Elzafir Elsheikh

Associations of chronic hepatitis C with metabolic and cardiac outcomes.

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.

Ledipasvir/Sofosbuvir Treatment of Hepatitis C Virus is Associated With Reduction in Serum Apolipoprotein Levels

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.

Markers of endothelial dysfunction in patients with non-alcoholic fatty liver disease and coronary artery disease.

Non‐alcoholic fatty liver disease (NAFLD) has been associated with coronary artery disease (CAD) and cardiac‐related mortality.

The levels of monoamine neurotransmitters and measures of mental and emotional health in HCV patients treated with ledipasvir (LDV) and sofosbuvir (SOF) with or without ribavirin (RBV)

AbstractMental and emotional health (MEH) impairment is commonly encountered in hepatitis C patients. Although the exact mechanism remains unknown, alterations in neurotransmitter and cytokine levels maybe associated with hepatitis C virus (HCV)-related MEH issues.The aim of the study was to assess association of serum biomarkers with self-reports of MEH in HCV patients before treatment and after achieving sustained virologic response (SVR).The HCV genotype-1-infected patients who achieved SVR at 12 weeks after treatment with ledipasvir (LDV)/sofosbuvir (SOF) ± ribavirin (RBV) were selected. Frozen serum samples from baseline, end of treatment (EOT), and posttreatment week 4 (PTW4) were used to assay 16 cytokines and monoamine neurotransmitters. Validated self-reports were used to assess MEH.Hundred patients were evaluated. Mean age was 53 years (57% male, 86% white). Compared with baseline, emotional well-being and emotional health significantly increased by EOT, and role emotional, emotional well-being, and emotional health significantly increased at PTW4 in the RBV-containing arm (P < 0.05). In patients taking LDV/SOF + RBV, serotonin levels were significantly decreased at PTW4 compared with baseline (P = 0.046). Compared with baseline, there were significant decreases in interleukin (IL)-10 levels at EOT and PTW4 in both treatment groups. The changes in IL-8 also differed significantly between LDV/SOF + RBV and LDV/SOF groups (P < 0.05). Changes in dopamine and tryptophan levels at EOT correlated with increasing emotional health scores, whereas changes in monocyte chemoattractant protein-1 at EOT and IL-8 at PTW4 correlated with increasing mental health scores. The neurotransmitters and cytokines were found to be independent predictors of MEH scores in multiple regression analysis.Cytokine and neurotransmitter changes are associated with mental and emotional health. Patient-reported outcome scores change during and after treatment.

Current management of patients with nonalcoholic fatty liver disease

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.

139 CD45−CD34+ Circulating Progenitor Cells Levels Are Associated With the Presence of Coronary Artery Disease (CAD) in Patients With Nonalcoholic Fatty Liver Disease (NAFLD)

Background and Aim: Angiogenic growth factors (AGF) play a crucial role in regulating hematopoietic stem and progenitor cell homing and differentiation. Patients with NAFLD and CAD have lower levels of AGF (Elsheikh et al. DDW 2014). Thus, in this study we investigated the level and functions of circulating progenitor cells (CPC) in patients with NAFLD and CAD. Methods: We prospectively enrolled 82 patients undergoing elective coronary angiography. Each patient had fasting serum, clinical data and abdominal ultrasound (US). All US were read centrally using a standard protocol. NAFLD was defined as radiologic fatty liver in the absence of other causes of liver disease and excessive alcohol use. Patients were divided into NAFLD with CAD (n=24), NAFLD without CAD (n=13), only CAD (n= 31) and Non-NAFLD and Non-CAD (n=14). Circulating progenitor cells (CPC) were quantified by flow cytometry based on the expression of (CD34+, CD133+, CD34+ CD133+) in presence or absence of the hematopoietic marker (CD45). To study the functional capacity of CPC, colony-forming unit (CFU) assay was used. These include erythroid progenitors (burst-forming unit erythroid (BFU-E)); granulocyte/macrophage progenitors (CFU-granulocyte, macrophage (CFU-GM); and multi-potential progenitors (CFU-granulocyte, erythroid, macrophage, megakaryocyte (CFU-GEMM)). Results: The levels of the CD45-CD34+, CD45CD133+ and BFU-E were higher in NAFLD patients with CAD (median, 15%, 2% and 60 colonies, respectively) than NAFLD patients without CAD (median, 9%, 1% and 37 colonies , respectively, all p-values≤0.05). We also found that the levels of the CD45-CD133+ were higher in NAFLD patients with CAD (median, 15%) than patients with only CAD (median, 11%, p 25th quartile of CD45-CD34+, CD45-CD133+ and total CFU levels had the highest risk for CAD [OR: 7.00 (1.34-36.68), 5.00 (1.07-23.46) and 7.00 (1.10-44.61) respectively]. After age adjustment, only CD45-CD34+ circulating progenitor cells remain associated with increased risk of CAD in patients with NAFLD [OR: 8.71 (1.21-62.51)]. Conclusions: Our results indicate that, levels of circulating progenitor cells CD45-CD34+ may be associated with increased risk of CAD in NAFLD patients. Increased circulating progenitor cells levels could be due to the low levels of AGF leading to impaired homing and differentiation capacity.