Structural Retinal Assessment Using Optical Coherence Tomography and Fundus Fluorescein Angiography in Systemic Lupus Erythematosus Patients.

BACKGROUND: Ocular manifestations in systemic lupus erythematosus (SLE) can be the presenting symptom of the disease or a sight-threatening complication. OBJECTIVES: To detect different structural retinal changes in patients with SLE who had no ophthalmological symptoms and investigate the relationship between different retinal changes and the disease activity assessed by the Systemic Lupus Erythromatosus Disease Activity Index score. STUDY DESIGN: A descriptive pilot study from January 2016 to January 2017. METHODS: Fifty-two eyes of 26 patients diagnosed to have SLE were examined using visual acuity assessment, fundus examination, optical coherence tomography (OCT), and fundus fluorescein angiography (FFA). RESULTS: Fundus fluorescein angiography showed different changes in the form of venular occlusion and optic nerve leakage. There were also degenerative changes in the form of alternating hyperfluorescent and hypofluorescent areas outside the arcades as well as peripapillary areas and capillary dropout. Optical coherence tomography detected signs of degenerative thinning, incomplete posterior vitreous detachment, and epiretinal membrane. A significant correlation was found between SLE activity and the changes detected by FFA (p = 0.017). However, there was no significant correlation between disease activity and changes detected by OCT. Optical coherence tomography changes were significantly correlated with the duration of hydroxychloroquine use of more than 5 years (p = 0.032). There was no correlation between FFA or OCT changes and proteinuria or antiphospholipid antibodies. CONCLUSIONS: Fundus fluorescein angiography is more sensitive in detecting early subclinical retinal changes in patients with SLE, which correlates with disease activity, whereas OCT is more sensitive in detecting changes resulting from hydroxychloroquine use.

Circulating microRNAs as predictive biomarkers for liver disease progression of chronic hepatitis C (genotype-4) Egyptian patients.

Egypt is one of the highest prevalence rates of hepatitis C virus (HCV) infection worldwide. HCV is among major reasons for chronic liver diseases. MicroRNA (miRNAs), small noncoding regulatory molecules play a key role in the pathogenesis of liver. Circulating miRNAs represent potential noninvasive biomarkers for diagnosis and monitoring patients with liver diseases progression. To investigate the potential role of circulating miRNAs for surveillance of liver disease progression, we assessed the expression of 20 liver-related miRNAs in sera of 47 chronic hepatitis C Egyptian patients compared with 25 controls using quantitative reverse-transcription polymerase chain reaction assay. The sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curve. The correlations between their levels and the clinicopathological features were assessed. Fourteen miRNAs showed upregulation and six miRNAs showed downregulation. ROC curve analyses revealed that the explored miRNAs could serve as valuable biomarkers for chronic hepatitis with an area under the curve ranged from 0.708 (95% confidence interval [95% CI], 0.587 to 0.829; P = 0.004) for miR-199 up to 0.974 (95% CI, 0.943 to 1.00; P < 0.001) for miR-23b. The expression level of miR-21 demonstrated significant correlation with age, liver enzymes, ALT/AST, and α-fetoprotein level. AST level was directly correlated with miR-122, while an inversely correlated with miR-23b. Fibrosis and steatosis stages possessed positive correlation with miR-199 expression and negative correlation with miR-27a and miR-93. In conclusion, miR-23b and miR-106 might be a useful biomarker for chronic hepatitis C (CHC). MiR-27a, miR-93, and miR-199 might have a potential role in the progression of liver diseases. Unravel the role of these miRNAs in CHC patients might lead to precise prognosis and management.

Atorvastatin: In-Vivo Synergy with Metronidazole as Anti-Blastocystis Therapy.

Blastocystis is an enteric Straminopile in tropical, subtropical and developing countries. Metronidazole has been a chemotheraputic for blastocystosis. Failures in its regimens were reported and necessitate new studies searching for alternative therapeutic agents. Aim of current study is to investigate potential effects of Atorvastatin (AVA) compared to the conventional chemotherapeutic MTZ in experimentally Blastocystis-infected mice. Anti-Blastocystis efficacy of AVA was evaluated parasitologically, histopathologically and by transmission electron microscopy using MTZ (10 mg/kg) as a control. Therapeutic efficacy of AVA was apparently dose-dependent. Regimens of AVA (20 and 40 mg/kg) proved effective against Blastocystis infections with high reduction in Blastocystis shedding (93.4-97.9%) compared to MTZ (79.3%). The highest reductions (98.1% and 99.4%) were recorded in groups of combination treatments AVA 20-40 mg/kg and MTZ 10 mg/kg. Blastocystis was nearly eradicated by the 20th day post infection. Genotype analysis revealed that genotype I was most susceptible, genotype III was less. Histopathologic and ultrastructural studies revealed apoptotic changes in Blastocystis and significant improvement of intestinal histopathological changes more remarkable in combinational therapy groups. Thus, the present study offers AVA as a potential candidate for Blastocystis therapy combined with MTZ.

The Liver MicroRNA Expression Profiles Associated With Chronic Hepatitis C Virus (HCV) Genotype-4 Infection: A Preliminary Study.

BACKGROUND: MicroRNAs (miRNAs) have been repeatedly shown to play important roles in liver pathologies, including hepatitis, liver cirrhosis, and liver cancer. Egypt has the highest hepatitis C virus (HCV) infection rate worldwide, predominantly involving genotype-4. OBJECTIVES: In this study, we attempted to characterize the miRNA profile of the poorly studied genotype 4 of HCV in chronically infected Egyptian patients to obtain a better understanding of the disease and its complications and help in the design of better management protocols. PATIENTS AND METHODS: We analyzed the expression levels of a selected panel of 94 miRNAs in fresh liver biopsies collected from 50 Egyptian patients diagnosed with chronic HCV infection using quantitative real-time polymerase chain reaction (PCR) assay. Non-parametric tests were used to analyze the expression level of each miRNA and association with the clinicopathological features of enrolled patients in this study. RESULTS: Our results revealed differential expression levels of the analyzed miRNAs compared to the normal controls. Twenty-seven miRNAs (including miR-105, miR-147, miR-149-3p, and miR-196b) showed up-regulation, while 17 miRNAs (including miR-21, miR-122, miR-199a-3p, and miR-223) showed down-regulation. An inverse correlation was observed between levels of miR-95, miR-130a, and miR-142-5p with the blood albumin level. Increased expression levels of seven miRNAs (miR-29c, miR-30c, miR-126, miR-145, miR-199a, miR-199a-3p, and miR-222) were observed with severe chronic hepatic inflammation. Several deregulated miRNAs found in this study have been previously linked to chronic liver inflammation and the risk of hepatocellular carcinoma (HCC) development. CONCLUSIONS: The identified expression profiles of some examined miRNAs might offer important points to consider for the treatment of naive patients and the management of chronically infected HCV patients in Egypt and around the world.

SOCIO-DEMOGRAPHIC RISK FACTORS OF SCHISTOSOMIASIS MANSONI IN PATIENTS WITH GASTROINTESTINAL SYMPTOMS: A SEROPREVALANCE STUDY IN EGYPT.

Limited data is available on the epidemiologic status of schistosomiasis mansoni in Egypt. The present work aimed to explore the seroepidemiological status of Schistosoma inansoni infection in Egypt by screening inhabitants of different Egyptian govemorates and its correla- tion with morbid symptoms and risk factors. Health questionnaires and indirect haemagglutination test (IHAT) were performed upon a cross-sectional study of 1788 individuals from 22 govemorates. Socio-demographic varjables included sex, age, residence and.canal water contact. A multivariate regressi6n model was used to assess associations betWeen S.mansoni infection and socio-demographic variables; S.mansoni significant titre ≥ 1:160 was detected in 43% of samples. S. mansoni showed the highest prevalence in Al-Fayoum (15.2%), Kafr EI-Sheikh (11.2%) then Assiut (10.9%) while the least positiveresults were from Matrouh (0.2%). This may be the first indication to emerging foci in Cairo, Luxor, Aswan, Suez, Port Said and the Red Sea Govemorates. Anti-S.mansoni antibodies were least de- tected at 1 1-2Oys while they were the highest at 41-SOys, the highest titres (1/1280) were achieved by the age group 31 -4Oys.Male gender was a risk factor as 48.2% of males were IHAT +ve. Contacting canal water tends to be advantageous for schistosomiasis mansoni as 72.6% had a histoxy of canal contact and 96.7% of them achieved the highest titre. The alteration in the actual prevalence of schistosomiasis mansoni in Egypt with emergence of new foci including Cairo, Luxor, Aswan, Mersa-Matrouh and the north-eastern province alongside Suez Canal that may be explained by the associated socioepidemiologic risk factors.

Plasma Osteopontin Level in Chronic Liver Disease and Hepatocellular Carcinoma.

BACKGROUND: Osteopontin (OPN) is a secreted glycoprotein and is frequently associated with various tumors. OBJECTIVES: We sought to investigate the clinical usefulness of the level of plasma OPN, compared to α-fetoprotein (AFP), as a biomarker for hepatocellular carcinoma (HCC) and to evaluate its diagnostic value in nonalcoholic fatty liver disease (NAFLD) and its relationship with clinical and laboratory features of HCC and NAFLD. PATIENTS AND METHODS: The study was performed on 120 subjects classified into 5 groups: Group I included 25 chronic non-cirrhotic hepatitis C virus (HCV)-infected patients; Group II encompassed 25 patients with chronic HCV infection with liver cirrhosis; Group III comprised 25 patients with chronic HCV with liver cirrhosis and HCC; Group IV was comprised of 25 patients with NAFLD; and Group V consisted of 20 healthy age- and sex-matched controls. All the participants were subjected to history taking and clinical and abdominal ultrasonographic examinations as well as the following laboratory investigations: liver function tests, complete blood count, blood sugar, hepatitis B surface antigen, hepatitis C virus antibodies, HCV-RNA by qualitative polymerase chain reaction (for Groups I, II, and III) and serum AFP and plasma OPN levels. RESULTS: There were statistically significant differences in plasma OPN levels between the HCC group (401 ± 72 ng/mL) and the other groups, between the cirrhotic group (258.3 ± 35 ng/mL) and the non-cirrhotic group (HCV group, 168.7 ± 41 ng/mL; fatty liver group, 106.7 ± 35 ng/mL), and between the chronic non-cirrhotic HCV group and the fatty liver group (I and IV) and the controls (35.1 ± 6 ng/mL). In the HCC group, the diagnostic value of OPN was comparable to that of AFP at a cutoff value of 280 ng/mL, achieving sensitivity, specificity, and overall accuracy of 100%, 98%, and 96%, respectively. Regarding the validity of plasma OPN as a predictor of fatty change, our results revealed a diagnostic accuracy of 50% with 70% sensitivity, 45% specificity, 50% positive predictive value, and 75% negative predictive value at a cutoff value of 134 ng/mL. CONCLUSIONS: Plasma OPN is comparable to AFP as a diagnostic marker and is related to the severity of liver involvement in HCC patients. Plasma OPN is of diagnostic potential value in NAFLD.

Diagnostic Value of Serum Level of Soluble Tumor Necrosis Factor Receptor IIα in Egyptian Patients With Chronic Hepatitis C Virus Infection and Hepatocellular Carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is unfavorable and needs serum markers that could detect it early to start therapy at a potentially curable phase. OBJECTIVES: The aim of this study was to determine the value of serum soluble tumor necrosis factor (TNF) receptor-IIα (sTNFR-IIα) in diagnosis of HCC in patients with chronic hepatitis C virus (HCV) infection. PATIENTS AND METHODS: The study was performed on 110 subjects who were classified into five groups. Group I included 20 patients with chronic noncirrhotic HCV infection and persistently normal transaminases for ≥6 months. Group II included 20 patients with chronic noncirrhotic HCV infection and elevated transaminases. Group III included 20 patients with Chronic HCV infection and liver cirrhosis. Group IV included 20 patients with chronic HCV infection with liver cirrhosis and HCC. Group V included 30 healthy age and sex-matched controls. Medical history was taken from all participants and they underwent clinical examination and abdominal ultrasonography. in addition, the following laboratory tests were requested: liver function tests, complete blood count, HBsAg, anti-HCVAb, HCV-RNA by qualitative PCR, and serum levels of α-fetoprotein (AFP) and sTNFR-IIα. RESULTS: The serum level of sTNFR-IIα was significantly higher in patients with HCC in comparison to the other groups. A positive correlation was found between the serum levels of sTNFR-IIα and AST and ALT in patients of group-II. Diagnosis of HCC among patients with HCV infection and cirrhosis could be ascertained when sTNFR-IIα is assessed at a cutoff value of ≥ 250 pg/mL. CONCLUSIONS: Serum sTNFR-IIα could be used as a potential serum marker in diagnosing HCC among patients with HCV infection.

Molecular identification of giardia intestinalis in patients with dyspepsia.

BACKGROUND/AIMS: Giardia intestinalis triggers symptoms of functional dyspepsia. The aim of this study was to distinguish genotypes of G. intestinalis isolated from dyspeptic patients to evaluate their correlation with dyspeptic symptoms. METHODS: In total, 120 dyspeptic subjects were investigated by upper endoscopy, including gastric and duodenal biopsies for histopathological examination, and parasitological examination of their stools and duodenal aspirates was performed. The patients were classified into five groups: group I (G. intestinalis) included 19 patients, group II (Helicobacter pylori) included 36 patients, group III (coeliac disease) included 3 patients, group IV (mixed G. intestinalis and H. pylori infection) included 4 patients, and group V (unexplained aetiology) included 58 patients. Genotyping of G. intestinalis was performed for groups I and IV using PCR-RFLP. The urease test was performed for H. pylori. Serum anti-gliadin, anti-endomysial and anti-transglutaminase antibody estimation was performed for the diagnosis of coeliac disease. RESULTS: Genotype A of G. intestinalis was detected in the stool samples of 68.42% (13/19) and the duodenal aspirates of 42.1% (8/19) of dyspeptic patients harbouring the parasite. Genotype B was detected in 31.58% (6/19) of cases in stool samples and in 3 cases in duodenal aspirates. CONCLUSIONS: H. pylori, G. intestinalis and coeliac disease are common causes of dyspepsia. G. intestinalis genotype A demonstrated a greater association with dyspeptic symptoms.

P selectins and immunological profiles in HCV and Schistosoma mansoni induced chronic liver disease.

BACKGROUND: Hepatitis C virus (HCV) and Schistosoma mansoni are major causes of chronic liver disease (CLD) in which immune alteration is common. Recent studies suggested that certain platelets and lymphocytes activation markers may have an impact on progression of CLD. This study aimed to evaluate the potential of platelets and lymphocytes activation molecules expression on the pathogenesis of CLD in distinct or concomitant chronic HCV and schistosomiasis mansoni infections. METHODS: The study populations were divided into group-I: patients with chronic schistosomiasis mansoni, group-II: HCV patients without cirrhosis, group-III: patients with combined liver diseases without cirrhosis, group-IV: patients with chronic HCV and liver cirrhosis and group-V: Age and sex matched healthy individuals as normal controls. All groups were subjected to full clinical evaluation, ELISA anti-HCV antibodies screening, parasitological examination for diagnosing S. mansoni and flow cytometry for lymphocyte (CD3, CD4, CD8, CD19, CD22, & CD56) and platelets activation (CD41, CD42 & CD62P (P- selectins)) markers. RESULTS: The platelet count was significantly decreased in HCV and/or S. mansoni patients. The total T-lymphocytes and T-helper cells were significantly reduced, while T-cytotoxics were increased. The patients possessed a significantly higher platelets activation marker; CD62P (P-selectins) and higher mean fluorescent intensity (MFI) positivity. There were considerable correlations between platelets count and both of CD62P and MFI. CONCLUSION: Our Findings suggest an increased expression of certain platelets and lymphocytes activation markers in chronic HCV and S. mansoni induced CLD that may have a role in disease progression.

Impact of vitamin D receptor gene polymorphisms in pathogenesis of Type-1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus (TIDM) results from an immune-mediated destruction of insulin-producing-cells in the pancreatic islets of Langerhans. There are clear differences in immunogenetic predisposition to type1 diabetes among countries. Studies have indicated that vitamin D supplementation in early childhood decreases the risk of TIDM. Vitamin D exerts its action via the nuclear vitamin D receptor (VDR), which shows an extensive polymorphism. VDR gene polymorphisms have been associated with altered gene expression or gene function. Four single nucleotide polymorphisms (SNPs) in the VDR gene produce variation in four recognition sites. These recognition sites variants include Fok I, Bsm I, Apa I and Taq I. AIM OF THE STUDY: TO investigate the relationship between VDR gene polymorphisms (at positions Taq I and Apa I) and the incidence of TIDM in Egyptian peoples. SUBJECTS AND METHODS: This study included 74 patients with type 1 DM in addition to 28 healthy age and sex matched control subjects. All of them were subjected to full history taking and clinical examination. Three ml of venous blood were withdrawn from each patient at fasting and postprandial times and used for genomic DNA extraction, estimation of Hb A1C, as well as, fasting and postprandial C-peptide and blood glucose levels. RESULTS: Apa I recognition site was found in low frequency in diabetic patients (14/74) 18.9% while, its frequency was high (16/28) 57.1% among normal subjects. Taq I has two recognition sites. The first was found at nucleotide number 293 that was found in a frequency of (2/28) 7.1% in normal non-diabetic individuals while it was detected in (14/74) 18.9% in diabetic patients. The second Taq I recognition site was found at nucleotide number 494 without any differences between diabetic and normal individuals. CONCLUSION: This study indicates that there is an association between VDR genetic polymorphism and incidence of TIDM in Egyptian patients.

Noninvasive assessment of hepatic fibrosis in Egyptian patients with chronic hepatitis C virus infection.

AIM: To evaluate the accuracy of specific biochemical markers for the assessment of hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection. METHODS: One hundred and fifty-four patients with chronic HCV infection were included in this study; 124 patients were non-cirrhotic, and 30 were cirrhotic. The following measurements were obtained in all patients: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total bilirubin, prothrombin time and concentration, complete blood count, hepatitis B surface antigen (HBsAg), HCVAb, HCV-RNA by quantitative polymerase chain reaction, abdominal ultrasound and ultrasonic-guided liver biopsy. The following ratios, scores and indices were calculated and compared with the results of the histopathological examination: AST/ALT ratio (AAR), age platelet index (API), AST to platelet ratio index (APRI), cirrhosis discriminating score (CDS), Pohl score, Göteborg University Cirrhosis Index (GUCI). RESULTS: AAR, APRI, API and GUCI demonstrated good diagnostic accuracy of liver cirrhosis (80.5%, 79.2%, 76.6% and 80.5%, respectively); P values were: < 0.01, < 0.05, < 0.001 and < 0.001, respectively. Among the studied parameters, AAR and GUCI gave the highest diagnostic accuracy (80.5%) with cutoff values of 1.2 and 1.5, respectively. APRI, API and GUCI were significantly correlated with the stage of fibrosis (P < 0.001) and the grade of activity (P < 0.001, < 0.001 and < 0.005, respectively), while CDS only correlated significantly with the stage of fibrosis (P < 0.001) and not with the degree of activity (P > 0.05). In addition, we found significant correlations for the AAR, APRI, API, GUCI and Pohl score between the non-cirrhotic (F0, F1, F2, F3) and cirrhotic (F4) groups (P values: < 0.001, < 0.05, < 0.001, < 0.001 and < 0.005, respectively; CDS did not demonstrate significant correlation (P > 0.05). CONCLUSION: The use of AAR, APRI, API, GUCI and Pohl score measurements may decrease the need for liver biopsies in diagnosing cirrhosis, especially in Egypt, where resources are limited.

The pathogenic role of different Blastocystis hominis genotypes isolated from patients with irritable bowel syndrome.

BACKGROUND AND STUDY AIMS: The pathogenic role of Blastocystis hominis is still regarded by some as controversial. Studies have been in progress for years to evaluate the role of blastocystosis in irritable bowel syndrome (IBS) and demonstrated that faecal carriage of B. hominis was frequent in these patients. This study attempted to distinguish different genotypes of B. hominis isolates obtained from patients with IBS and to evaluate their pathogenic potentials. PATIENTS AND METHODS: One hundred subjects (51 patients with IBS and 49 asymptomatic infected subjects) harbouring B. hominis were investigated by a direct smear examination and in vitro culture of stool samples followed by genotyping of B. hominis by PCR using STS primers. Sigmoidoscopy was done in all subjects and biopsies were taken and subjected to histopathologic examination. RESULTS: Genotyping proved that only four genotypes of B. hominis were identified. In patients with IBS, genotypes III, I, and IV were detected (28, 15 and 14 isolates, respectively). On the other hand, genotypes III, IV, and II were identified in asymptomatic infected individuals (21, 19 and 13 isolates, respectively). The degrees of chronic inflammatory changes in sigmoidoscopic biopsies caused by B. hominis genotypes among IBS patients revealed that severe inflammation was present mainly in patients harboring genotype I isolates (4/15) (26.66%), while genotype III caused severe inflammation only in 9.09%. Genotype II isolates were not detected in IBS cases. Asymptomatic infected individuals harboring genotypes II, III and IV exhibited mild to moderate inflammatory changes. Genotype I isolates were not detected in asymptomatic infected group. The correlation between different B. hominis genotypes and degree of inflammation was statistically insignificant. CONCLUSION: Genotype I was the most pathogenic genotype of B. hominis isolates in patients with IBS while genotype II was not detected among those patients. Also, our results suggest the presence of pathogenic and non-pathogenic strains among genotypes III and IV.