Multidrug resistance Gene-1 polymorphisms (C3435T and G2677T) and the risk of inflammatory bowel disease in Egyptian patients.

BACKGROUND AND STUDY AIMS: The multidrug resistance 1 (MDR1) gene is a gene involved in the pathogenesis of inflammatory bowel disease (IBD).The aim of the study is to investigate the association of MDR-1 gene polymorphisms (C2345T and G2677T) and IBD incidence in Egyptian patients, and its relation with disease severity. PATIENTS AND METHODS: This is a case-control study where genotyping of MDR-1 gene C3435T and G2677T single nucleotide polymorphisms (SNPs) were assayed. RESULTS: Forty naïve IBD patients, who were composed of 25 UC and 15CD, were compared to 60 healthy controls. They were young aged with significant female predominance, particularly in CD (P = 0.004). UC was mainly (48 %) presented in moderate severity while CD was mainly (53.3 %) presented with mild severity. MDR-1 gene C3435T SNP was not statistically related to IBD, whether in terms of genotypes or alleles, yet its T allele was significantly related to moderate cases of UC (P = 0.014). However, GG genotype of G2677T SNP was significantly low in IBD (P = 0.013), while TT genotype and T allele were significantly related to CD (P = 0.011, and 0.012 respectively). Moreover, G allele proved to be associated significantly with moderate cases of UC (P = 0.001) and mild cases of CD (P = 0.002). CONCLUSIONS: MDR-I gene G2677T SNP GG genotype proved to be protective against IBD, thus may be considered in diagnostic workup of IBD including its severity.

Diabetic patients with chronic hepatitis C virus response compared to non diabetics when treated with directly acting antiviral therapy.

BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) impairs glucose homoestasis, thus influences its clinical picture and prognosis. This study aimed at evaluating Diabetes mellitus (DM) on Egyptian patients with chronic hepatitis C (CHC), and its impact on their virologic response when treated with directly acting antiviral (DAA) medications. PATIENTS AND METHODS: Adult patients with CHC were divided into 2 groups; Diabetic patients, and Non diabetic patients serving as control group. All patients were subjected to thorough clinical evaluation, basic biochemical laboratory tests including fasting blood glucose/glycosylated haemoglobin (HbA1C), and virologic assay. They were treated with various combined DAAs, and were monitored during, at and after end of treatment. RESULTS: Diabetic patients constituted 9.85 % of CHC, and had generally worse laboratory tests (significantly higher transaminases, platelet count, Fib4 and hepatic steatosis) than non diabetic patients, and a less sustained virologic response (SVR) (significantly in Sofosbuvir (SOF) + pegylated interferon (PegIFN) + ribavirin (RBV), SOF + RBV, SOF + daclatasvir (DAC)). Although DM did not play a significant influence on SVR, yet Fib4 and SOF + RBV + PEG-IFN were significant factors affecting SVR among diabetics, while female gender and viraemia were significant factors affecting SVR among non diabetics. Hepatic fibrosis and SOF/RBV significantly influenced SVR in both groups. CONCLUSIONS: Diabetic patients with CHC have worse liver biochemical profile, yet DM per se did not influence the virologic response to DAAs, however, some factors played roles in affecting SVR among them.

Virulent Escherichia coli strains among Egyptian patients with acute diarrhoea versus urinary tract infection, and their antibiotic susceptibility.

BACKGROUND AND STUDY AIMS: Diarrhoea and urinary tract infection (UTI) are common clinical problems. Meanwhile, Escherichia coli (E. coli), is the commonest bacterial pathogen reported in both of them. This study aimed to evaluate the pathogenic E. coli (PEC) in stool of acute diarrhoea and urine of UTI regarding their virulence genes and their influence on the susceptibility to routinely prescribed antibiotics. PATIENTS AND METHODS: Twenty two stool and another 22 urine samples of patients with acute diarrhoea and UTI respectively were collected from patients admitted at Kasr Al-Ainy Hospital, Faculty of Medicine, Cairo University, Egypt. E. coli isolation, identification of their phyla; chuA, yjaA, and TspE4.C2, and further identification of 10 virulent genes; fimH, papC, papG//, papG///, papEF, afa, sfa, CNF1, iroN & hlyA was performed. Antibiotic susceptibility was studied against quinolones, gentamicin (GM), and trimethoprim-sulphamethoxazole (TMP-SMX). RESULTS: The studied virulence genes were comparably detected in both pathogenic samples. In diarrheogenic E. coli (DEC); phylum A was significantly related to both ciprofloxacin (CIP) and TMP-SMX resistance, and both of the virulence genes fimH and iroN were significantly related to all the studied antibiotics resistance, while afa was significantly related to nalidixic acid (NA) resistance. In uropathogenic E. coli (UEC); phylum D was significantly related to CIP and levofloxacin resistance, and both of the virulence genes fimH and iroN were significantly related to most of the studied antibiotics resistance. CONCLUSION: The isolated PEC was evidently and broadly resistant to the studied antibiotics, with limited influence of their phyla and virulence genes (fimH and iroN).

Wavelet-based Computationally-Efficient Computer-Aided Characterization of Liver Steatosis using Conventional B-mode Ultrasound Images.

Hepatic steatosis occurs when lipids accumulate in the liver leading to steatohepatitis, which can evolve into cirrhosis and consequently may end with hepatocellular carcinoma. Several automatic classification algorithms have been proposed to detect liver diseases. However, some algorithms are manufacturer-dependent, while others require extensive calculations and consequently prolonged computational time. This may limit the development of real-time and manufacturer-independent computer-aided detection of liver steatosis. This work demonstrates the feasibility of a computationally-efficient and manufacturer-independent wavelet-based computer-aided liver steatosis detection system using conventional B-mode ultrasound (US) imaging. Seven features were extracted from the approximation part of the second-level wavelet packet transform (WPT) of US images. The proposed technique was tested on two datasets of ex-vivo mice livers with and without gelatin embedding, in addition to a third dataset of in-vivo human livers acquired using two different US machines. Using the gelatin-embedded mice liver dataset, the technique exhibited 98.8% accuracy, 97.8% sensitivity, and 100% specificity, and the frame classification time was reduced from 0.4814 s using original US images to 0.1444 s after WPT preprocessing. When the other mice liver dataset was used, the technique showed 85.74% accuracy, 84.4% sensitivity, and 88.5% specificity, and the frame classification time was reduced from 0.5612s to 0.2903 s. Using human liver image data, the best classifier exhibited 92.5% accuracy, 93.0% sensitivity, 91.0% specificity, and the classification time was reduced from 0.660 s to 0.146 s. This technique can be useful for developing computationally-efficient and manufacturer-independent noninvasive CAD systems for fatty liver detection.

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.

Evaluation of fluvastatin in combination with the standard of care therapy (PEG-IFN/Ribavirin) in Egyptian patients with hepatitis C virus.

BACKGROUND/AIMS: Cholesterol biosynthesis suppresses the replication of HCV-1b replicons, thus influencing hepatitis C virus (HCV) natural history. This study aimed at comparing the efficacy and safety of fluvastatin (FLV) as an adjuvant therapy to the standard of care (SOC) therapy, i.e., pegylated interferon (PEG-IFN) and ribavirin, for the treatment of HCV patients. MATERIALS AND METHODS: Sixty HCV patients were enrolled and allocated to either group I, who received the triple therapy (fluvastatin + SOC), or group II, who received SOC; the duration for both treatments was 48 weeks. All patients were subjected to pretreatment liver biopsy and monthly biochemical tests (liver profile, CBC), and quantitative HCV-RNA test was performed at weeks 0, 4, 12, 48, and 72. RESULTS: All virological responses were higher in group I than in group II, with no statistical difference. Group I showed no manifestations of hepatotoxicity. CONCLUSION: Fluvastatin yielded a borderline, significantly higher complete early virological response than SOC; therefore, it is a safe adjuvant to the SOC therapy.

Evaluation of microRNAs-29a, 92a and 145 in colorectal carcinoma as candidate diagnostic markers: An Egyptian pilot study.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant neoplasms in Egypt, and interestingly in young age. Adenomatous polyps and inflammatory bowel diseases (IBD) are considered the commonest pre-malignant lesions for CRC. A possible diagnostic role for different microRNAs on CRC has been suggested by numerous studies. AIM OF WORK: To assess the serum expression of 3 microRNA markers (miR-29a, miR-92a and miR-145) in pre-malignant and malignant colorectal lesions. PATIENTS AND METHODS: The 60 patients studied were divided into 4 groups: CRC group (25 patients), IBD group (11 patients), adenomatous polyps group (14 patients) and control group (10 patients). The serum expression of the 3 markers (miR-29a, miR-92a and miR-145) has been assessed by RT-PCR. RESULTS: All CRCs were sporadic cases. Significant downregulation of miR-145 in CRC group was reported at all levels, i.e. when compared to normal, among the 3 studied groups, and when compared between CRC and non-CRC groups. Significant upregulation of miR-29a in CRC was reported when compared to normal, but no significant difference existed either among the 3 studied groups or between CRC and the other 2 groups. All 3 miRNAs studied were positively inter-correlated. CONCLUSIONS: miR-145 may be considered a promising non-invasive reliable diagnostic marker in CRC. Extended studies are needed to ascertain the diagnostic role of miRNAs in CRC.

Fungal infections in liver transplant patients admitted to the intensive care unit.

BACKGROUND: Fungal infections have a significant impact on patient survival after liver transplantation, mostly caused by Candida and Aspergillus. The clinical manifestations vary, and range from colonization, active local infection, to severe invasive form. A high degree of suspicion is required for the early diagnosis and, accordingly, the optimal management of these infections. This study aimed to evaluate fungal infection in the Intensive care Unit (ICU) in admitted liver transplant patients, focussing of etiologic agent, clinical/laboratory presentation (including mortality), and risk factors. MATERIAL AND METHODS: This retrospective study included living related liver transplanted patients admitted to the ICU. Clinical data was collected, thorough clinical evaluation was done, and laboratory tests were performed. Microbiological examination detecting the presence of fungus in various samples, using cultures and serology, and imaging investigations were carried out in all patients. RESULTS: This study included 23 cases of ICU-admitted liver transplant patients who were diagnosed with fungal infection. Candida was the most common fungal infection and occurred at a mean of 2 months after transplantation; while Aspergillus was less common and occurred later with worse laboratory findings. Invasive fungal infection constituted 43% of the diagnosed cases. Difference in mortality between Aspergillus and Candida was insignificant, as was difference between patients with and without fungal infection. CONCLUSIONS: Fungal infection among LT patients was common, including the invasive forms.

Plasma proteosome level as a potential marker for hepatocellular carcinoma.

BACKGROUND AND STUDY AIMS: Hepatocellular carcinoma (HCC) is a fatal malignancy. Effective curative surgery is achieved when HCC is detected earlier. Proteosomes, the main non-lysosomal proteolytic structures organising the cellular mechanisms of cleaving proteins, can be considered a tumour marker in many kinds of malignancies. The aim of this study was to assess the plasma proteosome level in HCC and cirrhosis and, accordingly, evaluate its potential diagnostic ability in the detection of HCC in cirrhosis. PATIENTS AND METHODS: This study included 60 patients, divided into two groups: the HCC group and the liver cirrhosis group. Twenty normal subjects served as a control group. Serum levels of proteosome and alpha-foetoprotein (AFP) were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Plasma proteosome levels were significantly higher in patients with HCC and in patients with cirrhosis without HCC when compared to controls individually (p>0.002 and p>0.001, respectively) but did not reach a significant differentiating level between them (area under curve (AUC)=0.641, p=0.061). Moreover, the plasma proteosome level was not correlated with the severity of HCC by the Milan criteria or with AFP level. In addition, it was not significantly related to laboratory or Child-Pugh scoring. Moreover, the combined use of plasma proteosome level and AFP measurements for the diagnosis of HCC was not effective. CONCLUSIONS: In this study, the plasma proteosome level was comparably recorded in both patients with cirrhosis and patients with HCC (mean value±standard deviation were 5.796±1.46 and 7.176±2.48µgml(-1), respectively), not reaching a significant differentiating level between them, although predictability of HCC using the plasma proteosome level was significant (p=0.017).

Evaluation of liver tissue by polymerase chain reaction for hepatitis B virus in patients with negative viremia.

AIM: To assess the clinical significance of Hepatitis B virus (HBV) DNA localization in the liver tissue of patients with positive HBsAg and negative viremia. METHODS: HBV virological parameters of 33 HBsAg positive chronic hepatitis patients, including seromarkers and HBV DNA amplification in both sera and liver biopsies, were evaluated. RESULTS: Ten patients had negative viremia and positive HBV DNA in their liver biopsies. Most of them had HBeAg-negative/HBeAb-positive chronic hepatitis. Their liver biochemical and histopathological profiles were different from the viremic patients. Their disease pattern was designated as "hepatitis B in situ". CONCLUSION: Hepatitis B in situ is a consequential entity which can be missed in clinical practice. It is a new clinical pattern of chronic HBV infection that considers HBV in liver biopsy and adds a new indication for antiviral therapy.