Elzafir Elsheikh

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (22)187.5 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The interaction of lipoproteins with hepatitis C virus (HCV) has pathogenic and therapeutic implications. Our aim was to evaluate changes in the apolipoprotein profile of patients with chronic hepatitis C during and after successful cure with ledipasvir and sofosbuvir (LDV/SOF) with and without ribavirin (RBV). One hundred HCV genotype 1 patients who had achieved SVR-12 after treatment with 12 weeks of LDV/SOF ± RBV were selected from the ION-1 clinical trial. Frozen serum samples from baseline, end of treatment and week 4 of follow-up were used to assay apolipoproteins (apoAI, apoAII, apoB, apoCII, apoCIII, apoE) using the Multiplex platform to assess for changes in the apolipoprotein levels. At the end of treatment compared to baseline, a significant reduction in apoAII levels (-14.97 ± 63.44 μg/mL, P = 0.0067) and apoE levels (-4.38 ± 12.19 μg/mL, P < 0.001) was noted. These declines from baseline in apoAII (-16.59 ±66.15 μg/mL, P = 0.0075) and apoE (-2.66 ± 12.64 μg/mL, P = 0.015) persisted at 4 weeks of post-treatment follow-up. In multivariate analysis, treatment with LDV/SOF + RBV was independently associated with reduction in apoE (beta = 5.31 μg/mL, P = 0.002) (compared to RBV-free LDV/SOF) (P < 0.05). In contrast, apoCII levels overall increased from baseline to end of treatment (+2.74 ±11.76 μg/mL, P = 0.03) and persisted at 4 weeks of follow-up (+4.46 ± 12.81 μg/mL from baseline, P = 0.0005). Subgroup analysis revealed an increase in apoCII during treatment only in patients receiving LDV/SOF without RBV (+5.52 ± 11.92 μg/mL, P = 0.0007) but not in patients receiving LDV/SOF + RBV (P = 0.638). Treatment with LDV/SOF ± RBV is associated with a persistent reduction in the apolipoprotein AII and E after achieving cure. These data suggest that treatment with LDV/SOF ± RBV may be associated with alterations in serum apolipoproteins which could potentially impact viral eradication. © 2015 John Wiley & Sons Ltd.
    Journal of Viral Hepatitis 08/2015; 22(12). DOI:10.1111/jvh.12448 · 3.91 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-37. DOI:10.1016/S0016-5085(15)30128-1 · 16.72 Impact Factor

  • Journal of Hepatology 04/2015; 62:S599. DOI:10.1016/S0168-8278(15)30934-X · 11.34 Impact Factor

  • Journal of Hepatology 04/2015; 62:S721-S722. DOI:10.1016/S0168-8278(15)31199-5 · 11.34 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-1049. DOI:10.1016/S0016-5085(15)33578-2 · 16.72 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-1014. DOI:10.1016/S0016-5085(15)33466-1 · 16.72 Impact Factor

  • Gastroenterology 05/2014; 146(5):S-271. DOI:10.1016/S0016-5085(14)60959-8 · 16.72 Impact Factor

  • Gastroenterology 05/2014; 146(5):S-710. DOI:10.1016/S0016-5085(14)62577-4 · 16.72 Impact Factor

  • Gastroenterology 05/2014; 146(5):S-710. DOI:10.1016/S0016-5085(14)62576-2 · 16.72 Impact Factor
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    ABSTRACT: Background Nonalcoholic fatty liver disease (NAFLD) has been associated with coronary artery disease (CAD) and cardiac-related mortality. AimTo assess the association between endothelial dysfunction markers [Endocan, High mobility group box 1 (HMGB1), and Anti-endothelial cell antibodies (AECA)] and the risk of CAD in NAFLD. Methods We included 91 patients scheduled for coronary angiography for chest pain. Of these, 77 had NAFLD (85% with documented CAD). NAFLD was diagnosed after exclusion of other causes of liver diseases and by hepatic ultrasound and/or fatty liver index. Diagnosis and severity of CAD were established with coronary angiography. Endocan (ng/ml) and HMGB1 (ng/ml) concentrations were determined in the serum using ELISA technique. AECA were quantified in sera using flow cytometry. ResultsNAFLD patients with CAD had higher serum endocan level as compared to NAFLD without CAD (P=0.006). Furthermore, levels of endocan [OR: 38.66 (95% CI: 1.10-999.99)] and hyperlipidemia [OR: 5.62 (95%: 1.36-23.19)] were significantly associated with the risk of CAD and high serum HDL cholesterol level [OR: 0.92 (95% CI: 0.87-0.97)] was protective against CAD. On the other hand, serum level of HMGB1 was significantly lower in NAFLD patients with CAD than NAFLD patients without CAD (P=0.0003). Interestingly, in our NAFLD cohort, serum endocan levels positively correlated the severity of CAD (r=0.27; P<0.05), whereas, HMGB1 levels negatively correlated with severity of CAD (r=-0.35; P<0.05). The levels of AECA were not significantly associated with CAD in NAFLD. Conclusion Markers of endothelial dysfunction in patients NAFLD patients may be associated with the risk for CAD.
    Journal of Gastroenterology and Hepatology 02/2014; 29(7). DOI:10.1111/jgh.12549 · 3.50 Impact Factor
  • Elzafir Elsheikh · Linda L Henry · Zobair M Younossi ·
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH) are the most common causes of chronic liver disease in industrialized countries. NAFLD has also been strongly associated with type II diabetes and cardiovascular diseases. This study was a multipurposed review, which included discussion of recent studies investigating the cellular and genetic basis of these diseases, the pathogenesis of NAFLD and the current treatment and management of nonalcoholic steatohepatitis. Currently, maintaining a healthy weight through dietary changes and exercise, the use of insulin-modulating pharmacologic agents for diabetes control and the use of lipid-lowering, anti-oxidants have been the most widely recommended treatments. Inclusion of pathogenic mechanisms in treatment design will allow future therapies to target-specific pathways involved in NAFLD pathogenesis.
    Expert Review of Endocrinology &amp Metabolism 01/2014; 8(6). DOI:10.1586/17446651.2013.846212
  • E Elsheikh · E Andersson · C Sylvén · B-G Ericzon · J Palmblad · M Mints ·
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    ABSTRACT: Do plasma levels of stromal cell-derived factor-1 (CXCL12, sometimes termed SDF-1) and the numbers of circulating endothelial progenitor cells (EPCs), EPC colony-forming units (EPC-CFU) and mature endothelial cells (ECs) differ between women with idiopathic heavy menstrual bleeding of endometrial origin (HMB-E) and controls and are they related to plasma levels of other angiogenic growth factors? Angiogenesis is altered in women with HMB-E, characterized by a reduction in mean plasma levels of CXCL12, a low number of EPCs-CFUs and a high level of circulating ECs. Plasma levels of CXCL12 are significantly higher during the proliferative than the secretory phase of the menstrual cycle in healthy women and exhibit a negative correlation with blood EPC-CFUs. A prospective cohort study in a university hospital setting. Between 2008 and 2009 10 HMB-E patients were recruited from Karolinska University Hospital. Ten healthy women were also included in the analysis. Ten healthy control women and 10 HMB-E patients, all with regular menstrual cycles, provided 4 blood samples during a single menstrual cycle: 2 in the proliferative phase, 1 at ovulation and 1 in the secretory phase. We assessed plasma levels of CXCL12, vascular endothelial growth factor A165 (VEGFA), basic fibroblast growth factor (bFGF) and granulocyte and granulocyte-macrophage colony-stimulating factors by ELISA. We counted circulating EPC-CFUs by culture, and ECs and EPCs by flow cytometry and immunostaining for cell surface markers. Plasma levels of CXCL12 were significantly lower in HMB-E patients compared with control women (P < 0.0001), with a significant decrease (P = 0.013) between the proliferative phase and ovulation. VEGFA showed a trend towards the same decreasing pattern as CXCL12, although not statistically significant (P = 0.086), whereas systemic VEGFA levels in control women remained unchanged across the different phases of the menstrual cycle (P = 0.473). HMB-E patients had a lower number of EPC-CFUs compared with control women (P = 0.014), with a positive correlation between the level of CXCL12 and EPC-CFUs (r = 0.428; P = 0.047). Whilst the level of circulating endothelial cells in HMB-E patients was higher than in control women, this did not reach statistical significance. In contrast, the levels of the hematopoietic/EPC marker CD34 were significantly lower in HMB-E patients than control women (P < 0.020). Small sample, unknown source of CXCL12, unknown balance between influx and efflux of EPCs from bone marrow and to the endometrium. Our results indicate that CXCL12 may play an important role in physiological angiogenesis in the endometrium, and that low and dysregulated levels of CXCL12 in women with HMB-E could affect vessel quality, integrity and repair. Financial support was provided through the regional agreement on medical training and clinical research (ALF) between the Stockholm County Council and Karolinska Institutet (number 20110258). This study was also supported by grants from the Swedish Labor Market Insurance. The authors have no conflict of interest to declare.
    Human Reproduction 11/2013; 29(1). DOI:10.1093/humrep/det402 · 4.57 Impact Factor

  • Journal of Hepatology 04/2013; 58:S529-S530. DOI:10.1016/S0168-8278(13)61312-4 · 11.34 Impact Factor
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    Z M Younossi · M Stepanova · F Nader · E Elsheikh ·
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    ABSTRACT: BACKGROUND: Chronic hepatitis C virus (CH-C) infection is associated with metabolic conditions such as insulin resistance and type 2 diabetes (DM) and may increase the risk of cardiovascular diseases. AIM: To assess the association of CH-C with risk factors for cardiovascular diseases using US population data. METHODS: The National Health and Nutrition Examination Surveys (NHANES) collected between 1999 and 2010 were used. RESULTS: A total of 19 741 participants were considered eligible for the study. Of this cohort, 173 individuals (0.88%) had detectable HCV RNA and were considered to have CH-C. Compared with controls, CH-C patients were predominantly African American (23.5% vs. 10.5%, P < 0.0001), men (66.6% vs. 46.1%, P = 0.0001), more likely to be between 45 and 55 years of age (41.9% vs. 20.4%, P = 0.0001), had higher rate of insulin resistance (44.1% vs. 31.1%, P = 0.0301), hypertension (40.1% vs. 28.9%, P = 0.0201), and history of smoking (76.2% vs. 29.9%, P < 0.0001). In multivariate analysis, in addition to known risk factors for insulin resistance, CH-C was independently associated with the presence of insulin resistance [OR (95% CI) = 2.06 (1.19-3.57)], DM [OR = 2.31 (1.18-4.54)] and hypertension [OR = 2.06 (1.30-3.24)]. In addition, independent predictors of cardiovascular diseases included older age, presence of obesity and smoking. Furthermore, CH-C was independently associated with congestive heart failure subtype of cardiovascular diseases but not ischaemic heart disease and stroke. CONCLUSIONS: Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes and hypertension) and congestive heart failure.
    Alimentary Pharmacology & Therapeutics 02/2013; 37(6). DOI:10.1111/apt.12234 · 5.73 Impact Factor
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    ABSTRACT: To explore how cardiac regeneration and cell turnover adapts to disease, different forms of stress were studied for their effects on the cardiac progenitor cell markers c-Kit and Isl1, the early cardiomyocyte marker Nkx2.5, and mast cells. Adult female rats were examined during pregnancy, after myocardial infarction and ischemia-reperfusion injury with/out insulin like growth factor-1(IGF-1) and hepatocyte growth factor (HGF). Different cardiac sub-domains were analyzed at one and two weeks post-intervention, both at the mRNA and protein levels. While pregnancy and myocardial infarction up-regulated Nkx2.5 and c-Kit (adjusted for mast cell activation), ischemia-reperfusion injury induced the strongest up-regulation which occurred globally throughout the entire heart and not just around the site of injury. This response seems to be partly mediated by increased endogenous production of IGF-1 and HGF. Contrary to c-Kit, Isl1 was not up-regulated by pregnancy or myocardial infarction while ischemia-reperfusion injury induced not a global but a focal up-regulation in the outflow tract and also in the peri-ischemic region, correlating with the up-regulation of endogenous IGF-1. The addition of IGF-1 and HGF did boost the endogenous expression of IGF and HGF correlating to focal up-regulation of Isl1. c-Kit expression was not further influenced by the exogenous growth factors. This indicates that there is a spatial mismatch between on one hand c-Kit and Nkx2.5 expression and on the other hand Isl1 expression. In conclusion, ischemia-reperfusion injury was the strongest stimulus with both global and focal cardiomyocyte progenitor cell marker up-regulations, correlating to the endogenous up-regulation of the growth factors IGF-1 and HGF. Also pregnancy induced a general up-regulation of c-Kit and early Nkx2.5+ cardiomyocytes throughout the heart. Utilization of these pathways could provide new strategies for the treatment of cardiac disease.
    PLoS ONE 05/2012; 7(5):e36804. DOI:10.1371/journal.pone.0036804 · 3.23 Impact Factor
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    ABSTRACT: The endometrium goes through a unique cycle of physiological angiogenesis during the normal menstrual cycle (MC). We studied whether there is a correlation between endothelial progenitor cells (EPCs) and plasma and endometrial levels of angiogenic growth factors during the MC. Ten healthy, regularly menstruating women provided blood samples and another 16 supplied endometrial biopsies. Blood samples were obtained over a single MC: twice in the proliferative and once in the secretory phase and at ovulation. Endometrial biopsies were provided in the proliferative or in the secretory phase. We assessed plasma levels of vascular endothelial and fibroblast growth factors, granulocyte and granulocyte-macrophage colony-stimulating factors and stromal cell-derived factor-1 (SDF-1) by ELISA; EPCs by a colony-forming unit (CFU) assay; immunostaining for endometrial SDF-1 by computer-assisted software; and endothelial cell (EC) markers by flow cytometry. In the proliferative phase, SDF-1 levels were significantly higher than during the secretory phase. EPC-CFUs correlated negatively to SDF-1 levels. Endometrial SDF-1 expression tended to be higher in the secretory than in the proliferative phase. Furthermore, vascular endothelial growth factor receptors and Tie-2 EPCs showed a cyclic pattern over the MC. Our results point to SDF-1 as a novel mediator of EPC trafficking during the MC.
    International Journal of Molecular Medicine 02/2011; 27(2):221-6. DOI:10.3892/ijmm.2010.570 · 2.09 Impact Factor
  • Elzafir Elsheikh · Rami Genead · Christian Danielsson ·

    01/2011; 02(04). DOI:10.4172/2157-7099.1000122
  • Elzafir Elsheikh · Christer Sylvén · Loghman Henareh ·
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    ABSTRACT: Atherosclerosis is an inflammatory disease of multifactorial origin, in which immune cells together with metabolic risk factors may initiate, propagate, and activate lesions in the arterial tree. We investigated the role of auto-antibodies against endothelial cells in patients with previous myocardial infarction. One hundred and four patients were studied four to five years after acute myocardial infarction (aged 36-84 years) and 83 sex-matched healthy controls (aged 32-70 years). Anti-endothelial cells IgM and IgG auto-antibodies (AECA) were quantified in plasma using flow cytometry. IgM and IgG AECA were significantly higher (23.08 ± 0.81 and 10.63 ± 0.31 channel shifts, respectively; p < 0.001) in patients as compared to controls (13.40 ± 0.95 and 3.53 ± 0.54 channel shifts, respectively). Further, patients who got an invasive treatment had significantly higher levels of AECA as compared to patients with only medical treatment. Plasma concentration of IgG was positively (p < 0.05) correlated to the levels of high-sensitivity C-reactive protein (hsCRP). We report for the first time evidence that AECA are related to signs of inflammation and are increased in patients with atherosclerosis and previous myocardial infarction and with further increase with severity of disease.
    Scandinavian cardiovascular journal: SCJ 10/2010; 44(5):255-9. DOI:10.3109/14017431003797168 · 1.03 Impact Factor
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    ABSTRACT: The pathogenic role of anti-endothelial cell antibodies (AECA) in vascular injury is debated. It was previously shown that many patients with Wegener's granulomatosis (WG) have AECA that react with human kidney microvascular endothelial cells (EC). In addition, during active disease, renal endothelium strongly expresses the inflammatory molecules vascular adhesion protein-1 (VAP-1) and MHC class I-related antigen A (MICA). This study sought to determine whether AECA mediates this upregulation of VAP-1 and MICA and to define better the signaling pathways that are activated by these autoantibodies upon binding to EC in the kidney. Stimulation of human kidney microvascular EC with AECA IgG upregulated surface expression of MICA and VAP-1, elicited a rapid Ca2+ flux, induced high levels of the chemokines monocyte chemoattractant protein-1 and granulocyte chemotactic protein-2, induced specific phosphorylation of stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and the transcription factors c-Jun and activating transcription factor-2, and activated NF-kappaB. Specific inhibitors of SAPK/JNK significantly reduced AECA-induced chemokine production and phosphorylation of c-Jun and activating transcription factor-2 and abrogated protein expression of MICA but not VAP-1. In kidney sections from patients with WG, infiltrating cells that expressed the ligand for MICA (NKG2D+) were identified, as were CD8+ and 32 gamma delta+ T cells. In conclusion, AECA may be involved in the pathogenesis of WG, and the SAPK/JNK pathway and the endothelial inflammatory protein VAP-1 may be novel therapeutic targets for vasculitis.
    Journal of the American Society of Nephrology 10/2007; 18(9):2497-508. DOI:10.1681/ASN.2006111286 · 9.34 Impact Factor
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    ABSTRACT: We describe a female patient who, despite negative conventional cross-matches, lost her first kidney graft in an acute humoral rejection. Prior to the second, AB0-incompatible (A1B to A1) living-donor kidney transplant, the patient had negative T- and B-cell cross-matches but had a positive donor-reactive endothelial cell cross-match. Following pre-transplant protein A and GlycoSorb-ABO immunoadsorptions to remove blood group B and anti-endothelial cell antibodies, Mabthera, and IVIG administrations, she was successfully transplanted. By the second post-operative day, creatinine levels were down to 96 micromol/L from 611 micromol/L pre-operatively. On day 9 creatinine rose again, and on the same day the endothelial cell crossmatch became positive for IgG, whereas the T-cell cross-match remained negative and the anti-A1B titers remained low. A kidney biopsy taken on day 10 post-transplant showed a picture of an acute vascular, antibody-mediated rejection. Following rejection treatment and repeated protein A and Glyco-Sorb-ABO immunoadsorptions, the patient's kidney function was again normalized. The use of a recently developed kit (XM-ONE) for the detection of anti-endothelial cell antibodies allowed us to identify a patient at risk for developing acute antibody-mediated rejection as well as to monitor treatment efficacy and post-transplant complications.
    Clinical transplants 02/2006; 00:535-8.

Publication Stats

279 Citations
187.50 Total Impact Points


  • 2005-2013
    • Karolinska University Hospital
      • Department of Transplantation Surgery
      Tukholma, Stockholm, Sweden
  • 2012
    • Karolinska Institutet
      • Department of Cardiology
      Stockholm, Stockholm, Sweden