Current insight into enteropathogens in flare-up ulcerative colitis. An observational study.

OBJECTIVE: Incidence of ulcerative colitis is globally increased. Enteric infections and their role in ulcerative colitis flares present a common health problem and a unique clinical challenge. We aimed to identify enteropathogens in flared ulcerative colitis patients and their antimicrobial susceptibilities and relation with the disease activity. METHODS: Stool samples were collected from 95 patients with ulcerative colitis (17 inactive cases and 78 active cases) according to the Mayo score assessment of ulcerative colitis severity. Enteropathogens were examined using an automated VITEK2 system and FilmArray gastrointestinal pathogen panel. RESULTS: Enteric infections were found in 81 patients (85.3%) with a significantly higher percentage in active ulcerative colitis (96.2% vs. 35.3%, P  < 0.001). In 78 symptomatic patients, (78.7%) of bacteria as enteroaggregative and enteropathogenic E. coli , (11.5%) parasitic as Cryptosporidium and (7.7%) viral as Norovirus were the most detected microbial pathogens. Mixed, multidrug-resistant organisms (MDROs) and opportunistic infections were reported in 70.7%, 52.9% and 46.7% respectively. Raoultella ornithinolytica was reported for the first time as an enteropathogen in ulcerative colitis flare. Multiple organisms, MDROs, extended-spectrum beta-lactamases-producing and AmpC-resistant bacteria were significantly associated with disease severity. CONCLUSION: Identifying enteropathogens especially opportunistic and MDR organisms as a cause of ulcerative colitis flare-ups is a matter of worry increasing their diagnostic and therapeutic burden. Periodic studies evaluating changes in microbial profiles and their antimicrobial susceptibilities are needed to achieve antibiotic stewardship and improve management.

Impact of Sarcopenia on Short-Term Complications and Survival After Liver Transplant.

OBJECTIVES: Sarcopenia is a common entity in cirrhosis with significant morbidity and mortality. However,the effects of sarcopenia on the risk of complications and survival after liver transplant remain controversial.We aimed to evaluate the effect of sarcopenia on survival and complications after liver transplant. MATERIALS AND METHODS: Our study cohort included 61 adult patients with hepatitis C-related cirrhosis who underwent living donor liver transplant. Pretransplant clinical and anthropometric assessments included body mass index, hand grip, mid-arm circumference, triceps skin fold thickness, and gait speed. Sarcopenia was determined by computed tomography using the skeletal muscle index at the third lumbar vertebra cut-off value of <38.5 cm2/m2 for women and <52.4 cm2/m2 for men; these patients were then followed up for 6 months after transplant to determine survival and complications. RESULTS: At time of liver transplant, sarcopenia was present in 27/61 patients (44.3%). At follow-up after transplant, sarcopenia was found in 14 patients (30.4%) among 46 survivors; all patients who survived were male patients. Among patients with sarcopenia posttransplant, 12 had sarcopenia before transplant and 2 developed sarcopenia after transplant. Liver dysfunction, lower triceps skin fold thickness, recent infections, and sarcopenia pretransplant were associatedwithposttransplant complications, especially infection(42.8%) and prolonged intensive careunit stay. Age and pretransplant sarcopenia were found to be independent predictors of posttransplant mortality. CONCLUSIONS: Sarcopenia is a common entity in patients with cirrhosis who are on liver transplant wait lists and may continue after liver transplant. De novo sarcopenia after liver transplant is also a common finding. Sarcopenia can affect patient outcomes, including prolonged intensive care unit stay and poor short-term survival.

Impact of Geographical Location on the Gut Microbiota Profile in Egyptian Children with Type 1 Diabetes Mellitus: A Pilot Study.

Purpose: To investigate the compositional and functional characteristics of T1DM-associated gut microbiota in two Egyptian cities and to study the geographical locality effects. Patients and Methods: This case-control study included 32 children with controlled T1DM and 16 controls, selected from two different regions of Egypt. The gut microbiota of both diabetic and control children was analyzed through 16S rRNA gene sequencing; this was done using the Illumina MiSeq platform. Results: Consistent findings among the diabetic children included significantly lower alpha diversity than the control children, as well as a lower mean Firmicutes/Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and the genera Prevotella and Ruminococcus. In the diabetic children, there were also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and the genera Lactobacilli, Bacteroides, and Faecalibacterium. When comparing the two diabetic groups, the Ismailia group (IsDM) was found to have a significantly higher F/B ratio and diversity indices, with resultant differences at the functional level. Conclusion: There are a number of consistent changes in the microbiota profile characterizing the diabetic groups irrespective of the geographical location including significantly lower alpha diversity, mean Firmicutes/ Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and genera Prevotella and Ruminococcus. There are also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and genera Lactobacilli, Bacteroides, and Faecalibacterium pointing to the greater driving power of the disease.

Role of Serum Vitamin D, Interleukin 13, and microRNA-135a in Hepatocellular Carcinoma and Treatment Failure in Egyptian HCV-Infected Patients Receiving Direct Antiviral Agents.

Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.

Is bronchoscopic view a reliable method in diagnosis of tracheobronchial aspergillosis in critically ill non-neutropenic patients?

INTRODUCTION: Pulmonary aspergillosis is the main respiratory fungal infection however; its diagnosis is missed or delayed in critically ill non-neutropenic patients. Despite the utility of fiberoptic bronchoscopy for the evaluation of tracheobronchial aspergillosis (TBA) in immunocompromised patients has been extensively studied, however its utility in critically ill non-neutropenic patients is underestimated. OBJECTIVES: To assess the bronchoscopic changes suspected TBA relative to the microbiological and histopathological aspects in critically ill non-neutropenic patients admitted to respiratory intensive care unit (RICU). METHODS: We prospectively studied 139 critically ill non-neutropenic patients admitted to RICU and had a clinical suspicion of broncho-pulmonary Aspergillus infection. Those patients were subjected to clinical and bronchoscopic assessment for the evaluation of suspected TBA. Microbiological culture of bronchoalveolar lavage (BAL) and histopathological examination of tracheobronchial biopsies were done. RESULTS: Bronchoscopic changes suspected TBA were found in 48.2% of patients (67/139), where Aspergillus infection was confirmed microbiologically in 59.7% (40/67) and histopathologically in 56.7% (38/67). Of these changes, whitish plaques ± ulcers, pseudomembrane and/or sticky secretion with hyperemic mucosa were detected in 68.7%, 26.9% and 16.4% respectively. These changes were mostly seen in the main bronchi (54/67; 80.6%). The sensitivity, specificity, positive, negative predictive values and overall accuracy of these bronchoscopic changes as compared with BAL fluid results were 83.3%, 70.3%, 53.2%, 91.2% and 74.1% respectively. CONCLUSIONS: Bronchoscopy could be a reliable procedure for TBA diagnosis in critically ill non-neutropenic patients. Whitish plaques ± ulcers were the prominent bronchoscopic changes with reasonable diagnostic accuracy for prediction of TBA.

Usefulness of Circulating Methylated p16 as a Noninvasive Molecular Biomarker for Hepatitis C-Related Hepatocellular Carcinoma with Normal Serum Alpha-Fetoprotein Levels.

BACKGROUND: Screening of hepatocellular carcinoma (HCC) is challenged especially in patients with normal alpha-fetoprotein (AFP) levels. Aberrant p16 methylation has been implicated in HCC. OBJECTIVES AND AIMS: This study aimed to assess serum methylated p16 (MP16) expression levels and to evaluate MP16 diagnostic performance in HCC detection among HCV-infected Egyptian patients with normal AFP levels. METHODS: MP16 levels were quantified using real-time PCR in 230 serum samples (30 healthy controls, 95 with HCV-HCC, 40 with chronic hepatitis C "CHC" and 65 with HCV cirrhosis). Diagnostic performance of MP16 for diagnosis of HCC was done using receiver operator characteristic curve analysis. RESULTS: Serum MP16 levels were significantly higher in HCC than CHC, cirrhosis, and healthy subjects and significantly higher in HCC with normal AFP levels than those with higher AFP. ROC curves revealed promising diagnostic performance for MP16 in discriminating HCC with normal AFP levels from non-HCC cases. This predictive ability improved by combining MP16 and AFP (AUC of 0.872 with 100% sensitivity, 76.5% specificity, 79.1% positive predictive value, 100% negative predictive value, and 87.5% accuracy). CONCLUSION: MP16 can be a potential noninvasive molecular biomarker for HCC detection in patients with hepatic mass(es) and normal AFP levels especially in those where liver biopsy and radiological imaging cannot be done.

Differential expression of Tim-3, PD-1, and CCR5 on peripheral T and B lymphocytes in hepatitis C virus-related hepatocellular carcinoma and their impact on treatment outcomes.

BACKGROUND AND OBJECTIVE: Activation of the immune checkpoints and expression of chemokines and chemokine receptors have been reported to promote HCC progression. This study aimed to assess the differential expression of Tim-3, PD-1, and CCR5 on peripheral blood lymphocytes from patients with HCV-related HCC and correlate their expression with the treatment outcomes. PATIENTS AND METHODS: The study incorporated 40 patients with chronic HCV-related HCC and 40 healthy controls. Patients were radiologically assessed for hepatic focal lesions and portal vein thrombosis. Response to HCC treatment and overall survival (OS) outcomes were determined. The expression of Tim-3, PD-1, and CCR5 among CD19+, CD4+, and CD8+ lymphocytes was assessed by flow cytometry. RESULTS: Higher frequencies of CD4+ and CD8+ cells expressing each of Tim-3 and PD-1 and PD-1+CD19+ cells were observed in the HCV-related HCC patients in comparison with controls. The highest expression of Tim-3 and PD-1 was by the CD8+ cells. Strong relations were detected among PD-1+CD19+, PD-1+CD4+ and PD-1+CD8+ cells. Elevated levels of PD-1+ lymphocytes were significantly associated with poor treatment response and shorter OS. CONCLUSION: Modulation of the expression of immune checkpoints as Tim-3 and PD-1, and of CCR5 on T cells is somehow related to HCC. CD8+ T cells expressing PD-1 were the most relevant to HCC prognosis (OS and treatment response) and could represent a promising target for immune therapy against HCC. Future studies need to focus on exploring PD-1+ B cells and Tim-3+CD4+ cells, which seem to play a significant role in the pathogenesis of HCC.

Hepatitis C Virus Affects Tuberculosis-Specific T Cells in HIV-Negative Patients.

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.

Are there differences in risk factors, microbial aspects, and prognosis of cellulitis between compensated and decompensated hepatitis C virus-related cirrhosis?

BACKGROUND/AIMS: Cellulitis is a common infection in patients with liver cirrhosis. We aimed to compare risk factors, microbial aspects, and outcomes of cellulitis in compensated and decompensated hepatitis C virus (HCV)-related cirrhosis. METHODS: Six hundred twenty consecutive HCV-related cirrhotic patients were evaluated for cellulitis. Demographic and clinical data were evaluated, along with blood and skin cultures. Severity of cirrhosis was assessed using Child-Pugh score. In-hospital mortality was assessed. RESULTS: Seventy-seven (12.4%) cirrhotic patients had cellulitis (25 with compensated and 52 with decompensated disease). Smoking and venous insufficiency were risk factors of cellulitis in compensated cirrhosis. Leg edema, ascites, hyperbilrubinemia and hypoalbuminemia were risk factors in decompensated cirrhosis. Gram-positive bacteria (Staphylococcus spp. and Streptococcus pyogenes) were the infective organisms in compensated patients, while gram negative bacteria (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were the predominant organisms in decompensated cirrhosis. Fungi (Candida albicans and Aspergillus niger) were detected in 3 decompensated cases. In-hospital mortality in patients with cellulitis was 27.3%, approaching 100% in decompensated patients with gram-negative cellulitis. Prolonged hospitalization, higher model for end-stage liver disease (MELD)-Na score, septic shock, local complication, and recurrent cellulitis were predictors of mortality. CONCLUSION: Cellulitis in compensated cirrhosis is different from that of decompensated patients regarding microorganisms, pathogenesis, and prognosis. Cellulitis has a poor prognosis, with mortality rates approaching 100% in decompensated patients with gram-negative cellulitis. Stratifying patients according to severity of cirrhosis is important to identify the proper empirical antibiotic and to decide the proper means of care.

Role of T-Helper 9 Cells in Chronic Hepatitis C-Infected Patients.

Hepatitis C virus is a hepatotropic virus that is transmitted parenterally. Viral infections are usually associated with modulations of the immune cells, leading to enhanced viral survival and spreading, and accordingly, life-threatening complications. Recently, it has been proposed that a new subset of T-helper, named T-helper 9, is involved in the pathogenesis of different immunopathological conditions, such as allergies, tumors, and viral infections. Some studies reported a protective role, and others described a pathogenic potential for the T-helper 9 cells. Here, we present evidence that T-helper 9 cells are dynamically increased with increasing the pathogenic strategy for hepatitis C virus (HCV). Furthermore, viral clearance is associated with a decrease in T-helper 9. The increase in T-helper 9 was paralleled with an increase in its receptor expression. Taken together, our data suggest that T-helper 9 cells play an important role in the pathogenesis of HCV, and is directly associated with HCV-related complications.

Creatinine modified Child-Turcotte-Pugh and integrated model of end-stage liver disease scores as predictors of spontaneous bacterial peritonitis-related in-hospital mortality: Applicable or not.

BACKGROUND AND AIMS: Despite intensive management, spontaneous bacterial peritonitis (SBP) is associated with poor prognosis especially in hospitalized patients. Therefore, the aim of this study was to determine prognostic factors for SBP-related in-hospital mortality, and to evaluate the predictive power of Child-Pugh (CP), model of end-stage liver disease (MELD), creatinine modified Child-Turcotte-Pugh (CrCTP), and integrated MELD (iMELD) for identifying the best score to predict mortality. METHODS: Predictors of SBP-related in-hospital mortality were assessed using regression analysis over 100 cirrhotic patients. Predictive abilities of CP, MELD, CrCTP, and iMELD were compared using the area under receiver operating characteristic curve (AUC). RESULTS: SBP-related in-hospital mortality was 22%. Age, serum creatinine, bilirubin, sodium, CrCTP, MELD, and iMELD were associated with mortality. Using AUC, CrCTP, and iMELD was significantly better than CP and MELD in predicting in-hospital mortality, where iMELD had the highest AUC (0.862). The cut-off with the best ability to predict in-hospital mortality was 43.5 for iMELD. CONCLUSION: Age, serum creatinine, bilirubin, and sodium were associated with SBP-related in-hospital mortality. The incorporation of these variables into CP and MELD significantly improves their predictive ability. iMELD followed by CrCTP provided useful prognostic information for critically ill patients with SBP.

A revised scope in different prognostic models in cirrhotic patients: Current and future perspectives, an Egyptian experience.

BACKGROUND AND STUDY AIM: The prognosis of cirrhosis is of great interest for liver transplantation and new therapies of related complications. Traditional prognostic models such as Child-Pugh (CP) and Model for End-stage Liver Disease (MELD) were developed to predict mortality in decompensated cirrhosis, but lack parameter(s) related to complications. Recently, new models such as creatinine-modified Child-Turcotte-Pugh (CrCTP) and sodium-based MELD variants were developed to improve prognostic accuracy and enhance outcome predictive capability. Our aim was to investigate the prognostic ability of these models and their relation to complications among Egyptian cirrhotic patients to determine the best one and to assess adding new variables to improve the prognostic ability of that model. PATIENTS AND METHODS: A total of 1000 cirrhotic patients were enrolled in a retrospective study; traditional and new prognostic models such as CP, MELD, CrCTP, integrated MELD (iMELD), MELD plus sodium (MELD-Na, MELDNa) and MELD:sodium ratio (MESO) were calculated. The predictive abilities of prognostic models were compared using the area under receiver operating characteristic curve (AUC) and 1-year survival rates were evaluated by Kaplan-Meier survival analysis. An index of cirrhosis-related complications was added to reveal the best prognostic model. RESULTS: Using AUC, MELD and its sodium variants was significantly better than CP and CrCTP scores in predicting risk of 1-year mortality, where MELD-sodium (MELD-Na) had the highest AUC (0.743). Adding an index of cirrhosis-related complications (C) to MELD-Na creating a new scoring system (MELD-Na-C) improved its prognostic accuracy (AUC 0.753). Kaplan-Meier survival curves predicted increased mortality with higher prognostic scores. CONCLUSIONS: All prognostic models were good predictors of 1-year mortality in patients with decompensated cirrhosis; however, MELD-Na was the best for outcome prediction. MELD-Na-C was a new model enhancing the predictive accuracy in assessing cirrhotic patients with related complications.