.

CONCLUSION: The Egy-Score is a promising, accurate, easily calculated, cost-effective score in the prediction of hepatic fibrosis in chronic HCV patients with superiority over APRI, FIB-4 and Forns' index in advanced hepatic fibrosis and cirrhosis.

Bonnard, P., A. Elsharkawy, K. Zalata, E. Delarocque-Astagneau, L. Biard, L. Le Fouler, A. B. Hassan, M. Abdel-Hamid, M. El-Daly, M. E. Gamal et al. "Comparison of liver biopsy and noninvasive techniques for liver fibrosis assessment in patients infected with HCV-genotype 4 in Egypt." Journal of viral hepatitis (2014). Abstract

In Egypt, as elsewhere, liver biopsy (LB) remains the gold standard to assess liver fibrosis in chronic hepatitis C (CHC) and is required to decide whether a treatment should be proposed. Many of its disadvantages have led to develop noninvasive methods to replace LB. These new methods should be evaluated in Egypt, where circulating virus genotype 4 (G4), increased body mass index and co-infection with schistosomiasis may interfere with liver fibrosis assessment. Egyptian CHC-infected patients with G4 underwent a LB, an elastometry measurement (Fibroscan(©) ), and serum markers (APRI, Fib4 and Fibrotest(©) ). Patients had to have a LB ≥15 mm length or ≥10 portal tracts with two pathologists blinded readings to be included in the analysis. Patients with hepatitis B virus co-infection were excluded. Three hundred and twelve patients are reported. The performance of each technique for distinguishing F0F1 vs F2F3F4 was compared. The area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75 for APRI, Fib-4, Fibrotest© and Fibroscan©, respectively (no influence of schistosomiasis was noticed). An algorithm using the Fib4 for identifying patients with F2 stage or more reduced by nearly 90% the number of liver biopsies. Our results demonstrated that noninvasive techniques were feasible in Egypt, for CHC G4-infected patients. Because of its validity and its easiness to perform, we believe that Fib4 may be used to assess the F2 threshold, which decides whether treatment should be proposed or delayed.

Hézode, Christophe, Gideon M. Hirschfield, Wayne Ghesquiere, William Sievert, Maribel Rodriguez-Torres, Stephen D. Shafran, Paul J. Thuluvath, Harvey A. Tatum, Imam Waked, Gamal Esmat et al. "Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study." Gut (2014). Abstract

OBJECTIVE: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin.

DESIGN: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA

Waked, Imam, Waheed Doss, Manal Hamdy El-Sayed, Chris Estes, Homie Razavi, Gamal Shiha, Ayman Yosry, and Gamal Esmat. "The current and future disease burden of chronic hepatitis C virus infection in Egypt." Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology 15, no. 2 (2014): 45-52. Abstract
Umar, Muhammed, Aamir G. Khan, Zaigham Abbas, Sanjeev Arora, Naqvi Asifabbas, Andre Elewaut, Gamal Esmat, Graham Foster, Michael Fried, Khean-L Goh et al. "World Gastroenterology Organisation global guidelines: diagnosis, management and prevention of hepatitis C April 2013." Journal of clinical gastroenterology 48, no. 3 (2014): 204-17. Abstract
Bruggmann, P., T. Berg, A. L. H. Øvrehus, C. Moreno, C. E. Brandão Mello, F. Roudot-Thoraval, R. T. Marinho, M. Sherman, S. D. Ryder, J. Sperl et al. "Historical epidemiology of hepatitis C virus (HCV) in selected countries." Journal of viral hepatitis 21 Suppl 1 (2014): 5-33. Abstract

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Razavi, H., I. Waked, C. Sarrazin, R. P. Myers, R. Idilman, F. Calinas, W. Vogel, M. C. Mendes Correa, C. Hézode, P. Lázaro et al. "The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm." Journal of viral hepatitis 21 Suppl 1 (2014): 34-59. Abstract

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Wedemeyer, H., A. S. Duberg, M. Buti, W. M. Rosenberg, S. Frankova, G. Esmat, N. Örmeci, H. Van Vlierberghe, M. Gschwantler, U. Akarca et al. "Strategies to manage hepatitis C virus (HCV) disease burden." Journal of viral hepatitis 21 Suppl 1 (2014): 60-89. Abstract

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Alboraie, Mohamed, Marwa Khairy, Aisha Elsharkawy, Marwa Elsharkawy, Noha Asem, Amany R. Abo El-Seoud, Fathy G. Elghamry, and Gamal Esmat. "Egy-score as a noninvasive score for the assessment of hepatic fibrosis in chronic hepatitis C: a preliminary approach." Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association 20, no. 3 (2014): 170-4. Abstract

BACKGROUND AND AIMS: Egy-Score is a new noninvasive score for prediction of severe hepatic fibrosis in patients with chronic liver diseases. The aim of this study was to validate Egy-Score as a noninvasive score for predicting stage of hepatic fibrosis in a group of Egyptian chronic hepatitis C patients.

PATIENTS AND METHODS: One hundred Egyptian patients with chronic hepatitis C were enrolled. Mean age was 40.25 ± 9.39 years. They were subjected to CA19-9, alpha-2-macroglobulin, total bilirubin, platelet count and albumin, liver biopsy, and histopathological staging of hepatic fibrosis according to METAVIR scoring system as part of their assessment for treatment. Egy-Score was calculated according to the following formula: Egy-Score = 3.52 + 0.0063 × CA19-9 + 0.0203 × age + 0.4485 × alpha-2-macroglobulin + 0.0303 × bilirubin - 0.0048 × platelet - 0.0462 × albumin. Egy-Score results were correlated to the stage of hepatic fibrosis.

RESULTS: Egy-Score correlates positively with the stage of hepatic fibrosis (F0-F4). Egy-Score was able to differentiate significant hepatic fibrosis, severe hepatic fibrosis, and cirrhosis accurately. Cutoff values of Egy-Score were 2.91850 (for significant fibrosis), 3.28624 (for severe fibrosis), and 3.67570 (for cirrhosis). Sensitivity, specificity, and areas-under-ROC curve (AUROCs) were 75.8%, 68.42%, and 0.776 (for significant fibrosis "≥F2"), 91.67%, 77.63%, and 0.875 (for severe fibrosis "≥F3"), and 81.82%, 86.52%, and 0.874 (for cirrhosis "F4"), respectively.

CONCLUSION: Egy-Score is a useful noninvasive panel of surrogate biomarkers that could accurately predict different stages of hepatic fibrosis in patients with chronic hepatitis C.

Saad, Yasmin, Olfat Shaker, Yasser Nassar, Lama Ahmad, Mohamed Said, and Gamal Esmat. "A polymorphism in the microsomal triglyceride transfer protein can predict the response to antiviral therapy in Egyptian patients with chronic hepatitis C virus genotype 4 infection." Gut and liver 8, no. 6 (2014): 655-61. Abstract

BACKGROUND/AIMS: A polymorphism in the microsomal triglyceride transfer protein (MTP) is associated with hepatic fibrosis, and carriers showed higher levels of steatosis, higher levels of hepatitis C virus (HCV) RNA and advanced fibrosis. The aim of this study was to study MTP expression pattern in HCV patients and impact of the MTP polymorphism on the response to antiviral therapy.

METHODS: One hundred consecutive naive HCV genotype 4 patients were recruited to receive antiviral therapy, and 40 control subjects were also recruited. Demographic, laboratory, and histopathology data were collected. DNA was isolated, and the samples were subjected to polymerase chain reaction analysis and genotyping for MTP by restriction fragment length polymorphism analysis.

RESULTS: Patients and controls were age- and sex-matched (male/female, 56/44, age, 39.2±7.8 years for patients with HCV; male/female, 18/22, age, 38.1±8.1 years for controls). MTP single nucleotide polymorphisms (SNPs) (GG, GT, TT) and alleles (G, T) in the patients versus the controls were 70%, 21%, 9% & 80.5%, 19.5% versus 10%, 87.5%, 2.5% & 53.8%, 46.3%, respectively (p=0.0001). The sustained viral response (SVR) of the patients was 60%. SNPs in MTP genotypes (GG, GT, and TT) and alleles (G and T) in the responders and nonresponders were 71.7%, 25%, 3.3% & 84.2%, 15.8% versus 67.5%, 15%, 17.5% & 75%, 25% (p=0.038 and p=0.109, respectively). A multivariate analysis showed that the GT genotype was an independent predictor of SVR (area under the curve 90% and p=0.0001).

CONCLUSIONS: MTP could be a new predictor for SVR to antiviral therapy in patients with HCV genotype 4 infection.

Elhelw, Dalia Sherif, Radwa Yehia Mekky, Nada El-Ekiaby, Rasha Ahmed, Mohammad Ahmed Mohey Eldin, Mohammad El-Sayed, Mahmoud Mohammad Abouelkhair, Ayman Salah, Abdel Rahman Zekri, Gamal Esmat et al. "Predictive prognostic role of miR-181a with discrepancy in the liver and serum of genotype 4 hepatitis C virus patients." Biomedical reports 2, no. 6 (2014): 843-848. Abstract

microRNA (miRNA) expression in organs does not always represent their quantity in serum. A disparity in the expression of miR-181a has been reported in the tissues and serum of hepatocellular carcinoma (HCC) patients. Since hepatitis C virus (HCV) is a major cause of HCC and miR-181a has never been studied in HCV, the present study aimed to investigate the miR-181a expression profile in genotype 4 (GT4)-HCV patients to evaluate whether this pattern is also apparent in HCV. RNA was extracted from liver tissues, peripheral mononuclear cells (PBMCs) and serum samples from GT4-HCV-infected patients and healthy donors to evaluate the relative miR-181a expression using quantitative reverse transcription-polymerase chain reaction. miR-181a was significantly higher in the serum of naïve patients compared to controls, and an inverse correlation with the viral load and liver enzymes was apparent. By contrast, no difference in miR-181a expression was observed in the liver tissues and PBMCs of patients compared to controls. This expression observed in HCV is conflicting to that previously reported in HCC. The study also demonstrates a significant upregulation of miR-181a post-interferon/ribavirin treatment in the serum of sustained virological responders (SVRs) compared to non-responders and treatment-naïve SVRs. In conclusion, miR-181a may be considered to be a possible prognostic marker in GT4-HCV infection.

Breban, Romulus, Naglaa Arafa, Sandrine Leroy, Aya Mostafa, Iman Bakr, Laura Tondeur, Mohamed Abdel-Hamid, Wahid Doss, Gamal Esmat, Mostafa K. Mohamed et al. "Effect of preventive and curative interventions on hepatitis C virus transmission in Egypt (ANRS 1211): a modelling study." The Lancet. Global health 2, no. 9 (2014): e541-9. Abstract

BACKGROUND: Most hepatitis C virus (HCV) transmission in Egypt is related to medical injections and procedures. To control the spread of HCV, the Egyptian Ministry of Health initiated awareness and education campaigns, strengthened infection control in health-care facilities, and subsidised anti-HCV treatment. We aimed to investigate the effect of these interventions on the spread of HCV by mathematical modelling.

METHODS: We developed a mathematical model of HCV transmission in Zawyat Razin, a typical rural community. Our model assumes that each individual has two distinct types of medical procedures: injections and more invasive medical procedures. To quantify the severity of the spread of HCV, we used the notion of the basic reproduction number R0, a standard threshold parameter signalling whether transmission of an infectious disease is self-sustained and maintains an epidemic. If R0 is greater than 1, HCV is self-sustained; if R0 is 1 or less, HCV transmission is not self-sustained. We investigated whether heterogeneity in the rate of injection or invasive medical procedures is the determinant factor for HCV transmission and whether most iatrogenic transmission is caused by a small group of individuals who receive health-care interventions frequently. We then assessed whether interventions targeted at this group could reduce the spread of HCV.

FINDINGS: The R0 of the spread of HCV without treatment was 3·54 (95% CI 1·28-6·18), suggesting a self-sustained spread. Furthermore, the present national treatment programme only decreased R0 from 3·54 to 3·03 (95% CI 1·10-5·25). Individuals with high rates of medical injections seem to be responsible for the spread of HCV in Egypt; the R0 of the spread of HCV without treatment would be 0·64 (95% CI 0·41-0·93) if everybody followed the average behaviour. The effect of treatment on HCV transmission is greatly enhanced if treatment is provided a mean of 2·5 years (95% CI 0·1-9·2) after chronic infection and with drug regimens with more than 80% efficacy. With these treatment parameters, preventive and curative interventions targeting individuals with high rates of medical injections might decrease R0 below 1 for treatment coverage lower than 5%.

INTERPRETATION: Targeting preventive and curative interventions to individuals with high rates of medical injections in Egypt would result in a greater reduction the spread of HCV than would untargeted allocation. Such an approach might prove beneficial in other resource-limited countries with health-care-driven epidemics.

FUNDING: Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS 1211), ANR grant Labex Integrative Biology of Emerging Infectious Diseases.

Mekky, Radwa Yehia, Nada Magdy El-Ekiaby, Mohammed Tarif Hamza, Noha Mousaad Elemam, Mohammed El-Sayed, Gamal Esmat, and Ahmed Ihab Abdelaziz. "Mir-194 is a hepatocyte gate keeper hindering HCV entry through targeting CD81 receptor." The Journal of infection (2014). Abstract

OBJECTIVE: The tetraspanin CD81 is one of the main receptors involved in hepatitis C virus entry. Herein, we aimed to explore the role of microRNAs in regulating CD81 receptor expression and function.

PATIENTS AND METHODS: Bioinformatics analysis was carried out to select potential mircroRNAs that binds CD81 3'untranslated region. Liver biopsies taken from 28 HCV genotype- 4 patients and 10 healthy donors were screened. Naïve, JFH1 and ED43/JFH1- infected- Huh7 cells were transfected with mimics and inhibitors followed by analyzing CD81 protein and mRNA expression. This was done using flow cytometry and Q-RT PCR, respectively. HCV entry into Huh7 cells was investigated post-transfection. Binding confirmation was done using luciferase reporter vector harboring wild/mutant target sites of microRNA. The impact of Epigallocatechin-gallate on modulating microRNA/CD81 expression was assessed.

RESULTS: Bioinformatics revealed that CD81 is a potential down-stream target for miR-194. A significant inverse correlation was found between miR-194 and CD81 expression in liver biopsies of HCV patients. Forcing the expression of miR-194 showed a down-regulation of CD81 protein, mRNA expression and significantly abrogated the HCV infectivity of Huh7 cells. Stimulation with EGCG enhanced mir-194 expression and down-regulated CD81 expression.

CONCLUSION: This study showed that mir-194 hinders HCV entry through targeting CD81 receptors.

Imam Waked, Gamal Shiha, Roula Qaqish B., Gamal Esmat, Mohamed Hassany Ayman Yosry, Mohammad Mohey A. Reham Soliman, Naglaa Allam, Tarik Asselah Naglaa Zayed, Rebecca Redman Coleen Hall, and Wahid Doss Niloufar Mobashery. "Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial." The Lancet Gastroenterology and Hepatology 111, no. 1 (2016): 36-44.
Iman Ramzy, Aisha Elsharkawy, Rabab Fouad Hanan Abdel Hafez, Mohammad El-Sayed Hany khattab Maissa El Raziky, Wafaa El Akel, Amr Radwan Mohamed Shehata, Marwa Elsharkawy, and Gamal Esmat. "Impact of old Schistosomiasis infection on the use of transient elastography (Fibroscan) for staging of fibrosis in chronic HCV patients." Acta Tropica 176 (2017): 283-287.impact_of_schisto_on_fibroscan.pdf
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Mohamed Gamil, Mohamed Alboraie, Noha Asem Mohammad El-Sayed, Aisha Elsharkawy, Bahaa Abbas Mai Mehrez Tamer Elbaz, Mohammad Mohey, and Gamal Esmat. "Novel scores combining AFP with non-invasive markers for prediction of liver fibrosis in chronic hepatitis C patients." Journal of Medical Virology 90 (2018): 1080-1086.gamil_et_al-2018-journal_of_medical_virology1.pdf
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