Publications by authors named "Dalia Omran"

56 Publications

IL28B rs12979860 polymorphism and zinc supplementation affect treatment outcome and liver fibrosis after direct-acting antiviral hepatitis C therapy.

J Genet Eng Biotechnol 2021 Oct 8;19(1):150. Epub 2021 Oct 8.

Faculty of Medicine, Cairo University, Cairo, Egypt.

Background: Impact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis.

Results: Three hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes.

Conclusion: Absolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis.
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http://dx.doi.org/10.1186/s43141-021-00250-yDOI Listing
October 2021

Anxiety, depression and coping strategies among chronic medical patients with coronavirus disease-2019: a multicenter follow-up cohort study.

J Ment Health 2021 Sep 30:1-9. Epub 2021 Sep 30.

Endemic medicine department, Faculty of Medicine, Helwan University, Helwan, Egypt.

Background: Studies have shown that COVID-19 patients experience high levels of anxiety, depression, and stress during the pandemic. Patients adopt different coping strategies to reduce their psychological distress.

Aim: To compare the immediate and long-term psychological impact of COVID-19 disease on patients with and without chronic medical illnesses (CMI) and identify coping styles of both groups during the peak of COVID-19 disease in Egypt.

Methods: This is a cohort follow-up study, that included an online survey consisting of General Health Questionnaire-12, Taylor Manifest Anxiety Scale, Beck Depression Inventory and Brief-COPE scale. The Post-Traumatic Stress Disorder (PTSD) Checklist was completed after 6 months. Questionnaires were distributed to adult patients with a confirmed diagnosis of SARS-CoV-2 virus infection during their quarantine in Egypt.

Results: There was no significant difference between the two groups regarding anxiety and depression during the acute infection. Patients without CMI relied significantly on the use of informational support to cope with COVID-19 disease. Patients with CMI continued to show significant depressive symptoms after 6 months without significant PTSD symptoms.

Conclusions: COVID-19 has similar immediate psychological impact on patients with and without CMI. However, patients with CMI continue to show depression on long-term follow-up.
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http://dx.doi.org/10.1080/09638237.2021.1979491DOI Listing
September 2021

Safety and efficacy of sofosbuvir/ledipasvir and sofosbuvir/daclatasvir in the treatment of hepatitis C in patients with decompensated cirrhosis.

Eur J Gastroenterol Hepatol 2021 Sep 21. Epub 2021 Sep 21.

Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo Tropical medicine, Faculty of Medicine, Alexandria University, Alexandria Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University Department of Internal Medicine, Al-Azhar University Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo Department of community medicine, Faculty of Medicine, Suez Canal University Hepatogastroenterology Department, National Hepatology & Tropical Medicine Research Institute, Cairo Gastroenterology Department, Damietta Cardiology and Gastroenterology Center, Damietta Hepatology and Gastroenterology Department, AGOZA Police Hospital, Cairo Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia, Egypt Hepatology and gastroenterology department, national liver institute.Menoufia University, Egypt.

Background: Hepatitis C virus (HCV)-related decompensated cirrhosis is a severe life-threatening illness. The safety of direct-acting antivirals (DAAs) has opened a gate of hope for that subgroup of patients who were previously contraindicated for interferon therapy.

Objective: We aimed at the investigation of the safety and efficacy of different DAAs regimens in the treatment of HCV-related decompensated cirrhosis patients, to determine sustained virological response (SVR)12 rates and to analyze the factors associated with response.

Methods: A retrospective, single-center study including HCV-related decompensated cirrhosis patients who received DAAs. Demographic, laboratory and clinical data were analyzed. The SVR12 rate was the primary outcome measure. Secondary outcomes included the predictors of response, changes in the baseline model for end-stage liver disease and child-turcotte-pugh (CTP) scores, and fibroindices (APRI and fibrosis-4 index) at 12 weeks after treatment.

Results: In total, 145 eligible patients (141 with CTP class B and 4 with class C) were enrolled in this study. SVR12 was achieved by 88.06% (118/134) of efficacy population on different DAAs regimens, Treatment was discontinued in 11 patients because of severe side effects without any deaths. Younger age showed a significant positive association with SVR12.

Conclusions: DAAs can be used for the treatment of HCV-related decompensated liver disease, with acceptable SVR12 rates and safety profiles.
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http://dx.doi.org/10.1097/MEG.0000000000002287DOI Listing
September 2021

Predictors of severity and development of critical illness of Egyptian COVID-19 patients: A multicenter study.

PLoS One 2021 23;16(9):e0256203. Epub 2021 Sep 23.

Gastroenterology & Infectious Diseases Department, Ahmed Maher Teaching Hospital, Cairo, Egypt.

Objectives: We conducted the present multicenter, retrospective study to assess the epidemiological, clinical, laboratory, and radiological characteristics associated with critical illness among patients with COVID-19 from Egypt.

Methods: The present study was a multicenter, retrospective study that retrieved the data of all Egyptian cases with confirmed COVID-19 admitted to hospitals affiliated to the General Organization for Teaching Hospitals and Institutes (GOTHI) through the period from March to July 2020. The diagnosis of COVID-19 was based on a positive reverse transcription-polymerase chain reaction (RT-PCR) laboratory test.

Results: This retrospective study included 2724 COVID-19 patients, of whom 423 (15.52%) were critically ill. Approximately 45.86% of the critical group aged above 60 years, compared to 39.59% in the non-critical group (p = 0.016). Multivariate analysis showed that many factors were predictors of critically illness, including age >60 years (OR = 1.30, 95% CI [1.05, 1.61], p = 0.014), low oxygen saturation (OR = 0.93, 95% CI [0.91, 0.95], p<0.001), low Glasgow coma scale (OR = 0.75, 95% CI [0.67, 0.84], p<0.001), diabetes (OR = 1.62, 95% CI [1.26, 2.08], p<0.001), cancer (OR = 2.47, 95% CI [1.41, 4.35], p = 0.002), and serum ferritin (OR = 1.004, 95% CI [1.0003, 1.008], p = 0.031).

Conclusion: In the present report, we demonstrated that many factors are associated with COVID-19 critical illness, including older age groups, fatigue, elevated temperature, increased pulse, lower oxygen saturation, the preexistence of diabetes, malignancies, cardiovascular disease, renal diseases, and pulmonary disease. Moreover, elevated serum levels of ALT, AST, and ferritin are associated with worse outcomes. Further studies are required to identify independent predictors of mortality for patients with COVID-19.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256203PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459940PMC
October 2021

Systematic analysis of CD39, CD103, CD137, and PD-1 as biomarkers for naturally occurring tumor antigen-specific TILs.

Eur J Immunol 2021 Sep 10. Epub 2021 Sep 10.

Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

The detection of tumor-specific T cells in solid tumors is integral to interrogate endogenous antitumor responses and to advance downstream therapeutic applications. Multiple biomarkers are reported to identify endogenous tumor-specific tumor-infiltrating lymphocytes (TILs), namely CD137, PD-1, CD103, and CD39; however, a direct comparison of these molecules has yet to be performed. We evaluated these biomarkers in primary human ovarian tumor samples using single-cell mass cytometry to compare their relative phenotypic profiles, and examined their response to autologous tumor cells ex vivo. PD-1 , CD103 , and CD39 TILs all contain a CD137 cell subset, while CD137 TILs highly co-express the aforementioned markers. CD137 TILs exhibit the highest expression of cytotoxic effector molecules compared to PD-1 , CD103 , or CD39 TILs. Removal of CD137 cells from PD-1 , CD103 , or CD39 TILs diminish their IFN-γ secretion in response to autologous tumor cell stimulation, while CD137 TILs maintain high HLA-dependent IFN-γ secretion. CD137 TILs exhibited an exhausted phenotype but with CD28 co-expression, suggesting possible receptiveness to reinvigoration via immune checkpoint blockade. Together, our findings demonstrate that the antitumor abilities of PD-1 , CD103 , and CD39 TILs are mainly derived from a subset of CD137-expressing TILs, implicating CD137 as a more selective biomarker for naturally occurring tumor-specific TILs.
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http://dx.doi.org/10.1002/eji.202149329DOI Listing
September 2021

infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade.

Pathog Glob Health 2021 Sep 8:1-9. Epub 2021 Sep 8.

Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

infection (SMI) is suspected to be directly and indirectly involved in hepato-carcinogenesis. This study evaluated the association of a previous SMI with hepatocellular carcinoma (HCC) development, patients, tumor characteristics, treatment outcomes, and survival. This observational study included patients with HCC with and without previous SMI who presented to the multidisciplinary HCC clinic, Kasr-Alainy hospital (November 2009 to December 2019). It also included 313 patients with liver cirrhosis without HCC. Clinical and laboratory features of the patients (complete blood count, liver/renal functions , alpha-fetoprotein, and hepatitis B/C status), tumor characteristics (Triphasic CT and/or dynamic MRI), liver stiffness (transient elastography), HCC treatment outcome, and overall survival were studied. This study included 1446 patients with HCC; 688(47.6%) composed group-1, defined by patients having a history of SMI, and 758(52.4%) were in group-2 and without history of SMI. Male sex, smoking, diabetes mellitus, splenomegaly, deteriorated performance status, synthetic liver functions, and platelet count were significantly higher in group-1. The groups did not differ with regard to liver stiffness, tumor characteristics, or the occurrence of post-HCC treatment hepatic decompensation or recurrence. HCC treatment response was better in group-2. Group-1 showed lower sustained virological response to hepatitis C direct-acting antivirals (DAAs) compared with group-2 (60% versus 84.3%, respectively, P = 0.027). Prior SMI was associated with HCC (adjusted odds ratio = 1.589, 95% confidence interval = 1.187-2.127), and it was concluded that it increases the risk of HCC. In addition, it significantly affects the performance status, laboratory characteristics, response to DAAs, and overall survival.
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http://dx.doi.org/10.1080/20477724.2021.1975081DOI Listing
September 2021

COVID-19 clinical and laboratory diagnosis overview.

J Egypt Public Health Assoc 2021 Aug 18;96(1):25. Epub 2021 Aug 18.

Department of Forensic Medicine and Toxicology, Faculty of Medicine, Cairo University, Cairo, Egypt.

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.
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http://dx.doi.org/10.1186/s42506-021-00087-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371420PMC
August 2021

Effect of omega-3 fatty acids supplementation on adipokines: a systematic review and meta-analysis of randomized controlled trials.

Crit Rev Food Sci Nutr 2021 May 17:1-15. Epub 2021 May 17.

Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Although a large body of literature reported the beneficial effects of omega-3 fatty acids (omega-3 FAs) consumption on adipokines levels, but recent findings from clinical trials are not univocal. The aim of this systematic review and meta-analysis was to evaluate the effect of omega-3 FAs supplements on adipokines.

Methods: We searched Medline, Web of Science, Scopus, Embase, and Cochrane Library from inception to August 2020 without any particular language limitations. Outcomes were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) estimated from Hedge's g and random effects modeling.

Results: Fifty-two trials involving 4,568 participants were included. Omega-3 FAs intake was associated with a significant increase in plasma adiponectin levels ( = 43; 3,434 participants; SMD: 0.21, 95% CI: 0.04, 0.37;  = 0.01; = 80.14%). This meta-analysis indicates that supplementing participants with omega-3 fatty acids more than 2000 mg daily and more than 10 weeks resulted in a significant and more favorable improvement in plasma adiponectin levels. However, omega-3 FAs intake had no significant effect on leptin levels (SMD: -0.02, 95% CI: -0.20, 0.17, = 54.13%).

Conclusion: The evidence supports a beneficial effect of omega-3 FAs intake on serum adiponectin levels but does not appear to impact on leptin concentrations. Larger well-designed RCTs are still required to evaluate the effect of omega-3 FAs on leptin in specific diseases.
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http://dx.doi.org/10.1080/10408398.2021.1915743DOI Listing
May 2021

Evaluation of Serum and Gene Expression of Galectin-4, Interleukin-27, and Complement-7 in Hepatitis C Virus-Infected Egyptian Patients.

Biomed Res Int 2020 15;2020:8879758. Epub 2020 Dec 15.

Medical Biochemistry Department, Faculty of Medicine, Beni-Suef University, Egypt.

Background: Hepatitis C virus (HCV) is considered a major global public health problem. Recently, there are great advances in HCV therapy, but there are some limitations that are creating an urgent need for assessment of some cytokines that have a potent antiviral effect in the immune system and anti-inflammatory effects to provide a potential novel immunotherapeutic target in HCV infection.

Objective: This study was directed to assess the serum levels and gene expression levels of Galectin-4 (LEG4), Interleukin-27 (IL-27), and Complement-7 (C-7) and their correlation with the viral load in HCV infection. . This work was conducted on 80 subjects, Group 1 ( = 40) early detected HCV patients and Group 2 ( = 40) healthy controls. LEG4, IL-27, and C-7 were assessed at the protein levels by ELISA, and their gene expression was assessed by RT-qPCR. The viral load was measured by PCR.

Results: There were significant elevations in the mean levels of gene expression and serum levels of all studied parameters LEG4, IL-27, and C-7 in the HCV group compared to the control group. Significant negative correlations between the viral load and each of the serum proteins and gene expressions of both LEG4 and IL-27 in HCV patients were found. The gene expression levels of LEG4, IL-27, and C-7 were positively correlated with their corresponding serum proteins in HCV patients.

Conclusion: LEG4 and IL-27 showed significant negative correlations with the viral load, which could be an immune response to the control of the extent of hepatic inflammation, thus creating a potential novel immunotherapeutic approach in HCV infection for further studies or therapeutic clinical trials.
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http://dx.doi.org/10.1155/2020/8879758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758134PMC
June 2021

Clinical features and laboratory characteristics of patients hospitalized with COVID-19: single centre report from Egypt.

J Infect Dev Ctries 2020 12 31;14(12):1352-1360. Epub 2020 Dec 31.

Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt.

Introduction: The recently discovered novel coronavirus disease (COVID-19) has emerged in Wuhan, China, since January 2020. Egypt reported a low incidence of infection when compared with other countries. The aim of the study was to assess the characterization of COVID-19 infection among the Egyptian population.

Methodology: Data were collected from a single COVID-19 quarantine hospital in Cairo. A total number of 195 cases were included with their clinical, laboratory, and radiological data.

Results: Three different age groups behaved differently for COVD-19 infection. The pediatric age group was asymptomatic entirely, the middle age group (18-50 years) were asymptomatic in 53.3% of cases, while 77.9% of those above 50 years were symptomatic (p ≤ 0.001). The latter group had a high incidence of COVID-pneumonia in (83.1%), and moderate to critical presentations were encountered in 66.3% of them. Neutrophil to lymphocyte (N/L) ratio correlated directly with the age and case severity. C-reactive protein (CRP) and computed tomography scan chest (CT-chest) had added value on COVID-19 diagnosis in suspected cases.

Conclusions: In Egypt, patients above 50 years are at a higher risk for symptomatic COVID-19 infection and leaner for moderate to critical COVID-19 presentation. The triad of CT-chest, CRP, and N/L ratio could be an integrated panel for assessing disease severity.
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http://dx.doi.org/10.3855/jidc.13156DOI Listing
December 2020

PARP Theranostic Auger Emitters Are Cytotoxic in BRCA Mutant Ovarian Cancer and Viable Tumors from Ovarian Cancer Patients Enable Ex-Vivo Screening of Tumor Response.

Molecules 2020 Dec 19;25(24). Epub 2020 Dec 19.

Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Theranostics are emerging as a pillar of cancer therapy that enable the use of single molecule constructs for diagnostic and therapeutic application. As poly adenosine diphosphate (ADP)-ribose polymerase 1 (PARP-1) is overexpressed in various cancer types, and is localized to the nucleus, PARP-1 can be safely targeted with Auger emitters to induce DNA damage in tumors. Here, we investigated a radioiodinated PARP inhibitor, [I]KX1, and show drug target specific DNA damage and subsequent killing of and non- mutant ovarian cancer cells at sub-pharmacological concentrations several orders of magnitude lower than traditional PARP inhibitors. Furthermore, we demonstrated that viable tumor tissue from ovarian cancer patients can be used to screen tumor radiosensitivity ex-vivo, enabling the direct assessment of therapeutic efficacy. Finally, we showed tumors can be imaged by single-photon computed tomography (SPECT) with PARP theranostic, [I]KX1, in a human ovarian cancer xenograft mouse model. These data support the utility of PARP-1 targeted radiopharmaceutical therapy as a theranostic option for PARP-1 overexpressing ovarian cancers.
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http://dx.doi.org/10.3390/molecules25246029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766161PMC
December 2020

Survival and recurrence rates of hepatocellular carcinoma after treatment of chronic hepatitis C using direct acting antivirals.

Eur J Gastroenterol Hepatol 2020 Nov 17. Epub 2020 Nov 17.

Endemic Medicine Department, Faculty of Medicine, Cairo University.

Background: Conflicting studies were proposed either suggested or denied the relationship between early hepatocellular carcinoma (HCC) recurrence and the use of direct-acting antivirals (DAAs) for chronic hepatitis C management AIM OF THE STUDY: To evaluate HCC recurrence rate post-DAAs and potential predictive factors.Study This prospective cohort study included all HCC patients achieved complete response attending our multidisciplinary HCC clinic, Cairo University, from November 2013 to February 2018. Group I (60 patients) who received DAAs after HCC ablation and group II (273 patients) who were DAAs-untreated. We studied factors that could play a role in HCC recurrence.

Results: The sustained virological response rate was 88.3% among DAA-treated patients. HCC recurrence rate was 45% in the post-DAA group vs. 19% in the non-DAAs group; P < 0.001. Mean survival was significantly higher in the post-DAA group (34.23 ± 16.16 vs. 23.92 ± 13.99 months respectively; P value <0.001). There was a significant correlation between HCC recurrence rate and age, male gender, mean size of tumors and time interval between complete HCC ablation and occurrence of HCC recurrence.

Conclusion: Our study reports high rate of HCC recurrence post-DAA therapy in patients treated with transarterial chemoembolization but not in those treated with curative measures. DAA therapy after curative treatment for HCC led to significantly earlier HCC recurrence, which correlated with specific clinic-pathologic features in our prospective single-institution study. However, future independent prospective randomized studies are warranted to evaluate this correlation which may lead to a change in the current standard-of-care approach to patients with hepatitis C virus-related HCC.
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http://dx.doi.org/10.1097/MEG.0000000000001972DOI Listing
November 2020

P53 is a risk factor of de-novo hepatitis C-related hepatocellular carcinoma treated with direct-acting antivirals: a case-control study.

Eur J Gastroenterol Hepatol 2020 Oct 16. Epub 2020 Oct 16.

Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background: The mechanisms underlying de-novo hepatocellular carcinoma (HCC) after direct-acting antivirals (DAAs) is still under investigation. This work aims to study P53 and hepatocyte growth factor (HGF) as possible diagnostics of de-novo hepatocellular carcinoma (HCC) following DAAs in comparison to alpha-fetoprotein (AFP).

Method: This case-control study included 166 patients with liver cirrhosis divided into group-1: patients without HCC (n = 50), group-2: patients with de-novo HCC following DAAs, and achieved sustained virological response (n = 50), and group-3: patients with HCC without DAAs (n = 66). P53 antibody and HGF were determined using a quantitative sandwich enzyme immunoassay technique (Cusabio Co, Houston, USA).

Results: Patients with HCC showed significantly higher HGF. Patients with de-novo HCC following DAAs had significantly higher P53 than HCC without DAAs (P < 0.0001). The multiple logistic regression analysis showed that the P53 levels were significantly associated with susceptibility to de-novo HCC (P value = 0.004). The best overall formula was constructed for HCC diagnosis by entering significant markers into the regression model. A three markers model was developed = (1.22 + AFP X 0.002 + HGF X 0.001 + P53 X 0.001). The medians (percentiles) of combined three markers were 1.8 (1.0-2.1) in liver cirrhosis and 2.2 (2.0-2.9) in all HCC (P < 0.00001). The AUC of combined markers was greater than a single marker. The AUC was 0.87 to differentiate HCC from liver cirrhosis; AUC 0.91 to differentiate de-novo HCC after DAAs from liver cirrhosis.

Conclusion: P53 may serve as a diagnostic marker for de-novo HCC after DAAs therapy. HGF may serve as a diagnostic marker for HCC but not specific for de-novo HCC after DAAs therapy.
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http://dx.doi.org/10.1097/MEG.0000000000001962DOI Listing
October 2020

Hepatocellular Carcinoma Multidisciplinary Clinic-Cairo University (HMC-CU) score: A new simple score for diagnosis of HCC.

Arab J Gastroenterol 2020 Jun 18;21(2):102-105. Epub 2020 May 18.

Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background And Study Aims: The risk of hepatocarcinogenesis depends on background liver factors, of which fibrosis is a major determinant. Serum markers and scores are of increasing importance in non-invasive diagnosis of hepatic fibrosis. Our aim was to predict the occurrence of hepatocellular carcinoma (HCC) using a non-invasive fibrosis score calculated using routine patient data.

Patients And Mthods: Our retrospective study included 1,291 hepatitis C related-HCC Egyptian patients (Group 1) recruited from the multidisciplinary HCC clinic, Faculty of Medicine, Cairo University in the period between February 2009 and June 2016 and 1072 chronic hepatitis C-naïve patients (Group 2) with advanced fibrosis (≥F3) and cirrhosis (F4). King score, Fibro Q score, Aspartate aminotransferase-to-platelet ratio index (APRI), AST to ALT ratio (AAR), LOK score, Göteborg University Cirrhosis Index (GUCI), Fibro-α and Biotechnology Research Center (BRC) scores were calculated for all patients. Regression analysis and receiver operating characteristics (ROC) were used to calculate the sensitivity, specificity and predictive values for significant scores with the best cut-off for predicting HCC. A regression equation was used to calculate predicted probabilities of HCC using the following variables; age, gender, haemoglobin, international normalised ratio (INR), albumin and alpha fetoprotein. The appropriate score cut-off points yielding optimal sensitivity and specificity were determined by ROC curve analysis.

Results: There was a highly significant difference between the two groups for all calculated scores (P = 0.0001). Our new score, the Hepatocellular Carcinoma Multidisciplinary Clinic-Cairo University (HMC-CU) score (Logit probability of HCC =  - 2.524 + 0.152*age - 0.121*Hb - 0.696*INR - 1.059*Alb + 0.022*AFP + 0.976*Sex. Male = 1, Female = 0), with a cut-off of 0.559 was superior to other scores for predicting HCC, having a sensitivity of 90% and specificity of 80.6%.

Conclusion: The HMC-CU score is a promising, easily calculated, accurate, cost-effective score for HCC prediction in chronic HCV patients with advanced liver fibrosis.
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http://dx.doi.org/10.1016/j.ajg.2020.04.001DOI Listing
June 2020

CAR T Cells Targeting MISIIR for the Treatment of Ovarian Cancer and Other Gynecologic Malignancies.

Mol Ther 2020 02 6;28(2):548-560. Epub 2019 Dec 6.

Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

The prognosis of patients diagnosed with advanced ovarian or endometrial cancer remains poor, and effective therapeutic strategies are limited. The Müllerian inhibiting substance type 2 receptor (MISIIR) is a transforming growth factor β (TGF-β) receptor family member, overexpressed by most ovarian and endometrial cancers while absent in most normal tissues. Restricted tissue expression, coupled with an understanding that MISIIR ligation transmits apoptotic signals to cancer cells, makes MISIIR an attractive target for tumor-directed therapeutics. However, the development of clinical MISIIR-targeted agents has been challenging. Prompted by the responses achieved in patients with blood malignancies using chimeric antigen receptor (CAR) T cell therapy, we hypothesized that MISIIR targeting may be achieved using a CAR T cell approach. Herein, we describe the development and evaluation of a CAR that targets MISIIR. T cells expressing the MISIIR-specific CAR demonstrated antigen-specific reactivity in vitro and eliminated MISIIR-overexpressing tumors in vivo. MISIIR CAR T cells also recognized a panel of human ovarian and endometrial cancer cell lines, and they lysed a battery of patient-derived tumor specimens in vitro, without mediating cytotoxicity of a panel of normal primary human cells. In conclusion, these results indicate that MISIIR targeting for the treatment of ovarian cancer and other gynecologic malignancies is achievable using CAR technology.
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http://dx.doi.org/10.1016/j.ymthe.2019.11.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001088PMC
February 2020

An autologous humanized patient-derived-xenograft platform to evaluate immunotherapy in ovarian cancer.

Gynecol Oncol 2020 01 7;156(1):222-232. Epub 2019 Dec 7.

Ovarian Cancer Research Center, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address:

Objective: The aim of this study was to "humanize" ovarian cancer patient-derived xenograft (PDX) models by autologous transfer of patient-matched tumor infiltrating lymphocytes (TILs) to evaluate immunotherapies.

Methods: Orthotopic high-grade serous ovarian cancer (HGSOC) PDX models were established from three patient donors. Models were molecularly and histologically validated by immunohistochemistry. TILs were expanded from donor tumors using a rapid expansion protocol. Ex vivo TIL and tumor co-cultures were performed to validate TIL reactivity against patient-matched autologous tumor cells. Expression of TIL activation markers and cytokine secretion was quantitated by flow cytometry and ELISA. As proof of concept, the efficacy of anti-PD-1 monotherapy was tested in autologous TIL/tumor HGSOC PDX models.

Results: Evaluation of T-cell activation in autologous TIL/tumor co-cultures resulted in an increase in HLA-dependent IFNγ production and T-cell activation. In response to increased IFNγ production, tumor cell expression of PD-L1 was increased. Addition of anti-PD-1 antibody to TIL/tumor co-cultures increased autologous tumor lysis in a CCNE1 amplified model. Orthotopic HGSOC PDX models from parallel patient-matched tumors maintained their original morphology and molecular marker profile. Autologous tumor-reactive TIL administration in patient-matched PDX models resulted in reduced tumor burden and increased survival, in groups that also received anti-PD-1 therapy.

Conclusions: This study validates a novel, clinically relevant model system for in vivo testing of immunomodulating therapeutic strategies for ovarian cancer, and provides a unique platform for assessing patient-specific T-cell response to immunotherapy.
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http://dx.doi.org/10.1016/j.ygyno.2019.10.011DOI Listing
January 2020

Correction to: Prevalence of prolonged QT interval in patients with HCV-related chronic liver disease.

Egypt Heart J 2019 Oct 29;71(1):21. Epub 2019 Oct 29.

Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt.

Following publication of the original article [1], the authors reported that the family name of Mohamed El Kassas was incorrectly published as Mohamed ElKassas.
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http://dx.doi.org/10.1186/s43044-019-0020-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821435PMC
October 2019

Prevalence of prolonged QT interval in patients with HCV-related chronic liver disease.

Egypt Heart J 2019 Sep 7;71(1):15. Epub 2019 Sep 7.

Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt.

Background: Hepatitis C virus (HCV) is a common disease in Egypt with a high socioeconomic burden and extra-hepatic manifestations as QT prolongation, but previous studies included mainly patients with advanced liver disease, so in this study, we aimed to delineate the prevalence of QT prolongation in early-stage HCV patients.

Results: The study included 874 HCV patients with early cirrhosis; in Child's class A, 57 (6.5%) patients had prolonged QT interval corrected (QTc). There was significant higher proportion of cirrhotic patients in the prolonged QTc group (31.6%) vs. in the normal QTc group (11.5%). QTc was 424.39 ± 36.6 vs. 411.51 ± 32.89 ms in cirrhotic and non-cirrhotic patients, respectively (P, 0.001). There was significant higher proportion of Fibrosis 4 (FIB-4) ≥ 1.45 score in the prolonged QTc (77.2%) vs. in the normal QTc group (56.8%) (P, 0.003). QTc interval was 417.76 ± 34.12 ms in patients with FIB-4 score ≥ 1.45 vs. 406.78 ± 31.95 ms in those with FIB-4 < 1.45 (P, < 0.001). FIB-4 score value of 2.108 predicted prolonged QTc with a sensitivity of 63.2% and a specificity of 64.5% (P, < 0.001). Twenty-four patients of long QTc group sent ECGs after HCV eradication, and 19 patients (79%) showed QTc normalization.

Conclusions: HCV is associated with QTc prolongation even in patients with early chronic liver disease stages without significant fibrosis. Also, it is related to the degree of fibrosis and cirrhosis. At a cutoff value of 2.108, FIB-4 score can predict prolonged QTc. HCV eradication is associated with a high incidence of QTc normalization.
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http://dx.doi.org/10.1186/s43044-019-0016-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821436PMC
September 2019

Influence of some methylated hepatocarcinogenesis-related genes on the response to antiviral therapy and development of fibrosis in chronic hepatitis C patients.

Clin Mol Hepatol 2020 01 22;26(1):60-69. Epub 2019 Oct 22.

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyate, Kingdom of Saudi Arabia.

Epigenetics involved in multiple normal cellular processes. Previous research have revealed the role of hepatitis C virus infection in accelerating methylation process and affecting response to treatment in chronic hepatitis patients. This work aimed to elucidate the role of promoter methylation (PM) in response to antiviral therapy, and its contribution to the development of fibrosis through hepatocarcinogenesis-related genes. A total of 159 chronic hepatitis Egyptian patients versus 100 healthy control group were included. The methylation profile of a panel 9 genes (SFRP1, p14, p73, APC, DAPK, RASSF1A, LINE1, O6MGMT, and p16) was detected in patients' plasma using methylation-specific polymerase chain reaction (MSP). Clinical and laboratory findings were gathered for patients with combined pegylated interferon and ribavirin antiviral therapy. Regarding the patients' response to antiviral therapy, the percentage of non-responders for APC, O6MGMT, RASSF1A, SFRP1, and p16 methylated genes were significantly higher versus responders (P<0.05). Of the 159 included patients, the most frequent methylated genes were SFRP1 (102/159), followed by p16 (100/159), RASSF1A (98/159), then LINE1 (81/159), P73 (81/159), APC (78/159), DAPK (66/159), O6MGMT (66/159), and p14 (54/159). A total of 67/98 (68.4%) cases of RASSF1A methylated gene (P=0.0.024), and 62/100 (62%) cases of P16 methylated gene (P=0.03) were associated with mild-degree fibrosis. To recapitulate, the PM of SFRP1, APC, RASSF1A, O6MGMT, and p16 genes increases in chronic hepatitis C patients, and can affect patients' response to antiviral therapy. The RASSF1A and P16 genes might have a role in the distinction between mild and marked fibrosis.
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http://dx.doi.org/10.3350/cmh.2019.0051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940485PMC
January 2020

A significant upsurge of body mass index in patients with chronic hepatitis C successfully treated with direct-acting antiviral regimens.

Turk J Gastroenterol 2019 08;30(8):708-713

Endemic Medicine and Hepato-Gastroenterology Department, Cairo University School of Medicine, Cairo, Egypt.

Background/aims: There is less data regarding the changes in body mass index (BMI) after treating hepatitis C virus (HCV) patients with new direct-acting antiviral agents (DAAs). This study aimed to assess the changes in BMI in chronic HCV patients treated with DAAs in Egypt and to explore other factors influencing this change.

Materials And Methods: The data of chronic HCV patients who received antiviral therapy with new DAAs in one of Egypt's specialized viral hepatitis treatment centers were retrospectively analyzed. In addition to the routine clinical and laboratory workup, changes in body weight during and after treatment were monitored and BMI was calculated. Viral load was measured at 12 weeks post-treatment to assess a sustained virological response. Patients with documented thyroid abnormalities, bariatric surgery, or ensuing special diets were excluded. BMI of >30 was taken as the cutoff for pa¬tients with obesity.

Results: The study included 162 patients with a mean age of 48.56±11.49 years, of whom 61.1% were males, 16% were treatment-experienced, 12% were diabetic, and 29% were obese. Treatment duration was 12 weeks in 84% of patients and 24 weeks in 16% of patients. There was a significant increase in BMI post-treatment as compared to pretreatment measures (28.68±5.35 vs 28.18±4.55) (p=0.03). BMI changes were constant regardless of cirrhosis or previous treatment experience.

Conclusion: Treatment of chronic HCV with DAAs was associated with increased body mass index. Further studies are needed to explore if this effect is secondary to treatment with DAAs or is an improvement in the liver function and lifestyle of treated patients.
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http://dx.doi.org/10.5152/tjg.2019.18514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699564PMC
August 2019

Egyptian liver library: An indexed database for liver disease evidence in Egypt.

Arab J Gastroenterol 2019 Jun 4;20(2):109-113. Epub 2019 Jun 4.

Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt.

Liver diseases are among the most challenging health care problems worldwide. In Egypt, we established different care programs to combat liver diseases including schistosomiasis and viral hepatitides. A lot of research work addressing liver diseases in Egypt have been published with special focus on these two major fields. Other liver disease seems to be neglected although present and contributing to the liver disease burden in Egypt. In this report we reviewed the available evidence published from Egypt and elucidate areas of weakness and future research needs. Our search for Egyptian liver disease evidence retrieved 4683 articles, 67% of them were relevant to the topic. Out of the relevant articles; 1646/3265 (50.4%) were discussing clinical science, 1131 (34.7%) were discussing basic science and 488 (14.9%) were discussing both basic and clinical sciences. Cairo university (16.8%, n = 513) and Mansoura university (9.3%, n = 285) had the largest number of publications related to liver disease in Egypt respectively. The most commonly reported diseases were hepatitis C in 719/3361 articles (21.4%), parasitic liver infestations in 663 articles (19.7%), hepatocellular carcinoma in 544 articles (16.2%), liver fibrosis or cirrhosis in 537 articles (16%), and drug induced liver injury in 516 articles (15.4%). Most of the reviewed articles (36%) were discussing treatment of chronic liver diseases (n = 1201) followed by diagnostics (28%, n = 940), pathogenesis and pathophysiology (21%, n = 706). This review will direct attention to areas with less research like hepatitis B related liver disease, HIV/HCV co-infections, and non-alcoholic fatty liver disease (NAFLD) to encourage future research in these topics. In conclusion; our results ring a bell inviting the development of a roadmap for liver research in Egypt targeting to put future policies to cover areas of weakness in liver research with an ultimate goal of tackling liver disease and its overwhelming socioeconomic burden in our developing country.
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http://dx.doi.org/10.1016/j.ajg.2019.05.004DOI Listing
June 2019

Towards hepatitis C virus elimination: Egyptian experience, achievements and limitations.

World J Gastroenterol 2018 Oct;24(38):4330-4340

Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11599, Egypt.

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.
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http://dx.doi.org/10.3748/wjg.v24.i38.4330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189850PMC
October 2018

Tumor behavior of hepatocellular carcinoma after hepatitis C treatment by direct-acting antivirals: comparative analysis with non-direct-acting antivirals-treated patients.

Eur J Gastroenterol Hepatol 2019 01;31(1):75-79

Endemic Medicine Department.

Introduction: Scarce reports have commented on hepatocellular carcinoma (HCC) behavior after direct-acting antivirals (DAAs).

Aim: To analyze differences in tumor behavior between patients with hepatitis C virus (HCV)-induced HCC and were either treated or not using DAAs.

Patients And Methods: This case-control study includes patients with HCV-related HCC who received generic DAAs (group I) and all non-DAA treated patients with HCC who presented to our clinic during the same period (group II). Patient and tumor characteristics, treatment types and outcome were compared between the two groups.

Results: Group I included 89 patients and group II included 207 patients. No significant difference was detected between groups regarding HCC number or size. Group I showed a more infiltrative HCC pattern, whereas group II had more circumscribed and delineated lesions. The incidence of portal vein thrombosis and significant lymphadenopathy was significantly higher in group I (P=0.03 and 0.03, respectively). Serum levels of α-fetoprotein were significantly higher in group I (P=0.02). These factors significantly affected the response to HCC management (P=0.03). Incidence of complete responses were 47.2 and 49.8% for groups I and II, respectively, whereas incomplete responses were 12.4 and 25.1%, respectively. Supportive treatment was applied to 40.4% in group I and 25.1% in group II.

Conclusion: HCC behavior was more aggressive in DAA-treated patients regarding portal vein thrombosis, malignant lymphadenopathy, and HCC imaging characteristics, which affected the chance of ablation and the treatment response.
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http://dx.doi.org/10.1097/MEG.0000000000001264DOI Listing
January 2019

Extracellular Matrix Proteins Substantiate IL-28B T allele Effect on Histological Outcome of Chronic Hepatitis C.

Ann Hepatol 2018 July - August ,;17(4):569-576

Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Egypt.

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 (0.96- 1.0), 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.
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http://dx.doi.org/10.5604/01.3001.0012.0918DOI Listing
April 2019

An account of the real-life hepatitis C management in a single specialized viral hepatitis treatment centre in Egypt: results of treating 7042 patients with 7 different direct acting antiviral regimens.

Expert Rev Gastroenterol Hepatol 2018 Dec 24;12(12):1265-1272. Epub 2018 May 24.

c Endemic Medicine and Hepato-Gastroenterology Department, Faculty of Medicine , Cairo University , Cairo , Egypt.

Background: A large Egyptian treatment program for HCV was launched in2014 after the introduction of direct-acting antiviral agents (DAAs). This program depended mainly on establishing specialized independent centres for HCV treatment. These centres represent the major strengths in the Egyptian model of care, as they provide integrated care for HCV patients and have enabled Egypt to treat more than one million patients in 3 years. The New Cairo Viral Hepatitis Treatment Center (NCVHTC) is an example of these specialized centres.

Methods: The Egyptian experience in the management of HCV was evaluated by analysing the data of real-life HCV management in the NCVHTC from 2014 to 2017. Results of different treatment regimens in addition to their strengths, limitations and areas for improvement are discussed in this report.

Results: A total of 7042 HCV patients have been evaluated for treatment in the NCVHTC. Among them, 5517 patients received treatment by seven different DAA regimens with excellent results.

Conclusions: All regimens were highly effective at treating HCV in a real-life setting, apart from SOF/RBV, which was the least effective. A nationwide screening program and enhancing the follow-up of treated patients are the main missing pillars in the Egyptian model.
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http://dx.doi.org/10.1080/17474124.2018.1476137DOI Listing
December 2018

Evaluating Diagnostic Accuracy of Noninvasive Tests in Assessment of Significant Liver Fibrosis in Chronic Hepatitis C Egyptian Patients.

Viral Immunol 2018 05 9;31(4):315-320. Epub 2018 Apr 9.

1 Department of Endemic Medicine and Hepato-Gastroenterology, Faculty of Medicine, Cairo University , Cairo, Egypt .

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 8.5 kPa 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.
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http://dx.doi.org/10.1089/vim.2017.0134DOI Listing
May 2018

Spur-of-the-Moment Modification in National Treatment Policies Leads to a Surprising HCV Viral Suppression in All Treated Patients: Real-Life Egyptian Experience.

J Interferon Cytokine Res 2018 02 22;38(2):81-85. Epub 2018 Jan 22.

2 Endemic Medicine and Hepato-Gastroenterology Department, Faculty of Medicine, Cairo University , Cairo, Egypt .

The aim of this study was to retrospectively analyze the outcome of an unscheduled change in national Egyptian policies for the treatment of hepatitis C virus (HCV), which was transpired as a result of a reduction in interferon supplies, and to manage patients who already started interferon-based therapy. After completing a priming 4-weeks course of sofosbuvir/pegylated interferon/ribavirin (SOF/PEG IFN/RBV), a 12-weeks course of sofosbuvir/daclatasvir (SOF/DCV) combination was initiated. We evaluated the sustained virologic response at 12 weeks posttreatment (SVR12) for 2 groups of patients; Group 1, which included patients who had the previous regimen with IFN priming, and group 2, which included the first consecutive group of patients who received SOF/DCV for 12 weeks from the start without IFN priming. All group 1 patients (1,214 patients) achieved SVR12 (100%) and this was statistically significant when compared with the overall SVR12 in group 2 [8,869 patients with sustained virologic response [SVR] of 98.9%] (P value <0.001). No serious adverse events were reported in both groups. In this real-life treatment experience, interferon-based directly acting antiviral treatment with SOF/PEG IFN/RBV as a priming for 4 weeks, followed by SOF/DCV combination for 12 weeks, led to HCV viral suppression in all treated patients.
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http://dx.doi.org/10.1089/jir.2017.0121DOI Listing
February 2018

Data Mining and Machine Learning Algorithms Using IL28B Genotype and Biochemical Markers Best Predicted Advanced Liver Fibrosis in Chronic Hepatitis C.

Jpn J Infect Dis 2018 Jan 26;71(1):51-57. Epub 2017 Dec 26.

Endemic Medicine Department, Faculty of Medicine, Cairo University.

IL28B single nucleotide polymorphism (rs12979860) is an etiology-independent predictor of hepatitis C virus (HCV)-related hepatic fibrosis. Data mining is a method of predictive analysis which can explore tremendous volumes of information from health records to discover hidden patterns and relationships. The current study aims to evaluate and compare the prediction accuracy of scoring system like aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index versus data mining for the prediction of HCV-related advanced fibrosis. This retrospective study included 427 patients with chronic hepatitis C. We used data mining analysis to construct a decision tree by reduced error (REP) technique, followed by Auto-WEKA tool to select the best classifier out of 39 algorithms to predict advanced fibrosis. APRI and FIB-4 had sensitivity-specificity parameters of 0.523-0.831 and 0.415-0.917, respectively. REPTree algorithm was able to predict advanced fibrosis with sensitivity of 0.749, specificity of 0.729, and receiver operating characteristic (ROC) area of 0.796. Out of the 16 attributes, IL28B genotype was selected by the REPTree as the best predictor for advanced fibrosis. Using Auto-WEKA, the multilayer perceptron (MLP) neural model was selected as the best predictive algorithm with sensitivity of 0.825, specificity of 0.811, and ROC area of 0.880. Thus, MLP is better than APRI, FIB-4, and REPTree for predicting advanced fibrosis for patients with chronic hepatitis C.
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http://dx.doi.org/10.7883/yoken.JJID.2017.089DOI Listing
January 2018

SNPs in the Insulin-Like Growth Factor Gene and Obesity Impact on Colorectal Cancer in Egyptians

Asian Pac J Cancer Prev 2017 11 26;18(11):2959-2964. Epub 2017 Nov 26.

Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Egypt.Email:

Background and aims: The insulin pathway may play a role in development of colorectal cancer (CRC). In this study, we investigated associations between CRC and obesity in Egyptians with reference to single nucleotide polymorphisms (SNPs) in the insulin-like growth factor-1 (IGF-I) gene. We also studied serum levels of IGF-1in Egyptian CRC patients with different BMI values. Methods: This prospective study included 66 CRC patients and 30 healthy individuals, for whom body mass index (BMI) was estimated, patients and controls being categorized into overweight or obese in one group and average weight in the other. Serum levels of IGF-1 were assessed by ELISA and SNPs in the IGF-I gene at rs6214C/T, rs6220 T/C and rs35767 C/T were examined by PCR- RFLP. Results: Serum levels of IGF-1 were significantly lower in both CRC average weight and overweight cases. IGF-1 could negatively predict CRC at a cut-off of 154 ng/ml with 87.5% sensitivity and 72.6 specificity. IGF-1 rs6214 CT and TT (T allele) genotypes were associated with a significantly increased risk of CRC. Univariate logistic regression showed that CRC risk significantly decreases by 0.14 for each one unit increase in IGF1. Conclusion: BMI could be considered as effect modifier for CRC risk. IGF-1 SNP rs6214 (TT and CT) are significantly associated with risk regardless of the BMI.
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http://dx.doi.org/10.22034/APJCP.2017.18.11.2959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773777PMC
November 2017

De-novo versus recurrent hepatocellular carcinoma following direct-acting antiviral therapy for hepatitis C virus.

Eur J Gastroenterol Hepatol 2018 Jan;30(1):39-43

Departments of Endemic Medicine and Hepato-gastroenterology.

Introduction: A recent appearance of direct-acting antivirals (DAAs) led to a surge in hepatitis C virus (HCV) management. Nowadays, a large proportion of treated patients have cirrhosis with a retained possibility to develop hepatocellular carcinoma (HCC) even after complete cure. We aimed to study tumoral differences between patients who developed HCC after DAAs as either a recurrence or de-novo HCC.

Methods: We retrospectively analyzed 89 patients who presented to our HCC multidisciplinary clinic with HCC lesions following DAA therapy. A total of 45 patients had complete response to HCC according to the modified Response Evaluation Criteria in Solid Tumors before DAAs intake. Another 44 patients developed de-novo lesions after DAA treatment. Both groups were compared regarding their baseline characteristics, tumor criteria, response to DAAs as well response to HCC treatment.

Results: Both groups showed no significant difference regarding their baseline characteristics (age, sex, Child-Pugh score, and performance status) or response to DAAs (P=0.5). No significant difference was present between groups according to number, site, and size of lesions. However, time elapsed between the end of DAAs therapy and first diagnosis of HCC was significantly longer in de-novo group (15.22±16.39 months) versus recurrence group (6.76±5.1 months) (P=0.008). In addition, response to ablation was significantly better in de-novo lesions compared with recurrent HCC (P=0.03).

Conclusions: Although de-novo HCC lesions significantly developed later than recurrent lesions in DAAs-treated patients, their response rates were significantly better. No differences were detected between both groups in their response to DAAs and their tumoral characteristics.
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http://dx.doi.org/10.1097/MEG.0000000000001004DOI Listing
January 2018
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