End-stage liver disease (ESLD) is associated with dysregulation of the immune system and increased susceptibility to infections. Although invasive fungal infection (IFI) is a growing public health problem, studies of IFI in ESLD are lacking. The aims of this study were to screen for IFI in ESLD and to assess risk factors and serum interleukin 17 (IL-17) as a marker of the cellular immune response. Both blood and ascitic fluid samples were collected from 46 patients with ESLD for fungal culture and PCR. Serum IL-17 levels were determined. Seven patients had isolated IFI (four had spontaneous fungal peritonitis, two had fungemia, and one had a disseminated fungal infection) and five cases had combined fungal and bacterial infections. Spontaneous fungal peritonitis was attributed to Candida species, while fungemia was caused by Aspergillus species. Patients with IFI had higher serum IL-17 levels and increased mortality compared to patients without IFI. A history of antibiotic use (p = 0.002), higher model for end-stage liver disease (MELD) scores (p = 0.04), and hepatorenal syndrome (p = 0.006) were risk factors for IFI. Patients with ESLD had a low frequency of IFI; however, in patients with these infections, delayed diagnosis and treatment may contribute to a high fatality rate. Thus, clinicians should have a high index of suspicion for this unusual but lethal entity, as prompt detection and appropriate treatment can improve the outcome.

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder with complex immunopathogenesis. Dysbiosis has been linked to many autoimmune diseases, but its detailed role in autoimmune hepatitis (AIH) still needs rigorous evaluation, especially in Egypt. We aimed to identify the shift in the gut microbiota profile and resultant metabolic pathways in AIH Egyptian patients compared to healthy individuals. Stool samples were collected from 15 AIH-naive patients and from 10 healthy individuals. The V3-V4 hyper-variable regions in16S rRNA gene was amplified and sequenced using Illumina MiSeq platform. Significantly lower bacterial diversity in AIH patients was found compared to the controls. A phylum-level analysis showed the overrepresentation of Firmicutes, Bacteroides, and Proteobacteria. At the genus level, AIH-associated enrichment of Faecalibacterium, Blautia, Streptococcus, Haemophilus, Bacteroides, Veillonella, Eubacterium, Lachnospiraceae and Butyricicoccus was reported in contrast to Prevotella, Parabacteroides and Dilaster, which were significantly retracted in such patients. Overall, the predicted metabolic pathways associated with dysbiosis in AIH patients could orchestrate the potential pathogenic roles of gut microbiota in autoimmune disease, though not in a disease-specific manner, calling for future large-scale studies.

Background: Health care-associated infections (HAIs) threaten patient's safety worldwide especially in the intensive care units (ICU). In end-stage liver disease (ESLD), the condition is much more complicated. Data regarding HAIs among ESLD patients is lacking. We aimed to assess the incidence of HAIs, risk factors, causative micro-organisms, antimicrobial susceptibilities and mortality rates among patients with end-stage liver disease (ESLD) admitted to pre-transplant liver intensive care unit (LICU). Method: This prospective observational study included 337 ESLD patients admitted to LICU, Al-Rajhi liver center, Assiut University Hospital, Assiut, Egypt between January 2016 and June 2016 and they were followed up for the development of HAI manifestations. The medical history, physical examination and severity of underlying disease were determined. Clinical samples were taken from patients who developed HAIs for microbiological diagnosis and antimicrobial susceptibility testing. Results: A total of 57 (16.9%) ESLD patients developed HAIs with the incidence density of 26.8 per 1000 patient-days. Blood stream infection was the most common (49.1%). Escherichia coli (21.1%) followed by methicillin-resistant Staphylococcus aureus (MRSA) (15.8%) were the commonest bacteria. Multidrug resistant organisms were reported in 52.6% of the isolates. Fungal causes were 15.8% with Candida species dominance. Sphingomonas paucimobilis and Achromobacter dentrificans were reported for the first time as pathogens for HAIs in LICU. Prolonged hospital stay, intravenous line duration, prolonged use of proton pump inhibitors and paracentesis were predictors for HAIs. No significant difference between ESLD patients with and without HAIs regarding mortality (36.8% vs. 48.6%, P = 0.2). Conclusion: High HAI rate among ESLD patients is a matter of worry. Effective surveillance program, active infection control measures and national antibiotic policies are necessary to reduce the burden of HAIs. (C) 2018 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences.

On and mucosal healing after infliximab induction therapy in refractory UC patients. Patients and Methods: Serum and fecal biomarkers, including hemoglobin, white blood cells, erythrocyte sedimentation rate, C-reactive protein (CRP), and fecal calprotectin (FC), and colonoscopy were assessed in 44 patients with refractory UC before and after (week 12) infliximab induction. Clinical and endoscopic responses were measured by clinical Mayo score and endoscopic Mayo subscore, respectively. Results: After infliximab induction, 54.5% and 65.9% had clinical remission and mucosal healing, respectively. Post-induction CRP and FC were significantly lower in clinical responders versus nonresponders (P = 0.01 and 0.001, respectively) and in patients with mucosal healing than without (P < 0.001). Among all the parameters tested, FC had the best predictive value of clinical remission [Area under the curve (AUC = 0.826)] and mucosal healing (AUC = 0.949). Post-induction FC had 87.5% sensitivity and 89% specificity (cut-off <100 μg/g) for predicting clinical remission and 89.7% sensitivity and 93.3% specificity (cut-off <58 μg/g) for predicting mucosal healing. Conclusions: Post-infliximab induction FC can be used as a surrogate marker for predicting clinical remission and mucosal healing in refractory UC patients....

This study aimed to investigate whether plasma miR-21 and miR-92a levels may be used to differentiate between patients with irritable bowel syndrome (IBS), ulcerative colitis (UC), and colorectal cancer (CRC). miRNA expression profiles are well characterized in CRC, but these expression profiles in UC and IBS remain promising. Screening of high-risk individuals for these diseases has substantial clinical benefits. This was a case-control study. We quantified plasma miR-21 and miR-92a expression levels in 100 samples (37 with active UC, 33 with CRC, and 30 with IBS as well as 30 healthy controls) using real-time PCR. Their diagnostic performance for discriminating these diseases was assessed using receiver-operation characteristic curve (AUC-ROC). The studied miRNAs were differentially expressed among all participated groups. Plasma miR-21 and miR-92a levels exhibited significant upregulation in CRC as compared to IBS, UC, and healthy subjects. Both miRNAs were upregulated in the UC group as compared to IBS and healthy subjects. ROC analysis revealed promising diagnostic performance for miR-21 and miR-92a in discriminating UC from non-UC groups (IBS and healthy subjects) with AUCs of 0.844 and 0.979 respectively. It also distinguished between CRC and UC with AUCs of 0.968 and 0.887 respectively and with reasonable sensitivities and specificities. Circulating miR-21 and miR-92a can be exploited not only as potential noninvasive biomarkers for detection of CRC, but also for differentiation between functional and organic colorectal disorders.

The occurrence of tuberculosis (TB) and hepatitis C virus (HCV) infections in the same patient presents a unique clinical challenge. The impact of HCV infection on the immune response to TB remains poorly investigated in TB⁺/HCV⁺ patients. This study was conducted to evaluate the impact of HCV on the T-cell-mediated immune response to TB in coinfected patients. Sixty-four patients with active TB infections were screened for coinfection with HCV. The expression of immune activation markers IFN-γ, CD38, and HLA-DR on TB-specific CD4⁺ T cells was evaluated by flow cytometry in TB-monoinfected patients, TB/HCV-coinfected patients, and healthy controls. IL-2, IL-4, IFN-γ, TNF-α, and IL-10 levels were measured using ELISA. The end-of-treatment response to anti-TB therapy was recorded for both patient groups. Significantly lower levels of CD4⁺IFN-γ⁺CD38⁺ and CD4⁺IFN-γ⁺HLA-DR⁺ T cells were detected in TB/HCV-coinfected patients compared to TB monoinfected patients and controls. TB⁺/HCV⁺-coinfected patients showed higher serum levels of IL-10. The baseline frequencies of TB-specific activated T-cell subsets did not predict the response to antituberculous therapy in TB⁺/HCV⁺ patients. We concluded that different subsets of TB-specific CD4⁺ T cells in TB/HCV-infected individuals are partially impaired in early-stage HCV infection. This was combined with increased serum IL-10 level. Such immune modulations may represent a powerful risk factor for disease progression in patients with HCV/TB coinfection.