Serum MicroRNA profiles in chronic hepatitis C Egyptian patients before and after combined sofosbuvir and daclatasvir treatment.

BACKGROUND: MicroRNAs (miR) are small sequence of nucleotides that can affect multiple genes involved in the hepatitis C virus (HCV) life cycle and disease development. The purpose of the present study was to investigate the clinical significance of serum microRNA profiles in a cohort of Egyptian patients with chronic HCV infection before and after combined sofosbuvir and daclatasvir treatment, as well as to gain a better understanding of the exact interaction mechanism in HCV transcriptional activity via differentially expressed miRNAs. For 12 weeks, 50 patients were eligible for and received sofosbuvir (400 mg daily) and daclatasvir (60 mg daily) treatment. Each patient's blood was obtained twice: once before therapy began and again three months afterwards. RESULTS: The current study found that serum levels of circulating miR-122, miR-221, miR-23a, miR-125, miR-217, miR-224, and miR-181a were high in HCV pre-treatment patients, but after 12 weeks of direct-acting antiviral (DAAs) treatment, there was a statistically significant reduction in expression levels of miR-122, miR-221, miR-23a, miR-125, miR-217, and miR-224 (p < 0.001). There is no statistical significance for miR-181a. CONCLUSION: The key differentially expressed microRNAs before and after the direct-acting antiviral (DAA) regimen were connected to the dynamics of chronic HCV infection, suggesting their potential as predictive biomarkers for HCV clearance after sofosbuvir and daclatasvir therapy.

The need for a risk-assessment tool among patients with chronic liver diseases interested in intermittent fasting: Ramadan model.

Liver diseases, especially the chronic type, are a global concern. There is a growing interest in the intermittent fasting model due to its presumed health benefits. Ramadan fasting, although religious fasting, is one of the best examples of intermittent fasting, with some differences, and is observed by more than 1 billion Muslims around the world. This month follows the Arabic Hijri calendar, which is 12 days shorter than the Gregorian calendar; hence, this entire month of fasting may occur in any season of the year. There is evidence that many patients with chronic liver disease are prone to adverse events upon observing this month of continuous intermittent fasting, particularly during the hot summer with prolonged hours of fasting, if they are not adequately addressed and prevented from fasting. There is a need to sound the alarm to develop a risk-assessment tool to omit vulnerable patients with chronic liver disease-who are exempted on religious grounds from observing this pattern of fasting.

Schistosomal (bilharzial) polyps: Travel through the colon and beyond.

Schistosomiasis (bilharziasis) is a major neglected tropical disease. It is endemic in many tropical and subtropical communities. Schistosomal polyps (S. polyps) are not uncommon presentation of this infection. Although the colon is the most commonly affected organ, many other organs are affected. S. polyps are associated with a variable range of morbidity independent of the Schistosomal infection. S. polyps are frequently described in endemic areas and increasingly reported in non-endemic areas mainly among immigrants and visitors to the endemic areas. This review aimed to increase awareness of practitioners, especially gastroenterologists, for this peculiar type of polyps caused by this neglected infection hence improving patient outcomes. Web-based search of different databases was conducted for the literature focusing the development of S. polyps in the colon and other organs with analysis of the clinical manifestations, diagnosis and treatment. The following key words were used in the search, "Schistosomiasis" OR "Bilharziasis" AND "Polyps" OR "Polyp" AND "Colon" OR "Small intestine" OR " Duodenum" OR " Stomach" OR "Esophagus" OR " Gallbladder" OR" Pharynx" OR "Larynx" OR "Trachea" OR "Urinary bladder" OR " Ureter" OR "Renal Pelvis" OR "Urethra". All publication types including case reports, case series, original research, and review articles were retrieved and analyzed. S. polyps are not infrequent presentation of acute or chronic Schistosomal infection. S. polyps are described in many organs including the bowel, genitourinary tract, skin, gallbladder and the larynx. Presentation of S. polyps is variable and depends on the site, number as well as the polyp size. The relationship of S. polyps to malignant transformation is a matter of discussion. Presence of S. polyps is sometimes the only manifestation of Schistosomiasis. Small polyps can be treated medically with praziquantel, while large accessible polyps are amendable for endoscopic excision through different polyp resection techniques. However, huge, complicated, non-accessible and suspicious polyps are indicated for surgical management or advanced endoscopic resection when appropriate. Clinicians and endoscopists should be aware about these facts when treating patients living in, immigrated from or visiting endemic areas.

Sonographic gallbladder wall thickness measurement and the prediction of esophageal varices among cirrhotics.

Acute variceal bleeding in patients with liver cirrhosis and portal hypertension (PHT) is the most serious emergency complication among those patients and could have catastrophic outcomes if not timely managed. Early screening by esophago-gastro-duodenoscopy (EGD) for the presence of esophageal varices (EVs) is currently recommended by the practice guidelines for all cirrhotic patients. Meanwhile, EGD is not readily accepted or preferred by many patients. The literature is rich in studies to investigate and validate non-invasive markers of EVs prediction aiming at reducing the unneeded endoscopic procedures. Gallbladder (GB) wall thickness (GBWT) measurement has been found promising in many published research articles. We aim to highlight the validity of sonographic GBWT measurement in the prediction of EVs based on the available evidence. We searched databases including Cochrane library, PubMed, Web of Science and many others for relevant articles. GBWT is associated with the presence of EVs in cirrhotic patients with PHT of different etiologies. The cut-off of GBWT that can predict the presence of EVs varied in the literature and ranges from 3.1 mm to 4.35 mm with variable sensitivities of 46%-90.9% and lower cut-offs in viral cirrhosis compared to non-viral, however GBWT > 4 mm in many studies is associated with acceptable sensitivity up to 90%. Furthermore, a relation was also noticed with the degree of varices and portal hypertensive gastropathy. Among cirrhotics, GBWT > 3.5 mm predicts the presence of advanced (grade III-IV) EVs with a sensitivity of 45%, the sensitivity increased to 92% when a cut-off ≥ 3.95 mm was used in another cohort. Analysis of these results should carefully be revised in the context of ascites, hypoalbuminemia and other intrinsic GB diseases among cirrhotic patients. The sensitivity for prediction of EVs improved upon combining GBWT measurement with other non-invasive predictors, e.g., platelets/GBWT.

The Impact of interferon lambda 3 Polymorphism on Hepato-Cellular Carcinoma Progression in Hepatitis C Virus Patients: Treatment-Naïve and Experienced.

OBJECTIVES: In this study, we investigated the association between the IFN-λ3 rs12979860 single nucleotide polymorphism (SNP) and the transition from late fibrosis to HCC in Egyptian HCV-chronically infected patients. METHODS: The rs12979860 SNP was genotyped using real-time PCR in DNA from the whole blood of healthy subjects (n=60) and HCV patient   s (n=342). We stratified the patients into (1) treatment-naïve patients (n=218) with advanced fibrosis (F2-F4, n=123) and HCC (n=95 Treatment-experienced patients (n=124)  who received SOF-based therapy for 12 weeks and achieved SVR (SVR12). DAA-treated patients were divided into 2 groups: group I (n=63) included patients with advanced hepatic fibrosis (F2-F4) who did not develop HCC within a year after treatment, and group II (n=61) included patients who were free of focal hepatic lesions before starting DAA therapy but developed HCC within a year. RESULTS: Our results demonstrated that treatment-naïve patients with the CT/TT genotypes and the T allele were more likely to have HCC (odds ratio 3.1, 95% CI 1.44-6.71, P = 0.003 and odds ratio 1.89, 95% CI 1.28-2.76, P = 0.001, respectively). Binary regression analysis defined 3 independent predictors associated with HCC development: age (odds ratio 1.039, 95% CI 1.004-1.076, P = 0.028), alanine aminotransferase (odds ratio 1.008, 95% CI 1.002-1.015, P = 0.010), and rs12979860 (odds ratio 3.65, 95% CI 1.484-8.969, P = 0.005). CONCLUSIONS: However, the rs12979860 SNP did not show any correlation with the progression of HCC post-treatment. Despite the debate on the contribution of IFN-λ3 rs12979860 to susceptibility to HCV-related HCC, our data confirm the role of this SNP in this context.

Different patterns of esophageal motility disorders among patients with dysphagia and normal endoscopy: A 2-center experience.

Esophageal motility disorders (EMDs) are the main etiology of nonobstructive dysphagia (NOD), but they are underestimated in Egypt. High-resolution manometry (HRM) with Chicago Classification version 3.0 (CC v3.0) is the current gold standard diagnostic modality to assess EMD in patients with NOD. In this HRM-based study, we aimed to classify EMD among Egyptian patients and explore the relationship between the severity of symptoms and the various groups of EMD. From January 2020 to January 2021, patients with dysphagia were subjected to diagnostic workup, which included symptom questionnaire for Eckardt score, esophagogastroduodenoscopy, barium esophagogram, and HRM. All patients were categorized based on the HRM results using CC version 3.0 after exclusion of those with obstructive esophageal lesions. Of 252 patients with dysphagia, 55 patients with NOD were analyzed according to CC version 3.0. Achalasia was diagnosed in 31 patients (56.4%) (type I: 18 [58.06%]; type II: 9 [29.03%], and type III: 4 [12.9%]), 3 patients (5.5%) with esophagogastric junction outflow obstruction, 2 patients (3.6%) with absent contractility, 4 patients (7.3%) with distal esophageal spasm, 7 patients (12.7%) with ineffective esophageal motility, and 8 patients (14.5%) with normal manometry. Patients with achalasia experienced significantly high regurgitation (96.8% vs 70.8%; P = .016) compared with those without achalasia. Achalasia was the most common EMD in Egyptian patients with NOD. Eckardt score was higher in patients with outflow obstruction and major motor disorder, but it could not differentiate different categories of CC of EMD. HRM is effective in characterization of EMD.

The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients.

Hepatitis C virus (HCV) is the leading cause of liver diseases worldwide. At present, combinations of different classes of direct-acting antiviral agents (DAAs) are used as treatment options for HCV, in which sofosbuvir (SOF) is the common DAA among different therapeutic regimes. In Egypt, SOF plus daclatasvir (DCV) is the widely used anti-HCV treatment protocol. Herein, we aimed to assess the association between 3 single-nucleotide polymorphisms (SNPs) at the genes coding for 2 SOF metabolizing enzymes: histidine triad nucleotide-binding protein 1 (HINT1) rs4696/rs7728773 and nucleoside diphosphate kinase 1 (NME1) rs3760468, together with the most potent anti-HCV innate molecule, i.e., interferon lambda 3 (IFNL3) rs12979860 and the response to SOF/DCV in Egyptian patients chronically infected with genotype 4 (GT4). SNPs were genotyped using real-time PCR in DNA from patients who achieved sustained virological response (SVR) at 12 weeks post-SOF/DCV treatment (i.e., responders; n = 188), patients who failed to achieve SVR12 (i.e., non-responders; n = 109), and healthy controls (n = 62). Our results demonstrated that patients bearing HINT1 rs7728773 CT/TT (odds ratio 2.119, 95% CI 1.263-3.559, p = 0.005) and IFNL3 rs12979860 CC (odds ratio 3.995, 95% CI 2.126-7.740, p = 0.0001) were more likely to achieve SVR12. However, neither HINT1 rs4696 nor NME1 rs3760468 seems to contribute to the responsiveness to SOF/DCV. Binary regression analysis defined 5 predictor factors independently associated with SVR12: age, bilirubin, hemoglobin, early stages of fibrosis, and combined HINT1 rs7728773 and IFNL3 rs12979860 favorable and mixed genotypes (odds ratio 3.134, 95% CI 1.518-6.47, p = 0.002), and that was confirmed by the combined ROC curve for the 5 predictor factors (AUC = 0.91, 95% CI 0.869-0.95, P = 0.0001). In conclusion, these data suggest that the two SNPs have the potential in predicting the response rate to SOF/DCV treatment in patients infected with HCV GT4. This study is the first to investigate the pharmacogenetics of SOF metabolizing enzyme and introduce HINT1 rs7728773 as a novel SNP that predicts the treatment efficacy.

Laparoscopy-Assisted Endoscopic Retrograde Cholangiopancreatography: New Insight in Management of Iatrogenic Bile Duct Injury.

Bile duct injury (BDI) is a severe and sometimes life-threatening complication of cholecystectomy. Several series have described a 0.5% to 0.6% incidence of BDI during laparoscopic cholecystectomy. We received an emergency call from the operating theater by the surgery team to assess an iatrogenic BDI in a 58-year-old man with cirrhosis who presented for laparoscopic cholecystectomy. After many trials by endoscopic retrograde cholangiopancreatography (ERCP) the guide wire passed to the peritoneal cavity and failed to pass proximally. Laparoscopy resumed, and the surgeon tried to pass the flexible guide wire proximally unsuccessfully. Then, a decision to hold the sphincterotome by laparoscopy and passing it proximally in harmony with ERCP was taken, which was successful. A regular ERCP with 10F plastic stent insertion was carried out, and the perforation was secured by the inserted stent without any further surgical intervention. Laparoscopy-assisted ERCP may give new insights into the immediate repair of iatrogenic bile duct injuries.

Ramadan fasting and liver diseases: A review with practice advices and recommendations.

Ramadan fasting is obligatory for Muslim healthy adults. However, there are many exemptions from fasting; including patients, whose diseases will be aggravated by fasting. Muslim patients with different liver diseases are frequently seen in the clinics discussing their intent to fast this month with their treating physicians. To answer our patients' inquiries about the expected benefits and/or risks of fasting and delivering them the best care, we carried out this review and we draw advices and recommendations based on the available evidence. A web-based search, combining multiple keywords representing different liver diseases with Ramadan fasting had been carried out. To answer the research question: Do adult Muslim patients with different liver diseases who fast the month of Ramadan have had a deleterious effect on their health in comparison to those who did not fast? Relevant publications were retrieved. No randomized controlled trials were focusing on Ramadan fasting and liver diseases in the filtered databases, eg Cochrane library. Consequently, non-filtered databases, eg PubMed, Google Scholar and Egyptian Knowledge Bank searched and full-text high-quality research articles were carefully analysed to draw recommendations. Other relevant publications with low quality of evidence like case studies and short communications were also reviewed to address practice advices. Although Ramadan fasting was found beneficial for patients with NAFLD, it was found deleterious to patients with Child B and C cirrhosis and patients with peptic ulcer. Patients with chronic hepatitis, Child A cirrhosis and those with non-complicated liver transplant can fast with prefasting assessment and strict follow up.