Rehab Badawi

Efficacy and safety of sofosbuvir–ledipasvir for treatment of a cohort of Egyptian patients with chronic hepatitis C genotype 4 infection

Background and aims Treatment of hepatitis C virus (HCV) infection has significantly changed during the last few years. The combination of ledipasvir and sofosbuvir has been shown to treat high proportions of patients with HCV genotype 1 with remarkable tolerability. The aim of the work was to assess the efficacy and safety of sofosbuvir plus ledipasvir in treating treatment-naïve Egyptian patients with genotype 4 HCV infection. Patients and methods In this open-label randomized study, 200 treatment-naive patients who were HCV antibody positive and HCV RNA positive by polymerase chain reaction, aged >18 years, were enrolled. The patients were classified into two groups: group I included 100 patients who received single therapy with sofosbuvir plus ledipasvir for 12 weeks and group II included 100 patients who received sofosbuvir plus oral weight-based ribavirin for 24 weeks. The primary end point was a sustained virological response at 12 weeks (SVR12) after the end of treatment, determined by quantitative polymerase chain reaction for HCV RNA. Results Group I patients showed statistically significant (p<0.05) higher SVR12 compared with group II patients (99% vs. 80%). There was no statistical difference (p>0.05%) between the studied groups regarding the frequencies of the side effects (26% vs. 29%). The most common adverse effects were headache, fatigue, myalgia, and cough. Conclusion Sofosbuvir and ledipasvir treatment for 12 weeks was well tolerated by patients with HCV genotype 4 and resulted in 99% SVR for all patients who received 12 weeks of the study drugs. ClinicalTrials.gov Identifier: NCT02992457.

Anti-Nuclear Cytoplasmic Antibody–Associated Vasculitis: A Probable Adverse Effect of Sofosbuvir Treatment in Chronic Hepatitis C Patients

Background Egypt has the largest hepatitis C virus (HCV) epidemic worldwide. Sofosbuvir is an antiviral drug acting by inhibition of the HCV NS5B polymerase. It has shown high efficacy in combination with several other drugs and has a low reported rate of side effects. Objective The aim of this prospective cohort study was to assess the safety of sofosbuvir-based treatment regimens used to treat chronic hepatitis C infections and to detect any side effects of sofosbuvir not previously reported. Methods We studied treatment side effects in 3,000 patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24 weeks or treated by pegylated interferon, sofosbuvir, and ribavirin triple therapy for 12 weeks. The endpoint of the study was the end of treatment. Results Hyperbilirubinemia occurred frequently during treatment in both groups. Treatment was discontinued in 72 cases due to hepatic decompensation and drug complications; 8 of the cases had deep vein thrombosis (DVT) and 7 had cerebral ischemia. Surprisingly, 177/3,000 (5.9%) patients presented with abnormal bleeding, 85 of whom had a vasculitic skin rash. Conclusion We report the occurrence of previously nonrecorded side effects with sofosbuvir, namely DVT and bleeding disorders associated with anti-nuclear cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We believe this to be the first report of sofosbuvir-induced AAV skin lesions and bleeding disorders.

Pilot study of orphenadrine as a novel treatment for muscle cramps in patients with liver cirrhosis

Background and aims Muscle cramps markedly affect the quality of life in cirrhotic patients with no available highly effective treatment. The aim of this study was to assess the safety and efficacy of orphenadrine in the treatment of muscle cramps in cirrhotic patients. Methods The study enrolled 30 liver cirrhosis patients complaining of frequent muscle cramps (≥3 per week), who were randomized to receive either orphenadrine 100 mg or calcium carbonate 500 mg twice daily as a control for one month. Severity, frequency, and duration of the muscle cramps were assessed before and after treatment as well as recurrence after washout of the drug for two weeks. Side effects were recorded. Results One month after treatment with orphenadrine; the frequency of muscle cramps decreased significantly to 0.6 ± 0.74 per week compared to 12.53 ± 6.01 at baseline (p < 0.001), the duration of muscle cramps decreased from 1 min to 0.1 min after treatment (p < 0.001). The pain score improved significantly from a score of 8/10 to 0/10 (p < 0.001). The side effects were few, such as dry mouth, drowsiness, and nausea, with no significant difference between their occurrences in the two groups. Conclusion Orphenadrine is safe and effective in treatment of muscle cramps in patients with liver cirrhosis.

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.

Serum FBLN1 and STK31 as biomarkers of colorectal cancer and their ability to noninvasively differentiate colorectal cancer from benign polyps

PURPOSE The aim of this work is to evaluate Fibulin-1 (FBLN1) and serine threonine kinase-31 (STK31) as colorectal cancer (CRC) tumour markers and their ability to differentiate it from colorectal benign lesions. MATERIAL AND METHODS In this case-control study, FBLN1 and STK31 serum levels were measured in 120 participants; 49 CRC patients (group I), 26 patients with benign colorectal polyps (group II) and 45 healthy controls (group III). RESULTS The means of serum FBLN1 were 1.02 ± 0.95, 6.36 ± 2.55 and 6.26 ± 2.76 in group I, II and III respectively. Significant lower levels were found in group I compared to group II and III (both p < 0.001) with no significant difference between group II and III (p = .983). The means of serum STK31 were 13.51 ± 7.67, 5.98 ± 3.3 and 1.37 ± 1.22 in group I, II and III respectively with significant differences in-between the 3 groups (p < 0.001). Both FBLN1 and STK31 were superior to CEA as CRC screening biomarkers; with sensitivity 90.1% and 93% respectively and specificity 93.9% and 95.9% respectively. FBLN1 differentiated CRC from benign polyps with 91.8% sensitivity and 100% specificity. STK31 differentiated CRC from benign polyps with 93.9% sensitivity and 84.6% specificity. CONCLUSION FBLN1 and STK31 can be possible screening and differentiating biomarkers of CRC.

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.

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.