Anti-cancer effect of nano-encapsulated boswellic acids, curcumin and naringenin against HepG-2 cell line.

BACKGROUND: liver cancer is one of the most common cancers in the world. So far, there is no gold standard treatment for hepatocellular carcinoma. We conducted this in vitro study to assess the effect of three natural products: Boswellic acids, curcumin and naringin versus corresponding nanoparticles (NPs) on Hep G2 cells proliferation. METHODS: Boswellic acid, curcumin, naringin-loaded NPs were prepared using nanoprecipitation method. Human liver (HepG2) cell line was cultured in Dulbecco's modified Eagle's medium (DMEM). The cell growth inhibition and cytotoxicity were evaluated by MTT assay. RESULTS: Boswellic acid, curcumin, naringin were able to inhibit HepG2 cells proliferation. IC50 at 24 h, 48 h showed significant lower values in NPs versus Free herbs. IC50 values of free Boswellic acids and NPs at 24 h were (24.60 ± 1.89 and 7.78 ± 0.54, P < 0.001), at 48 h were (22.45 ± 1.13 and 5.58 ± 0.27, P < 0.001) respectively. IC50 values of free curcumin and NPs at 24 h were (5.89 ± 0.8 and 3.46 ± 0.23, P < 0.05), at 48 h were (5.57 ± 0.94 and 2.51 ± 0.11, P < 0.05), respectively. For free and naringenin NPs, IC50 values at 24 h were (14.57 ± 1.78 and 7.25 ± 0.17, P < 0.01), at 48 h were (11.37 ± 1.45 and 5.21 ± 0.18, P < 0.01) respectively. CONCLUSION: Boswellic acid, curcumin, naringin and their nanoprecipitation prepared nanoparticles suppressed Hep G2 cells proliferation.

Quadruple Therapy Offers High SVR Rates in Patients with HCV Genotype 4 with Previous Treatment Failure.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) have made a revolution in hepatitis C virus (HCV) treatment with promising reduction of HCV infection and disease morbidities. However, unfortunately, treatment failure still occurs in about 5-15% of patients treated with DAA-based combination regimens. The primary aim of the study was to assess the efficacy and safety of a quadruple regimen of (sofosbuvir, daclatasvir, and simeprevir with a weight-based ribavirin) in chronic HCV DAAs-experienced patients. METHODS: This observational, open-label prospective study was carried out on 103 genotype 4 hepatitis C virus-infected patients who failed to achieve SVR12 after sofosbuvir-daclatasvir with or without ribavirin. Patients were treated for three months with sofosbuvir (400 mg), daclatasvir (60 mg), and simeprevir (150 mg) with a weight-based ribavirin dosage (1000-1200 mg/d). Response to treatment was determined by quantitative PCR for HCV at 3 months after the end of treatment (SVR12), and adverse events during the treatment were recorded. RESULTS: SVR was achieved in 100 patients (97.1%) at week 12 after treatment. No dangerous or life-threatening adverse events were recorded. CONCLUSIONS: Retreatment of HCV genotype 4 patients with quadruple therapy is a good therapeutic option and achieves high response rates with minimal side effects.

Sofosbuvir, Pegylated Interferon and Ribavirin in the Treatment of an Egyptian Cohort with Hepatitis C Virus Infection in Real-Life Clinical Practice.

BACKGROUND & AIMS: Hepatitis C virus infection is a major public health problem in Egypt with a risk for morbidity and mortality due to chronic liver disease complications. Worldwide, Egypt has the highest prevalence of HCV infection with the overall prevalence of about 14.7%. The aim of this study was to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir (SOF) plus Pegylated Interferon (Peg- IFNa) and Ribavirin (RBV) in Egyptian patients with chronic hepatitis C virus (HCV) infection. METHODS: This study was carried out in 1200 patients with chronic hepatitis C virus infection who were eligible for interferon therapy. They were treated with the triple therapy of sofosbuvir 400 mg once daily, Peg-INF subcutaneous injection weekly for 12 weeks in combination with oral weight-based ribavirin. The primary outcome measures were the number of patients with successful eradication of the virus evidenced by the sustained virologic response (SVR) at 12 Weeks. After discontinuation of Therapy (SVR12), the secondary outcome measures were the incidence of adverse effects associated with the tested HCV therapy. RESULT: The mean age of the patients was 49.32 ± 6.97 years. 45.9% of them were males and 54.1% were females.70 patients (5.8%) had a history of previous HCV treatment. ''1077 (89.8%)'' of patients achieved successful eradication of virus while ''106 (8.8%)'' were resistant to treatment and ''17 (1.4%)'' stopped treatment. Good predictors of response to the triple therapy were female gender, treatment naive and non-cirrhotic patients. CONCLUSION: The triple regimen of Pegylated interferon, sofosbuvir plus ribavirin is safe and effective in the treatment of Egyptian patients with hepatitis C virus and is associated with real-life SVR12 rates of 89.8%.

Predicting Esophageal Varices in Cirrhotic Hepatitis C Virus Patients Using Noninvasive Measurement of Insulin Resistance Variables.

BACKGROUND & AIMS: Esophageal varices (EV) are a major complication of portal hypertension in cirrhotic patients. Screening is essential for all patients with cirrhosis. Performing non-invasive methods for screening is a cost-effective and time-saving measure. The aim of this work is to evaluate whether insulin resistance (IR) assessed by HOMA-IR score can predict the presence of EV or not. METHODS: This cross-sectional study was carried out on sixty Egyptian cirrhotic HCV patients divided into 3 groups: Group I: 20 cirrhotic patients without esophageal varices, Group II: 20 cirrhotic patients, with small esophageal varices and Group III: 20 cirrhotic patients with large esophageal varices. Fasting insulin level was measured and HOMA- IR score was calculated. Abdominal ultrasound and Fibroscan were done to all patients. RESULTS: Insulin resistance assessed by HOMA -IR score showed a statistically significant difference among the three groups (P<0.001) with a cutoff value equal to or more than 3.40. It could significantly predict EV (AUROC= 0.841) with high sensitivity of 75 %, and excellent specificity 80%. Liver stiffness measurement (LSM) with a cutoff value 40.95 kPa could significantly predict EV (AUROC= 0.629) with sensitivity 75 %, specificity 50 %. CONCLUSION: HOMA-IR score is a new independent predictor of the presence of EV.

A novel scoring system for prediction of esophageal varices in critically ill patients.

BACKGROUND AND AIMS: Patients with advanced systemic illness or critically ill patients may present with upper gastrointestinal tract (GIT) bleeding which may need endoscopic intervention; however, this may expose them to unnecessary endoscopy. The aim was to validate a novel scoring system for risk stratification for urgency of GIT endoscopy in critically ill patients. METHODS: This is an observational study conducted from January 2013 to January 2016 to analyze 300 patients with critical medical conditions and presenting with upper gastrointestinal bleeding. Meticulous clinical, laboratory, and sonographic evaluations were performed to calculate Glasgow Blatchford score (GBS) and variceal metric score for risk stratification and prediction of the presence of esophageal varices (OV). Finally, this score was applied on a validation group (n=100). RESULTS: The use of GBS and variceal metric scores in critically ill patients revealed that patients who showed a low risk score value for OV (0-4 points) and GBS <2 can be treated conservatively and discharged safely without urgent endoscopy. In patients with a low risk for varices but GBS >2, none of them had OV on endoscopy. In patients with intermediate risk score value for OV (5-8 points) and with GBS >2, 33.33% of them had varices on endoscopy. In patients with high risk score value for varices (9-13) and GBS >2, endoscopy revealed varices in 94.4% of them. Finally, in patients with very high risk score for varices (14-17), endoscopy revealed varices in 100% of them. CONCLUSION: GBS and variceal metric score were highly efficacious in identifying critically ill patients who will benefit from therapeutic endoscopic intervention.

Randomized Controlled Study Comparing Use of Propofol Plus Fentanyl versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients with Advanced Liver Disease.

OBJECTIVES: We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy. METHODS: A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopist rating, and hemodynamic parameters including oxygen saturation, heart rate, mean arterial pressure, incidence of side effect as (bradycardia, hypotension, hypoxia, nausea and vomiting, cough, shivering, or diplopia), time needed for complete recovery, and time needed for discharge. RESULTS: There was no statistical significant difference between the studied groups regarding age, sex, weight, Child-Pugh classification score, type and duration of endoscopic intervention, time needed for complete recovery, or time needed for discharge. Complication rates were similar in both groups except for mean arterial blood pressure which was significantly lower in group of patients receiving propofol and fentanyl (P = 0.001). CONCLUSION: The use of either propofol or midazolam in combination to fentanyl is effective in sedation of patients with advanced liver diseases presented for upper GIT endoscope. The trial is registered with ClinicalTrials.gov Identifier: NCT03063866.