Oral midodrine is comparable to albumin infusion in cirrhotic patients with refractory ascites undergoing large-volume paracentesis: results of a pilot study.

BACKGROUND AND AIMS: Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites compared with no treatment. Less costly treatment alternatives such as vasoconstrictors have been investigated, but the results are controversial. Midodrine, an oral α1-adrenergic agonist, increases effective circulating blood volume and renal perfusion by increasing systemic and splanchnic blood pressure. Our aim is to assess whether or not morbidity in terms of renal dysfunction, hyponatremia, systemic, or portal hemodynamics derangement or mortality differed in patients receiving albumin versus midodrine. PATIENTS AND METHODS: Seventy-five patients with cirrhosis and refractory ascites were randomized to receive albumin infusion, oral midodrine for 2 days, or oral midodrine for 30 days after therapeutic large volume paracentesis (LVP). The primary endpoints were development of renal impairment or hyponatremia, change in systemic and portal hemodynamics, cost, and mortality in the short-term and long-term follow-up. RESULTS: No significant difference was found between groups in the development of renal impairment, hyponatremia, or mortality 6 and 30 days after LVP. A significant increase in 24-h urine sodium excretion was noted in the midodrine 30-day group. Renal perfusion improved significantly with the midodrine intake for 30 days only. The cost of midodrine therapy was significantly lower than albumin. CONCLUSION: Midodrine is as effective as albumin in reducing morbidity and mortality among patients with refractory ascites undergoing LVP at a significantly lower cost. Long-duration midodrine intake can be more useful than shorter duration intake in terms of improvement of renal perfusion and sodium excretion.

Role of Serum Soluble CD163 in the Diagnosis, Risk of Bleeding, and Prognosis of Gastro-Esophageal Varices in Cirrhotic Patients.

Research is continuous for noninvasive tools for the prediction of portal hypertension than upper gastrointestinal endoscopy. Serum sCD163 correlates with hepatic venous pressure gradient, aiding in the prediction of portal hypertension. We aimed at investigating the role of sCD163 in the prediction of the presence and size of varices as well as a stratification tool for surveillance or prophylaxis by assessment of prognosis and risk of bleeding. Two hundred forty-three cirrhotic patients were divided into 3 groups: group I: no varices, group II: small-sized varices, and group III: medium-sized and large-sized varices. Serum sCD163 levels were assessed and correlated with abdominal ultrasound and laboratory investigations. Follow-up for 1 year was conducted to assess the risk of bleeding, and band ligation was performed for significant varices with follow-up of obliteration. sCD163 levels were significantly higher in patients with varices requiring prophylactic interventions (P = 0.03) and in large varices (P = 0.012), patients at risk of bleeding (P = 0.04), and the bleeder patients (P = 0.001). No relationship between the sCD163 levels and the rate of variceal obliteration was reported. sCD163 levels were positively correlated with the Child score (P = 0.05), the portal vein diameter (P = 0.02), and the splenic size (P = 0.04). Although sCD163 level cannot predict the development of varices, it serves as a good predictor for the detection of size of varices (large varices), the need of prophylactic interventions, and risk of variceal bleeding. sCD163 level is a helpful indicator with the progression of cirrhosis and portal hypertension.

Serum miRNA Panel in Egyptian Patients with Chronic Hepatitis C Related Hepatocellular Carcinoma.

BACKGROUND: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. MicroRNAs (miRNAs) have great HCC diagnostic potential and circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. AIM: To explore the potential benefit of serum miR-126, miR-129, miR-155, miR-203 and miR-223 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related HCC. MATERIALS AND METHODS: The expression of miRNA was evaluated using real-time quantitative RT-PCR in 78 serum samples (30 treatment-naive chronic HCV, 25 post-HCV compensated cirrhosis and 23 treatment- naive HCC cases). RESULTS: Comparing miRNA fold changes in the HCC group vs the non HCC groups, there was significant fold decrease in miR-126 (P= 0.034), miR-129 (P= 0.006), miR-155 (P= 0.011), miR-203 (<0.001) and miR-223 (P= 0.013). The highest AUC to differentiate HCC patients from non-HCC was 0.76 for miR-203. CONCLUSIONS: Among studied miRNAs, serum miR-203 has the highest potential as a non-invasive biomarker of HCC.

Thyroid Dysfunction in Chronic Hepatitis C Patients Treated with the Combined Pegylated Interferon-Ribavirin Therapy.

Hepatitis C virus (HCV) is an Egyptian serious national health problem. The combination of pegylated interferon (PEG-IFN) with ribavirin (RIB) was considered the established therapy for chronic hepatitis C (CHC), and it was associated with several adverse effects, including thyroid dysfunction (TD). The aim of this work was to study TD in CHC patients receiving PEG-IFN+ RIB therapy. This retrospective study included 100 adult patients attending the outpatient clinics at AL-Kahera Al-Fatemya hospital and were eligible candidates for PEG-IFN+ RIB therapy. Thyroid hormonal profile (thyroid-stimulating hormone, free triiodothyronine, and free thyroxine) was done before initiation of treatment (week 0) and at weeks 12, 24, 48, and 72. The incidence of TD was more evident by the end of treatment (week 48); it was found to be 35%, mostly in the form of hypothyroidism, while the least incidence was detected by week 12 (2%), all in the form of hyperthyroidism. Generally, hypothyroidism was higher than hyperthyroidism in multiple folds. Thyroid profile was not significantly related to viral load.

GENETIC MUTATIONS AFFECTING THE FIRST LINE ERADICATION THERAPY OF Helicobacter pylori-INFECTED EGYPTIAN PATIENTS.

INTRODUCTION:: Several genetic mutations affect the first-line triple therapy for Helicobacter pylori. We aimed to study the most common genetic mutations affecting the metronidazole and clarithromycin therapy for H. pylori-infected Egyptian patients. PATIENTS AND METHODS:: In our study, we included 100 successive dyspeptic patients scheduled for diagnosis through upper gastroscopy at Cairo's University Hospital, Egypt. Gastric biopsies were tested for the presence of H. pylori by detection of the 16S rRNA gene. Positive biopsies were further studied for the presence of the rdxA gene deletion by Polymerase Chain Reaction (PCR), while clarithromycin resistance was investigated by the presence of nucleotide substitutions within H. pylori 23S rRNA V domain using MboII and BsaI to carry out a Restricted Fragment Length Polymorphism (RFLP) assay. RESULTS:: Among 70 H. pylori positive biopsies, the rdxA gene deletion was detected in 44/70 (62.9%) samples, while predominance of the A2142G mutations within the H. pylori 23S rRNA V domain was evidenced in 39/70 (55.7%) of the positive H. pylori cases. No statistically significant difference was found between the presence of gene mutations and different factors such as patients 'age, gender, geographic distribution, symptoms and endoscopic findings. CONCLUSION:: Infection with mutated H. pylori strains is considerably high, a finding that imposes care in the use of the triple therapy to treat H. pylori in Egypt, since the guidelines recommend to abandon the standard triple therapy when the primary clarithromycin resistance rate is over 20%1.

Transforming growth factor-ß1 gene expression in hepatocellular carcinoma: a preliminary report.

BACKGROUND AND STUDY AIMS: The transforming growth factor (TGF)-ß signalling pathway plays a dual role in hepatocarcinogenesis. It has been recognised for its role as a tumour suppressor as well as a tumour promoter depending on the cellular context. The aim of this study was to investigate the clinical significance of serum TGF-ß1 level and TGF-ß1 messenger RNA (mRNA) in the peripheral blood of liver cirrhosis and hepatocellular carcinoma (HCC) patients as noninvasive biomarkers in diagnosing HCC. PATIENTS AND METHODS: Twenty patients were allocated to each of the liver cirrhosis and HCC groups, in addition to 20 healthy volunteers. TGF-ß1 gene expression in peripheral blood was quantitated using real-time polymerase chain reaction (PCR), while serum TGF-ß1 was analysed using enzyme-linked immunosorbent assay (ELISA). RESULTS: TGF-ß1 gene expression was significantly lower in HCC patients (median 0.401 (0.241-0.699) fold change) than in liver cirrhosis patients (median 0.595 (0.464-0.816)) (p=0.042) and normal controls (median 1.00 (0.706-1.426) fold change) (p=0.001). TGF-ß1 gene expression showed significant positive correlation with serum TGF-ß1 (r=0.272, p=0.036) and significant negative correlation with alpha-fetoprotein (AFP) (r=-0.528, p=0.001). Receiver operating characteristic (ROC) analysis was conducted for TGF-ß1 gene expression in comparison with AFP. The area under the curve for TGF-ß1 gene expression was 0.688 (95% CI=0.517-0.858) (p=0.042) and AFP was 0.869 (95% CI=0.761-0.976) (p=0.001). The sensitivity and specificity of TGF-ß1 gene expression were 65% and 75%, respectively, at a cutoff value of 0.462 fold change. CONCLUSION: TGF-ß1 gene expression in the peripheral blood may be used as a molecular marker for the diagnosis of HCC. Additional studies on a large-scale population are necessary to gain greater insight into the impact of TGF-ß1 gene expression in the pathogenesis of HCC.

The first Egyptian experience using new self-expandable metal stents in acute esophageal variceal bleeding: pilot study.

UNLABELLED: BACKGROUND / AIM: Balloon tamponade has been widely available in emergency situations of acute variceal bleeding. To lessen the complications of Balloon tamponade, a new special type of stent for exclusive use in acute variceal bleeding has been developed. This study aims to investigate the effectiveness and safety of the new self-expandable metal stents (SEMS) in the initial control of acute variceal bleeding. We also hypothesized that using SEMS can bridge the acute bleeding episode converting endoscopic management by sclerotherapy or band ligation to an elective procedure. PATIENTS AND METHODS: Twenty patients with acute variceal bleeding were included in the study and 16 of them were allocated to receive stent treatment. RESULTS: Stent deployment was successful in 15 of 16 patients (93.75%). Technical errors were reported in 3 (18.75%) patients. Initial control of variceal bleeding was reported in 14 (out of 16) (87.5%) patients. The mean duration of the procedure was 10 (±6) min. Mortality was reported in 4 (25.0%) patients. CONCLUSION: SEMS is a safe and effective mean to control acute variceal bleeding.

Highly pathogenic avian influenza virus subtype H5N1 in Africa: a comprehensive phylogenetic analysis and molecular characterization of isolates.

Highly pathogenic avian influenza virus A/H5N1 was first officially reported in Africa in early 2006. Since the first outbreak in Nigeria, this virus spread rapidly to other African countries. From its emergence to early 2008, 11 African countries experienced A/H5N1 outbreaks in poultry and human cases were also reported in three of these countries. At present, little is known of the epidemiology and molecular evolution of A/H5N1 viruses in Africa. We have generated 494 full gene sequences from 67 African isolates and applied molecular analysis tools to a total of 1,152 A/H5N1 sequences obtained from viruses isolated in Africa, Europe and the Middle East between 2006 and early 2008. Detailed phylogenetic analyses of the 8 gene viral segments confirmed that 3 distinct sublineages were introduced, which have persisted and spread across the continent over this 2-year period. Additionally, our molecular epidemiological studies highlighted the association between genetic clustering and area of origin in a majority of cases. Molecular signatures unique to strains isolated in selected areas also gave us a clearer picture of the spread of A/H5N1 viruses across the continent. Mutations described as typical of human influenza viruses in the genes coding for internal proteins or associated with host adaptation and increased resistance to antiviral drugs have also been detected in the genes coding for transmembrane proteins. These findings raise concern for the possible human health risk presented by viruses with these genetic properties and highlight the need for increased efforts to monitor the evolution of A/H5N1 viruses across the African continent. They further stress how imperative it is to implement sustainable control strategies to improve animal and public health at a global level.