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.

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.

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.